bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Food and Drug Administration–Approved Anticancer Agents in the NCI60 Panel of Human Tumor Cell Lines
Authors: Holbeck Susan L. , Collins Jerry M. , Doroshow James H. 
Published: May 2010

AbstractSince the early 1990s the Developmental Therapeutics Program of the National Cancer Institute (NCI) has utilized a panel of 60 human tumor cell lines (NCI60) representing 9 tissue types to screen for potential new anticancer agents. To date, about 100,000 compounds and 50,000 natural product extracts have been screened. Early in this program it was discovered that the pattern of growth inhibition in these cell lines was similar for compounds of similar mechanism. The development of the COMPARE algorithm provided a means by which investigators, starting with a compound of interest, could identify other compounds whose pattern of growth inhibition was similar. With extensive molecular characterization of these cell lines, COMPARE and other user-defined algorithms have been used to link patterns of molecular expression and drug sensitivity. We describe here the results of screening current Food and Drug Administration (FDA)-approved anticancer agents in the NCI60 screen, with an emphasis on those agents that target signal transduction. We analyzed results from agents with mechanisms of action presumed to be similar; we also carried out a hierarchical clustering of all of these agents. The addition of data from recently approved anticancer agents will increase the utility of the NCI60 databases to the cancer research community. These data are freely accessible to the public on the DTP website (http://dtp.cancer.gov/). The FDA-approved anticancer agents are themselves available from the NCI as a plated set of compounds for research use. Mol Cancer Ther; 9(5); 1451–60. ©2010 AACR.
Left Ventricular Hypertrophy Influences Cardiac Prognosis in Patients Undergoing Dobutamine Cardiac Stress Testing
Authors: Charoenpanichkit Charaslak , Morgan Timothy M. , Hamilton Craig A. , Wallace Eric L. , Robinson Killian , Ntim William O. , Hundley W. Gregory 
Published: May 2010

Background—
This study was performed to determine the utility of dobutamine stress test results for predicting myocardial infarction (MI) and cardiac death in patients with chest pain and left ventricular hypertrophy (LVH).

Methods and Results—

Three hundred fifty-three participants with a mean±SD age of 64±12 years (54%men) underwent dobutamine cardiovascular magnetic resonance stress testing and then were followed up for 6±2 years (mean±SD; range, 0.5–11.5) to assess the post–dobutamine cardiovascular magnetic resonance stress test occurrence of MI or cardiac death. LV mass and the presence or absence of ischemia were determined; LVH was defined as an LV mass index >96 g/m
2
in men and >77 g/m
2
in women. LVH was present in 62 participants (18% of the men and 17% of the women,
P
=0.90). Seventy-one (20%) participants experienced an MI or cardiac death during follow-up. The MI and cardiac death rate was more frequent in those with versus without LVH (32% vs 17%,
P
=0.009). In multivariable analysis that accounted for the presence of preexisting coronary artery disease, hypertension, diabetes, stress-induced ischemia, and reduced LV ejection fraction, LVH was an independent predictor of MI and cardiac death (hazard ratio=1.99; 95% CI, 1.13–3.50;
P
=0.02).

Conclusions—
LVH is predictive of future MI and cardiac death in patients with or without inducible ischemia during dobutamine cardiac stress testing. As a result, LVH should be reported in those referred for dobutamine cardiac stress tests, particularly in those without inducible ischemia, in whom one would otherwise assume a favorable cardiac prognosis.
Increased Risk of Bleeding in Patients on Clopidogrel Therapy After Drug-Eluting Stents Implantation
Authors: Tsai Thomas T. , Ho P. Michael , Xu Stanley , Powers J. David , Carroll Nikki M. , Shetterly Susan M. , Maddox Thomas M. , Rumsfeld John S. , Margolis Karen , Go Alan S. , Magid David J. 
Published: May 2010

Background—
Studies suggest that extended clopidogrel use after drug-eluting stent (DES) implantation may decrease the risk of myocardial infarction (MI) and death. Little is known about the competing risk of bleeding from clopidogrel in “real world” clinical practice.

Methods and Results—
We studied 7689 patients undergoing drug-eluting stent implantation enrolled in the HMO Research Network-Stent Registry between 2004 and 2007. Patients were analyzed in 6-month intervals for the occurrence of major bleeding, MI, and death. Clopidogrel use was determined by pharmacy dispensing data. Regression models assessed the association between clopidogrel use and outcomes. Overall, 3603 patients (49.1%) received clopidogrel for >6 months. During a mean follow-up of 418 days (SD, ±168 days), 217 (2.9%) patients died, 279 (3.7%) had a MI, and 271 (3.6%) had major bleeding. After adjustment, patients on clopidogrel therapy were associated with increased major bleeding in all time intervals (0 to 6 months: relative risk (RR)=2.70, 95% CI=1.41 to 5.19; 7 to 12 months: RR=1.71, 95% CI=1.05 to 2.79; 13 to 18 months: RR=2.34, 95% CI=1.26 to 4.34), compared with patients off clopidogrel. Clopidogrel use was also associated with decreased risk of MI for all time intervals (0 to 6 months: RR=0.52, 95% CI=0.36 to 0.77; 7 to 12 months: RR=0.46, 95% CI=0.30 to 0.70; 13 to 18 months: RR=0.53, 95% CI=0.29 to 0.99) and decreased death in the 7 to 12 month interval (RR=0.50, 95% CI=0.30 to 0.83).

Conclusions—
Clopidogrel use was associated with increased major bleeding and decreased MI persisting to 18 months. Bleeding risks on clopidogrel therapy deserve consideration in the ongoing debate regarding optimal clopidogrel duration after PCI.
Previous Coronary Stent Implantation and Cardiac Events in Patients Undergoing Noncardiac Surgery
Authors: Cruden Nicholas L.M. , Harding Scott A. , Flapan Andrew D. , Graham Cat , Wild Sarah H. , Slack Rachel , Pell Jill P. , Newby David E. ,   on behalf of the Scottish Coronary Revascularisation Register Steering Committee
Published: May 2010

Background—
Noncardiac surgery performed after coronary stent implantation is associated with an increased risk of stent thrombosis, myocardial infarction, and death. The influence of stent type and period of risk still have to be defined.

Methods and Results—

We linked the Scottish Coronary Revascularisation Register with hospital admission data to undertake a Scotland-wide retrospective cohort study examining cardiac outcomes in all patients who received drug-eluting or bare-metal stents between April 2003 and March 2007 and subsequently underwent noncardiac surgery. Of 1953 patients, 570 (29%) were treated with at least 1 drug-eluting stent and 1383 (71%) with bare-metal stents only. There were no differences between drug-eluting and bare-metal stents in the primary end point of in-hospital mortality or ischemic cardiac events (14.6% versus 13.3%;
P
=0.3) or the secondary end points of in-hospital mortality (0.7% versus 0.6%;
P
=0.8) and acute myocardial infarction (1.2% versus 0.7%;
P
=0.3). Perioperative death and ischemic cardiac events occurred more frequently when surgery was performed within 42 days of stent implantation (42.4% versus 12.8% beyond 42 days;
P
<0.001), especially in patients revascularized after an acute coronary syndrome (65% versus 32%;
P
=0.037). There were no temporal differences in outcomes between the drug-eluting and bare-metal stent groups.

Conclusions—
Patients undergoing noncardiac surgery after recent coronary stent implantation are at increased risk of perioperative myocardial ischemia, myocardial infarction, and death, particularly after an acute coronary syndrome. For at least 2 years after percutaneous coronary intervention, cardiac outcomes after noncardiac surgery are similar for both drug-eluting and bare-metal stents.
A Progressive Pedagogy for Online Learning With High-Ability Secondary School Students: A Case Study
Authors: Wan Ng  , Nicholas Howard 
Published: May 2010

This article describes a case study of a group of ten 14-year-old students who engaged with an online extended-learning project as an extracurricular activity for about 6 months. The students were physically located in Australia, Malaysia, and the United Kingdom. The facilitation and online learning made use of a progressive pedagogy that moved from structured, whole group online participation to a more individual, open approach to learning. The study investigated students’ motivation to participate in the online learning and explored the nature of the interactions in an online learning environment. The findings show that students interacted differently online, depending on the task at hand. Seven of the 10 students completed the final task of creating learning products. The implications of the study for online learning with high-ability school students are discussed. Putting the Research to Use This research demonstrates that online support for high ability students is both possible and practical. Implementing this approach requires a structured approach to move the students progressively to more open-ended enquiry. This incremental approach reduces the extent of student drop-out and increases task completion when compared to more challenging open-ended tasks. Teachers or schools seeking to provide this kind of support to overcome geographic isolation of high ability students need to (a) plan carefully for the structured engagement with topics and with other students (b) remain closely involved in the initial stages of engagement and (c) only gradually remove their scaffolding as students demonstrate capacity to sustain independent interactions. Having a public purpose for the activity is also important.
Review of the evidence for oral health promotion effectiveness
Authors: Satur Julie G , Gussy Mark G , Morgan Michael V , Calache Hanny , Wright Clive 
Published: May 2010

Dental caries, periodontal diseases, tooth loss and oral cancers have significant burden of disease effects *, quality of life and cost implications for the Australian community. Oral health promotion is a key approach to addressing these conditions endorsed as part of the National Oral Health Plan. Understanding the evidence for effectiveness of oral health promotion is integral to strategic planning for both oral and general health settings. Objective: The objective of this article is to report the key findings of a systematic review of the evidence for oral health promotion commissioned by the Victorian Department of Human Services in 2006. Methods: Evidence was collected and evaluated using a combined approach incorporating the Cochrane Public Health and Health Promotion Field Handbook and the Health Gains Notation in order to a develop a synthesis approach to reporting, framed around the Ottawa Charter. Findings: Findings included evidence supporting the continued fluoridation of water supplies, interventions aimed at early childhood and aged care settings, smoking cessation and capacity building with non-oral health care providers. Emerging evidence supporting multi-strategy community based approaches is also reported along with gaps in the evidence. General Conclusions: The authors conclude that, while there is good support for the incorporation of oral health into general health promotion, it will be important to monitor the outcomes in oral health terms.
Young people’s use and views of a school-based sexual health drop-in service in areas of high deprivation
Authors: Ingram Jenny , Salmon Debra 
Published: May 2010

Objective: To describe patterns and reasons of attendance and young people’s views of the drop-in service. Design: Analysis of a prospective database, questionnaire survey and qualitative interviews and discussions. Setting: Sexual health drop-in clinics in 16 secondary schools (including three pupil-referral units) in deprived areas of a city in South West England Methods: Nurse-completed consultations with young people; self-report questionnaires distributed by youth workers at the clinics; and interviews with young people in personal, social and health education (PSHE) lessons and at lunchtimes. Results: 515 young people made 1,303 visits over 15 months for nurse consultations (mean age 14.7 years). The mean age of first sex was 13.8 years (range 10 to 16 years). The service attracted ‘hard-to-reach’ young people, including boys, those less academically able, and those engaging in sexual intercourse at younger ages. A wide range of services were taken up including contraception, emergency contraception, sexually transmitted infections (STIs) testing and treatment, pregnancy tests, and referral to other services. Young people reported high levels of satisfaction with staff attitudes and clinic environment. Youth workers saw a younger age group than nurses, giving advice prior to sexual activity, about relationships, ‘safer sex’ and delaying sex. Barriers to use included: worries about embarrassment, cultural issues, and confidentiality. Conclusions: Locating sexual health drop-in clinics in schools within deprived communities makes them accessible to many vulnerable young people. Those having sex early attended, often before they had sex, and a large number of boys came for advice and condoms.
Health beliefs about osteoporosis and osteoporosis screening in older women and men
Authors: Nayak Smita , Roberts Mark S , Chang Chung-Chou H , Greenspan Susan L 
Published: May 2010

Objective: To examine older adults’ beliefs about osteoporosis and osteoporosis screening to identify barriers to screening. Design: Cross-sectional mailed survey. Setting: Western Pennsylvania. Methods: Surveys were mailed to 1,830 women and men aged 60 years and older. The survey assessed socio-demographic characteristics, osteoporosis and general health-related characteristics, and beliefs about osteoporosis severity, susceptibility, screening self-efficacy, and screening response efficacy. Analyses included Wilcoxon rank-sum tests to compare belief dimension scores, and multivariable ordinal logistic regression analyses to evaluate association between osteoporosis beliefs and potential explanatory variables. Results: Surveys were completed by 1,268 individuals (69.3 per cent). Mean age of respondents was 73.3 years, and most were female (58.7 per cent). Individuals demonstrated greatest belief in the severity of osteoporosis and least belief in personal susceptibility (P < .001). Older individuals believed less strongly than younger individuals in osteoporosis severity (OR, 0.95 per one year increase in age; 95 per cent CI, 0.92—0.97) and response efficacy (OR, 0.97 per one year increase in age; 95 per cent CI, 0.95—0.99). Women believed more strongly than men in osteoporosis susceptibility (OR, 1.87; 95 per cent CI, 1.38—2.53) and screening self-efficacy (OR, 2.87; 95 per cent CI, 1.17—7.07). Individuals with high self-rated health status had greater belief than those with low self-rated health status in screening self-efficacy (OR, 3.59; 95 per cent CI, 1.89—6.83). Conclusion: Older adults demonstrate several beliefs that may be barriers to osteoporosis screening, including low belief in susceptibility to osteoporosis. These beliefs should be targeted with patient education to improve screening rates.
Integrating the chronic care model into a novel medical student course
Authors: Block Robert C , Tran Bill , McIntosh Scott 
Published: May 2010

Objective: To determine whether integration of the Chronic Care Model into undergraduate medical education is associated with anticipated use of the Model and whether student perceptions match actual integration of the Model into their community projects. Design: This was a cross-sectional study using qualitative and quantitative data. Setting: A novel fourth-year medical student community health improvement course. Method: The study included 45 students who had enrolled in the course before introduction of the Model and 32 formally introduced to the Model through a lecture. Perceptions were measured through a survey and a focus group with data analysed amongst and between cohorts. Projects were reviewed for actual integration of Model elements and these data were compared with reported student perceptions. Results: Although they were in general utilizing most elements of the Model, student perceptions of their use of Model elements significantly differed from actual use of particular elements ( p < 0.001). For instance, whereas the majority believed that their projects focused on the element of Community Resources, most projects actually focused on Self-Management Support. Students formally introduced to the Model trended toward the belief that it would enhance their ability to care for patients more than students without formal exposure to it ( p = 0.0516). Conclusions: Although medical students may not recognize it, they may already focus their actions and thinking regarding health improvement toward patient self-management of their chronic disease. Although students require education and training if the Model is to be widely used, they may be naturally attracted to it.
Down syndrome childhood acute lymphoblastic leukemia has a unique spectrum of sentinel cytogenetic lesions that influences treatment outcome: a report from the Children's Oncology Group
Authors: Maloney Kelly W. , Carroll William L. , Carroll Andrew J. , Devidas Meenakshi , Borowitz Michael J. , Martin Paul L. , Pullen Jeanette , Whitlock James A. , Willman Cheryl L. , Winick Naomi J. , Camitta Bruce M. , Hunger Stephen P. 
Published: May 2010

Abstract
Children with Down syndrome (DS) have an increased risk of acute lymphoblastic leukemia (ALL) and an inferior outcome. We reviewed data from 2811 children with ALL enrolled in Children's Oncology Group P9900, which included prospective testing for the major cytogenetic lesions in childhood ALL: ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL translocations and trisomies of chromosomes 4 and 10. Eighty (3%) B-precursor ALL patients had DS. Age, sex, white blood cell count, and risk group were similar between DS-ALL and non–DS-ALL but significantly more patients with DS-ALL were white (91.2% vs 76.4%, P = .001). Children with DS-ALL had lower rates of the favorable cytogenetic lesions ETV6-RUNX1 (2.5% vs 24%, P < .001) and trisomies 4 and 10 (7.7% vs 24%, P < .001). Five-year event-free (EFS) and overall survival (OS) were inferior in children with DS-ALL: 69.9% ± 8.6% versus 78.1% ± 1.2% (P = .078), and 85.8% ± 6.5% versus 90.0% ± 0.9% (P = .033). However, when children with MLL translocations, BCR-ABL1, ETV6-RUNX1, and trisomies 4 and 10 were excluded, the EFS and OS were similar for children with and without DS (EFS 68.0 %± 9.3% vs 70.5% ± 1.9%, P = .817; and OS 86.7% ± 6.7% vs 85.4% ± 1.5%; P = .852), both overall and adjusted for race. DS-ALL displays a unique spectrum of biologic subtypes with different frequencies of sentinel cytogenetic lesions having a large influence on outcome.
Constitutively active Stat5b in CD4+ T cells inhibits graft-versus-host disease lethality associated with increased regulatory T-cell potency and decreased T effector cell responses
Authors: Vogtenhuber Christine , Bucher Christoph , Highfill Steven L. , Koch Lisa K. , Goren Emily , Panoskaltsis-Mortari Angela , Taylor Patricia A. , Farrar Michael A. , Blazar Bruce R. 
Published: May 2010

Abstract
Overexpression of a constitutively active form of Stat5b (Stat5b-CA) increases regulatory T cells (Tregs). We show that Stat5b-CA transgenic (TG) CD4+ T cells had a markedly reduced graft-versus-host disease (GVHD) capacity versus wild-type (WT) T cells. Stat5b-CA TG versus WT CD4+ T cells had a higher proportion of Tregs, which were superior in suppressing alloresponses mediated by CD4+CD25− effector T cells (Teffs). By day 5 after transplantation, Stat5b-CA TG Tregs had expanded approximately 3-fold more than WT Tregs. Purified Stat5b-CA TG Tregs added to WT CD4+CD25− Teffs were superior on a per-cell basis for inhibiting GVHD versus WT Tregs. Surprisingly, rigorously Treg-depleted Stat5b-CA TG versus WT CD4+CD25− Teffs caused less GVHD lethality associated with diminished Teff proinflammatory and increased Th2 anti-inflammatory cytokine responses. Reduced GVHD by Stat5b-CA TG versus WT Teffs could not be explained by conversion into Tregs in day 10 posttransplantation spleen or small intestine. In addition, Stat5b-CA TG Teffs retained a graft-versus-leukemia response. These results indicate a major role for Stat5 in Treg expansion and potency along with a lesser but significant role in Teff activation and suggest a strategy of pharmacologic Stat5b up-regulation as a means of decreasing GVHD while retaining a graft-versus-leukemia effect.
A comparison of massively parallel nucleotide sequencing with oligonucleotide microarrays for global transcription profiling
Authors: Bradford James R , Hey Yvonne , Yates Tim , Li Yaoyong , Pepper Stuart D , Miller Crispin J 
Published: May 2010

Abstract

Background
RNA-Seq exploits the rapid generation of gigabases of sequence data by Massively Parallel Nucleotide Sequencing, allowing for the mapping and digital quantification of whole transcriptomes. Whilst previous comparisons between RNA-Seq and microarrays have been performed at the level of gene expression, in this study we adopt a more fine-grained approach. Using RNA samples from a normal human breast epithelial cell line (MCF-10a) and a breast cancer cell line (MCF-7), we present a comprehensive comparison between RNA-Seq data generated on the Applied Biosystems SOLiD platform and data from Affymetrix Exon 1.0ST arrays. The use of Exon arrays makes it possible to assess the performance of RNA-Seq in two key areas: detection of expression at the granularity of individual exons, and discovery of transcription outside annotated loci.

Results
We found a high degree of correspondence between the two platforms in terms of exon-level fold changes and detection. For example, over 80% of exons detected as expressed in RNA-Seq were also detected on the Exon array, and 91% of exons flagged as changing from Absent to Present on at least one platform had fold-changes in the same direction. The greatest detection correspondence was seen when the read count threshold at which to flag exons Absent in the SOLiD data was set to t<1 suggesting that the background error rate is extremely low in RNA-Seq. We also found RNA-Seq more sensitive to detecting differentially expressed exons than the Exon array, reflecting the wider dynamic range achievable on the SOLiD platform. In addition, we find significant evidence of novel protein coding regions outside known exons, 93% of which map to Exon array probesets, and are able to infer the presence of thousands of novel transcripts through the detection of previously unreported exon-exon junctions.

Conclusions
By focusing on exon-level expression, we present the most fine-grained comparison between RNA-Seq and microarrays to date. Overall, our study demonstrates that data from a SOLiD RNA-Seq experiment are sufficient to generate results comparable to those produced from Affymetrix Exon arrays, even using only a single replicate from each platform, and when presented with a large genome.