bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Analysis of Colorectal Tumors within a Diverse Patient Cohort at a Single Institution
Authors: Sylvester Brooke E. , Huo Dezheng , Khramtsov Andrey , Zhang Jing , Smalling Rana V. , Olugbile Sope , Polite Blase N. , Olopade Olufunmilayo I. 
Published: November 2011

Abstract
Purpose: African American colorectal cancer patients have worse survival outcomes than Caucasian patients. To determine whether differences exist in the molecular mechanisms driving colorectal cancer between African Americans and Caucasians, we characterized patient tumors from a single institution by assessing genetic alterations involved in colorectal cancer progression and response to treatment.
Experimental Design: We retrospectively examined 448 African Americans and Caucasians diagnosed with colorectal cancer at The University of Chicago Medical Center between 1992 and 2002. Microsatellite instability (MSI) status was determined by genotyping the BAT25, BAT26, BAT40, D5S346, and BAX loci. Mutations in KRAS codons 12 and 13 and BRAF codon 600 were identified by direct sequencing. MSI and detected mutations were correlated with clinicopathologic features.
Results: Overall, no difference existed in MSI or BRAF mutation frequencies between African Americans and Caucasians. However, African Americans with microsatellite stable (MSS)/MSI-low (MSI-L) tumors had a higher proportion of KRAS mutations than Caucasians (34% vs. 23%, P = 0.048) that was isolated to proximal colon cancers and primarily driven by mutations in codon 13. There was no racial difference in receipt of chemotherapy, but African Americans with MSS/MSI-L tumors had a 73% increased risk of death over Caucasians that could not be explained by known prognostic factors.
Conclusions: The significantly higher risk of death among African Americans with MSS/MSI-L tumors may be related to differences in the distribution of factors influencing response to standard therapies. These data underscore the need for further research into the molecular mechanisms driving colorectal cancer progression in underserved and understudied populations. Clin Cancer Res; 18(2); 350–9. ©2011 AACR.
Soluble Vascular Adhesion Protein-1 Correlates With Cardiovascular Risk Factors and Early Atherosclerotic Manifestations
Authors: Aalto Kristiina , Maksimow Mikael , Juonala Markus , Viikari Jorma , Jula Antti , Kähönen Mika , Jalkanen Sirpa , Raitakari Olli T. , Salmi Marko 
Published: November 2011

Objective—
Vascular adhesion protein-1 is an endothelial enzyme that regulates leukocyte traffic and contributes to vascular damage in animal models. The relations of soluble vascular adhesion protein-1 (sVAP-1) with cardiovascular risk factors and markers of subclinical atherosclerosis at a population level have not been studied.

Methods and Results—

We developed a new high-throughput method and measured sVAP-1 activities in serum of 2183 persons (The Cardiovascular Risk in Young Finns Study). In women, sVAP-1 activity correlated indirectly with body mass index (
r
=−0.15
, P
<0.0001), triglycerides (
r
=−0.13,
P
<0.0001), C-reactive protein (
r
=−0.23;
P
<0.0001), and brachial artery flow-mediated vasodilatation (
r
=−0.076,
P
=0.0089) and directly with carotid plaques (
r
=0.066,
P
=0.023). None of these correlations was significant in men. In women, all these univariate correlations remained significant after adjustment for body mass index, and direct correlations with LDL-cholesterol (
r
=0.094,
P
=0.0014) and carotid intima-media thickness (
r
=0.075,
P
=0.010) became evident. In men, sVAP-1 activity associated directly with glucose (
r
=0.074,
P
=0.020), intima-media thickness (
r
=0.072,
P
=0.025), metabolic syndrome (
P
=0.016), and type 1 (
P
=0.0002) and type 2 (
P
<0.0001) diabetes. In multivariable analyses, sVAP-1 activity was an independent determinant of carotid intima-media thickness (
P
=0.0072) and plaques [odds ratio 1.71 (95% confidence interval 1.07–2.72,
P
=0.025] in women, but not in men.

Conclusion—
sVAP-1 activity correlates directly with intima-media thickness and carotid plaques in general population and may play a role in the pathophysiology of preclinical atherosclerosis.
The transcription factor Erg regulates expression of histone deacetylase 6 and multiple pathways involved in endothelial cell migration and angiogenesis
Authors: Birdsey Graeme M. , Dryden Nicola H. , Shah Aarti V. , Hannah Rebecca , Hall Matthew D. , Haskard Dorian O. , Parsons Maddy , Mason Justin C. , Zvelebil Marketa , Gottgens Berthold , Ridley Anne J. , Randi Anna M. 
Published: November 2011

AbstractThe endothelial ETS transcription factor Erg plays an important role in homeostasis and angiogenesis by regulating many endothelial functions including survival and junction stability. Here we show that Erg regulates endothelial cell (EC) migration. Transcriptome profiling of Erg-deficient ECs identified ∼ 80 genes involved in cell migration as candidate Erg targets, including many regulators of Rho- GTPases. Inhibition of Erg expression in HUVECs resulted in decreased migration in vitro, while Erg overexpression using adenovirus caused increased migra-tion. Live-cell imaging of Erg-deficient HUVECs showed a reduction in lamellipodia, in line with decreased motility. Both actin and tubulin cytoskeletons were disrupted in Erg-deficient ECs, with a dramatic increase in tubulin acetylation. Among the most significant microarray hits was the cytosolic histone deacetylase 6 (HDAC6), a regulator of cell migration. Chromatin immunoprecipitation (ChIP) and transactivation studies demonstrated that Erg regulates HDAC6 expression. Rescue experiments confirmed that HDAC6 mediates the Erg-dependent regulation of tubulin acetylation and actin localization. In vivo, inhibition of Erg expression in angiogenic ECs resulted in decreased HDAC6 expression with increased tubulin acetylation. Thus, we have identified a novel function for the transcription factor Erg in regulating HDAC6 and multiple pathways essential for EC migration and angiogenesis.
A retrospective multicenter analysis of elderly Hodgkin lymphoma: outcomes and prognostic factors in the modern era
Authors: Evens Andrew M. , Helenowski Irene , Ramsdale Erika , Nabhan Chadi , Karmali Reem , Hanson Britt , Parsons Benjamin , Smith Scott , Larsen Annette , McKoy June M. , Jovanovic Borko , Gregory Stephanie , Gordon Leo I. , Smith Sonali M. 
Published: November 2011

AbstractWe investigated a recent (January 1999 to December 2009) cohort of 95 elderly Hodgkin lymphoma subjects. At diagnosis, median age was 67 years (range, 60-89 years), whereas 61% had significant comorbidity, 26% were unfit, 17% had a geriatric syndrome, and 13% had loss of activities of daily living. Overall response rate to therapy was 85%, whereas incidence of bleomycin lung toxicity was 32% (with associated mortality rate, 25%). With 66-month median follow-up, 2-year and 5-year overall survival were 73% and 58%, respectively (advanced-stage, 63% and 46%, respectively). Most International Prognostic Score factors were not prognostic on univariate analyses, whereas Cox multivariate regression identified 2 risk factors associated with inferior overall survival: (1) age more than 70 years (2.24; 95% CI, 1.16-4.33, P = .02) and (2) loss of activities of daily living (2.71; 95% CI, 1.07-6.84, P = .04). Furthermore, a novel survival model based on number of these risk factors (0, 1, or 2) showed differential 2-year OS of 83%, 70%, and 13%, respectively (P < .0001) and 5-year OS of 73%, 51%, and 0%, respectively (P < .0001).
Dexamethasone exposure and asparaginase antibodies affect relapse risk in acute lymphoblastic leukemia
Authors: Kawedia Jitesh D. , Liu Chengcheng , Pei Deqing , Cheng Cheng , Fernandez Christian A. , Howard Scott C. , Campana Dario , Panetta John C. , Bowman W. Paul , Evans William E. , Pui Ching-Hon , Relling Mary V. 
Published: November 2011

Abstract
We have previously hypothesized that higher systemic exposure to asparaginase may cause increased exposure to dexamethasone, both critical chemotherapeutic agents for acute lymphoblastic leukemia. Whether interpatient pharmaco-kinetic differences in dexamethasone contribute to relapse risk has never been studied. The impact of plasma clearance of dexamethasone and anti–asparaginase antibody levels on risk of relapse was assessed in 410 children who were treated on a front-line clinical trial for acute lymphoblastic leukemia and were evaluable for all pharmacologic measures, using multivariate analyses, adjusting for standard clinical and biologic prognostic factors. Dexamethasone clearance (mean ± SD) was higher (P = 3 × 10−8) in patients whose sera was positive (17.7 ± 18.6 L/h per m2) versus nega-tive (10.6 ± 5.99 L/h per m2) for anti–asparaginase antibodies. In multivariate analyses, higher dexamethasone clearance was associated with a higher risk of any relapse (P = .01) and of central nervous system relapse (P = .014). Central nervous system relapse was also more common in patients with anti–asparaginase antibodies (P = .019). In conclusion, systemic clearance of dexamethasone is higher in patients with anti–asparaginase antibodies. Lower exposure to both drugs was associated with an increased risk of relapse.
Ste11p MEKK signals through HOG, mating, calcineurin and PKC pathways to regulate the FKS2 gene
Authors: Wang Xiaoyan , Sheff Mark A , Simpson David M , Elion Elaine A 
Published: November 2011

Abstract

Background
The S. cerevisiae MAPKKK Ste11p, a homologue of mammalian MEKK1, regulates three MAPK cascades for mating, invasive growth and osmotic stress and provides functions that are additive with the cell wall integrity pathway. Cell wall integrity requires the FKS2 gene that encodes a stress-induced alternative subunit of beta-1, 3 glucan synthase that is the target of echinocandin 1,3- beta glucan synthase inhibitors. The major signal transduction pathways that activate transcription of the FKS2 gene include the cell wall integrity and calcineurin pathways, and the Ste11p pathway.

Results
Here it is shown that catalytically active Ste11p regulates FKS2-lacZ reporter genes through Ste12, calcineurin/Crz1p- and PKC pathways and the high osmolarity pathway. Ste11p stimulated the cell wall integrity MAPK Mpk1p (Erk5 homologue) and FKS2 independently of the mating pathway. Ste11p regulated FKS2 through all known and putative substrates: Pbs2p MAPKK, Ste7 MAPKK, Cmk2p calmodulin dependent kinase and Ptk2p kinase. Ste11p increased the expression level of Cmk2p through transcription-dependent and -independent mechanisms.

Conclusions
The data suggest Ste11p regulates the FKS2 gene through all its known and putative downstream kinase substrates (Pbs2p, Ste7p, Cmk2p, and Ptk2p) and separately through Mpk1p MAPK. The patterns of control by Ste11p targets revealed novel functional linkages, cross-regulation, redundancy and compensation.
Characteristics of meta-analyses and their component studies in the Cochrane Database of Systematic Reviews: a cross-sectional, descriptive analysis
Authors: Davey Jonathan , Turner Rebecca M , Clarke Mike J , Higgins Julian PT 
Published: November 2011

Abstract

Background
Cochrane systematic reviews collate and summarise studies of the effects of healthcare interventions. The characteristics of these reviews and the meta-analyses and individual studies they contain provide insights into the nature of healthcare research and important context for the development of relevant statistical and other methods.

Methods
We classified every meta-analysis with at least two studies in every review in the January 2008 issue of the Cochrane Database of Systematic Reviews (CDSR) according to the medical specialty, the types of interventions being compared and the type of outcome. We provide descriptive statistics for numbers of meta-analyses, numbers of component studies and sample sizes of component studies, broken down by these categories.

Results
We included 2321 reviews containing 22,453 meta-analyses, which themselves consist of data from 112,600 individual studies (which may appear in more than one meta-analysis). Meta-analyses in the areas of gynaecology, pregnancy and childbirth (21%), mental health (13%) and respiratory diseases (13%) are well represented in the CDSR. Most meta-analyses address drugs, either with a control or placebo group (37%) or in a comparison with another drug (25%). The median number of meta-analyses per review is six (inter-quartile range 3 to 12). The median number of studies included in the meta-analyses with at least two studies is three (inter-quartile range 2 to 6). Sample sizes of individual studies range from 2 to 1,242,071, with a median of 91 participants.

Discussion
It is clear that the numbers of studies eligible for meta-analyses are typically very small for all medical areas, outcomes and interventions covered by Cochrane reviews. This highlights the particular importance of suitable methods for the meta-analysis of small data sets. There was little variation in number of studies per meta-analysis across medical areas, across outcome data types or across types of interventions being compared.
Factors associated with job satisfaction among Chinese community health workers: a cross-sectional study
Authors: Ge Cuixia , Fu Jialiang , Chang Ying , Wang Lie 
Published: November 2011

Abstract

Background
With the medical reform, the function of community health centres emerged to be more important recently in China. However, the health service capabilities were tremendously different between metropolitan cities and small cities. This study aims to clarify the level of job satisfaction of Chinese community health workers between a metropolitan (Shenyang) and a small city (Benxi) in Liaoning province and explore its associated factors.

Methods
A cross-sectional survey was conducted from December 2009 to February 2010. A multi-stage sample was used and a total of 2,100 Chinese community health workers from the two cities completed self-administered questionnaire pertaining to job satisfaction indicated by Minnesota Satisfaction Questionnaire (MSQ), demographic characteristic and working situations, stress and job burnout. The effective response rate was 80.7%. Hierarchical regression analysis was performed to explore the related factors. All data analyses for the two cities were performed separately.

Results
The averages of overall job satisfaction score of Chinese community health workers were 67.17 in Shenyang and 69.95 in Benxi. Intrinsic job satisfaction and extrinsic job satisfaction among Chinese community health workers were significantly different between Shenyang and Benxi (p < 0.05). In Shenyang, hierarchical regression analysis showed that the fourth model explained 36%, 32% of the variance of intrinsic and extrinsic job satisfactions, respectively. In Benxi, the fourth model explained 48%, 52% of the variance of intrinsic and extrinsic job satisfactions, respectively. Three significant predictors of intrinsic and extrinsic job satisfactions for the two cities were the two dimensions (social support and decision latitude) of stress and cynicism of burnout.

Conclusion
From this study, the job satisfaction among Chinese community health workers in the two cities enjoyed a moderate level of job satisfactions, which represented they are not fully satisfied with their jobs. Community health workers in Shenyang had lower job satisfaction as compared to those in Benxi. This study strengthened the evidence that stress and burnout were important predictors of intrinsic and extrinsic job satisfactions.
Economic evaluation of increasing population rates of cardiac catheterization
Authors: Clement Fiona M , Ghali William A , Rinfret Stephane , Manns Braden J ,   the APPROACH Investigators
Published: November 2011

AbstractBackgroundIncreasing population rates of cardiac catheterization can lead to the detection of more people with high risk coronary disease and opportunity for subsequent revascularization. However, such a strategy should only be undertaken if it is cost-effective.MethodsBased on data from a cohort of patients undergoing cardiac catheterization, and efficacy data from clinical trials, we used a Markov model that considered 1) the yield of high-risk cases as the catheterization rate increases, 2) the long-term survival, quality of life and costs for patients with high risk disease, and 3) the impact of revascularization on survival, quality of life and costs. The cost per quality-adjusted life year was calculated overall, and by indication, age, and sex subgroups.ResultsIncreasing the catheterization rate was associated with a cost per QALY of CAN$26,470. The cost per QALY was most attractive in females with Acute Coronary Syndromes (ACS) ($20,320 per QALY gained), and for ACS patients over 75 years of age ($16,538 per QALY gained). However, there is significant model uncertainty associated with the efficacy of revascularization.ConclusionA strategy of increasing cardiac catheterization rates among eligible patients is associated with a cost per QALY similar to that of other funded interventions. However, there is significant model uncertainty. A decision to increase population rates of catheterization requires consideration of the accompanying opportunity costs, and careful thought towards the most appropriate strategy.
Using personality as a predictor of diet induced weight loss and weight management
Authors: Munro Irene A , Bore Miles R , Munro Don , Garg Manohar L 
Published: November 2011

Abstract

Background
A major challenge for successful weight management is tailoring weight loss programs to individual needs. The aim of this study was to investigate whether personality traits could be used to match individuals to a compatible weight loss program that would maximize weight loss.

Method
Two different weight loss trials were conducted, both with a weight loss greater than 5% the measure of success. Fifty-four individuals, BMI 30-40 kg/m2, either followed a slow, healthy eating weight loss diet (HEWLD) of 5000-6000 kJ/day for 12 weeks (n = 22), or a fast, very low energy diet (VLED) of 3000 kJ/day for 4 weeks (n = 32). Anthropometric measurements were recorded at baseline, at the end of the weight loss period and, for VLED, at the end of 10 weeks of weight maintenance. Personality traits were measured at baseline using the Tangney Self Control Scale plus 3 of the scales from the Five Factor Model - Neuroticism, Conscientiousness and Extraversion.

Results
The percentage weight loss was significantly greater in VLED (-7.38%) compared to HEWLD (-4.11%), (p < 0.001). Weight loss in HEWLD was positively correlated with Anxiety, a facet of Neuroticism. Weight loss in VLED was positively correlated with Neuroticism (r = 0.5, p < 0.01), and negatively correlated with Dutifulness and Discipline, facets of Conscientiousness, (p < 0.05 for both). No link was observed between weight loss and the personality trait, Self Control, in either HEWLD or VLED.

Conclusion
The personality factor, Neuroticism, was linked to successful weight loss (that is ≥ 5%) with a particular weight loss treatment, suggesting that there is a potential to use measures of personality to identify appropriate weight loss/management strategies for individuals.

Trial registration
Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000716965
Long-term fenofibrate treatment impaired glucose-stimulated insulin secretion and up-regulated pancreatic NF-kappa B and iNOS expression in monosodium glutamate-induced obese rats: Is that a latent disadvantage?
Authors: Liu Shuai-nan , Liu Quan , Li Lin-yi , Huan Yi , Sun Su-juan , Shen Zhu-fang 
Published: November 2011

Abstract

Background
Fenofibrate, a PPAR alpha agonist, has been widely used in clinics as lipid-regulating agent. PPAR alpha is known to be expressed in many organs including pancreatic beta cells and regulate genes involved in fatty acid metabolism. Some reports based on cell lines or animals have provided evidences that PPAR alpha agonists may affect (increased or suppressed) beta cell insulin secretion, and several studies are producing interesting but still debated results.

Methods
In this research, we investigated the long term effects of fenofibrate on beta cell function in a metabolic syndrome animal model, monosodium glutamate (MSG) induced obese rats. Obese MSG rats were administered by gavage with fenofibrate at a dose of 100 mg/kg for 12 weeks. Oral glucose tolerance and insulin tolerance tests were performed to evaluate glucose metabolism and insulin sensitivity. We have used the hyperglycemic clamp technique to evaluate the capacity of beta cell insulin secretion. This technique provides an unbiased approach to understand the beta cell function in vivo. The changes of gene and protein expression in the pancreas and islets were also analyzed by Real-Time-PCR, Western blot and immunostaining.

Results
Fenofibrate reduced the plasma lipid levels within a few days, and showed no beneficial effects on glucose homeostasis or insulin sensitivity in obese MSG rats. But the animals treated with fenofibrate exhibited significantly decreased fasting plasma insulin and impaired insulin secretory response to glucose stimulation. Further studies confirmed that fenofibrate increased MDA level and decreased total ATPase activity in pancreatic mitochondrion, accompanied by the upregulation of iNOS and NF-kappa B and TNF alpha expression in pancreatic islets of obese MSG rats.

Conclusions
Long-term fenofibrate treatment disrupted beta cell function, and impaired glucose-stimulated insulin secretion in obese MSG rats, perhaps to some extent associated with the activated inflammatory pathway and increased formation of oxidative products, especially the up-regulation of NF-kappa B and iNOS expression in islets.