bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and prognostic implications of WT1 mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group
Authors: Ho Phoenix A. , Zeng Rong , Alonzo Todd A. , Gerbing Robert B. , Miller Kristen L. , Pollard Jessica A. , Stirewalt Derek L. , Heerema Nyla A. , Raimondi Susana C. , Hirsch Betsy , Franklin Janet L. , Lange Beverly , Meshinchi Soheil 
Published: April 2010

AbstractRecent studies of WT1 mutations in acute myeloid leukemia (AML) mostly report an association with unfavorable clinical outcome. We screened 842 patients treated on 3 consecutive pediatric AML trials for WT1 zinc-finger mutations. Eighty-five mutations were detected in 70 of 842 patients (8.3%). Mutations occurred predominantly in exon 7 (n = 74) but were also found in exons 8 (n = 5) and 9 (n = 6). Normal karyotype was observed in 35.3% of WT1mut patients, whereas 27.5% WT1mut patients harbored favorable risk cytogenetics. Patients with or without mutations had similar rates of complete remission after one course of induction chemotherapy. Overall survival (OS) for patients with WT1 mutations was 41% versus 54% for those without mutations (P = .016). Corresponding event-free survival (EFS) was also significantly worse for those with WT1 mutations (28% vs 42%; P = .01). However, FLT3/ITD was present in 36% of the WT1mut cohort; WT1mut patients without FLT3/ITD had similar OS (56% vs 56%, respectively; P = .8) and EFS (35% and 44%, respectively; P = .34) to patients who were wild type for both mutations. In current risk stratification schemes incorporating cytogenetics and FLT3/ITD status, the presence of WT1 mutations has no independent prognostic significance in predicting outcome in pediatric AML. The clinical trials are registered at www.clinicaltrials.gov as #NCT00002798 and #NCT00070174.
Reduced carotid atherosclerosis in asthmatic patients treated with inhaled corticosteroids
Authors: Otsuki M. , Miyatake A. , Fujita K. , Hamasaki T. , Kasayama S. 
Published: April 2010

Although inflammation is an important component of atherosclerosis, it is unknown whether inhaled corticosteroids (ICS) as anti-inflammatory drugs prevent atherosclerosis.In the present study, carotid atherosclerosis was evaluated by ultrasonography in 150 asthmatic patients who had been regularly treated with ICS, and in 150 matched nonasthmatic controls, with an assessment of atherosclerotic risk factors.Carotid intima-media thickness was significantly lower in the asthmatic patients than in the controls. The prevalence of carotid plaque tended to be lower in the asthmatic patients than in the controls. Defined carotid atherosclerosis was diagnosed in 51 of the asthmatic patients, who were older, with a higher prevalence of males, a higher prevalence of dyslipidaemia and a lower mean daily dose of ICS than the 99 patients without carotid atherosclerosis. Stepwise multiple logistic regression analysis identified age, male sex and dyslipidaemia as positive risk factors for carotid atherosclerosis. The mean daily dose of ICS was a negative risk factor.Carotid atherosclerosis is reduced in asthmatic patients treated with ICS compared with matched controls. This study suggests that ICS may have protective effects against atherosclerosis.
Mechanisms of clearance of nontypeableHaemophilus influenzaefrom cigarette smoke-exposed mouse lungs
Authors: Gaschler G.J. , Zavitz C.C.J. , Bauer C.M.T. , Stämpfli M.R. 
Published: April 2010

Inflammation is prevalent in all stages of chronic obstructive pulmonary disease, and, furthermore, individuals undergo periods of exacerbation, during which pulmonary inflammation increases, often a result of bacterial infection. The present study investigates thein vivoconsequences of cigarette smoke exposure on bacterial challenge with nontypeableHaemophilus influenzae(NTHi).BALB/c and C57 black 6 (C57BL/6) mice were exposed to cigarette smoke once or twice daily for a total period of 8 weeks.Exacerbated inflammation was observed in cigarette smoke-exposed compared to room-air-exposed mice following challenge with live or heat-inactivated NTHi. Accelerated clearance of live NTHi from cigarette smoke-exposed mice was independent of the establishment of chronic inflammation or direct toxic effects of cigarette smoke components on bacteria. Mechanistically, a cell-free factor in the bronchoalveolar lavage fluid contributed to accelerated clearance following passive transfer to naive mice. Further investigation demonstrated increased titres of immunoglobulin A in the bronchoalveolar lavage fluid, but not the blood, of cigarette smoke-exposed mice, including increased titres of NTHi-specific immunoglobulin A, whereas heavy chain joining element (JH)-/-B-cell-deficient cigarette smoke-exposed mice did not demonstrate decreased bacterial burden following challenge.The present results demonstrate that cigarette smoke exposure results in exacerbated inflammation following challenge with NTHi, as well as increased titres of antibodies that contribute to bacterial clearance.
Critical role of cytosolic phospholipase A2α in bronchial mucus hypersecretion in CFTR-deficient mice
Authors: Dif F. , Wu Y-Z. , Burgel P-R. , Ollero M. , Leduc D. , Aarbiou J. , Borot F. , Garcia-Verdugo I. , Martin C. , Chignard M. , Israel-Biet D. , Kita Y. , Scholte B.J. , Touqui L. 
Published: April 2010

Cystic fibrosis (CF) is due to mutations in the CF transmembrane conductance regulator geneCFTR. CF is characterised by mucus dehydration, chronic bacterial infection and inflammation, and increased levels of cytosolic phospholipase A2α (cPLA2α) products in airways.We aimed to examine the role of cPLA2α in the modulation of mucus production and inflammation in CFTR-deficient mice and epithelial cells. Mucus production was assessed using histological analyses, immuno-histochemistry and MUC5AC ELISA. cPLA2α activation was measured using an enzymatic assay and lung inflammation determined by histological analyses and polymorphonuclear neutrophil counts in bronchoalveolar lavages.In lungs fromCftr-/-mice, lipopolysaccharide induced mucus overproduction and MUC5AC expression associated with an increased cPLA2α activity. Mucus overproduction was mimicked by instillation of the cPLA2α product arachidonic acid, and abolished by either a cPLA2α null mutation or pharmacological inhibition. An increased cPLA2α activity was observed in bronchial explants from CF patients. CFTR silencing induced cPLA2α activation and MUC5AC expression in bronchial human epithelial cells. This expression was enhanced by arachidonic acid and reduced by cPLA2α inhibition. However, inhibition of CFTR chloride transport function had no effect on MUC5AC expression.Reduction of CFTR expression increased cPLA2α activity. This led to an enhanced mucus production in airway epithelia independent of CFTR chloride transport function. cPLA2α represents a suitable new target for therapeutic intervention in CF.
Body composition and plasma levels of inflammatory biomarkers in COPD
Authors: Eagan T.M.L. , Aukrust P. , Ueland T. , Hardie J.A. , Johannessen A. , Mollnes T.E. , Damås J.K. , Bakke P.S. , Wagner P.D. 
Published: April 2010

Previous studies suggest a relationship between systemic inflammation and body composition in chronic obstructive pulmonary disease (COPD). We examined the relationships between body composition (fat free mass index (FFMI) kg·m−2and fat mass index (FMI) kg·m−2) and three plasma inflammatory markers C-reactive Protein (CRP), soluble tumour necrosis factor receptor 1 (sTNF-R1) and osteoprotegerin (OPG) in 409 stable COPD patients (aged 40–75 yrs, Global Initiative for Obstructive Chronic Lung Disease (GOLD) categories II-IV, 249 male) from the Bergen COPD Cohort Study in Norway.FFMI and FMI were measured by bioelectrical impedance. Plasma CRP (μg·mL−1), sTNF-R1 (pg·mL−1) and OPG (ng·mL−1) were determined by enzyme immunoassays. Correlations and Kruskal–Wallis tests were used for bivariate analyses. Linear regression models were fitted for each of the three markers, CRP, sTNF-R1 and OPG, with FFMI and FMI as explanatory variables including sex, age, smoking habits, GOLD category, hypoxaemia, Charlson Comorbidity Index and inhaled steroid use as potential confounders.CRP and sTNF-R1 levels correlated positively with both FFMI and FMI. The adjusted regression coefficients for an increase in logCRP per unit increase in FFMI was 1.23 (1.14–1.33) kg·m−2and 24.9 (11.8–38.1) kg·m−2for sTNF-R1. Higher FMI was associated with a lower OPG, with adjusted regression coefficient -0.14 (-0.23– -0.04), whereas FFMI was unrelated to OPG.In conclusion, COPD patients with low FFMI had lower not higher plasma levels of CRP and sTNF-R1, whereas higher fat mass was associated with higher CRP and sTNF-R1 and lower OPG.
Factor V Leiden mutation does not affect coagulopathy or outcome in lethal H1N1 influenza
Authors: Schouten M. , van der Sluijs K.F. , Roelofs J.J.T.H. , Levi M. , van't Veer C. , van der Poll T. 
Published: April 2010

Influenza A is a major cause of mortality. Knowledge on coagulation activation in influenza infection is limited. The factor V Leiden (FVL) mutation is possibly subject to positive selection pressure. It is unknown whether this mutation impacts on the outcome of severe influenza. In the present study, the effect of lethal influenza on pulmonary and systemic coagulation activation and whether or not FVL mutation alters coagulation activation in and the course of lethal influenza, was determined.Wild-type mice, and mice heterozygous or homozygous for FVL were infected intranasally with a lethal dose of H1N1 (haemagglutinin 1 and neuraminidase 1) influenza A. Mice were sacrificed after 48 or 96 h for determination of coagulation activation, histopathology, pulmonary inflammatory parameters and viral load, or were observed in a survival study.Extensive local and systemic coagulation activation during lethal influenza was demonstrated by increased lung and plasma levels of thrombin–antithrombin complexes and fibrin degradation products, and by pulmonary fibrin deposition. FVL mutation did not influence the procoagulant response, lung histopathology or survival. FVL mice demonstrated elevated viral loads 48 h after infection.In conclusion, coagulation is activated locally and systemically during lethal murine influenza A infection. The FVL mutation does not influence coagulation activation, lung inflammation or survival in lethal influenza A.
Duplication and independent selection of cell-wall invertase genes GIF1 and OsCIN1 during rice evolution and domestication
Authors: Wang Ertao , Xu Xun , Zhang Lin , Zhang Hong , Lin Lin , Wang Qin , Li Qun , Ge Song , Lu Bao-Rong , Wang Wen , He Zuhua 
Published: April 2010

Abstract

Background
Various evolutionary models have been proposed to interpret the fate of paralogous duplicates, which provides substrates on which evolution selection could act. In particular, domestication, as a special selection, has played important role in crop cultivation with divergence of many genes controlling important agronomic traits. Recent studies have indicated that a pair of duplicate genes was often sub-functionalized from their ancestral functions held by the parental genes. We previously demonstrated that the rice cell-wall invertase (CWI) gene GIF1 that plays an important role in the grain-filling process was most likely subjected to domestication selection in the promoter region. Here, we report that GIF1 and another CWI gene OsCIN1 constitute a pair of duplicate genes with differentiated expression and function through independent selection.

Results
Through synteny analysis, we show that GIF1 and another cell-wall invertase gene OsCIN1 were paralogues derived from a segmental duplication originated during genome duplication of grasses. Results based on analyses of population genetics and gene phylogenetic tree of 25 cultivars and 25 wild rice sequences demonstrated that OsCIN1 was also artificially selected during rice domestication with a fixed mutation in the coding region, in contrast to GIF1 that was selected in the promoter region. GIF1 and OsCIN1 have evolved into different expression patterns and probable different kinetics parameters of enzymatic activity with the latter displaying less enzymatic activity. Overexpression of GIF1 and OsCIN1 also resulted in different phenotypes, suggesting that OsCIN1 might regulate other unrecognized biological process.

Conclusion
How gene duplication and divergence contribute to genetic novelty and morphological adaptation has been an interesting issue to geneticists and biologists. Our discovery that the duplicated pair of GIF1 and OsCIN1 has experienced sub-functionalization implies that selection could act independently on each duplicate towards different functional specificity, which provides a vivid example for evolution of genetic novelties in a model crop. Our results also further support the established hypothesis that gene duplication with sub-functionalization could be one solution for genetic adaptive conflict.
Practical application of cure mixture model for long-term censored survivor data from a withdrawal clinical trial of patients with major depressive disorder
Authors: Arano Ichiro , Sugimoto Tomoyuki , Hamasaki Toshimitsu , Ohno Yuko 
Published: April 2010

AbstractBackgroundSurvival analysis methods such as the Kaplan-Meier method, log-rank test, and Cox proportional hazards regression (Cox regression) are commonly used to analyze data from randomized withdrawal studies in patients with major depressive disorder. However, unfortunately, such common methods may be inappropriate when a long-term censored relapse-free time appears in data as the methods assume that if complete follow-up were possible for all individuals, each would eventually experience the event of interest.MethodsIn this paper, to analyse data including such a long-term censored relapse-free time, we discuss a semi-parametric cure regression (Cox cure regression), which combines a logistic formulation for the probability of occurrence of an event with a Cox proportional hazards specification for the time of occurrence of the event. In specifying the treatment's effect on disease-free survival, we consider the fraction of long-term survivors and the risks associated with a relapse of the disease. In addition, we develop a tree-based method for the time to event data to identify groups of patients with differing prognoses (cure survival CART). Although analysis methods typically adapt the log-rank statistic for recursive partitioning procedures, the method applied here used a likelihood ratio (LR) test statistic from a fitting of cure survival regression assuming exponential and Weibull distributions for the latency time of relapse.ResultsThe method is illustrated using data from a sertraline randomized withdrawal study in patients with major depressive disorder.ConclusionsWe concluded that Cox cure regression reveals facts on who may be cured, and how the treatment and other factors effect on the cured incidence and on the relapse time of uncured patients, and that cure survival CART output provides easily understandable and interpretable information, useful both in identifying groups of patients with differing prognoses and in utilizing Cox cure regression models leading to meaningful interpretations.
Educational games in geriatric medicine education: a systematic review
Authors: Alfarah Ziad , Schünemann Holger J , Akl Elie A 
Published: April 2010

AbstractObjectiveTo systematically review the medical literature to assess the effect of geriatric educational games on the satisfaction, knowledge, beliefs, attitudes and behaviors of health care professionals.MethodsWe conducted a systematic review following the Cochrane Collaboration methodology including an electronic search of 10 electronic databases. We included randomized controlled trials (RCT) and controlled clinical trials (CCT) and excluded single arm studies. Population of interests included members (practitioners or students) of the health care professions. Outcomes of interests were participants' satisfaction, knowledge, beliefs, attitude, and behaviors.ResultsWe included 8 studies evaluating 5 geriatric role playing games, all conducted in United States. All studies suffered from one or more methodological limitations but the overall quality of evidence was acceptable. None of the studies assessed the effects of the games on beliefs or behaviors. None of the 8 studies reported a statistically significant difference between the 2 groups in terms of change in attitude. One study assessed the impact on knowledge and found non-statistically significant difference between the 2 groups. Two studies found levels of satisfaction among participants to be high. We did not conduct a planned meta-analysis because the included studies either reported no statistical data or reported different summary statistics.ConclusionThe available evidence does not support the use of role playing interventions in geriatric medical education with the aim of improving the attitudes towards the elderly.
The effects of acylation stimulating protein supplementation VS antibody neutralization on energy expenditure in wildtype mice
Authors: Paglialunga Sabina , Fisette Alexandre , Munkonda Mercedes , Gao Ying , Richard Denis , Cianflone Katherine 
Published: April 2010

Abstract

Background
Acylation stimulating protein (ASP) is an adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes. Previous studies have shown that ASP-deficient C3 knockout mice are hyperphagic yet lean, as they display increased oxygen consumption and fatty acid oxidation compared to wildtype mice. In the present study, antibodies against ASP (Anti-ASP) and human recombinant ASP (rASP) were tested in vitro and in vivo. Continuous administration for 4 weeks via osmotic mini-pump of Anti-ASP or rASP was evaluated in wildtype mice on a high-fat diet (HFD) to examine their effects on body weight, food intake and energy expenditure.

Results
In mature murine adipocytes, rASP significantly stimulated fatty acid uptake (+243% vs PBS, P < 0.05) while Anti-ASP neutralized the rASP response. Mice treated with Anti-ASP showed elevated energy expenditure (P < 0.0001), increased skeletal muscle glucose oxidation (+141%, P < 0.001), reduced liver glycogen (-34%, P < 0.05) and glucose-6-phosphate content (-64%, P = 0.08) compared to control mice. There was no change in body weight, food intake, fasting insulin, adiponectin, CRP or TG levels compared to controls. Interestingly, HFD mice treated with rASP showed the opposite phenotype with reduced energy expenditure (P < 0.0001) and increased body weight (P < 0.05), cumulative food intake (P < 0.0001) and liver glycogen content (+59%, P < 0.05). Again, there was no change in circulating insulin, adiponectin, CRP or TG levels, however, plasma free fatty acids were reduced (-48%, P < 0.05).

Conclusion

In vitro, Anti-ASP effectively neutralized ASP stimulated fatty acid uptake. In vivo, Anti-ASP treatment increased whole body energy utilization while rASP increased energy storage. Therefore, ASP is a potent anabolic hormone that may also be a mediator of energy expenditure.
Alterations in urine, serum and brain metabolomic profiles exhibit sexual dimorphism during malaria disease progression
Authors: Basant Angika , Rege Mayuri , Sharma Shobhona , Sonawat Haripalsingh M 
Published: April 2010

AbstractBackgroundMetabolic changes in the host in response toPlasmodiuminfection play a crucial role in the pathogenesis of malaria. Alterations in metabolism of male and female mice infected withPlasmodium bergheiANKA are reported here.Methods1H NMR spectra of urine, sera and brain extracts of these mice were analysed over disease progression using Principle Component Analysis and Orthogonal Partial Least Square Discriminant Analysis.ResultsAnalyses of overall changes in urinary profiles during disease progression demonstrate that females show a significant early post-infection shift in metabolism as compared to males. In contrast, serum profiles of female mice remain unaltered in the early infection stages; whereas that of the male mice changed. Brain metabolite profiles do not show global changes in the early stages of infection in either sex. By the late stages urine, serum and brain profiles of both sexes are severely affected. Analyses of individual metabolites show significant increase in lactate, alanine and lysine, kynurenic acid and quinolinic acid in sera of both males and females at this stage. Early changes in female urine are marked by an increase of ureidopropionate, lowering of carnitine and transient enhancement of asparagine and dimethylglycine. Several metabolites when analysed individually in sera and brain reveal significant changes in their levels in the early phase of infection mainly in female mice. Asparagine and dimethylglycine levels decrease and quinolinic acid increases early in sera of infected females. In brain extracts of females, an early rise in levels is also observed for lactate, alanine and glycerol, kynurenic acid, ureidopropionate and 2-hydroxy-2-methylbutyrate.ConclusionsThese results suggest thatP. bergheiinfection leads to impairment of glycolysis, lipid metabolism, metabolism of tryptophan and degradation of uracil. Characterization of early changes along these pathways may be crucial for prognosis and better disease management. Additionally, the distinct sexual dimorphism exhibited in these responses has a bearing on the understanding of the pathophysiology of malaria.
Myocardial ultrasonic tissue characterization in patients with thyroid dysfunction
Authors: Romano Minna MD , Maciel Léa MZ , Almeida-Filho Oswaldo C , Pazin-Filho Antonio , Schmidt André , Maciel Benedito C 
Published: April 2010

Abstract

Background
Structural myocardial abnormalities have been extensively documented in hypothyroidism. Experimental studies in animal models have also shown involvement of thyroid hormones in gene expression of myocardial collagen. This study was planned to investigate the ability of ultrasonic tissue characterization, as evaluated by integrated backscatter (IBS), to early identify myocardial involvement in thyroid dysfunction.

Patients and Methods
We studied 15 patients with hyperthyroidism (HYPER), 8 patients with hypothyroidism (HYPO), 14 patients with subclinical hypothyroidism (SCH) and 19 normal (N) subjects, who had normal LV systolic function. After treatment, 10 HYPER, 6 HYPO, and 8 SCH patients were reevaluated. IBS images were obtained and analyzed in parasternal short axis (papillary muscle level) view, at left ventricular (LV) posterior wall. The following IBS variables were analyzed: 1) the corrected coefficient (CC) of IBS, obtained by dividing IBS intensity by IBS intensity measured in a rubber phantom, using the same equipment adjustments, at the same depth; 2) cardiac cyclic variation (CV) of IBS - peak-to-peak difference between maximal and minimal values of IBS during cardiac cycle; 3) cardiac cyclic variation index (CVI) of IBS - percentual relationship between the cyclic variation (CV) and the mean value of IBS intensity.

Results
CC of IBS was significantly larger (p < 0.05) in HYPER (1.57 ± 0.6) and HYPO (1.53 ± 0.3) as compared to SCH (1.32 ± 0.3) or N (1.15 ± 0.27). The CV (dB) (HYPO: 7.5 ± 2.4; SCH: 8.2 ± 3.1; HYPER: 8.2 ± 2.0) and the CVI (HYPO: 35.6 ± 19.7%; SCH: 34.7 ± 17.5%; HYPER: 37.8 ± 11.6%) were not significantly different in patients with thyroid dysfunction as compared to N (7.0 ± 2.0 and 44.5 ± 15.1%).

Conclusions
CC of IBS was able to differentiate cardiac involvement in patients with overt HYPO and HYPER who had normal LV systolic function. These early myocardial structural abnormalities were partially reversed by drug therapy in HYPER group. On the other hand, although mean IBS intensity tended to be slightly larger in patients with SCH as compared to N, this difference was not statistical significant.