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['Post-flight data suggests immunity is dysregulated immediately following spaceflight, however this data may be influenced by the stress effects of high-G entry and readaptation to terrestrial gravity. It is unknown if immunity is altered during spaceflight.', 'Blood samples were collected from 19 US Astronauts onboard the Space Shuttle ~24 h prior to landing and returned for terrestrial analysis. Assays consisted of leukocyte distribution, T cell blastogenesis and cytokine production profiles.', 'Most bulk leukocyte subsets (WBC, differential, lymphocyte subsets) were unaltered during spaceflight, but were altered following landing. CD8+ T cell subsets, including cytotoxic, central memory and senescent were altered during spaceflight. T cell early blastogenesis varied by culture mitogen. Functional responses to staphylococcal enterotoxin were reduced during and following spaceflight, whereas response to anti-CD3/28 antibodies was elevated post-flight. The level of virus specific T cells were generally unaltered, however virus specific T cell function was depressed both during and following flight. Plasma levels of IFNα, IFNγ, IL-1β, IL-4, IL-10, IL-12, and TNFα were significantly elevated in-flight, while IL-6 was significantly elevated at R\u2009+\u20090. Cytokine production profiles following mitogenic stimulation were significantly altered both during, and following spaceflight. Specifically, production of IFNγ, IL-17 and IL-10 were reduced, but production of TNFα and IL-8 were elevated during spaceflight.'] Does immune system dysregulation occur during short duration spaceflight on board the space shuttle? | qiaojin/PubMedQA | 2 | [
-2.4293479919433594,
-1.1338222026824951,
2.601267099380493
] |
['Inhibition of PARP is a promising therapeutic strategy for homologous recombination-deficient tumors, such as BRCA1-associated cancers. We previously reported that BRCA1-deficient mouse mammary tumors may acquire resistance to the clinical PARP inhibitor (PARPi) olaparib through activation of the P-glycoprotein drug efflux transporter. Here, we show that tumor-specific genetic inactivation of P-glycoprotein increases the long-term response of BRCA1-deficient mouse mammary tumors to olaparib, but these tumors eventually developed PARPi resistance. In a fraction of cases, this resistance is caused by partial restoration of homologous recombination due to somatic loss of 53BP1. Importantly, PARPi resistance was minimized by long-term treatment with the novel PARP inhibitor AZD2461, which is a poor P-glycoprotein substrate. Together, our data suggest that restoration of homologous recombination is an important mechanism for PARPi resistance in BRCA1-deficient mammary tumors and that the risk of relapse of BRCA1-deficient tumors can be effectively minimized by using optimized PARP inhibitors.'] Does loss of 53BP1 cause PARP inhibitor resistance in Brca1-mutated mouse mammary tumors? | qiaojin/PubMedQA | 2 | [
-2.443787097930908,
-1.1121662855148315,
2.5872726440429688
] |
['HIV-infected patients have a greater burden of sub-clinical and clinical atherosclerotic disease compared to the general population. The primary objective of this study was to compare the relative roles of inflammation, endothelial alterations, and metabolic factors in the induction and maintenance of atherosclerosis in antiretroviral therapy (ART)-treated or ART-naive patients.', 'Cross-sectional study; 79 HIV-infected patients (55 ART-treated and 24 naive individuals) were consecutively enrolled. In both groups, nearly 50% of the individuals had a high cardiovascular risk (Framingham value >20%).', "Echo-Doppler [intima-media thickness (IMT)], inflammatory, thrombophilic, endothelial, metabolic indexes, and cholesterol efflux molecules were evaluated. Multivariate analysis adjusted for age, CD4 nadir, BMI, and Framingham's score were used to analyze the results.", 'A complex pathogenesis drives atherogenesis in HIV infection. Thus, whereas inflammation could be responsible for this process in ART-naive individuals, metabolic factors [low-density lipoprotein (LDL), apolipoprotein B (ApoB), lipoprotein A] seem to play a more prevalent role in ART-treated patients. Notably, ABCA-1, an ATP-binding transporter cassette protein involved in cholesterol efflux, which is inhibited by Nef, is up-regulated in ART-treated individuals.'] Is atherosclerosis associated with multiple pathogenic mechanisms in HIV-infected antiretroviral-naive or treated individuals? | qiaojin/PubMedQA | 2 | [
-2.5555593967437744,
-1.209607720375061,
2.880302906036377
] |
['The pharmacokinetics (PK) of labetalol show wide inter-subject variability, but the genetic causes for this are largely undetermined. This study was performed to examine whether common polymorphisms in UGT1A1, UGT2B7, CYP2C19 and ABCB1 affect the PK of labetalol.', 'The PK of labetalol were determined in 37 Chinese healthy male subjects who took a single oral dose of 200 mg labetalol. Plasma concentrations of labetalol were determined by a high-performance liquid chromatographic method. Subjects were genotyped for the CYP2C19 2 and 3, UGT1A1 6, 28 and 60, UGT2B7 2 and ABCB1 1236C>T, 2677G>T/A and 3435C>T polymorphisms.', 'Subjects with the CYP2C19 2/ 2 genotype had a higher peak concentration (255.5\u2009±\u200980.1 vs. 156.0\u2009 ±\u2009 66.3 ng/mL; P\u2009<\u20090.05) and area under the concentration-time curve (AUC0-∞; 1,473.7\u2009±\u2009493.6 vs. 502.8\u2009±\u2009176.1 ng[Symbol: see text]h/mL; P\u2009<\u20090.001) than subjects with 60 or 28, and UGT2B7 2 did not result in a significant effect. Subjects with ABCB1 2677TA or TT or ABCB1 3435TT genotypes had higher AUC0-∞ and lower total clearance than the wild-types (P\u2009<\u20090.05), but this appeared to be related to the distribution of CYP2C19 genotypes. The CYP2C19 genotype appeared to be the only predictor of labetalol concentrations, accounting for approximately 60 % of the total variance in the AUC0-∞.'] Does cYP2C19 genotype have a major influence on labetalol pharmacokinetics in healthy male Chinese subjects? | qiaojin/PubMedQA | 2 | [
-0.8650161027908325,
-1.651341199874878,
1.5134730339050293
] |
['Donor brain death (BD) triggers inflammatory graft activation that leads to impaired graft quality and outcome. We used a mouse BD model to investigate graft inflammation in cardiac transplants from immune-competent and immune-deficient donor animals. Effects of donor T-cell depletion were tested in an additional group of cardiac transplant recipients.', 'We analyzed systemic and graft-specific inflammatory activation after BD in donors and in syngeneic recipients of hearts retrieved from BD donors. To dissect the role of donor-specific immune cells in communicating BD-triggered inflammation, immune-deficient T-cell-, B-cell-, and natural killer cell-deficient Rag2/double knockout mice and naïve C57BL6 treated with anti-thymocyte globulin (Thymoglobulin; Genzyme Transplant, Cambridge, MA) were observed.', 'Donor BD boosted lymphocyte activation in donors and recipients of syngeneic BD grafts. Lymphocyte activation was mitigated in recipients of immune-deficient and Thymoglobulin-treated BD donor grafts. Likewise, systemic and intra-graft levels of inflammatory cytokines interleukin -1, interleukin-6, interferon-γ, and tumor necrosis factor-α were significantly reduced in immune-deficient and anti-thymocyte globulin-treated recipients. Dense lymphocyte infiltrates were detected in the hearts from untreated BD donors; in contrast, the hearts from donors treated with Thymoglobulin demonstrated a preserved structure with minimal infiltrates comparable with naïve controls.'] Do graft-specific immune cells communicate inflammatory immune responses after brain death? | qiaojin/PubMedQA | 2 | [
-2.453035593032837,
-1.306640625,
2.8326148986816406
] |
['To investigate the expression of myofibrillogenesis regulator-1 (MR-1) in relation to clinicopathological parameters and postoperative survival in a group of Chinese patients with gastric cancer.', 'In our previous study of human whole-genome gene expression profiling, the differentially expressed genes were detected in the gastric cancer and its adjacent noncancerous mucosa. We found that MR-1 was associated with the location and differentiation of tumors. In this study, MR-1 protein expression was determined by immunohistochemistry in specimens of primary cancer and the adjacent noncancerous tissues from gastric cancer patients. A set of real-time quantitative polymerase chain reaction assays based on the Universal ProbeLibrary-a collection of 165 presynthesized, fluorescence-labeled locked nucleic acid hydrolysis probes-was designed specifically to detect the expression of MR-1 mRNA. The correlation was analyzed between the expression of MR-1 and other tumor characteristics which may influence the prognosis of gastric cancer patients. A retrospective cohort study on the prognosis was carried out and clinical data were collected from medical records.', 'MR-1 mRNA and protein could be detected in gastric cancer tissues as well as in matched noncancerous tissues. MR-1 was up-regulated at both mRNA (5.459 ± 0.639 vs 1.233 ± 0.238, P < 0.001) and protein levels (34.2% vs 13.2%, P = 0.003) in gastric cancer tissues. Correlation analysis demonstrated that high expression of MR-1 in gastric cancer was significantly correlated with clinical stage (P = 0.034). Kaplan-Meier analysis showed that the postoperative survival of the MR-1 positive group tended to be poorer than that of the MR-1 negative group, and the difference was statistically significant (P = 0.002). Among all the patients with stage\u2005I-IV carcinoma, the 5-year survival rates of MR-1 positive and negative groups were 50.40% and 12.70%, respectively, with respective median survival times of 64.27 mo (95%CI: 13.41-115.13) and 16.77 mo (95%CI: 8.80-24.74). Univariate and multivariate analyses were performed to compare the impact of MR-1 expression and other clinicopathological parameters on prognosis. In a univariate analysis on all 70 specimens, 6 factors were found to be significantly associated with the overall survival statistically: including MR-1 expression, depth of invasion, distant metastasis, lymph node metastasis, vascular invasion and the tumor node metastasis (TNM) stage based on the 7th edition of the International Union against Cancer TNM classification. To avoid the influence caused by univariate analysis, the expressions of MR-1 as well as other parameters were examined in multivariate Cox analysis. Clinicopathological variables that might affect the prognosis of gastric cancer patients were analyzed by Cox regression analysis, which showed that MR-1 expression and TNM stage were independent predictors of postoperative survival. The best mathematical multivariate Cox regression model consisted of two factors: MR-1 expression and TNM stage. Our results indicated that MR-1 protein could act as an independent marker for patient overall survival [Hazard ratio (HR): 2.215, P = 0.043].'] Is myofibrillogenesis regulator-1 overexpression associated with poor prognosis of gastric cancer patients? | qiaojin/PubMedQA | 2 | [
-1.9719624519348145,
-1.4630272388458252,
2.4788942337036133
] |
['About 15% of colorectal adenocarcinomas have a deficient DNA mismatch repair phenotype. The frequency of deficient DNA mismatch repair tumours increases with age due to the hypermethylation of hMLH1 promoter. The study aimed to determine the prognostic value of deficient DNA mismatch repair phenotype in elderly patients.', 'Mismatch repair phenotype was retrospectively determined by molecular analysis in consecutive resected colorectal adenocarcinoma specimens from patients over 75 years of age from 4 Oncology centres.', '231 patients (median age: 81, range: 75-100) were enrolled from 2005 to 2008. Mean prevalence of deficient DNA mismatch repair phenotype was 22.5%, and 36% for patients over 85 years. Deficient DNA mismatch repair status was significantly associated with older age, female sex, proximal colon primary and high grade tumour. For stage II tumours no deficient DNA mismatch repair tumours had a recurrence at end of follow-up compared to 17% for tumours with proficient phenotype. The proficient phenotype status was significantly associated with worse age-adjusted overall survival [HR 2.60; 95% CI 1.05-6.44; p=0.039]. For stage III tumours a trend for less recurrence was observed for deficient DNA mismatch repair phenotype (16%) compared to proficient phenotype (36%).'] Is deficient mismatch repair phenotype a prognostic factor for colorectal cancer in elderly patients? | qiaojin/PubMedQA | 2 | [
-1.8041296005249023,
-1.5360407829284668,
2.3776228427886963
] |
["Critically ill patients are characterized as individuals hospitalized in the Intensive Care Unit (ICU) and can evolve to sepsis, septic shock or even death. Among others, genetic factors can influence the outcome of critically ill patients. HLA-G is a non-classical class Ib molecule that has limited protein variability, presenting seven isoforms generated by alternative splicing, and presents immunomodulatory properties. Polymorphisms at the 3'UTR are thought to influence HLA-G gene expression. It was previously observed that increased sHLA-G5 levels were predictive of survival among septic shock patients. We assessed the frequencies of 7 polymorphisms in exon 8 at the 3' UTR of HLA-G and associated these variants with different clinical outcomes in critically ill patients.", "Exon 8 at the 3' UTR of the HLA-G gene from 638 critically ill subjects was amplified by PCR and sequenced. Genotypes were identified using FinchTV software v.1.4.0 and the most probable haplotype constitution of each sample was determined by PHASE software v.2.1. Haplotype frequencies, linkage disequilibrium, heterozygosity test and Hardy-Weinberg Equilibrium were estimated using ARLEQUIN software v.3.5.", 'Among all critically ill patients, an association between carriers of the +2960IN_+3142 G_+3187A haplotype and septic shock (P = 0.047) was observed. Septic patients who carried the +2960IN_+3142G_+3187A haplotype presented an increased risk for septic shock (P = 0.031).'] Are polymorphic variants in exon 8 at the 3 ' UTR of the HLA-G gene associated with septic shock in critically ill patients? | qiaojin/PubMedQA | 2 | [
-2.128626823425293,
-1.4555644989013672,
2.5820674896240234
] |
['Neutrophil recruitment to the inflammatory sites is regulated by a variety of adhesion molecules including β2 integrins. The dependency of neutrophil recruitment on β2 integrins is variable in different tissues, but has not yet been verified in the cutaneous passive reverse Arthus reaction. We examined this question and also evaluated the impact of isoflurane on neutrophil recruitment to the skin because we previously showed in vitro that isoflurane binds and inhibits β2 integrins.', 'The dependency on β2 integrins in neutrophil recruitment to the skin in the Arthus reaction was examined using αL, αM and β2 knockout mice. Then, we evaluated the effect of isoflurane on neutrophil recruitment to the skin. In addition, the effects of isoflurane on neutrophil binding to intercellular adhesion molecule-1 (ICAM-1), one of the β2 integrin ligands, were studied in vitro using cell adhesion assays.', 'Neutrophil recruitment to the skin in the Arthus reaction model was totally dependent on β2 integrins, as β2 knockout mice completely abolished it. However, the defect of only one of the β2 integrins was not sufficient to abolish neutrophil recruitment. Isoflurane reduced neutrophil recruitment to the skin by approximately 90\xa0%. Also, isoflurane inhibited neutrophil adhesion to β2 integrin ligand ICAM-1.'] Does isoflurane inhibit neutrophil recruitment in the cutaneous Arthus reaction model? | qiaojin/PubMedQA | 2 | [
-2.318497896194458,
-1.2467440366744995,
2.5860705375671387
] |
['Short telomeres are often associated with cardiovascular risk factors and age-related diseases, while the angiotensin converting enzyme (ACE) gene insertion/deletion polymorphism (DD, ID, II) has shown such associations less consistently. We hypothesized that telomere length and association of telomere length with cardiovascular risk is affected by ACE (I/D) genotype.', 'We measured leucocyte telomere length (LTL) by Southern blot and analysed ACE I/D genotypes in 1249 subjects with hypertension and left ventricular hypertrophy (LVH). We examined interactions of ACE I/D genotype with LTL and cardiovascular risk.', 'Mean LTL in DD or ID genotype was shorter (8.15 and 8.14 kb, respectively), than in II genotype (8.27 kb, p=0.0005). This difference was significant in the younger subjects (55-64 years, p=0.02) but not in the older group (65-80 years, p=0.56 ). In DD but not I/D or II genotype, proportion of short telomeres (<5 kb) was related to Framingham risk score.'] Is telomere length associated with ACE I/D polymorphism in hypertensive patients with left ventricular hypertrophy? | qiaojin/PubMedQA | 2 | [
-1.447171688079834,
-1.5527846813201904,
2.0164778232574463
] |
['We aim to evaluate the effects of atorvastatin on the expression of Toll-like receptor (TLR4) protein and mRNA, and to explore their effects on TLR4-dependent downstream signaling in human monocytic leukemia (THP-1) cells.', 'TLR4 protein and mRNA expression, levels of NF-κB protein, and expression of TNF-α, IL-6, and IL-1β in lipopolysaccharide-induced THP-1 cells after incubation with different concentrations of atorvastatin (0.1, 1, 10, 20μM) were quantified via flow-cytometry, quantitative RT-PCR, western blotting, and ELSIA kits.', 'Atorvastatin incubation resulted in significant decreases in the levels of TLR4 protein and mRNA, NF-κB expression, and levels of TNF-α, IL-6, and IL-1β in LPS-induced THP-1 cells (P<0.01). However, compared with the untreated control, the expression of these were significantly increased (P<0.01).'] Does atorvastatin decrease Toll-like receptor 4 expression and downstream signaling in human monocytic leukemia cells? | qiaojin/PubMedQA | 2 | [
-2.304365873336792,
-1.2599811553955078,
2.568695306777954
] |
['Cocaine exposure has been reported to alter central μ-opioid receptor (MOR) expression in vivo. The present study employed an in vitro cellular model to explore possible mechanisms that may be involved in this action of cocaine.', 'To assess the effects of cocaine on MOR levels, two treatment regimens were tested in PC12 cells: single continuous or multiple intermittent. MOR protein levels were assessed by western blot analysis and quantitative PCR was used to determine relative MOR mRNA expression levels. To evaluate the role of nitric oxide (NO) and histone acetylation in cocaine-induced MOR expression, cells were pre-treated with the NO synthase inhibitor Nω-nitro-L-arginine methylester (L-NAME) or the non-selective histone acetyltransferase inhibitor curcumin.', 'Both cocaine treatment regimens significantly increased MOR protein levels and protein stability, but only multiple intermittent treatments increased MOR mRNA levels as well as c-fos mRNA levels and activator protein 1 binding activity. Both regimens increased NO production, and pre-treatment with L-NAME prevented cocaine-induced increases in MOR protein and mRNA levels. Single and multiple cocaine treatment regimens inhibited histone deacetylase activity, and pre-treatment with curcumin prevented cocaine-induced up-regulation of MOR protein expression.'] Do nitric oxide and histone deacetylases modulate cocaine-induced mu-opioid receptor levels in PC12 cells? | qiaojin/PubMedQA | 2 | [
-2.4840614795684814,
-1.2166926860809326,
2.719068765640259
] |
['CHK1 is an important effector kinase that regulates the cell cycle checkpoint. Previously, we showed that CHK1 is cleaved in a caspase (CASP)-dependent manner during DNA damage-induced programmed cell death (PCD) and have examined its physiological roles.', 'In this study, we investigated the behavior of CHK1 in PCD. Firstly, we found that CHK1 is cleaved at three sites in PCD, and all cleavages were inhibited by the co-treatment of a pan-CASP inhibitor or serine protease inhibitors. We also showed that CHK1 is cleaved by CASP3 and/or CASP7 recognizing at (296)SNLD(299) and (348)TCPD(351), and that the cleavage results in the enhancement of CHK1 kinase activity. Furthermore, as a result of the characterization of cleavage sites by site-directed mutagenesis and an analysis performed using deletion mutants, we identified (320)EPRT(323) as an additional cleavage recognition sequence. Considering the consensus sequence cleaved by CASP, it is likely that CHK1 is cleaved by non-CASP family protease(s) recognizing at (320)EPRT(323). Additionally, the cleavage catalyzed by the (320)EPRT(323) protease(s) markedly and specifically increased when U2OS cells synchronized into G1 phase were induced to PCD by cisplatin treatment.'] Is cHK1 cleavage in programmed cell death intricately regulated by both caspase and non-caspase family proteases? | qiaojin/PubMedQA | 2 | [
-2.2361929416656494,
-1.065966248512268,
2.313467502593994
] |
['To evaluate whether co-administration of R/S-α-lipoic acid can prevent the development of oxidative stress and metabolic changes induced by a fructose-rich diet (F).', 'We assessed glycemia in the fasting state and during an oral glucose tolerance test, triglyceridemia and insulinemia in rats fed with standard diet (control) and fructose without or with R/S-α-lipoic acid. Insulin resistance and hepatic insulin sensitivity were also calculated. In liver, we measured reduced glutathione, protein carbonyl groups, antioxidant capacity by ABTS assay, antioxidant enzymes (catalase and superoxide dismutase 1 and 2), uncoupling protein 2, PPARδ and PPARγ protein expressions, SREBP-1c, fatty acid synthase and glycerol-3-phosphate acyltransferase-1 gene expression, and glucokinase activity.', 'R/S-α-lipoic acid co-administration to F-fed rats a) prevented hyperinsulinemia, hypertriglyceridemia and insulin resistance, b) improved hepatic insulin sensitivity and glucose tolerance, c) decreased liver oxidative stress and increased antioxidant capacity and antioxidant enzymes expression, d) decreased uncoupling protein 2 and PPARδ protein expression and increased PPARγ levels, e) restored the basal gene expression of PPARδ, SREBP-1c and the lipogenic genes fatty acid synthase and glycerol-3-phosphate acyltransferase, and f) decreased the fructose-mediated enhancement of glucokinase activity.'] Does lipoic acid prevent liver metabolic changes induced by administration of a fructose-rich diet? | qiaojin/PubMedQA | 2 | [
-2.724428415298462,
-0.9382879734039307,
2.688260555267334
] |
['We report the first use of a sterile elastic exsanguination tourniquet (SET) in performing hemodialysis vascular access procedures in 27 patients. The main advantages of this tourniquet are the reduction of blood loss and need for possible transfusions. Additional benefits are the near-perfect exsanguination and excellent exposure of the operative field.', 'This SET is a sterile elastic stockinet device that rolls up the arm starting from the hand by pulling on two handles. The elastic silicone ring provides sufficient pressure (220 ± 30 mmHg) to block arterial flow into the limb. The stockinet can be cut to provide access to the incision area while providing an additional sterile cover over the rest of the limb.', 'No transfusions were required in any patients. Minor adverse effects occurred in four patients, including a twisted vessel, a bleeding vascular branch, a tear in atrophic arm skin, and pain, all of which had resolved on subsequent follow-up. Operational recommendations to avoid these adverse effects are outlined.'] Is a sterile elastic exsanguination tourniquet effective in preventing blood loss during hemodialysis access surgery? | qiaojin/PubMedQA | 2 | [
-2.746393918991089,
-0.6049799919128418,
2.507103443145752
] |
['Drug resistance often causes treatment failure in neuroblastomas. Increasing evidence has implicated that the micro-RNAs (miRNAs) are involved in the development of drug resistance. In this report, we aimed to investigate the role of miRNA in cisplatin resistance of neuroblastoma cells.', 'The cell viability of the neuroblastoma cells after cisplatin treatment was analyzed. The expression of the miRNAs and phosphatase and tensin homolog (PTEN) messenger RNA in the neuroblastoma cells was studied by real-time polymerase chain reaction. Overexpression of miRNA or suppression of miRNA expression by antagomir was used to investigate the effects of miRNA on the cisplatin-induced cell death or proliferation.', 'The expression of miR-21 was increased in the cisplatin-resistant (CisR) neuroblastoma cells as compared with the parental cells, and the antagomir against miR-21 converted the resistant cells into sensitive ones. Ectopic expression of pre-miR-21 in parental cells resulted in decreased sensitivity to cisplatin treatment. In addition, overexpression of pre-miR-21 markedly increa sed the proliferation rate of neuroblastoma cells. The level of PTEN messenger RNA and protein in the CisR cells was lower than that in the parental cells. Transfection of pre-miR-21 into the parental cells reduced the PTEN expression, and transfection of anti-miR-21 into the CisR cells increased the PTEN expression.'] Does micro-RNA-21 regulate the sensitivity to cisplatin in human neuroblastoma cells? | qiaojin/PubMedQA | 2 | [
-2.5741665363311768,
-0.7880374789237976,
2.3295583724975586
] |
['Current diabetic care guidelines focus mainly on managing metabolic control and macro- and microvascular comorbidities. This focus may be too narrow given the number of geriatric conditions present in these often aged patients.', 'We studied the prevalence of multimorbidity, (undiagnosed) geriatric conditions and disabilities in diabetic patients with macrovascular complications.', "One hundred forty-three community dwelling, insulin-dependent diabetic patients with macrovascular complications, aged 55 years and above, who were concurrently enrolled in the diabetes care clinic in a university hospital in the Netherlands, participated. Data on healthcare utilization, activities of daily living, geriatric conditions and quality of life were self-reported using a systematic diagnostic questionnaire. Mean age was 66.9 years (8.5 years), 62% were male and 22% were of Surinamese-South Asian descent. Loneliness was reported by 47%. The majority rated their quality of life (QoL) from 'reasonable' (45%) to 'good' (31%). In patients without ADL impairments, 60% were in need of assistance, compared to 95% among those with more than one impairment (p<0.01). In total, 19% had cognitive impairment, and 63% perceived pain. 84% of patients with impairments experienced social problems compared to 32% of patients in the other group."] Do insulin-dependent diabetic patients with macrovascular complications suffer from many geriatric conditions? | qiaojin/PubMedQA | 1 | [
-1.6907978057861328,
0.5547971129417419,
0.319095253944397
] |
['Pregnane X, encoded by the gene NR112, is a nuclear receptor whose primary role is to promote the detoxification and clearance of drugs and other foreign compounds from the body.', 'The aim of this study was to analyze associations between NR1I2 polymorphisms, immunosuppressant drug exposure, and clinical outcomes in adult kidney transplant recipients.', 'Exposures to tacrolimus, mycophenolic acid, and total and free prednisolone were estimated at month 1 posttransplant using validated multiple regression-derived limited sampling strategies.', 'In the 158 subjects studied, median (interquartile range) dose-adjusted exposure to tacrolimus was significantly higher in individuals carrying the NR1I2 8055T variant allele, when compared with exposure in wild-type individuals [20 (14, 22) μg·h/L/mg versus 15 (9, 24) μg·h/L/mg; P =0.0007]. Using multivariable logistic regression, NR1I2 8055T carrier status was independently predictive of higher dose-adjusted tacrolimus exposure (P=0.0005). Moreover, BK viremia was seen significantly more frequently in NR1I2 8055T allele carriers compared with wild-type individuals (38% vs 18%, P=0.005) and possession of the NR1I2 8055T allele imposed significantly higher odds of BK viremia (adjusted odds ratio, 2.76 [95% confidence interval, 1.33-7.73]; P=0.006). No significant difference in geometric mean peak BK viral replication titer was observed between 8055T carriers and noncarriers. No NR1I2 SNP or haplotype was significantly, independently associated with total or free prednisolone or MPA exposure.'] Are nR1I2 polymorphisms related to tacrolimus dose-adjusted exposure and BK viremia in adult kidney transplantation? | qiaojin/PubMedQA | 2 | [
-1.6611288785934448,
-1.6612874269485474,
2.280938148498535
] |
['To study associations between severity stages of early and late age-related macular degeneration (AMD) and genetic variations in age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) and to investigate potential interactions between smoking and ARMS2.', 'Population-based, cross-sectional European Eye Study in 7 countries in Europe.', 'Four thousand seven hundred fifty participants, 65 years of age and older, recruited through random sampling.', 'Participants were classified on the basis of the more severely affected eye into 5 mutually exclusive AMD severity stages ranging from no AMD, 3 categories of early AMD, and late AMD. History of cigarette smoking was available and allowed classification into never, former, and current smokers, with the latter 2 groups combined into a single category of ever smokers for analysis. Genotyping was performed for single nucleotide polymorphisms rs10490924 and rs4146894 in ARMS2 and rs1061170 in CFH. Associations were analyzed by logistic regression.', 'Odds ratios (ORs) for stage of AMD associated with genetic variations in ARMS2 and CFH and interactions between ARMS2 and smoking status.', 'Early AMD was present in 36.4% and late AMD was present in 3.3% of participants. Data on both genotype and AMD were available for 4276 people. The ORs for associations between AMD stage and ARMS2 increased monotonically with more severe stages of early AMD and were altered little by adjustment for potential confounders. Compared with persons with no AMD, carriers of the TT genotype for rs10490924 in ARMS2 had a 10-fold increase in risk of late AMD (P<3 × 10(-20)). The ORs for associations with CFH were similar for stage 3 early AMD and late AMD. Interactions between rs10490924 in ARMS2 and smoking status were significant in both unadjusted and adjusted models (P = 0.001). The highest risk was observed in those doubly homozygous for rs10490924 and rs1061170 in CFH (OR, 62.3; 95% confidence interval, 16-242), with P values for trend ranging from 0.03 (early AMD, stage 1) to 1 × 10(-26) (late AMD).'] Does aRMS2 increase the risk of early and late age-related macular degeneration in the European Eye Study? | qiaojin/PubMedQA | 2 | [
-1.4660719633102417,
-1.4647166728973389,
1.8929171562194824
] |
['Chronic kidney disease (CKD) is a growing public health problem and end stage renal disease (ESRD) represents a large human and economic burden. It is important to identify patients at high risk of ESRD. In order to determine whether renal Doppler resistive index (RI) may discriminate those patients, we analyzed whether RI was associated with identified prognosis factors of CKD, in particular histological findings, and with renal outcome.', "RI was measured in the 48 hours before renal biopsy in 58 CKD patients. Clinical and biological data were collected prospectively at inclusion. Arteriosclerosis, interstitial fibrosis and glomerulosclerosis were quantitatively assessed on renal biopsy in a blinded fashion. MDRD eGFR at 18 months was collected for 35 (60%) patients. Renal function decline was defined as a decrease in eGFR from baseline of at least 5 mL/min/ 1.73 m2/year or need for chronic renal replacement therapy. Pearson's correlation, Mann-Whitney and Chi-square tests were used for analysis of quantitative and qualitative variables respectively. Kaplan Meier analysis was realized to determine renal survival according to RI value using the log-rank test. Multiple logistic regression was performed including variables with p < 0.20 in univariate analysis.", 'Most patients had glomerulonephritis (82%). Median age was 46 years [21-87], eGFR 59 mL/min/ 1.73m2 [5-130], percentage of interstitial fibrosis 10% [0-90], glomerulosclerosis 13% [0-96] and RI 0.63 [0.31-1.00]. RI increased with age (r = 0.435, p = 0.0063), pulse pressure (r = 0.303, p = 0.022), renal atrophy (r = -0.275, p = 0.038) and renal dysfunction (r = -0.402, p = 0.0018). Patients with arterial intima/media ratio ≥ 1 (p = 0.032), interstitial fibrosis > 20% (p = 0.014) and renal function decline (p = 0.0023) had higher RI. Patients with baseline RI ≥ 0.65 had a poorer renal outcome than those with baseline RI < 0.65 (p = 0.0005). In multiple logistic regression, RI≥0.65 was associated with accelerated renal function decline independently of baseline eGFR and proteinuria/creatininuria ratio (OR=13.04 [1.984-85.727], p = 0.0075). Sensitivity, specificity, predictive positive and predictive negative values of RI ≥ 0.65 for renal function decline at 18 months were respectively 77%, 86%, 71% and 82%.'] Is renal arterial resistive index associated with severe histological changes and poor renal outcome during chronic kidney disease? | qiaojin/PubMedQA | 2 | [
-1.4072245359420776,
-1.659674882888794,
2.0732836723327637
] |
['An early serum tumor marker (TM) decline during chemotherapy was shown to independently predict survival in patients with poor-prognosis disseminated non-seminomatous germ-cell tumors (NSGCTs). The aim of this study was to assess whether a TM decline (TMD) also correlates with the outcome in the salvage setting.', 'Data regarding 400 patients with progressive or relapsed disseminated NSGCTs after first-line chemotherapy prospectively accrued onto two phase III clinical trials were obtained. Serum alpha-fetoprotein (AFP) and/or human chorionic gonadotropin (hCG) were assessed at baseline and after 6 weeks of chemotherapy. A total of 297 patients, 185 and 112 in the training and validation sets, with initially abnormal TMs for whom a change from baseline could be established were used for this analysis.', 'An unfavorable decline in either AFP or hCG was predictive of progression-free survival (PFS) [hazard ratio, HR = 2.15, (95% CI 1.48-3.11); P < 0.001; 2-year PFS rate: 50% versus 26%] as was the Lorch prognostic score (LPS). In the multivariate analysis, an unfavorable TMD, stratified based on the LPS, was an independent adverse prognostic factor for PFS and OS.'] Do tumor marker kinetics predict outcome in patients with relapsed disseminated non-seminomatous germ-cell tumors? | qiaojin/PubMedQA | 2 | [
-2.0307669639587402,
-1.509609341621399,
2.596203565597534
] |
['Vitamin D has been known to be closely associated with periodontitis while the exact mechanisms remain unclear. The present study aimed to discover the effects of 1a,25-dihydroxyvitamin D3 (1,25D) on the expressions of interleukin (IL)-6 and IL-8 in human periodontal ligament cells (hPDLCs) stimulated with Porphyromonas gingivalis (P. gingivalis) W83.', 'Primary cultures of hPDLCs from ten donors were established and the cells of passage four were treated with 1,25D or P. gingivalis individually or 1,25D combined with P. gingivalis. The levels of IL-6 and IL-8 protein in hPDLCs were detected with enzyme-linked immunosorbent assay (ELISA) and the mRNA levels were detected with real-time RT-PCR.', 'P. gingivalis significantly promoted the protein expressions of IL-6 and IL-8. P. gingivalis at the multiplicity of infection (MOI) 100 exerted the strongest promotion effect on the IL-6 protein expression by 5.83-fold compared with the controls (2482.88±26.53pg/ml versus 425.80±77.25pg/ml, P<0.0005) and the IL-8 protein expression by 12.39-fold (4965.81±1072.55pg/ml versus 400.75±2.27pg/ml, P=0.005) in hPDLCs at 24h. At 48h, 10(-8)mol/L 1,25D had the best inhibition on the IL-8 protein expression in hPDLCs by 2.00-fold compared with the controls (100.76±21.11pg/ml versus 201.75±18.15pg/ml, P<0.0005) and the IL-8 mRNA expression by 2.13-fold (P<0.0005). 10(-8)mol/L 1,25D combined with P. gingivalis (MOI 100) exerted the strongest inhibition effect on the IL-8 protein expression by 1.54-fold compared with P. gingivalis treatment alone (3077.33±210.04pg/ml versus 4738.24±1386.17pg/ml, P=0.018) and the IL-8 mRNA expression by 1.78-fold (P=0.012) in hPDLCs at 12h. 1,25D did not influence the expression of IL-6 in hPDLCs with or without P. gingivalis treatment.'] Does vitamin D inhibit the expression of interleukin-8 in human periodontal ligament cells stimulated with Porphyromonas gingivalis? | qiaojin/PubMedQA | 2 | [
-0.7923846244812012,
-1.831069827079773,
1.5218290090560913
] |
["Despite the strong association between turning and Freezing of gait (FOG) in Parkinson's disease (PD), there has been little research to evaluate the specific turn characteristics (i.e. turn angles) that might contribute to freezing. Therefore, the purpose of the present study has three aims: examine the turning gait kinematics in freezers, evaluate the prevalence of FOG at different turn angles, and characterize whether the specific turning strategies employed by PD patients might be associated with turning deficits.", '20 PD participants (10 freezers, 10 non-freezers) and 10 healthy controls walked down a 6-m pathway and completed randomized trials of 0°, 90°, 120°, and 180° turns. Spatiotemporal gait kinematics were analysed using motion capture, while presence of FOG and classification of turn types (step out, crossover, or mixed strategy) were identified by two independent raters using video analysis.', 'Freezers significantly increased step time variability and elicited more freezing episodes at sharper turns. Healthy controls consistently implemented a crossover turning strategy for all turning angles, while freezers tended to use a step out and mixed strategy especially during 180° turns. This strategy in freezers was associated with a failure to increase step width (as healthy controls do). Additionally, in contrast to healthy controls and non-freezers, a dramatic decrease in velocity was identified in freezers for all turning angles.'] Does dynamics of turning sharpness influence freezing of gait in Parkinson 's disease? | qiaojin/PubMedQA | 2 | [
-2.546449899673462,
0.10768768191337585,
1.482254981994629
] |
['FK506 (Tacrolimus) is an important immunosuppressant, produced by industrial biosynthetic processes using various Streptomyces species. Considering the complex structure of FK506, it is reasonable to expect complex regulatory networks controlling its biosynthesis. Regulatory elements, present in gene clusters can have a profound influence on the final yield of target product and can play an important role in development of industrial bioprocesses.', 'Three putative regulatory elements, namely fkbR, belonging to the LysR-type family, fkbN, a large ATP-binding regulator of the LuxR family (LAL-type) and allN, a homologue of AsnC family regulatory proteins, were identified in the FK506 gene cluster from Streptomyces tsukubaensis NRRL 18488, a progenitor of industrial strains used for production of FK506. Inactivation of fkbN caused a complete disruption of FK506 biosynthesis, while inactivation of fkbR resulted in about 80% reduction of FK506 yield. No functional role in the regulation of the FK506 gene cluster has been observed for the allN gene. Using RT-PCR and a reporter system based on a chalcone synthase rppA, we demonstrated, that in the wild type as well as in fkbN- and fkbR-inactivated strains, fkbR is transcribed in all stages of cultivation, even before the onset of FK506 production, whereas fkbN expression is initiated approximately with the initiation of FK506 production. Surprisingly, inactivation of fkbN (or fkbR) does not abolish the transcription of the genes in the FK506 gene cluster in general, but may reduce expression of some of the tested biosynthetic genes. Finally, introduction of a second copy of the fkbR or fkbN genes under the control of the strong ermE* promoter into the wild type strain resulted in 30% and 55% of yield improvement, respectively.'] Is fK506 biosynthesis regulated by two positive regulatory elements in Streptomyces tsukubaensis? | qiaojin/PubMedQA | 2 | [
-2.2924771308898926,
-1.2682838439941406,
2.6341285705566406
] |
['Diagnosis of drug resistance and timely initiation of multidrug-resistant (MDR) tuberculosis therapy are essential to reduce transmission and improve patient outcomes. We sought to determine whether implementation of the rapid MTBDRplus diagnostic shortened the time from specimen collection to patient MDR tuberculosis therapy initiation.', 'We conducted a retrospective cohort analysis of 197 MDR tuberculosis patients treated at Brewelskloof, a rural tuberculosis hospital in Western Cape Province, South Africa, between 2007 and 2011.', 'Eighty-nine patients (45%) were tested using conventional liquid culture and drug susceptibility testing (DST) on solid medium and 108 (55%) were tested using the MTBDRplus assay after positive acid-fast bacilli or culture. Median time from sample taken to therapy initiation was reduced from 80 days (interquartile range [IQR] 62-100) for conventional DST to 55 days (IQR 37.5-78) with the MTBDRplus. Although the laboratory processing time declined significantly, operational delays persisted both in the laboratory and the clinical infrastructure for getting patients started on treatment. In multivariate analysis, patients tested using the MTBDRplus test had a reduced risk of starting treatment 60 days or more after sputum collection of 0.52 (P < .0001) compared with patients tested with culture-based DST, after adjustment for smear status and site of disease.'] Does implementation of genotype MTBDRplus reduce time to multidrug-resistant tuberculosis therapy initiation in South Africa? | qiaojin/PubMedQA | 2 | [
-1.9290339946746826,
-1.3092355728149414,
2.359745502471924
] |
['Higher blood pressure and albuminuria are found in offspring of mothers who smoke during pregnancy. Whether or not kidney development is affected by maternal smoking is unknown.', 'Sprague-Dawley rats were randomly allocated to twice-daily cigarette smoke and nicotine condensate (1 mg/kg) or vehicle at day 10 of pregnancy until delivery.', 'Exposed offspring did not differ from control offspring with respect to body weight, kidney weight, albuminuria, and creatinine clearance. Both male and female offspring had higher tail-plethysmographic blood pressures and lower mean glomerular volume, podocyte, mesangial-cell, and endothelial-cell number, compared to control offspring.'] Does exposure of pregnant rats to cigarette-smoke condensate cause glomerular abnormalities in offspring? | qiaojin/PubMedQA | 2 | [
-2.476602792739868,
-0.3731744587421417,
1.8967152833938599
] |
['The purpose of this study was to determine the predictive factors for residual/recurrent disease and to analyze the timing for Pap smears and human papillomavirus (HPV) testing during follow-up after loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN) 2 or worse.', 'We retrospectively analyzed 183 patients (mean age, 39.3 years) with CIN 2/3 who were treated with LEEP. Post-LEEP follow-up was performed by Pap smear and HPV hybrid capture2 (HC2) testing. The definition of persistent/recurrent disease was biopsy-proven CIN 2 or worse.', 'Among 183 patients, punch biopsies were CIN 2 in 31 (16.9%) and CIN 3 in 152 (83.1%). HPV HC2 tests before LEEP were positive in 170 (95.5%) of 178 patients. During follow-up, 12 patients (6.6%) had residual/recurrent CIN 2+. LEEP margin status was a significant predictive factor for persistent/recurrent disease. Other factors such as age, HPV HC2 viral load (≥100 relative light units), and HPV typing (type 16/18 vs. other types) did not predict recurrence. Early HPV HC2 testing at 3 months after LEEP detected all cases of residual/recurrent disease. The sensitivity and negative predictive value of the HPV HC2 test for residual/recurrent disease were both 100% at 3 and 6 months.'] Does early human papillomavirus testing predict residual/recurrent disease after LEEP? | qiaojin/PubMedQA | 2 | [
-1.5046100616455078,
-1.6438813209533691,
2.1651313304901123
] |
['To investigate whether inhaled sevoflurane is capable of producing delayed cardioprotection effect in rats and its underlying mechanisms.', 'Male Sprague-Dawley rats inhaled 1.0 minimum alveolar concentration (MAC) sevoflurane, 1.5 MAC sevoflurane,or O(2) for 1 h. After 24 h and 48 h the left coronary artery of rats was occluded for 30 min,followed by 120 min of reperfusion. Hemodynamics was continuously recorded and myocardial infarct size was determined by Evans blue and triphenyltetrazolium chloride staining. The expression of nitric oxide synthase (NOS) was assessed by immunoblotting.', '1.0 MAC sevoflurane and 1.5 MAC sevoflurane improved cardiac pump function after reperfusion and reduced myocardial infarct size with the increased iNOS expression (P<0.05). However,the expression of eNOS and p-eNOS was not affected (P>0.05). A selective iNOS inhibitor 1400 W abolished the cardioprotection effect induced by inhalation of 1.0 MAC sevoflurane for 24 h.'] Does [ Sevoflurane preconditioning produce delayed cardioprotection effect through up-regulation of inducible nitric oxide synthase in rats ]? | qiaojin/PubMedQA | 2 | [
-2.2506988048553467,
-1.4359158277511597,
2.771104335784912
] |
['Approximately 20% to 30% of suspicious small renal tumors are benign. A significant proportion of malignant tumors are low grade and potentially indolent. We evaluated whether preoperative patient and tumor characteristics are associated with adverse pathological features.', 'A total of 886 patients underwent robot-assisted partial nephrectomy, as done by 1 of 5 high volume surgeons. Demographic and clinical data were compared between patients with benign/malignant disease, clear cell/nonclear cell renal cell carcinoma and high/low grade tumors. Tumor complexity was quantified by R.E.N.A.L. (radius, exophytic/endophytic, nearness of tumor to collecting system or sinus, anterior/posterior, hilar and location relative to polar lines) nephrometry score and described as low--4 to 6, intermediate--7 to 9 or high--10 or greater. Logistic regression analyses were performed to test the association between tumor and patient characteristics, and high grade renal cell carcinoma. Subanalyses were done for patients with renal tumors 4 cm or less.', 'High grade renal cell carcinoma was larger and more likely to develop in men. Patients with malignant tumors and with clear cell histology were more likely to have intermediate or high complexity tumors. Increasing tumor complexity independently predicted malignancy, high grade malignancy and clear cell histology on multivariate regression analysis (each p <0.05). Male gender was independently associated with malignancy and high grade renal cell carcinoma. When considering tumors 4 cm or less, tumor complexity predicted malignancy but not tumor grade.'] Does tumor complexity predict malignant disease for small renal masses? | qiaojin/PubMedQA | 2 | [
-1.7188692092895508,
-1.420318365097046,
2.2410354614257812
] |
['The decision to perform endoscopic versus the mini-open carpal tunnel release technique is most likely left to surgeons rather than patients with idiopathic carpal tunnel syndrome.', 'We hypothesized that (1) at 3 months after surgery, the subjective outcomes of endoscopic release, performed on one hand, and mini-incision release, performed on the other, would not differ in patients with bilateral carpal tunnel syndrome; however, (2) each patient would likely prefer one technique over the other for specific reasons.', 'Fifty-two patients with bilateral carpal tunnel syndrome had one hand randomized to undergo endoscopic release and the other to undergo mini-incision release. Each patient was assessed with the Boston Carpal Tunnel Questionnaire (BCTQ) and DASH preoperatively and at each followup. Three months after surgery, the patients commented on which technique they preferred and completed a questionnaire regarding the reasons for not preferring the other technique.', 'The mean BCTQ symptom/function score and DASH improved similarly in the endoscopic release group and the mini-incision release group. Thirty-four patients preferred endoscopic release and 13 preferred the mini-incision technique. Scar or pillar pain was the most commonly cited factor in not preferring either technique followed by postoperative pain for the open technique and transient worsening of symptoms for the endoscopic technique.'] Is endoscopic carpal tunnel release preferred over mini-open despite similar outcome : a randomized trial? | qiaojin/PubMedQA | 2 | [
-2.1418895721435547,
-0.9920844435691833,
2.2080788612365723
] |
['The role of adiponectin as a risk factor for mortality and recurrent ischemic cardiovascular events in patients with carotid artery disease is unknown.', 'Consecutive patients (n = 292) undergoing carotid endarterectomy for symptomatic and asymptomatic carotid stenosis were included in the study. Mortality and cardiovascular ischemic events were recorded during a median follow-up of 5.2 years. Baseline plasma concentrations of adiponectin were measured. Cox regression models stratified for gender were used for estimation of risk of events.', 'Fifty-two patients died and 73 had an ischemic event (ischemic stroke, n = 52 and/or MI, n = 28) during follow-up. In univariate analyses, adiponectin was associated with mortality, hazard ratio (HR) per standard deviation (SD) increase of adiponectin, 1.46 (95% confidence interval [CI], 1.14-1.86). In multivariate analysis age, type 2 diabetes mellitus (T2DM), coronary heart disease (CHD), plasma interleukin-6 (IL-6) and plasma adiponectin (HR per SD increase of adiponectin, 1.73 [95% CI, 1.29-2.32]) were independently associated with mortality. T2DM, CHD, fibrinogen, contralateral carotid artery stenosis, systolic blood pressure, symptomatic carotid artery stenosis were independently associated with ischemic events, whereas plasma adiponectin was not (HR per SD increase of adiponectin, 0.96 [95% CI, 0.75-1.23]).'] Is high plasma adiponectin concentration associated with all-cause mortality in patients with carotid atherosclerosis? | qiaojin/PubMedQA | 2 | [
-1.954405665397644,
-1.5631595849990845,
2.554645538330078
] |
['Elevated plasma level of asymmetric dimethylarginine (ADMA) has been reported to be associated with endothelial dysfunction and atherosclerotic risk factors, and may predict adverse cardiovascular events in patients with coronary artery disease. In this study, we aimed to assess the association between plasma ADMA and long-term outcome in patients with angiography-documented ischemic chronic heart failure (HF).', 'We evaluated 285 patients with ischemic chronic HF and measured their plasma ADMA levels by high performance liquid chromatography. The mean age was 70 ± 12 years and the mean left ventricular ejection fraction was 36 ± 8%. Plasma ADMA levels were positively correlated with NYHA functional class (p < 0.001) and log N-terminal pro-B type natriuretic peptide (NT-proBNP) level (p < 0.001). During the median follow-up period of 2.2 years, we observed 58 major adverse cardiovascular events (MACE) (20.4%) and 95 MACE plus cardiac decompensation (33.3%). Multivariate Cox regression analysis adjusted for age, ejection fraction, renal function and log NT-proBNP level revealed that ADMA might be a significant independent risk factor and the relative risk of MACE and MACE plus cardiac decompensation would increase by 23% and 25% respectively when plasma ADMA level increased by 1 SD of value (p = 0.05 and 0.007).'] Does asymmetric dimethylarginine predict clinical outcomes in ischemic chronic heart failure? | qiaojin/PubMedQA | 2 | [
-2.002146005630493,
-1.455881118774414,
2.5485668182373047
] |
['Rapid breast tumor development relies on formation of new vasculature to supply the growing malignancy with oxygenated blood. Previously we found that estrogen aided in this neovasculogenesis via recruitment of bone marrow derived endothelial progenitor cells (BM-EPCs), leading to increased vessel formation and vascular endothelial growth factor (VEGF) production in vivo. However, the cellular mechanism of this induction and the signaling pathways involved need elucidation.', "Using the murine mammary cell line TG1-1 we observed estrogen (E2) lead to an up regulation of hypoxia inducible factor-1 (HIF-1), an effect abrogated by the anti-estrogen Fulvestrant and the HIF-1 inhibitor YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole) suggesting the interchangeability of hypoxia and estrogen mediated effects. Estrogen modulation of HIF-1 and subsequent effects on endothelial cells is dependent on the Akt/PI3K pathway and protein synthesis as validated by the use of the inhibitors wortmannin and cycloheximide which abrogated estrogen's effects respectively. Estrogen treated TG1-1 cells secreted higher levels of VEGF which were comparable to secreted levels from cells grown under hypoxic conditions. Soluble factors in conditioned media from E2 treated breast cancer cells also lead to migration and tube formation of human umbilical vein endothelial cells (HUVEC) in vitro."] Are hypoxia and estrogen functionally equivalent in breast cancer-endothelial cell interdependence? | qiaojin/PubMedQA | 2 | [
-2.525407314300537,
-1.3065762519836426,
2.8673055171966553
] |
['A variety of studies have indicated that rural communities have fewer mental health services and professionals than their urban counterparts. This study will examine the shortages of mental health professionals in rural communities as well as the impact of inadequate mental health services access on rural hospitals.', 'A sample frame of 1162 rural hospitals was compiled, and a two-page survey was mailed to each hospital Chief Executive Officer (CEO).', 'Of the 1162 surveys mailed, 228 were returned. The majority of CEOs agreed that there was a shortage of mental health professionals, that referral centers were too distant, and that there were many barriers to care including infrastructure, poverty, and substance abuse. Solutions offered by CEOs included telemedicine and residency training programs.'] Does rural mental health workforce need assessment - a national survey? | qiaojin/PubMedQA | 1 | [
-1.7222381830215454,
2.1803033351898193,
-0.9967015981674194
] |
['Necrotizing enterocolitis (NEC) is a significant cause of morbidity and mortality in neonates with complex single-ventricle anatomy undergoing stage I palliation. Hybrid approach is another option for initial single-ventricle palliation. The goal of this study was to determine if there were differences in echocardiographic indices between patients undergoing the hybrid procedure who developed NEC vs. those that did not develop NEC.', 'Retrospective chart review was performed on patients who underwent the hybrid procedure. Patients were included if an echocardiogram with adequate Doppler tracings through the patent ductus arteriosus stent was available. Echocardiographic indices measured included antegrade velocity-time integral (VTI), retrograde VTI, effective VTI, VTI regurgitant fraction, VTI retrograde/VTI antegrade ratio, calculated cardiac output, peak antegrade velocity through the ductal stent, retrograde/antegrade time ratio, and percent regurgitant time. Indices were compared in patients who developed NEC (NEC Group) and those who did not develop NEC (No NEC Group). NEC was defined as a Bell Stage ≥2.', 'Sixty-nine patients met inclusion criteria. Eight of the 69 patients developed NEC. There was no significant difference between the NEC and No NEC Group for antegrade VTI (10.4\u2009±\u20093.2\u2009cm vs. 12.7\u2009±\u20094.4\u2009cm), retrograde VTI (5.3\u2009±\u20091.5\u2009cm vs. 6.1\u2009±\u20092.2\u2009cm), effective VTI (5.1\u2009±\u20092.9\u2009cm vs. 6.6\u2009±\u20093.3\u2009cm), VTI regurgitant fraction (53.6\u2009±\u200914.7% vs. 49.7\u2009±\u200913.6%), and VTI retrograde/VTI antegrade ratio (0.54\u2009±\u20090.15 vs.0.50\u2009±\u20090.14). Cardiac output (4.2\u2009±\u20091.4\u2009L/min/m(2) vs. 4.8\u2009±\u20091.8\u2009L/min/m(2) ) and peak velocity (117.5\u2009±\u200928.9\u2009cm/s and 142.4\u2009±\u200942.6\u2009cm/s) were also not different between the NEC and No NEC Groups. Furthermore, retrograde/antegrade time ratios (1.6\u2009±\u20090.2 vs. 1.7\u2009±\u20090.3) and percent retrograde time (60.6\u2009±\u20093.0% vs. 62.0\u2009±\u20094.0%) were not different between the NEC and No NEC Groups.'] Are diastolic flow parameters sensitive in predicting necrotizing enterocolitis in patients undergoing hybrid procedure? | qiaojin/PubMedQA | 2 | [
-1.1427706480026245,
-1.8611276149749756,
1.9563534259796143
] |
['To examine whether dietary fish oil supplementation reduces development of spontaneous endometriosis-associated adhesions using an established model.', 'Laboratory-based study.', 'Medical center research laboratory. PATIENT(S)/ANIMAL(S): Disease-free women of reproductive age and nude mice.', 'Women were not provided any intervention. Mice were randomized to receive fish oil supplementation or control diet.', 'Experimental endometriosis was established in mice via injection of human endometrial tissue within 16 hours of ovariectomy. Mice were provided standard or menhaden fish oil-supplemented diets for ≥ 2 weeks before initiation of experimental endometriosis and until killing them 1 week later. At necropsy, mice were examined for the presence and extent of adhesions and endometriotic-like lesions. Tissues were excised and morphologically characterized.', 'Adhesions/lesions were reduced in mice provided with dietary fish oil compared with control animals. Leukocytes were more numerous within the adhesions/lesions of the mice maintained on the standard diet compared with animals provided with fish oil. As indicated by staining intensity, collagen deposition was greater at adhesion sites within control mice compared with fish oil-supplemented animals.'] Does dietary fish oil supplementation inhibit formation of endometriosis-associated adhesions in a chimeric mouse model? | qiaojin/PubMedQA | 2 | [
-2.6472384929656982,
-0.9298308491706848,
2.6351075172424316
] |
['For children who require aortic valve replacement, the pulmonary autograft (Ross procedure) may be the ideal substitute. However, performing a modified Konno procedure at the time of autograft implantation (Ross-Konno) may be associated with significant morbidity and mortality. A retrospective study was undertaken to compare the outcomes of Ross-Konno (RK) and the Ross (R) procedures including the need for reinterventions and long-term survival.', 'Between 1993 and 2011, 78 children (mean age, 11.1 ± 5.6 years; range, 1 week to 18 years) underwent the Ross procedure. Modified Konno-type enlargement of the left ventricular outflow tract was performed in 18 of those patients.', 'There was no statistically significant difference between the groups with respect to pathologic process, sex, concomitant procedures, and aortic gradient. Our data demonstrate that mean age (R, 12.9 years versus RK, 5.3 years; p < 0.001), mean size of allograft (R, 23.3 mm versus RK, 20.1 mm; p < 0.001), previous surgery (R, 51% versus RK, 83%; p = 0.05), and postoperative morbidity (R, 3% versus RK, 28%; p = 0.003) were significantly different between the groups. There were 3 hospital deaths (all RK with mitral valve anomalies). Actuarial survival at 10 years was significantly better for Ross patients than Ross-Konno (R, 96% versus RK, 72%; p = 0.001). Freedom from autograft, right ventricular outflow tract obstruction, and cumulative reoperations at 10 years were not significantly different between groups.'] Is the Ross-Konno a high-risk procedure when compared with the Ross operation in children? | qiaojin/PubMedQA | 2 | [
-1.0602329969406128,
-1.7639814615249634,
1.704474925994873
] |
['Disruption of frontal-subcortical circuits by cerebral small-vessel disease is thought to predispose to depression characterized by motivational symptoms. We examined the influence of lacunar infarcts and white matter lesions (WML) on severity and course of depressive symptoms during 3 years follow-up.', 'Within the SMART-Medea study, analyses were performed in 650 patients with symptomatic atherosclerotic disease (62±9 years). Volumetric WML measures (deep and periventricular) were obtained with 1.5T magnetic resonance imaging at baseline; infarcts were rated visually. Depressive symptoms were assessed with Patient Health Questionnaire-9 at baseline and during five follow-up times and categorized into motivational and mood scores.', 'Using generalized estimating equation models, a relation between lacunar infarcts in deep white matter and an increased severity (mean difference=1.47, 95% confidence interval .33-2.60) and more fluctuating course (p value interaction infarcts * time=.04) of depressive symptoms during follow-up was found, adjusted for age, sex, education, vascular risk, and cognition. This relation was primarily driven by motivational symptoms. Lacunar infarcts were not associated with severity or course of depressive symptoms. Deep WML were associated with a more fluctuating but not more severe course of depressive symptoms. Excluding patients with major depressive disorder did not change the results.'] Are lacunar infarcts in deep white matter associated with higher and more fluctuating depressive symptoms during three years follow-up? | qiaojin/PubMedQA | 2 | [
-2.332689046859741,
-1.0272958278656006,
2.4271414279937744
] |
['Oxytocin (OT) is a hormone shown to be involved in social bonding in animal models. Intranasal OT is currently in clinical trials for use in disorders such as autism and schizophrenia. We examined long-term effects of intranasal OT given developmentally in the prairie vole (Microtus ochrogaster), a socially monogamous rodent, often used as an animal model to screen drugs that have therapeutic potential for social disorders.', 'We treated voles with one of three dosages of intranasal OT, or saline, from day 21 (weaning) through day 42 (sexual maturity). We examined both social behavior immediately following administration, as well as long-term changes in social and anxiety behavior after treatment ceased. Group sizes varied from 8 to 15 voles (n = 89 voles total).', 'Treatment with OT resulted in acute increases in social behavior in male voles with familiar partners, as seen in humans. However, long-term developmental treatment with low doses of intranasal OT resulted in a deficit in partner preference behavior (a reduction of contact with a familiar opposite-sex partner, used to index pair-bond formation) by male voles.'] Does chronic intranasal oxytocin cause long-term impairments in partner preference formation in male prairie voles? | qiaojin/PubMedQA | 2 | [
-2.5936119556427,
-0.44432350993156433,
2.027492046356201
] |
['Hyperglycaemia is associated with increased mortality in critically ill patients. A number of studies have highlighted an association between increased variability of blood glucose (BG) concentration and mortality, supporting a survival disadvantage if BG homeostasis is lost. By exploring the longitudinal BG profile of individual children over time, this study investigates the importance of intact homeostasis early after admission to the paediatric intensive care unit (PICU).', 'Retrospective single-centre observational study in a large multi-specialty PICU in the UK. Children admitted between August 2003 and February 2006 were included unless they met exclusion criteria. Data were merged from the PICU clinical database and blood gas analyser database by means of a unique PICU identifier. BG was measured frequently on a blood gas analyser (Bayer Rapidlink). Primary outcome was 100-day mortality. BG parameters were investigated for possible associations with mortality.', 'A total of 1,763 patients were included (median age 1.1 years; IQR 0.1-5.8). Although admission BG was not associated with mortality, a survival advantage was found in children who showed a reduction in BG on day 1 relative to the admission BG value (p < 0.001). This remained statistically significant (p = 0.007) after adjusting for severity of illness.'] Is early change in blood glucose concentration an indicator of mortality in critically ill children? | qiaojin/PubMedQA | 2 | [
-1.9215179681777954,
-1.1009209156036377,
2.1175780296325684
] |
['Ovarian cancer is the fifth leading cause of cancer-related deaths among American women. Platinum-based chemotherapy, such as cisplatin, represents the standard-of-care for ovarian cancer. However, toxicity and acquired resistance to cisplatin have proven challenging in the treatment of patients with ovarian cancer.', 'Using a genetically engineered mouse model of ovarian endometrioid adenocarcinoma (OEA) in combination with molecular-imaging technologies, we studied the activation of the AKT serine/threonine kinase in response to long-term cisplatin therapy.', 'Treatment of cells in culture and tumor-bearing animals with cisplatin resulted in activation of AKT, a key mediator of cell survival. On the basis of these results, we investigated the therapeutic use of AKT inhibition in combination with cisplatin, which resulted in enhanced and prolonged induction of apoptosis and in significantly improved tumor control as compared with either agent alone.'] Does molecular imaging reveal a role for AKT in resistance to cisplatin for ovarian endometrioid adenocarcinoma? | qiaojin/PubMedQA | 2 | [
-2.6830527782440186,
-0.8431988954544067,
2.6157593727111816
] |
['Cellular efflux transporters, especially P-glycoprotein (P-gp), impel berberine (BBR) out of cells, and therefore reduce bioavailability of the compound. This study was designed to overcome efflux of BBR using P-gp as a target.', 'Molecular docking study was done to identify BBR analogues that were with low affinity to P-gp. Flow cytometry was used to determine cellular efflux of chemicals. Pharmacokinetic study was performed in Wistar rats, following oral administration of the study compounds. The efficacies of chemicals on glucose homeostasis were determined both in cultured cells and diabetic KK-Ay and db/db mice.', 'In the molecular docking study, we found that among BBR analogues pseudo-berberine (IMB-Y53) has low affinity to P-gp. IMB-Y53 was retained in Caco-2, HL-7702 and C2C12 cells for a significantly longer period of time than BBR did. P-gp inhibitor tetrandrine (Tet) abolished the efflux of BBR at different extent depending on the expression level of P-gp; however, Tet had no impact on IMB-Y53 efflux. BBR increased P-gp expression dose-dependently in intestinal and liver cells; IMB-Y53 also up-regulated P-gp but at a much lower level as compared with BBR. Administered at equal dose in rats, the maximum plasma concentration (C(max)) and area under concentration-time curve (AUC(0-24)) of IMB-Y53 were 1.61 and 2.27-fold of those of BBR, respectively, indicating an improved bioavailability. IMB-Y53 stimulated glucose utility in cultured cells with a degree similar to that of BBR, but exhibited enhanced glucose-lowering efficacy in KK-Ay and db/db diabetic mice.'] Does berberine analogue IMB-Y53 improve glucose-lowering efficacy by averting cellular efflux especially P-glycoprotein efflux? | qiaojin/PubMedQA | 2 | [
-2.0165085792541504,
-1.4765660762786865,
2.4846243858337402
] |
['Activation of inflammatory pathways plays a critical role in the development of abdominal aortic aneurysms (AAA). Notch1 signaling is a significant regulator of the inflammatory response; however, its role in AAA is unknown.', 'In an angiotensin II-induced mouse model of AAA, activation of Notch1 signaling was observed in the aortic aneurysmal tissue of Apoe(-/-) mice, and a similar activation of Notch1 was observed in aneurysms of humans undergoing AAA repair. Notch1 haploinsufficiency significantly reduced the incidence of AAA in Apoe(-/-) mice in response to angiotensin II. Reconstitution of bone marrow-derived cells from Notch1(+/-);Apoe(-/-) mice (donor) in lethally irradiated Apoe(-/-) mice (recipient) decreased the occurrence of aneurysm. Flow cytometry and immunohistochemistry demonstrated that Notch1 haploinsufficiency prevented the influx of inflammatory macrophages at the aneurysmal site by causing defects in macrophage migration and proliferation. In addition, there was an overall reduction in the inflammatory burden in the aorta of the Notch1(+/-);Apoe(-/-) mice compared with the Apoe(-/-) mice. Last, pharmacological inhibition of Notch1 signaling also prevented AAA formation and progression in Apoe(-/-) mice.'] Does inhibition of Notch1 signaling reduce abdominal aortic aneurysm in mice by attenuating macrophage-mediated inflammation? | qiaojin/PubMedQA | 2 | [
-2.4110615253448486,
-1.2345600128173828,
2.6358718872070312
] |
['Cardiac hypertrophy is a common response to circulatory or neurohumoral stressors as a mechanism to augment contractility. When the heart is under sustained stress, the hypertrophic response can evolve into decompensated heart failure, although the mechanism(s) underlying this transition remain largely unknown. Because phosphorylation of cardiac myosin light chain 2 (MLC2v), bound to myosin at the head-rod junction, facilitates actin-myosin interactions and enhances contractility, we hypothesized that phosphorylation of MLC2v plays a role in the adaptation of the heart to stress. We previously identified an enzyme that predominantly phosphorylates MLC2v in cardiomyocytes, cardiac myosin light-chain kinase (cMLCK), yet the role(s) played by cMLCK in regulating cardiac function in health and disease remain to be determined.', 'We found that pressure overload induced by transaortic constriction in wild-type mice reduced phosphorylated MLC2v levels by ≈40% and cMLCK levels by ≈85%. To examine how a reduction in cMLCK and the corresponding reduction in phosphorylated MLC2v affect function, we generated Mylk3 gene-targeted mice and transgenic mice overexpressing cMLCK specifically in cardiomyocytes. Pressure overload led to severe heart failure in cMLCK knockout mice but not in mice with cMLCK overexpression in which cMLCK protein synthesis exceeded degradation. The reduction in cMLCK protein during pressure overload was attenuated by inhibition of ubiquitin-proteasome protein degradation systems.'] Is myosin light chain phosphorylation critical for adaptation to cardiac stress? | qiaojin/PubMedQA | 2 | [
-2.4179887771606445,
-1.2028757333755493,
2.6312127113342285
] |
['12(S)-Hydroxyeicosatetraenoic acid (12(S)-HETE) is a metabolite of arachidonic acid. 12(S)-HETE is involved in the pathogenesis of atherosclerosis and diabetes. However, the correlation between 12(S)-HETE and coronary artery disease (CAD) in the diabetic patient is unclear.', 'The study investigated the relationship between 12(S)-HETE and CAD in Type 2 diabetes (T2D).', 'Plasma 12(S)- HETE levels were detected by enzyme-linked immunosorbent assay in 103 healthy controls (control), 109 diabetic patients without CAD (diabetic), and 152 diabetic patients with CAD (diabetic-CAD).', '12(S)-HETE levels were higher in both diabetic and diabetic-CAD groups compared to control and in the diabetic-CAD group compared to the diabetic group. In the multiple linear stepwise regression analysis, 12(S)-HETE levels correlated independently with CAD, systolic blood pressure, and glycated hemoglobin.'] Do 12S-hydroxyeicosatetraenoic acid levels link to coronary artery disease in Type 2 diabetic patients? | qiaojin/PubMedQA | 2 | [
-2.18161678314209,
-1.3508366346359253,
2.5143017768859863
] |
['Disorders of thyroid function have been inconsistently described in cystic fibrosis (CF) patients and in CF transmembrane regulator protein knockout animals. The literature lacks reports on iodine status of CF individuals. We hypothesize, that iodine deficiency is common in CF and account for abnormal thyroid function in CF patients.', 'We investigated 129 children, adolescents, and adults with CF, who were living in the northern part of Bavaria/Germany. Malnutrition and lung function were analyzed. Urinary iodine excretion, TSH (thyroid-stimulating hormone), and ft4 (free thyroxine) were measured and set in relation to population-based, age-adjusted reference ranges.', 'Subclinical hypothyroidism (normal fT4, elevated TSH) was found in 11.6% of subjects, and iodine deficiency in 83.7%. No correlations were found with age, BMI, status of malnutrition, or lung function.'] Are iodine deficiency and subclinical hypothyroidism common in cystic fibrosis patients? | qiaojin/PubMedQA | 2 | [
-2.4855010509490967,
-0.8579379320144653,
2.461329460144043
] |
['The purpose of this prospective randomized trial was to examine the effect of tourniquet use on rehabilitation rate, return to work and sport activities, and muscle damage after arthroscopic meniscectomy.', 'Eighty patients who underwent arthroscopic partial meniscectomy were randomly allocated to the use of an inflated (group A, n = 40) or deflated (group B, n = 40) pneumatic tourniquet. Patients with concomitant ligamentous deficiency or grade III and IV chondral lesions were excluded. The primary outcome measures were pain, measured with a visual analog scale (VAS), and knee range of motion (ROM) on days 8 and 15 postoperatively; time required for patients to discontinue the use of crutches; time to return to light activities and moderate sporting activities such as jogging; and serum creatine phosphokinase (CPK) levels monitored preoperatively and on days 1, 8, and 15 postoperatively.', 'The 2 groups did not differ in terms of age; male-female ratio; body mass index; and preoperative International Knee Documentation Committee, Tegner, and Lysholm scores. Operative time was not significantly different between groups (mean, 27.5 for group A and 31.2 for group B; P = .83). VAS pain scores and knee ROM were not significant between groups (minimum P = .22). The patients progressed to weight-bearing without crutches within 13.4 and 12.9 days for groups A and B, respectively (P = .9). Return to work and jogging did not differ significantly between groups (minimum P = .34). Serum CPK values were also not significantly different between or within groups during consecutive measurements (P = .3). Tourniquet time did not significantly affect postoperative ROM, VAS pain scores, or serum CPK levels (minimum P = .14).'] Does tourniquet use affect rehabilitation , return to activities , and muscle damage after arthroscopic meniscectomy : a prospective randomized clinical study? | qiaojin/PubMedQA | 2 | [
-1.7499865293502808,
-1.5286381244659424,
2.287479877471924
] |
['Prostate cells are dependent on androgens for growth and proliferation. Androgen deprivation therapy is the recommended treatment for advanced/metastatic prostate cancer. Under this therapy, prostate cancer will inevitably progress to castration resistant prostate cancer (CRPC). Despite putative castration resistance, testosterone might still play a crucial role in the progression of CRPC. The goal of this study was to determine the role of testosterone in the formation of metastases of CRPC in both in vitro and in vivo settings.', 'In vitro, the effect of testosterone and the non-aromatizable androgen methyltrienolone on migration, invasion and proliferation of a castration-resistant prostate cancer rat cell line (Dunning R3327-MATLyLu) was assessed using a transwell assay and a sulforhodamine B assay and immunohistochemical detection of ki67. Androgen receptor status was determined using Western blot. In vivo, Copenhagen rats were divided in four groups (males, females, castrated males and females with testosterone suppletion) and inoculated with MATLyLu cells. Tumor size was assessed daily.', 'Testosterone increased cell migration and invasion in a concentration-dependent manner in vitro. Testosterone did not affect in vitro cell proliferation. No difference was shown between the effect of testosterone and methyltrienolone. In vivo, in groups with higher levels of circulating testosterone, more rats had (micro)metastases compared with groups with low levels of testosterone. No effect was observed on primary tumor size/growth.'] Does serum testosterone play an important role in the metastatic ability of castration resistant prostate cancer? | qiaojin/PubMedQA | 2 | [
-2.4563937187194824,
-1.2049446105957031,
2.660398483276367
] |
['We tested the hypothesis that neuroticism moderates the association between APOE (apolipoprotein E) genotype and two major outcomes, cognitive function and Alzheimer disease. We also explored whether other personality dimensions (extraversion, openness to experience, agreeableness, and conscientiousness) moderate the associations of APOE with these outcomes.', 'Primary analyses of existing randomized clinical trial data.', 'Six-hundred two older adults (mean age of 78 years at baseline).', "APOE genotype, the NEO-Five Factor Inventory, the Alzheimer's Disease Assessment Scale-Cognitive: measured every 6 months for 6.5 years) and relevant covariates.", 'Fully adjusted multivariate analyses showed that the association between the presence of APOE [Latin Small Letter Open E]-4 allele(s) and both outcomes was evident among individuals with high levels of neuroticism and extraversion but not among persons with low levels of these traits.'] Do personality factors moderate the associations between apolipoprotein genotype and cognitive function as well as late onset Alzheimer disease? | qiaojin/PubMedQA | 2 | [
-2.284044027328491,
-0.45907923579216003,
1.8083025217056274
] |
['Mucopolysaccharidoses (MPSs) are a group of lysosomal storage disorders (LSDs) caused by a defect in the degradation of glycosaminoglycans (GAGs). The accumulation of GAGs in MPS patients results in extensive, severe and progressive disease. Disease modifying therapy is available for three of the MPSs and is being developed for the other types. Early initiation of treatment, before the onset of irreversible tissue damage, clearly provides a favorable disease outcome. However, early diagnosis is difficult due to the rarity of these disorders in combination with the wide variety of clinical symptoms. Newborn screening (NBS) is probably the optimal approach, and several screening techniques for different MPSs have been studied. Here we describe a relatively simple and sensitive method to measure levels of dermatan and heparan sulfate derived disaccharides in dried blood spots (DBS) with HPLC-MS/MS, and show that this reliably separates MPS I, II and MPS III newborns from controls and heterozygotes.', 'Newborn DBS of 11 MPS I, 1 MPS II, and 6 MPS III patients, with phenotypes ranging from severe to relatively attenuated, were collected and levels of dermatan and heparan sulfate derived disaccharides in these DBS were compared with levels in DBS of newborn MPS I and MPS III heterozygotes and controls.', 'The levels of dermatan and heparan sulfate derived disaccharides were clearly elevated in all newborn DBS of MPS I, II and III patients when compared to controls. In contrast, DBS of MPS I and III heterozygotes showed similar disaccharide levels when compared to control DBS.'] Are heparan sulfate and dermatan sulfate derived disaccharides sensitive markers for newborn screening for mucopolysaccharidoses types I , II and III? | qiaojin/PubMedQA | 2 | [
-2.2596209049224854,
-1.4037784337997437,
2.6652636528015137
] |
['Human respiratory syncytial virus (HRSV) is one of the major etiologic agents of respiratory tract infections among children worldwide.', 'Here through a comprehensive analysis of the two major HRSV groups A and B (n=1983) which comprise of several genotypes, we present a complex pattern of population dynamics of HRSV over a time period of 50 years (1956-2006). Circulation pattern of HRSV revealed a series of expansions and fluctuations of co-circulating lineages with a predominance of HRSVA. Positively selected amino acid substitutions of the G glycoprotein occurred upon population growth of GB3 with a 60-nucleotide insertion (GB3 Insert), while other genotypes acquired substitutions upon both population growth and decrease, thus possibly reflecting a role for immune selected epitopes in linkage to the traced substitution sites that may have important relevance for vaccine design. Analysis evidenced the co-circulation and predominance of distinct HRSV genotypes in Brazil and suggested a year-round presence of the virus. In Brazil, GA2 and GA5 were the main culprits of HRSV outbreaks until recently, when the GB3 Insert became highly prevalent. Using Bayesian methods, we determined the dispersal patterns of genotypes through several inferred migratory routes.'] Does phylodynamics and dispersal of HRSV entail its permanence in the general population in between yearly outbreaks in children? | qiaojin/PubMedQA | 2 | [
-2.422290086746216,
-0.6926689743995667,
2.267594337463379
] |
['The aim of the study was to evaluate the association of the body mass index (BMI) with mortality and with non-fatal functional outcome in patients with acute stroke or transient ischaemic attack (TIA). Obesity is an established risk factors in primary cardiovascular disease prevention including stroke. The impact of overweight in patients with stroke or TIA on secondary fatal and non-fatal functional outcomes is less well established.', 'Data from 4428 patients with acute stroke or transient ischaemic attack (TIA) from the Telemedical Project for Integrative Stroke Care (TEMPiS) were studied in this post hoc analysis. The body mass index was available in 1521 patients. Patients were categorized as underweight (BMI <18.5), normal (BMI 18.5 to <25) overweight (BMI 25 to <30), obesity (BMI 30 to <35), advanced obesity (BMI ≥35 all kg/m(2)), and no body weight assessed. Outcome measures after 30 months were all-cause mortality and non-fatal outcomes: recurrent stroke, need for institutional care, and functional impairment (Barthel index <60, modified Rankin score >3). Mortality risk was lower in overweight patients [hazard ratio (HR): 0.69, 95% confidence interval (CI): 0.56-0.86) and lowest in obese (HR: 0.50, 95% CI: 0.35-0.71) and very obese patients (HR: 0.36, 95% CI: 0.20-0.66] compared with normal BMI. Functional, non-fatal outcomes, and recurrent stroke followed the same inverse pattern: underweight patients had the worst outcomes but obese patients had better outcomes than patients with normal BMI (all P < 0.01). After adjustment for multiple confounding factors, obese patients had a lower risk of the combined endpoints of death or institutional care (OR: 0.60, 95% CI: 0.38-0.92), death or high dependency (OR: 0.60, 95% CI: 0.39-0.91) and death or recurrent stroke (OR: 0.56, 95% CI: 0.37-0.86). Mortality was significantly lower in obese patients (all BMI >30 kg/m(2)) than patients with normal weight (HR: 0.70; 95% CI: 0.50-0.98). Underweight patients had consistently the highest risks for all endpoints.'] Are overweight and obesity associated with improved survival , functional outcome , and stroke recurrence after acute stroke or transient ischaemic attack : observations from the TEMPiS trial? | qiaojin/PubMedQA | 2 | [
-0.7719470858573914,
-1.5813077688217163,
1.348646640777588
] |
['In patients undergoing endovascular aneurysm repair (EVAR), the postimplantation syndrome (PIS), comprising fever and inflammation, occurs frequently. The cause of PIS is unclear, but graft composition and acute thrombus formation may play a role. The objective of this study was to evaluate these possible causes of the inflammatory response after EVAR.', 'One hundred forty-nine patients undergoing elective EVAR were included. Implanted stent grafts differed mainly in the type of fabric used: either woven polyester (n=82) or expanded polytetrafluorethylene (ePTFE; n=67). Tympanic temperature and C-reactive protein (CRP) were assessed daily during hospitalization. PIS was defined as the composite of a body temperature of ≥38°C coinciding with CRP>10 mg/L. Besides graft composition, the size of the grafts and the volume of new-onset thrombus were calculated using dedicated software, and results were correlated to PIS.', 'Implantation of grafts made of polyester was associated with higher postoperative temperature (P<.001), CRP levels (P<.001), and incidence of PIS (56.1% vs 17.9%; P<.001) compared to ePFTE. After multivariate analysis, woven polyester stent grafts were independently associated with an increased risk of PIS (hazard ratio, 5.6; 95% confidence interval, 1.6-19.4; P=.007). Demographics, amount of graft material implanted, or new-onset thrombus had no association with PIS.'] Does stent graft composition play a material role in the postimplantation syndrome? | qiaojin/PubMedQA | 2 | [
-1.956447720527649,
-1.5286383628845215,
2.5325841903686523
] |
['Well-differentiated follicular thyroid carcinomas (FTCs) usually act indolently, while aggressively acting tumors are difficult to detect early enough. Estrogen receptors (ERs) have prognostic significance in many cancers. Thyroid diseases, including neoplasms, are associated with the female sex. The prognostic significance of ERs in FTCs has not been reported previously.', 'We studied the role of ERα and ERβ in 83 cases of follicular thyroid adenoma (FTA) and 43 FTC cases, including seven cases of poorly differentiated FTC, obtained from the Department of Surgery, Helsinki University Central Hospital between 1990 and 2009. Patient follow-up was conducted until March 2011. Expression of ERα, ERβ, and MIB-1/Ki-67 was investigated by immunohistochemistry and correlated with clinicopathological characteristics, including survival.', 'Two major observations were apparent. First, ERβ expression was significantly higher in FTA than in FTC, and it was a stronger differential diagnostic marker than MIB-1/Ki-67. Second, low ERβ expression correlated with poor survival in FTC. All cancer-specific deaths due to FTC were among low ERβ-score patients.'] Does loss of estrogen receptor Beta expression in follicular thyroid carcinoma predict poor outcome? | qiaojin/PubMedQA | 2 | [
-2.384237289428711,
-0.9691680669784546,
2.4013900756835938
] |
['Positive fluid balance has been associated with an increased risk for mortality in critically ill patients with acute kidney injury with or without renal replacement therapy (RRT). Data on fluid accumulation prior to RRT initiation and mortality are limited. We aimed to study the association between fluid accumulation at RRT initiation and 90-day mortality.', 'We conducted a prospective, multicenter, observational cohort study in 17 Finnish intensive care units (ICUs) during a five-month period. We collected data on patient characteristics, RRT timing, and parameters at RRT initiation. We studied the association of parameters at RRT initiation, including fluid overload (defined as cumulative fluid accumulation > 10% of baseline weight) with 90-day mortality.', 'We included 296 RRT-treated critically ill patients. Of 283 patients with complete data on fluid balance, 76 (26.9%) patients had fluid overload. The median (interquartile range) time from ICU admission to RRT initiation was 14 (3.3 to 41.5) hours. The 90-day mortality rate of the whole cohort was 116 of 296 (39.2%; 95% confidence interval 38.6 to 39.8%). The crude 90-day mortality of patients with or without fluid overload was 45 of 76 (59.2%) vs. 65 of 207 (31.4%), P < 0.001. In logistic regression, fluid overload was associated with an increased risk for 90-day mortality (odds ratio 2.6) after adjusting for disease severity, time of RRT initiation, initial RRT modality, and sepsis. Of the 168 survivors with data on RRT use at 90 days, 34 (18.9%, 95% CI 13.2 to 24.6%) were still dependent on RRT.'] Is fluid overload associated with an increased risk for 90-day mortality in critically ill patients with renal replacement therapy : data from the prospective FINNAKI study? | qiaojin/PubMedQA | 2 | [
-1.315236210823059,
-1.487879753112793,
1.7902286052703857
] |
['The objective of this study was to compare the caries risk profiles obtained from the simplified Cariogram models and the conventional Cariogram model of Korean dental patients.', 'Data required for a caries risk assessment with the Cariogram were collected from 80 young adult patients (mean: 23 years old). Three different simplified Cariogram models were produced with exclusion of either or both salivary secretion rate and lactobacilli count: group 1, conventional model; group 2, both salivary secretion rate and lactobacilli count excluded; group 3, salivary secretion rate excluded; group 4, lactobacilli count excluded.', 'The mean chance of avoiding caries in group 1 (55.5%) was not significantly different from those in groups 2 and 3. Also four caries-related sectors of the Cariogram (diet, bacteria, susceptibility and circumstance) in group 1 were not significantly different than in groups 2 and 3. Group 4 showed significant differences from group 1 in the mean chance of avoiding caries and the diet, susceptibility and circumstance sectors (p < 0.05). Significant correlations were detected between all risk factors and their corresponding risk sectors (p < 0.05). Also there were significant correlations between each risk factor and the chance of avoiding caries, except for the amount of plaque, in groups 1, 2 and 3 (p < 0.05).'] Do caries risk profiles of Korean dental patients using simplified Cariogram models? | qiaojin/PubMedQA | 2 | [
-1.1636120080947876,
-0.7421661615371704,
1.06626296043396
] |
['To determine whether and to what extent the lower mortality rates for patients undergoing abdominal aortic aneurysm (AAA) repair in high-volume hospitals is explained by better nursing.', 'State hospital discharge data, Multi-State Nursing Care and Patient Safety Survey, and hospital characteristics from the AHA Annual Survey.', 'Cross-sectional analysis of linked patient outcomes for individuals undergoing AAA repair in four states.', 'Secondary data sources.', 'Favorable nursing practice environments and higher hospital volumes of AAA repair are associated with lower mortality and fewer failures-to-rescue in main-effects models. Furthermore, nurse staffing interacts with volume such that there is no mortality advantage observed in high-volume hospitals with poor nurse staffing. When hospitals have good nurse staffing, patients in low-volume hospitals are 3.4 times as likely to die and 2.6 times as likely to die from complications as patients in high-volume hospitals (p < .001).'] Is lower mortality for abdominal aortic aneurysm repair in high-volume hospitals contingent upon nurse staffing? | qiaojin/PubMedQA | 2 | [
-1.7561732530593872,
0.292765349149704,
0.6462225914001465
] |
['Histones are essential for chromatin packing, yet free histones not incorporated into chromatin are toxic. While in most cells multiple regulatory mechanisms prevent accumulation of excess histones, early Drosophila embryos contain massive extranuclear histone stores, thought to be essential for development. Excess histones H2A, H2B, and H2Av are bound to lipid droplets, ubiquitous fat storage organelles especially abundant in embryos. It has been proposed that sequestration on lipid droplets allows safe transient storage of supernumerary histones.', 'Here, we critically test this sequestration hypothesis. We find that histones are anchored to lipid droplets via the previously uncharacterized protein Jabba: Jabba localizes to droplets, coimmunoprecipitates with histones, and is necessary to recruit histones to droplets. Jabba mutants lack the maternal H2A, H2B, and H2Av deposits altogether; presumably, these deposits are eliminated unless sequestered on droplets. Jabba mutant embryos compensate for this histone deficit by translating maternal histone mRNAs. However, when histone expression is mildly compromised, the maternal histone protein deposits are essential for proper early mitoses and for viability.'] Do lipid droplets control the maternal histone supply of Drosophila embryos? | qiaojin/PubMedQA | 2 | [
-2.7078628540039062,
-0.24081985652446747,
1.9230490922927856
] |
['To investigate, using resting state (RS) functional connectivity (FC), the selectivity of involvement of the sensorimotor network in patients with acquired (A) and with hereditary (H) peripheral neuropathies (PN) and the correlations of RS FC abnormalities with clinical impairment and structural brain damage. Temporal associations among RS networks were also explored.', 'RS fMRI scans were acquired from 13 APN, 12 HPN, and 18 age- and sex-matched healthy controls. Independent component analysis and functional network connectivity were used to investigate RS FC within and among RS networks with potential functional relevance.', 'Compared to controls, patients had a decreased FC of the right precentral gyrus and an increased RS FC of the precuneus within the sensorimotor network. Both decreased and increased RS FC also involved the visual and auditory networks, which additionally had an increased coherence of function with the sensorimotor network (more pronounced in HPN). RS FC modifications in patients extended to several cognitive networks and were correlated with disease duration. In APN, they were also correlated with the severity of clinical impairment and corpus callosum atrophy.'] Do brain connectivity abnormalities extend beyond the sensorimotor network in peripheral neuropathy? | qiaojin/PubMedQA | 2 | [
-2.580307722091675,
-0.9085803627967834,
2.5705180168151855
] |
['High-intensity and high-frequency repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex was carried out in poststroke patients with increased spasticity, and the changes in F-wave parameters in comparison with M-wave parameters induced by rTMS were examined.', 'Ten-hertz rTMS pulses were delivered to the primary motor cortex of the lesion side at 110% intensity of the resting motor threshold, and F-waves were obtained from the first dorsal interosseous muscle. F-waves were recorded before (pre-stim) and immediately after the end of rTMS (post-stim) in poststroke patients.', 'F-wave persistence and F/M Amp.Ratio increased significantly in patients with lesions in upper motor tract as compared with healthy subjects (Wilcoxon rank sum test, p = 0.00023 and p = 0.0073, respectively). After the rTMS application, both F-wave persistence and F/M Amp.Ratio decreased significantly (paired t-test, p = 0.0095 and p = 0.037, respectively). However, the F-wave amplitude did not show a statistically significant variance in poststroke patients.'] Do f-wave suppression induced by suprathreshold high-frequency repetitive trascranial magnetic stimulation in poststroke patients with increased spasticity? | qiaojin/PubMedQA | 2 | [
-2.0805883407592773,
-1.289139986038208,
2.3398680686950684
] |
['Elevated plasma adrenomedullin (ADM) levels are associated with cardiovascular diseases. Single nucleotide polymorphisms (SNPs) in the gene encoding ADM (ADM) are associated with plasma ADM levels. The presence of a nuclear factor for interleukin-6 (IL-6) expression binding site in the promoter region of the ADM gene suggests a possible relationship between the expression of the ADM and IL-6. Therefore, we investigated whether plasma ADM levels are related to SNPs in the gene encoding IL-6 (IL6).', 'Plasma ADM levels were measured in 476 subjects in the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS2). The subjects were genotyped for three tagging SNPs in the IL6 gene.', 'The minor allele frequencies of the IL6 SNPs rs17147230, rs1800796 and rs2069837 were 41·8%, 20·0% and 15·4%, respectively. The tagging SNP, rs17147230, was associated with plasma ADM levels after adjusting for age and sex (β=-0·096, P\xa0=\xa00·034). The association was significant in women (β=-0·115, P\xa0=\xa00·021) but not in men. Among all subjects, plasma ADM levels decreased with an increasing number of minor alleles of rs17147230 in multivariate analysis (P\xa0=\xa00·034). Compared to subjects with the AA genotype, subjects with the TT genotype had plasma ADM levels 12·8% lower (95% CI: 0·6-23·5%, P\xa0=\xa00·041). Haplotype analysis demonstrated a significant association of the haplotype ACA with plasma ADM levels in women (P\xa0<\xa00·05).'] Is a single nucleotide polymorphism of interleukin-6 gene related to plasma adrenomedullin levels? | qiaojin/PubMedQA | 2 | [
-1.2814034223556519,
-1.6111769676208496,
1.8847410678863525
] |
['The antioxidant lycopene may be beneficial for patients with heart failure (HF). Processed tomato products are a major source of lycopene, although they are also high in sodium. Increased sodium intake may counter the positive antioxidant effect of lycopene.', 'This was a prospective study of 212 patients with HF. Dietary intake of lycopene and sodium was obtained from weighted 4-day food diaries. Patients were grouped by the median split of lycopene of 2471 µg/day and stratified by daily sodium levels above and below 3 g/day. Patients were followed for 1 year to collect survival and hospitalization data. Cox proportional hazards modeling was used to compare cardiac event-free survival between lycopene groups within each stratum of sodium intake.', 'Higher lycopene intake was associated with longer cardiac event-free survival compared with lower lycopene intake (p = 0.003). The worst cardiac event-free survival was observed in the low lycopene intake group regardless of sodium intake (> 3 g/day HR = 3.01; p = 0.027 and ≤ 3 g/day HR= 3.34; p = 0.023).'] Is higher dietary lycopene intake associated with longer cardiac event-free survival in patients with heart failure? | qiaojin/PubMedQA | 2 | [
-1.1429375410079956,
-1.4508354663848877,
1.6373426914215088
] |
['To measure the spontaneous and voluntary blinks of both younger and older people using a new device that simplifies the detailed recording of eye blinking.', "Fifty healthy volunteers (10 women and 15 men under 40 years of age, range: 22-38 years, and 20 women and 5 men above 60 years of age, range: 63-85 years) were examined after obtaining informed consent from each subject. Eyelid movements of all subjects were recorded using a high-speed blink analysis system. The spontaneous eye-blinks of the subjects were recorded during sessions consisting of a 40 seconds' period following which the subjects were instructed to blink as rapidly as possible for 5 seconds in which the blinks were again recorded. The upper lid position and movement data were plotted every millisecond by processing the recorded images.", 'The frequency of the spontaneous blinks did not differ between the younger and older subjects. The women tended to blink more frequently in both age groups. The average amplitude and duration time of the spontaneous blinks in the younger subjects were greater than those in the older subjects. Voluntary blinks in the younger subjects were more frequent than in the older subjects. Women tended to make deeper and faster voluntary blinks.'] Does [ Measurement of age-related changes in human blink using a high-speed blink analysis system ]? | qiaojin/PubMedQA | 2 | [
-2.1143620014190674,
0.7049223184585571,
0.7269946336746216
] |
['The purpose of this study is to examine whether physical disability is associated with faster rate of decline in cognitive function.', 'A longitudinal population-based cohort of 6,678 initially nondisabled older adults from a biracial urban community was interviewed at 3-year intervals from 1993 to 2012. Cognitive function was assessed using a standardized global cognitive score, and physical disabilities using activities of daily living (ADL) and instrumental activities of daily living (IADL).', 'During the follow-up period, 2,450 of 6,678 participants (37%) developed ADL and 2,069 of 4,287 participants (48%) developed IADL disability. After adjusting for demographic and physiologic confounders, cognitive function declined a mean of 0.048 unit per year before ADL disability and 0.047 unit per year before IADL disability. In comparison, the rate of cognitive decline accelerated further by 0.076 unit per year (156% increase) after ADL disability and 0.054 unit per year (115% increase) after IADL disability. Severity of ADL and IADL disabilities were also associated with faster cognitive decline following disability.'] Is disability in basic and instrumental activities of daily living associated with faster rate of decline in cognitive function of older adults? | qiaojin/PubMedQA | 2 | [
-2.065620183944702,
0.5123054385185242,
0.7127150893211365
] |
['The vast majority of patients with HER2-positive metastatic breast cancer (MBC) treated with trastuzumab eventually develop resistance to this agent. There is an unmet need therefore, for identifying biological markers with possible prognostic/predictive value in such patients. The aim of this study was to investigate the prognostic role of topoisomerase II alpha gene (TOP2A) amplification and protein (TopoIIa) expression in patients treated with trastuzumab-containing regimens.', 'Formalin-fixed paraffin-embedded tumor tissue samples were retrospectively collected from 225 eligible patients treated with trastuzumab. Protein expression of ER, PgR, Ki67, PTEN, HER2 and TopoIIa were centrally assessed by immunohistochemistry. HER2 and TOP2A gene amplification was evaluated by fluorescence in situ hybridization. PIK3CA mutations were identified by single nucleotide polymorphism genotyping. Survival was evaluated from the initiation of trastuzumab as 1st line treatment to the date of last follow-up or death.', "Among the 225 samples analyzed, only 137 (61%) were found to be HER2-positive. TOP2A was amplified in 41% and deleted in 16% of such tumors. TOP2A gene amplification was more frequent in ER-negative tumors. TopoIIa protein expression was observed in the majority (65%) of the samples and was associated with ER-positive status, high Ki67 expression, presence of PTEN protein and PIK3CA mutations. Median follow-up for patients treated in the 1st line was 51 months. Survival was more prolonged with trastuzumab-containing treatment in HER2-positive patients (50 months, log-rank, p=0.007). TOP2A non-amplified or deleted tumors were associated with increased risk for death compared to TOP2A amplified tumors (HR=2.16, Wald's p=0.010 and HR=2.67, p=0.009, respectively). In multivariate analysis, a significant interaction of TOP2A with anthracycline treatment (either in the adjuvant or the 1st line setting) was observed for survival (Wald's p=0.015). Among the TOP2A amplified subgroup, anthracycline-treated patients were associated with decreased risk for death."] Is topoisomerase II alpha gene amplification a favorable prognostic factor in patients with HER2-positive metastatic breast cancer treated with trastuzumab? | qiaojin/PubMedQA | 2 | [
-2.0565831661224365,
-1.5611975193023682,
2.607295513153076
] |
['Coactivation of tyrosine kinase limits the efficacy of tyrosine kinase inhibitors. We hypothesized that a strategic combination therapy could overcome tyrosine kinase coactivation and compensatory oncogenic signaling in patients with adrenocortical carcinoma (ACC).', 'We profiled 88 tyrosine kinases before and after treatment with sunitinib in H295R and SW13 ACC cells. The effects of monotherapy and strategic combination regimens were determined by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (ie, MTS) assay.', 'The minimum inhibitory concentrations (IC(min)) of sunitinib quenched its primary targets: FLT-3, VEGFR-2, and RET. In contrast, ERK, HCK, Chk2, YES, CREB, MEK, MSK, p38, FGR, and AXL were hyperactivated. Monotherapy with sunitinib or PD98059 at their IC(min) reduced proliferation by 23% and 19%, respectively, in H295R cells and by 25% and 24%, respectively, in SW13 cells. Sunitinib and PD98059 in combination decreased proliferation by 68% and 64% in H295R and in SW13 cells, respectively (P < .05 versus monotherapy). The effects of combination treatment exceeded the sum of the effects observed with each individual agent alone.'] Does strategic combination therapy overcome tyrosine kinase coactivation in adrenocortical carcinoma? | qiaojin/PubMedQA | 2 | [
-2.088198184967041,
-1.4719258546829224,
2.5735669136047363
] |
["Plants use a diverse range of visual and olfactory cues to advertize to pollinators. Australian Chiloglottis orchids employ one to three related chemical variants, all 2,5-dialkylcyclohexane-1,3-diones or 'chiloglottones' to sexually attract their specific male pollinators. Here an investigation was made of the physiological aspects of chiloglottone synthesis and storage that have not previously been examined.", 'The location of chiloglottone production was determined and developmental and diurnal changes by GC-MS analysis of floral tissue extracts was monitored in two distantly related Chiloglottis species. Light treatment experiments were also performed using depleted flowers to evaluate if sunlight is required for chiloglottone production; which specific wavelengths of light are required was also determined.', 'Chiloglottone production only occurs in specific floral tissues (the labellum calli and sepals) of open flowers. Upon flower opening chiloglottone production is rapid and levels remain more or less stable both day and night, and over the 2- to 3-week lifetime of the flower. Furthermore, it was determined that chiloglottone production requires continuous sunlight, and determined the optimal wavelengths of sunlight in the UV-B range (with peak of 300 nm).'] Is the production of a key floral volatile dependent on UV light in a sexually deceptive orchid? | qiaojin/PubMedQA | 2 | [
-2.696187973022461,
0.056750793009996414,
1.6086516380310059
] |
['Current treatment of glioblastoma after surgery consists of a combination of fractionated radiotherapy and temozolomide. However, it is difficult to completely remove glioblastoma because it has uncertain boundaries with surrounding tissues. Moreover, combination therapy is not always successful because glioblastoma has diverse resistances. To overcome these limitations, we examined the combined effects of chemotherapy and knockdown of mitogen-activated protein kinase phosphatase-1 (MKP-1).', 'We used ten different anti-cancer drugs (cisplatin, cyclophosphoamide, doxorubicin, epirubicin, etoposide, 5-fluorouracil, gemcitabine, irinotecan, mitomycin C, and vincristine) to treat glioblastoma multiforme (GBM) cells. Knockdown of MKP-1 was performed using siRNA and lipofectamine. The basal level of MKP-1 in GBM was analyzed based on cDNA microarray data obtained from the Gene Expression Omnibus (GEO) databases.', 'Anti-cancer drug-induced cell death was significantly enhanced by knockdown of MKP-1, and this effect was most prominent in cells treated with irinotecan and etoposide. Treatment with these two drugs led to significantly increased phosphorylation of c-Jun N-terminal kinase (JNK) in a time-dependent manner, while pharmacological inhibition of JNK partially inhibited drug-induced cell death. Knockdown of MKP-1 also enhanced drug-induced phosphorylation of JNK.'] Does constitutive Expression of MAP Kinase Phosphatase-1 confer Multi-drug Resistance in Human Glioblastoma Cells? | qiaojin/PubMedQA | 2 | [
-2.453397750854492,
-1.3503572940826416,
2.8573241233825684
] |
['Allergic asthma is a T(H)2-promoted hyperreactivity with an immediate, IgE, and mast cell-dependent response followed by eosinophil-dominated inflammation and airway obstruction.', 'Because costimulation by CD28 is essential for T(H)2 but not T(H)1 responses, we investigated the effect of selective interference with this pathway in mice using the models of ovalbumin and house dust mite-induced airway inflammation.', 'To study the role of CD28 in the effector phase of allergic airway inflammation, we developed an inducibly CD28-deleting mouse strain or alternatively used a CD28 ligand-binding site-specific mouse anti-mouse mAb blocking CD28 engagement.', 'We show that even after systemic sensitization to the allergen, interruption of CD28-mediated costimulation is highly effective in preventing airway inflammation during challenge. In addition to improving airway resistance and histopathologic presentation and reducing inflammatory infiltrates, antibody treatment during allergen challenge resulted in a marked relative increase in regulatory T-cell numbers among the CD4 T-cell subset of the challenged lung.'] Does interruption of CD28-mediated costimulation during allergen challenge protect mice from allergic airway disease? | qiaojin/PubMedQA | 2 | [
-2.6054608821868896,
-1.095544457435608,
2.7488603591918945
] |
['The circle of Willis (CoW) is a primary collateral pathway that compensates quickly for a drop in cerebral blood flow. Using the complete CoW as a surrogate marker for good collateral circulation, its prognostic value after intravenous thrombolysis was examined.', 'We prospectively studied 64 consecutive patients with acute ischemic stroke treated with tissue plasminogen activator within 3 hours of stroke onset between October 2005 and June 2012 in our hospital. The study protocol was based on standard guidelines for intravenous thrombolysis. On computed tomographic angiography 24 hours after thrombolysis, the CoW was complete in 21 (32.8%) cases and incomplete in 43 (67.2%).', 'Patients with complete CoW were more likely to have early improvement in National Institute of Health Stroke Scale (NIHSS) score (median improvement 2 vs 0 at 2 hours; 4 vs 1 at 24 hours), be independent at 3 months (42% vs 19%). In the incomplete CoW group, the rate of symptomatic intracerebral haemorrhage (SICH) according to the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) definition was almost 3 times higher. Complete CoW was one of the strongest predictors of good functional outcome at 3 months (odds ratio 2.32; P = .01).'] Is configuration of the circle of Willis associated with less symptomatic intracerebral hemorrhage in ischemic stroke patients treated with intravenous thrombolysis? | qiaojin/PubMedQA | 2 | [
-1.9512945413589478,
-1.4874721765518188,
2.5541598796844482
] |
['Primigravidity is one of the main risk factors for both malaria and anaemia. Since the implementation of intermittent preventive treatment (IPTp) in sub-Saharan Africa, the relationship between anaemia and gravidity and its evolution during pregnancy has been little explored. This study aimed to evaluate the impact of gravidity on the variation of haemoglobin during pregnancy according to the timing of gestation.', "Data from three studies carried out in nearby areas in south Benin (Ouidah, Comé, Allada) between 2005 and 2012 were analysed. At inclusion (first antenatal visit, ANV1) women's age, area of residence, schooling, gravidity, gestational age, weight and height were recorded. Thick blood smears were performed on ANV1, second visit (ANV2) and at delivery. In Allada, women's serum ferritin and CRP concentrations were also assessed. The impact of gravidity on maternal haemoglobin (Hb) was analysed using a logistic or linear regression depending on the outcome. The statistical significance was set to P < 0.05.", 'In total, data from 3,591 pregnant women were analysed. Both univariate and multivariate analyses showed a constant association between Hb concentrations and gravidity in the three periods of Hb assessment (ANV1, ANV2 and delivery). Mean Hb concentration was significantly lower in primigravidae than in multigravidae at ANV1 (mean difference = -2.4 g/L, CI 95%: [-3.4, -1.4], P < 0.001). Afterwards, there was a significant increase in primigravidae only, with a tendency to reversal between primigravidae and multigravidae, which was confirmed at delivery (mean difference = 2.8 g/L, CI 95%: [1.3, 4.2], P < 0.001). The prevalence of malaria infection was halved between ANV1 and delivery in primigravidae while it decreased by only 38% among multigravidae, who were less prone to malaria infection (prevalence at ANV1, 20% and 10% respectively). Iron deficiency was more common in multigravidae, and it decreased slightly in this group between ANV1 and delivery.'] Do malaria and gravidity interact to modify maternal haemoglobin concentrations during pregnancy? | qiaojin/PubMedQA | 2 | [
-1.2325431108474731,
-1.5786361694335938,
1.7713743448257446
] |
['Group IIa secretory phospholipase A2 (sPLA2 IIa) plays a role in the malignant potential of several epithelial cancers. Nuclear factor kappa B (NF-κB) regulates cancer cell growth and is modulated by phospholipase activity in many cancer cells. We hypothesized that knockdown of sPLA2 in lung cancer cells would reduce cell proliferation and NF-κB activity in vitro and attenuate tumor growth in vivo.', "Two human non-small cell lung cancer cell lines (A549 and H358) were transduced with short hairpin RNA targeting sPLA2 group IIa. Quantitative reverse transcriptase-polymerase chain reaction and immunoblotting confirmed knockdown of sPLA2 IIa messenger RNA and protein, respectively. Cell proliferation was evaluated by the 5-bromo-2'-deoxyuridine DNA labeling assay. NF-κB phosphorylation was assayed by western blot. 1 × 10(6) of A549 or A549 sPLA2 knockdown cells were injected into the left flanks of nude mice (aged 6 to 8 weeks). Tumors were followed for 23 days, then removed and stained with hematoxylin and eosin, stained with Ki-67, and analyzed for sPLA2 IIa messenger RNA expression.", 'sPLA2 knockdown reduced NF-κB phosphorylation and tumor growth in vivo. A549 wild-type tumors grew twice as fast as knockdown tumors. Ki-67 staining was more prominent throughout the wild-type tumors compared with knockdown tumors. Explanted knockdown tumors maintained lower sPLA2 levels compared with wild-type, confirmed by reverse transcriptase-polymerase chain reaction.'] Does knockdown of secretory phospholipase A2 IIa reduce lung cancer growth in vitro and in vivo? | qiaojin/PubMedQA | 2 | [
-2.1825056076049805,
-1.488106608390808,
2.6783607006073
] |
['The present study was designed to investigate the effect of a high-fat diet (HFD) on the inflammatory response of peritoneal macrophages.', 'Male Wistar rats were fed a control diet (n = 12) or an HFD (n = 12) for 12 wk. After euthanasia, peritoneal macrophages were collected and stimulated (or not) with lipopolysaccharide (LPS). Results from the assays using peritoneal macrophages were analyzed with one-way analysis of variance or an equivalent non-parametric test. The level of significance adopted was 0.05.', 'Consumption of the HFD was associated with significant increases in weight gain and fat depots (P < 0.05). Despite having no influence in systemic markers of inflammation, such as interleukin (IL)-6, tumor necrosis factor-α, and plasminogen activator inhibitor-1, the HFD intake significantly decreased insulin sensitivity, as evaluated by the homeostasis model assessment index (P < 0.05). A decreased production of IL-1β, IL-6, IL-10, and nitric oxide in response to the LPS stimulation was observed in peritoneal macrophages from the HFD group (P < 0.05). Also, in HFD-fed animals, LPS incubation did not increase IL-1β and IL-6 mRNA expression (P < 0.05). These effects were associated with an attenuation of IκB inhibitor kinase-β phosphorylation and nuclear factor-κB activation in response to LPS and with a failure to decrease IκB inhibitor-α expression (P < 0.05).'] Does high-fat diet blunt activation of the nuclear factor-κB signaling pathway in lipopolysaccharide-stimulated peritoneal macrophages of Wistar rats? | qiaojin/PubMedQA | 2 | [
-2.2837812900543213,
-1.3775019645690918,
2.7044999599456787
] |
['The anticancer action exerted by polyunsaturated fatty acid peroxidation may not be reproduced by commercially available lipid emulsions rich in vitamin E. Therefore, we evaluated the effects of fish oil (FO) emulsion containing α-tocopherol 0.19 g/L on human colorectal adenocarcinoma cells and tumors.', 'HT-29 cell growth, survival, apoptosis, and lipid peroxidation were analyzed after a 24-h incubation with FO 18 to 80 mg/L. Soybean oil (SO) emulsion was used as an isocaloric and isolipidic control. In vivo, nude mice bearing HT-29 tumors were sacrificed 7 d after an 11-d treatment with intravenous injections of FO or SO 0.2 g ∙ kg(-1) ∙ d(-1) FO or SO to evaluate tumor growth, necrosis, and lipid peroxidation.', 'The FO inhibited cell viability and clonogenicity in a dose-dependent manner, whereas SO showed no significant effect compared with untreated controls. Lipid peroxidation and cell apoptosis after treatment with FO 45 mg/L were increased 2.0-fold (P < 0.01) and 1.6-fold (P = 0.04), respectively. In vivo, FO treatment did not significantly affect tumor growth. However, immunohistochemical analyses of tumor tissue sections showed a decrease of 0.6-fold (P < 0.01) in the cell proliferation marker Ki-67 and an increase of 2.3-fold (P = 0.03) in the necrotic area, whereas malondialdehyde and total peroxides were increased by 1.9-fold (P = 0.09) and 7.0-fold (P < 0.01), respectively, in tumors of FO-treated compared with untreated mice.'] Does vitamin E content in fish oil emulsion prevent lipoperoxidative effects on human colorectal tumors? | qiaojin/PubMedQA | 2 | [
-1.9650803804397583,
-1.5213154554367065,
2.457775592803955
] |
['The purpose of this study was to investigate gender differences in binge eating and associated behavioral correlates in college students.', 'A webbased survey was conducted with 2073 students (mean age 19.8 yr; range 18-23 yr). Multiple logistic regression was used to calculate odds ratios and 95% confidence intervals for the factors associated with binge eating.', 'Twenty-nine percent of students reported recent bingeing. Factors associated with binge eating included being female, having a higher body mass index, current tobacco use, and exercising to lose weight. Women were more likely to binge eat (73.8%; χ(2)=32.3; p≤0.001), report loss of control (45%; χ(2)=16.3; p≤0.001), self induced vomiting (20.7%; χ(2)=15.9; p≤0.001), and laxative use (6.7%; χ(2)=8.93; p≤0.001).'] Does gender differences in binge eating and behavioral correlate among college students? | qiaojin/PubMedQA | 1 | [
-1.0026196241378784,
0.362947016954422,
-0.13696080446243286
] |
['Prolonged treatment of Allium cepa root meristems with changing concentrations of hydroxyurea (HU) results in either premature chromosome condensation or cell nuclei with an uncommon form of biphasic chromatin organization. The aim of the current study was to assess conditions that compromise cell cycle checkpoints and convert DNA replication stress into an abnormal course of mitosis.', 'Interphase-mitotic (IM) cells showing gradual changes of chromatin condensation were obtained following continuous 72 h treatment of seedlings with 0·75 mm HU (without renewal of the medium). HU-treated root meristems were analysed using histochemical stainings (DNA-DAPI/Feulgen; starch-iodide and DAB staining for H(2)O(2) production), Western blotting [cyclin B-like (CBL) proteins] and immunochemistry (BrdU incorporation, detection of γ-H2AX and H3S10 phosphorylation).', 'Continuous treatment of onion seedlings with a low concentration of HU results in shorter root meristems, enhanced production of H(2)O(2), γ-phosphorylation of H2AX histones and accumulation of CBL proteins. HU-induced replication stress gives rise to axially elongated cells with half interphase/half mitotic structures (IM-cells) having both decondensed and condensed domains of chromatin. Long-term HU treatment results in cell nuclei resuming S phase with gradients of BrdU labelling. This suggests a polarized distribution of factors needed to re-initiate stalled replication forks. Furthermore, prolonged HU treatment extends both the relative time span and the spatial scale of H3S10 phosphorylation known in plants.'] Does dNA replication stress induce deregulation of the cell cycle events in root meristems of Allium cepa? | qiaojin/PubMedQA | 2 | [
-2.4582905769348145,
-1.3225312232971191,
2.8861443996429443
] |
['To compare the accuracy and reproducibility of the endometrial receptivity array (ERA) versus standard histologic methods.', 'A comparative prospective study (May 2008-May 2012).', 'University-affiliated infertility clinic.', 'Eighty-six healthy oocyte donors, regularly cycling, aged 20-34 years with a body mass index (BMI) of 19-25 kg/m(2).', 'Endometrial biopsies were collected throughout the menstrual cycle. For the accuracy study, 79 samples were grouped into two cohorts: the training set (n = 79) for ERA machine-learning training and dating, and a dating subset (n = 49) for comparison between histologic and ERA dating. For the reproducibility study, seven women underwent ERA testing and it was repeated in the same patients on the same day of their cycle 29-40 months later.', 'Concordance of histologic and ERA dating related to LH as a reference, and interobserver variability between pathologists were statistically analyzed by the quadratic weighted Kappa index. The ERA reproducibility was tested and its gene expression visualized by principal component analysis.', 'For each pathologist, concordance against LH peak yielded values of 0.618 (0.446-0.791) and 0.685 (0.545-0.824). Interobserver variability between pathologists yielded a Kappa index of 0.622 (0.435-0.839). Concordance for ERA dating against LH peak showed a value of 0.922 (0.815-1.000). Reproducibility of the ERA test was 100% consistent.'] Is the accuracy and reproducibility of the endometrial receptivity array superior to histology as a diagnostic method for endometrial receptivity? | qiaojin/PubMedQA | 2 | [
-1.8211264610290527,
-1.4593052864074707,
2.3279690742492676
] |
['Synthetic biology allows the development of new biochemical pathways for the production of chemicals from renewable sources. One major challenge is the identification of suitable microorganisms to hold these pathways with sufficient robustness and high yield. In this work we analyzed the genome of the propionic acid producer Actinobacteria Propionibacterium acidipropionici (ATCC 4875).', 'The assembled P. acidipropionici genome has 3,656,170 base pairs (bp) with 68.8%\u2009G\u2009+\u2009C content and a low-copy plasmid of 6,868\u2009bp. We identified 3,336 protein coding genes, approximately 1000 more than P. freudenreichii and P. acnes, with an increase in the number of genes putatively involved in maintenance of genome integrity, as well as the presence of an invertase and genes putatively involved in carbon catabolite repression. In addition, we made an experimental confirmation of the ability of P. acidipropionici to fix CO2, but no phosphoenolpyruvate carboxylase coding gene was found in the genome. Instead, we identified the pyruvate carboxylase gene and confirmed the presence of the corresponding enzyme in proteome analysis as a potential candidate for this activity. Similarly, the phosphate acetyltransferase and acetate kinase genes, which are considered responsible for acetate formation, were not present in the genome. In P. acidipropionici, a similar function seems to be performed by an ADP forming acetate-CoA ligase gene and its corresponding enzyme was confirmed in the proteome analysis.'] Does the genome sequence of Propionibacterium acidipropionici provide insights into its biotechnological and industrial potential? | qiaojin/PubMedQA | 2 | [
-2.3585941791534424,
-1.1826460361480713,
2.686999559402466
] |
['Protein disulfide isomerase (PDI) is an abundant endoplasmic reticulum (ER)-resident chaperone and oxidoreductase that catalyzes formation and rearrangement (isomerization) of disulfide bonds, thereby participating in protein folding. PDI modification by nitrosative stress is known to increase protein misfolding, ER stress, and neuronal apoptosis. As LDL oxidation and ER stress may play a role in atherogenesis, this work was designed to investigate whether PDI was inactivated by oxLDLs, thereby participating in oxLDL-induced ER stress and apoptosis.', 'Preincubation of human endothelial HMEC-1 and of macrophagic U937 cells with toxic concentration of oxLDLs induced PDI inhibition and modification, as assessed by 4-HNE-PDI adducts formation. PDI inhibition by bacitracin potentiated ER stress (increased mRNA expression of CHOP and sXBP1) and apoptosis induced by oxLDLs. In contrast, increased PDI activity by overexpression of an active wild-type PDI was associated with reduced oxLDL-induced ER stress and toxicity, whereas the overexpression of a mutant inactive form was not protective. These effects on PDI were mimicked by exogenous 4-HNE and prevented by the carbonyl-scavengers N-acetylcysteine and pyridoxamine, which reduced CHOP expression and toxicity by oxLDLs. Interestingly, 4-HNE-modified PDI was detected in the lipid-rich areas of human advanced atherosclerotic lesions. Innovation and'] Do protein disulfide isomerase modification and inhibition contribute to ER stress and apoptosis induced by oxidized low density lipoproteins? | qiaojin/PubMedQA | 2 | [
-2.4830734729766846,
-1.276653528213501,
2.757809638977051
] |
['GPCRs undergo both homologous and heterologous regulatory processes in which receptor phosphorylation plays a critical role. The protein kinases responsible for each pathway are well established; however, other molecular details that characterize each pathway remain unclear. In this study, the molecular mechanisms that determine the differences in the functional roles and intracellular trafficking between homologous and PKC-mediated heterologous internalization pathways for the dopamine D₂ receptor were investigated.', 'All of the S/T residues located within the intracellular loops of D₂ receptor were mutated, and the residues responsible for GRK- and PKC-mediated internalization were determined in HEK-293 cells and SH-SY5Y cells. The functional role of receptor internalization and the cellular components that determine the post-endocytic fate of internalized D₂ receptors were investigated in the transfected cells.', 'T134, T225/S228/S229 and S325 were involved in PKC-mediated D₂ receptor desensitization. S229 and adjacent S/T residues mediated the PKC-dependent internalization of D₂ receptors, which induced down-regulation and desensitization. S/T residues within the second intracellular loop and T225 were the major residues involved in GRK-mediated internalization of D₂ receptors, which induced receptor resensitization. ARF6 mediated the recycling of D₂ receptors internalized in response to agonist stimulation. In contrast, GASP-1 mediated the down-regulation of D₂ receptors internalized in a PKC-dependent manner.'] Are aRF6 and GASP-1 post-endocytic sorting proteins selectively involved in the intracellular trafficking of dopamine D₂ receptors mediated by GRK and PKC in transfected cells? | qiaojin/PubMedQA | 2 | [
-2.3783438205718994,
-1.0140087604522705,
2.4497060775756836
] |
["This study mapped regions of genomic RNA (gRNA) important for packaging and propagation of mouse mammary tumor virus (MMTV). MMTV is a type B betaretrovirus which preassembles intracellularly, a phenomenon distinct from retroviruses that assemble the progeny virion at cell surface just before budding such as the type C human and feline immunodeficiency viruses (HIV and FIV). Studies of FIV and Mason-Pfizer monkey virus (MPMV), a type D betaretrovirus with similar intracellular virion assembly processes as MMTV, have shown that the 5' untranslated region (5' UTR) and 5' end of gag constitute important packaging determinants for gRNA.", "Three series of MMTV transfer vectors containing incremental amounts of gag or 5' UTR sequences, or incremental amounts of 5' UTR in the presence of 400 nucleotides (nt) of gag were constructed to delineate the extent of 5' sequences that may be involved in MMTV gRNA packaging. Real time PCR measured the packaging efficiency of these vector RNAs into MMTV particles generated by co-transfection of MMTV Gag/Pol, vesicular stomatitis virus envelope glycoprotein (VSV-G Env), and individual transfer vectors into human 293T cells. Transfer vector RNA propagation was monitored by measuring transduction of target HeLaT4 cells following infection with viral particles containing a hygromycin resistance gene expression cassette on the packaged RNA.", "MMTV requires the entire 5' UTR and a minimum of ~120 nucleotide (nt) at the 5' end of gag for not only efficient gRNA packaging but also propagation of MMTV-based transfer vector RNAs. Vector RNAs without the entire 5' UTR were defective for both efficient packaging and propagation into target cells."] Are sequences within both the 5 ' UTR and Gag required for optimal in vivo packaging and propagation of mouse mammary tumor virus ( MMTV ) genomic RNA? | qiaojin/PubMedQA | 2 | [
-2.0047109127044678,
-1.4189778566360474,
2.4785637855529785
] |
['Cardiovascular disease is prevalent and frequently unrecognized in patients with chronic obstructive pulmonary disease (COPD). NT-proBNP is an established risk factor in patients with heart failure. NT-proBNP may also be released from the right ventricle. Thus serum NT-proBNP may be elevated during acute exacerbations of COPD (AECOPD). The prognostic value of NT-proBNP in patients hospitalized with AECOPD is sparsely studied. Our objective was to test the hypothesis that NT-proBNP independently predicts long term mortality following AECOPD.', 'A prospective cohort study of 99 patients with 217 admissions with AECOPD. Clinical, electrocardiographic, radiological and biochemical data were collected at index and repeat admissions and analyzed in an extended survival analysis with time-dependent covariables.', 'Median follow-up time was 1.9 years, and 57 patients died during follow-up. NT-proBNP tertile limits were 264.4 and 909 pg/mL, and NT-proBNP in tertiles 1 through 3 was associated with mortality rates of 8.6, 35 and 62 per 100 patient-years, respectively (age-adjusted log-rank p<0.0001). After adjustment for age, gender, peripheral edema, cephalization and cTnT in a multivariable survival model, the corresponding hazard ratios for dying were 2.4 (0.95-6.0) and 3.2 (1.3-8.1) (with 95% confidence intervals in parentheses, p-value for trend 0.013).'] Does nT-proBNP independently predict long term mortality after acute exacerbation of COPD - a prospective cohort study? | qiaojin/PubMedQA | 2 | [
-1.141134262084961,
-1.668515682220459,
1.818894863128662
] |
['Differentiating between sterile inflammation and bacterial infection in critically ill patients with fever and other signs of the systemic inflammatory response syndrome (SIRS) remains a clinical challenge. The objective of our study was to mine an existing genome-wide expression database for the discovery of candidate diagnostic biomarkers to predict the presence of bacterial infection in critically ill children.', 'Genome-wide expression data were compared between patients with SIRS having negative bacterial cultures (n = 21) and patients with sepsis having positive bacterial cultures (n = 60). Differentially expressed genes were subjected to a leave-one-out cross-validation (LOOCV) procedure to predict SIRS or sepsis classes. Serum concentrations of interleukin-27 (IL-27) and procalcitonin (PCT) were compared between 101 patients with SIRS and 130 patients with sepsis. All data represent the first 24 hours of meeting criteria for either SIRS or sepsis.', 'Two hundred twenty one gene probes were differentially regulated between patients with SIRS and patients with sepsis. The LOOCV procedure correctly predicted 86% of the SIRS and sepsis classes, and Epstein-Barr virus-induced gene 3 (EBI3) had the highest predictive strength. Computer-assisted image analyses of gene-expression mosaics were able to predict infection with a specificity of 90% and a positive predictive value of 94%. Because EBI3 is a subunit of the heterodimeric cytokine, IL-27, we tested the ability of serum IL-27 protein concentrations to predict infection. At a cut-point value of ≥5 ng/ml, serum IL-27 protein concentrations predicted infection with a specificity and a positive predictive value of >90%, and the overall performance of IL-27 was generally better than that of PCT. A decision tree combining IL-27 and PCT improved overall predictive capacity compared with that of either biomarker alone.'] Is interleukin-27 a novel candidate diagnostic biomarker for bacterial infection in critically ill children? | qiaojin/PubMedQA | 2 | [
-1.8924323320388794,
-1.4576832056045532,
2.4044265747070312
] |
['The aim of this study was to determine the relationship between self-reported sleep quality, menopausal symptom intensity, and correlates (including ethnicity) among middle-aged women.', 'The present cross-sectional study involved 1,078 Colombian women aged 40 to 59 years who completed the Pittsburgh Sleep Quality Index (PSQI), the Menopause Rating Scale (MRS), and a general questionnaire exploring sociodemographic data.', 'The median [interquartile range] age of the whole sample was 49.0 [9.0] years. Among the participants, 45.4% were postmenopausal, 57.2% had increased body mass index values, 13.9% were black, 20.7% had hypertension, 74.1% had a stable partner, and 3.8% used hormone therapy. The prevalence of poor sleep quality was 57.1% (PSQI global score ≥5). Significant correlations between PSQI global scores and MRS total and subscale scores were found. Multiple linear regression analysis found that higher PSQI scores (poorer quality of sleep) correlated with higher MRS psychological and somatic subscale scores (more severe symptoms), smoking habit, and hypertension. Menopause status and black ethnicity were excluded from the final regression model.'] Does assessment of sleep quality and correlate in a large cohort of Colombian women around menopause? | qiaojin/PubMedQA | 2 | [
-1.5888092517852783,
-0.47609516978263855,
1.1855764389038086
] |
['Longitudinal quantitative evaluation of cartilage disease requires reproducible measurements over time. We report 8 years of quality assurance (QA) metrics for quantitative magnetic resonance (MR) knee analyses from the Osteoarthritis Initiative (OAI) and show the impact of MR system, phantom, and acquisition protocol changes.', 'Key 3T MR QA metrics, including signal-to-noise, signal uniformity, T2 relaxation times, and geometric distortion, were quantified monthly on two different phantoms using an automated program.', 'Over 8 years, phantom measurements showed root-mean-square coefficient-of-variation reproducibility of <0.25% (190.0 mm diameter) and <0.20% (148.0 mm length), resulting in spherical volume reproducibility of <0.35%. T2 relaxation time reproducibility varied from 1.5% to 5.3%; seasonal fluctuations were observed at two sites. All other QA goals were met except: slice thicknesses were consistently larger than nominal on turbo spin echo images; knee coil signal uniformity and signal level varied significantly over time.'] Do the Osteoarthritis Initiative ( OAI ) magnetic resonance imaging quality assurance update? | qiaojin/PubMedQA | 2 | [
-2.1355268955230713,
-1.2867939472198486,
2.52484393119812
] |
['Heavy metals generate free radicals and induce oxidative and nitrosative stress with depletion of antioxidants. In this study, we have evaluated the beneficial effects of α-tocopherol against nickel sulfate exposed testicular dysfunction.', 'We studied the effect of supplementation of α-tocopherol (10 mg/100 g body weight, i.m.) on nickel sulfate (2.0 mg/100 g body weight, i.p.) induced testicular oxidative and nitrosative stress in Wister strain male albino rats. Serum and testicular nitric oxide, L-ascorbic acid and serum α-tocopherol concentrations were evaluated. We also evaluated sperm count, motility and histopathology of testes.', 'Nickel treated rats showed significantly decreased body weight, testicular somatic index, sperm count, sperm motility, serum and testicular L-ascorbic acid concentration and serum α-tocopherol level as compared to their controls. However, simultaneous treatment with nickel sulfate and α-tocopherol produced a remarkable improvement of all the above parameters when compared with treatment with nickel alone. Nickel treated rats also had significantly increased serum and testicular nitric oxide concentrations as compared to their controls. However, simultaneous treatment with nickel sulfate and α-tocopherol significantly decreased nitric oxide concentrations in both serum and testes, respectively, as compared to nickel treatment alone. Histopathology of the testes revealed tortuous seminiferous tubules, loss of spermatogenesis process (>75%), congestion and necrosis in nickel sulfate treated rats, whereas rats simultaneously treated with nickel sulfate and α-tocopherol had almost normal seminiferous tubules and near normal spermatogenesis as compared to nickel alone treated rats.'] Does α-Tocopherol ameliorate nickel induced testicular oxidative and nitrosative stress in albino rats? | qiaojin/PubMedQA | 2 | [
-2.2956888675689697,
-1.3898775577545166,
2.6394236087799072
] |
['The purpose of the current study was to evaluate survival outcome according to the expression status of CD73 in patients with epithelial ovarian cancer.', 'A total of 167 patients with epithelial ovarian cancer were enrolled in the current study. For each patient, a retrospective review of medical records was conducted. Immunohistochemical staining for CD73, CD8, FoxP3, and CD68 was performed using tissue microarray made with paraffin embedded tissue block.', 'Among the enrolled patients, 29.9% of patients (n=50) showed negative expression for CD73, whereas 70.1% of patients (n=117) showed positive expression for CD73. The CD73 positive group showed better prognosis compared to the CD73 negative group (5-year overall survival of CD73 positive group, 73.0%; that of CD73 negative group, 50.1%; p=0.023). CD73 was more frequently expressed in mucinous adenocarcinoma and clear cell carcinoma compared to serous or endometrioid adenocarcinoma. In addition, CD73 overexpressions were more frequently detected in patients with known good prognostic factors, i.e., low stage, well/moderate differentiation, negative peritoneal cytology, no lymphovascular involvement, and no macroscopic residual tumor after debulking surgery. There was significantly more infiltration of regulatory T cells in the CD73 negative group compared to the CD73 positive group.'] Is overexpression of CD73 in epithelial ovarian carcinoma associated with better prognosis , lower stage , better differentiation and lower regulatory T cell infiltration? | qiaojin/PubMedQA | 2 | [
-2.166149377822876,
-1.5146589279174805,
2.6736502647399902
] |
['The prevalence of the metabolic syndrome and nonalcoholic fatty liver disease (NAFLD) in humans increases with age. It is unknown whether this association is secondary to the increased incidence of risk factors for NAFLD that occurs with aging, reflects the culmination of years of exposure to lifestyle factors such as a high-fat diet (HFD), or results from physiological changes that characterize aging. To examine this question, the development of NAFLD in response to a fixed period of HFD feeding was examined in mice of different ages. Mice aged 2, 8, and 18 months were fed 16 weeks of a low-fat diet or HFD. Increased body mass and insulin insensitivity occurred in response to HFD feeding irrespective of the age of the mice. The amount of HFD-induced hepatic steatosis as determined biochemically and histologically was also equivalent among the three ages. Liver injury occurred exclusively in the two older ages as reflected by increased serum alanine aminotransferase levels, positive terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick end-labeling, and caspase activation. Older mice also had an elevated innate immune response with a more pronounced polarization of liver and adipose tissue macrophages into an M1 phenotype. Studies of cultured hepatocytes from young and old mice revealed that aged cells were selectively sensitized to the Fas death pathway.'] Does aging promote the development of diet-induced murine steatohepatitis but not steatosis? | qiaojin/PubMedQA | 2 | [
-2.655940055847168,
-0.975296139717102,
2.6574227809906006
] |
['(131)I therapy is regularly used following surgery as a part of thyroid cancer management. Despite an overall relatively good prognosis, recurrent or metastatic thyroid cancer is not rare. CD133-expressing cells have been shown to mark thyroid cancer stem cells that possess the characteristics of stem cells and have the ability to initiate tumours. However, no studies have addressed the influence of CD133-expressing cells on radioiodide therapy of the thyroid cancer. The aim of this study was to investigate whether CD133(+) cells contribute to the radioresistance of thyroid cancer and thus potentiate future recurrence and metastasis.', 'Thyroid cancer cell lines were analysed for CD133 expression, radiosensitivity and gene expression.', 'The anaplastic thyroid cancer cell line ARO showed a higher percentage of CD133(+) cells and higher radioresistance. After γ-irradiation of the cells, the CD133(+) population was enriched due to the higher apoptotic rate of CD133(-) cells. In vivo (131)I treatment of ARO tumour resulted in an elevated expression of CD133, Oct4, Nanog, Lin28 and Glut1 genes. After isolation, CD133(+) cells exhibited higher radioresistance and higher expression of Oct4, Nanog, Sox2, Lin28 and Glut1 in the cell line or primarily cultured papillary thyroid cancer cells, and lower expression of various thyroid-specific genes, namely NIS, Tg, TPO, TSHR, TTF1 and Pax8.'] Are cD133-expressing thyroid cancer cells undifferentiated , radioresistant and survive radioiodide therapy? | qiaojin/PubMedQA | 2 | [
-2.37079119682312,
-1.295990228652954,
2.7512593269348145
] |
['Pharmacological activation of type-2 metabotropic glutamate receptors (mGlu2 receptors) causes analgesia in experimental models of inflammatory and neuropathic pain. Presynaptic mGlu2 receptors are activated by the glutamate released from astrocytes by means of the cystine/glutamate antiporter (System x(c)(-) or Sx(c)(-)). We examined the analgesic activity of the Sx(c)(-) activator, N-acetyl-cysteine (NAC), in mice developing inflammatory or neuropathic pain.', "A single injection of NAC (100 mg/kg, i.p.) reduced nocifensive behavior in the second phase of the formalin test. NAC-induced analgesia was abrogated by the Sxc- inhibitor, sulphasalazine (8 mg/kg, i.p.) or by the mGlu2/3 receptor antagonist, LY341495 (1 mg/kg, i.p.). NAC still caused analgesia in mGlu3(-/-) mice, but was inactive in mGlu2(-/-) mice. In wild-type mice, NAC retained the analgesic activity in the formalin test when injected daily for 7 days, indicating the lack of tolerance. Both single and repeated injections of NAC also caused analgesia in the complete Freund's adjuvant (CFA) model of chronic inflammatory pain, and, again, analgesia was abolished by LY341495. Data obtained in mice developing neuropathic pain in response to chronic constriction injury (CCI) of the sciatic nerve were divergent. In this model, a single injection of NAC caused analgesia that was reversed by LY341495, whereas repeated injections of NAC were ineffective. Thus, tolerance to NAC-induced analgesia developed in the CCI model, but not in models of inflammatory pain. The CFA and CCI models differed with respect to the expression levels of xCT (the catalytic subunit of Sx(c)(-)) and activator of G-protein signaling type-3 (AGS3) in the dorsal portion of the lumbar spinal cord. CFA-treated mice showed no change in either protein, whereas CCI mice showed an ipislateral reduction in xCT levels and a bilateral increase in AGS3 levels in the spinal cord."] Does n-Acetyl-cysteine cause analgesia by reinforcing the endogenous activation of type-2 metabotropic glutamate receptors? | qiaojin/PubMedQA | 2 | [
-2.313811779022217,
-1.4214123487472534,
2.752779960632324
] |
['Current prognostic information in ovarian cancer is based on tumor stage, tumor grade, and postoperative tumor size. Reliable molecular prognostic markers are scarce. In this article, the authors describe epigenetic events in a frequently deleted region on chromosome 8p22 that influence the expression of tumor suppressor candidate 3 (TUSC3), a putative tumor suppressor gene in ovarian cancer.', 'Messenger RNA expression and promoter hypermethylation of TUSC3 were studied in ovarian cancer cell lines and in tumor samples from 2 large, independent ovarian cancer cohorts using polymerase chain reaction-based methods.', 'The results indicated that TUSC3 expression is decreased significantly because of promoter methylation in malignant ovarian tumors compared with benign controls. Almost 33% of ovarian cancer samples had detectable TUSC3 promoter methylation. Furthermore, methylation status of the TUSC3 promoter had a significant and independent influence on progression-free and overall survival.'] Is methylation status of TUSC3 a prognostic factor in ovarian cancer? | qiaojin/PubMedQA | 2 | [
-2.3844635486602783,
-1.0882973670959473,
2.5574100017547607
] |
['Amongst the Yoruba tribe (Southwest Nigeria), water decoction of the leaf and seed of Phyllanthus amarus Schum. and Thonn. is reputably used for the local management of diabetes mellitus, obesity and hyperlipidemia.', 'The present study seeks to evaluate the effectiveness and elucidate mechanism(s) of action of the aqueous leaf and seed extract of Phyllanthus amarus (PAE) in normal and 10% sucrose-induced hyperglycemia and dyslipidemia as an experimental model of insulin resistance diabetes mellitus.', "In this study, the repeated oral antihyperglycemic action of 150-600 mg/kg/day of PAE was evaluated in normal and 10% sucrose-induced insulin resistance rats using indicators such as fasting blood glucose (FBG), insulin and insulin resistance indices. The extract's weight losing, antihyperlipidemic and anti-atherogenic effects were also evaluated by measuring the effect of the extract on the body weight, plasma levels of triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c) and atherogenic indices.", 'In normal rats, PAE caused significant (p<0.05, p<0.01 and p<0.001) and dose related decreases in body weight, FBG, TG, TC, LDL-c, and atherogenic indices. Repeated oral treatment with 10% sucrose drink for 30 days was associated with significant (p<0.001) weight gain, hyperglycemia, insulin resistance indices, hyperlipidemia and atherogenic indices. However, pre-treatment with PAE significantly (p<0.05, p<0.01 and p<0.001) and dose-dependently attenuated increase in any of these measured parameters.'] Does the leaf and seed aqueous extract of Phyllanthus amarus improve insulin resistance diabetes in experimental animal studies? | qiaojin/PubMedQA | 2 | [
-2.269861936569214,
-1.2947282791137695,
2.625511884689331
] |
['Although androgen deprivation therapy leads to weight gain within the first year in men with prostate cancer, longer term changes and the relationship to patient age are not well characterized. We examined long-term weight gain by age group in men on androgen deprivation therapy for up to 36 months.', 'Three cohorts matched by age and education were recruited in this prospective study, including men in whom continuous androgen deprivation therapy was initiated, controls with prostate cancer and healthy controls. All patients with prostate cancer had nonmetastatic disease. We performed age stratified (less than 65 vs 65 years or greater) comparisons. Univariate and multivariable associations with weight change with time were evaluated using linear regression.', 'We included 257 men with a mean age of 69.1 years. At baseline the cohorts were similar in age, education, body mass index, weight and comorbidity. Androgen deprivation therapy was associated with weight gain from baseline at 6, 12, 18, 24, 30 and 36 months compared to controls with prostate cancer and healthy controls (p = 0.006, 0.015, 0.028, 0.003, 0.014 and 0.0004, respectively). The proportion of men who gained weight was higher among androgen deprivation therapy users than controls with prostate cancer and healthy controls at most time points. Age stratified analyses showed that younger patients (age less than 65 years) on androgen deprivation therapy had significantly greater weight gain with time than older patients (4.7 vs 1.4 kg, p = 0.005). However, age did not appear to affect weight change with time in men not on androgen deprivation therapy (p = 0.37).'] Does impact of androgen deprivation therapy on weight gain differ by age in men with nonmetastatic prostate cancer? | qiaojin/PubMedQA | 2 | [
-0.8010284900665283,
-1.2392024993896484,
1.0925021171569824
] |
['In incident hemodialysis (HD) patients, the relationship between early systolic blood pressure (SBP) dynamics and mortality is unknown.', 'Baseline SBP levels were stratified into 5 categories ranging from <120 and ≥180 mm Hg. Early pre-HD SBP change was defined as the slope of pre-HD SBP from week 1 to 12 and categorized in quartiles (Q1, lowest slope). SBP slopes were computed for each patient by simple linear regression.', 'In 3,446 incident HD patients (42% females, 44% black, age 62 ± 15 years), the median pre-HD SBP slope was -1.7 (Q1) to +2.3 (Q4) mm Hg/week. In an adjusted multivariate Cox regression analysis, patients with declining SBP (slope Q1) had higher mortality compared to patients with increasing pre-HD SBP (slope Q4) at 12 months (hazard ratio 2.01, 95% confidence interval 1.35-3.01). In addition, patients with baseline pre-HD SBP <120 mm Hg showed higher mortality compared to the reference group (SBP ≥180 mm Hg) at 12 months (hazard ratio 1.89, 95% confidence interval 1.03-3.45).'] Are early systolic blood pressure changes in incident hemodialysis patients associated with mortality in the first year? | qiaojin/PubMedQA | 2 | [
-0.35323596000671387,
-1.5684311389923096,
1.0063841342926025
] |
['Embryonic development proceeds through finely tuned reprogramming of the parental genomes to form a totipotent embryo. Cells within this embryo will then differentiate and give rise to all the tissues of a new individual. Early embryonic development thus offers a particularly interesting system in which to analyze functional nuclear organization. When the organization of higher-order chromatin structures, such as pericentromeric heterochromatin, was first analyzed in mouse embryos, specific nuclear rearrangements were observed that correlated with embryonic genome activation at the 2-cell stage. However, most existing analyses have been conducted by visual observation of fluorescent images, in two dimensions or on z-stack sections/projections, but only rarely in three dimensions (3D).', 'In the present study, we used DNA fluorescent in situ hybridization (FISH) to localize centromeric (minor satellites), pericentromeric (major satellites), and telomeric genomic sequences throughout the preimplantation period in naturally fertilized mouse embryos (from the 1-cell to blastocyst stage). Their distribution was then analyzed in 3D on confocal image stacks, focusing on the nucleolar precursor bodies and nucleoli known to evolve rapidly throughout the first developmental stages. We used computational imaging to quantify various nuclear parameters in the 3D-FISH images, to analyze the organization of compartments of interest, and to measure physical distances between these compartments.'] Does 3D-FISH analysis of embryonic nuclei in mouse highlight several abrupt changes of nuclear organization during preimplantation development? | qiaojin/PubMedQA | 2 | [
-2.481084108352661,
-0.5230239033699036,
2.141385078430176
] |
['Despite seventeen decades of continuous clinical use, the neuronal mechanisms through which volatile anesthetics act to produce unconsciousness remain obscure. One emerging possibility is that anesthetics exert their hypnotic effects by hijacking endogenous arousal circuits. A key sleep-promoting component of this circuitry is the ventrolateral preoptic nucleus (VLPO), a hypothalamic region containing both state-independent neurons and neurons that preferentially fire during natural sleep.', 'Using c-Fos immunohistochemistry as a biomarker for antecedent neuronal activity, we show that isoflurane and halothane increase the number of active neurons in the VLPO, but only when mice are sedated or unconscious. Destroying VLPO neurons produces an acute resistance to isoflurane-induced hypnosis. Electrophysiological studies prove that the neurons depolarized by isoflurane belong to the subpopulation of VLPO neurons responsible for promoting natural sleep, whereas neighboring non-sleep-active VLPO neurons are unaffected by isoflurane. Finally, we show that this anesthetic-induced depolarization is not solely due to a presynaptic inhibition of wake-active neurons as previously hypothesized but rather is due to a direct postsynaptic effect on VLPO neurons themselves arising from the closing of a background potassium conductance.'] Does direct activation of sleep-promoting VLPO neurons by volatile anesthetics contribute to anesthetic hypnosis? | qiaojin/PubMedQA | 2 | [
-2.7672688961029053,
-0.8716984987258911,
2.6859192848205566
] |
['To investigate the pharmacokinetics, pharmacodynamics, and safety of higenamine, an active ingredient of Aconite root, in healthy Chinese volunteers.', "Ten subjects received continuous, intravenous infusion of higenamine at gradually escalating doses from 0.5 to 4.0 μg·kg(-1)·min(-1), each dose was given for 3 min. Blood and urine samples were collected at designated time points to measure the concentrations of higenamine. Pharmacodynamics was assessed by measuring the subject's heart rate. A nonlinear mixed-effect modeling approach, using the software Phoenix NLME, was used to model the plasma concentration-time profiles and heart rate.", 'Peak concentrations (C(max)) of higenamine ranged from 15.1 to 44.0 ng/mL. The half-life of higenamine was 0.133 h (range, 0.107-0.166 h), while the area under concentration-time curve (AUC), extrapolated to infinity, was 5.39 ng·h·mL(-1) (range, 3.2-6.8 ng·h·mL(-1)). The volume of distribution (V) was 48 L (range, 30.8-80.6 L). The total clearance (CL) was 249 L/h (range, 199-336 L/h). Within 8 h, 9.3% (range, 4.6%-12.4%) of higenamine was recovered in the urine. The pharmacokinetics of higenamine was successfully described using a two-compartment model with nonlinear clearance. In the pharmacodynamic model, heart rates were related to the plasma drug concentrations using a simple direct effect model with baseline. The E(0), E(max), and EC(50) were 68 bpm, 73 bpm and 8.1 μg/L, respectively.'] Do a phase I study on pharmacokinetics and pharmacodynamics of higenamine in healthy Chinese subjects? | qiaojin/PubMedQA | 2 | [
-1.469057321548462,
-1.631145715713501,
2.1107585430145264
] |
['Risk factors for exacerbation of congestive heart failure have not been consistently validated.', 'Our objective was to examine the role of short-term dietary sodium intake in acute decompensated heart failure.', 'Patients with chronic congestive heart failure presenting to the Emergency Department for either acute decompensated heart failure (cases) or for other reasons (controls) were included in a case-control study. Cases and controls were compared with respect to age, smoking, recent sodium intake, medication nonadherence, coronary artery disease, and hypertension. A food frequency questionnaire was utilized to estimate recent sodium intake, defined as the number of food types consumed in the previous 3 days from the 12 highest-sodium food categories.', 'There were 182 patients enrolled. One patient was excluded due to uncertainty about the primary diagnosis. When adjusted for age, smoking, medication nonadherence, coronary artery disease, and hypertension, acute decompensated heart failure was not associated with short-term dietary sodium intake. The odds ratio for acute decompensated heart failure for each increase in the number of high-sodium food types consumed was 1.1 (95% confidence interval 0.9-1.3; p = 0.3). Acute decompensated heart failure was associated with medication nonadherence, with an odds ratio for decompensation of 2.5 (95% confidence interval 1.2-5.1; p = 0.01).'] Is eating a larger number of high-salt foods associated with short-term risk of acute decompensation in patients with chronic heart failure? | qiaojin/PubMedQA | 2 | [
-1.3559499979019165,
-0.8774877190589905,
1.2780200242996216
] |
['Chronic urticaria (CU) may affect up to 1% of the general population. Anisakis simplex hypersensitivity is frequent in areas where raw fish is consumed and A. simplex allergy represents a relevant cause of acute urticaria. We assessed the possible association between CU and A. simplex sensitization in an area where marinated fish is very frequently eaten.', 'A thorough history of CU was sought in 919 adults seen at the Allergy Center, Bari. CU patients and 187 controls underwent skin-prick testing with a commercial extract of A. simplex, and reactors were recommended a 6-month raw-fish-free diet regimen. Responders were followed after a further 3 months.', 'Of 919 subjects, 213 (23%) met the criteria for CU and 106/213 (49.7%) were sensitized to A. simplex with a significant difference between patients aged >65 or <65 years (56 vs. 41%, respectively; p < 0.05). All patients hypersensitive to A. simplex were regular consumers of marinated fish. In a control population without CU, the prevalence of A. simplex sensitization was 16% (p < 0.001). The 6-month diet regimen led to the disappearance of urticaria in 82/106 cases (77%) versus 1/42 (2%) subjects who did not change their dietary habits (p < 0.001). All nonresponders were sensitized to house-dust mites. Of 75 responders who were followed-up after 3 months, CU relapsed in 88% of those who had reintroduced raw fish versus 14% of those who were still on the diet (p < 0.001).'] Is anisakis simplex hypersensitivity associated with chronic urticaria in endemic areas? | qiaojin/PubMedQA | 2 | [
-0.9865145683288574,
-1.2281935214996338,
1.2419594526290894
] |
['To fully define cytotoxic T-lymphocyte (CTL) escape variants of an HLA-B*51-restricted integrase epitope in early HIV-1 infection.', 'Ninety-four longitudinally sampled acute/early HIV-1 subtype B-infected participants were assessed to determine HLA-B*51-restricted LPPVVAKEI (LI9) escape variants.', 'LI9 was sequenced at baseline and subsequent time points. Interferon-γ (IFNγ) ELISpot assays were performed using serial log dilutions of variant LI9 peptides to determine the cellular response and functional avidity.', 'There is a significant association between HLA-B*51 expression and an evolving LI9 sequence from baseline to year 1 (P < 0.0001). We detected that the V32I and P30X polymorphisms emerged within HLA-B*51 participants over time. Reversion of the P30S polymorphism was observed by year 1 in one HLA-B*51 participant. LPPIIAKEI and LPSIVAKEI had significantly lower functional avidity compared with LPPVVAKEI and so may be less well recognized by LI9-specific CTLs; a positive IFNγ response to IPSVVAKEI was rarely seen. Functional avidity to wild-type LI9 inversely correlated with viral load (R = 0.448, P = 0.0485).'] Does longitudinal analysis of an HLA-B*51-restricted epitope in integrase reveals immune escape in early HIV-1 infection? | qiaojin/PubMedQA | 2 | [
-2.1445250511169434,
-1.4384491443634033,
2.6297879219055176
] |
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