bluuebunny/crossref_metadata_2025_split huggingface dataset:
Capturing paediatric injury in Ontario: differences in injury incidence using self-reported survey and health service utilisation data
Authors: White Heather L , Macpherson Alison K 
Published: June 2011

ObjectivePopulation-based health surveys are increasingly popular sources of data on injury occurrence. Self-reported surveys can yield estimates of the total incidence of non-fatal injuries while simultaneously capturing a rich repository of contextual data that may be informative for exploring determinants of injury risk. Although survey data are rarely recognised as complete, several researchers have expressed concerns about the sensitivity and validity of self-reported injury data, questioning whether captured cases are representative of the population experience of injury, particularly among children and youth. The present study sought to compare the population incidence of paediatric injury estimated from self-reported survey responses to those documented by a complete-capture health service utilisation database among Ontario children.MethodsInjury incidence rates documented from the National Longitudinal Survey of Children and Youth and the National Population Health Survey were compared with those reported in Canada's National Ambulatory Care Reporting System for Ontario youth aged 0–19 years for fiscal year 2002/3, stratified by the child's age and geographical location of residence.ResultsThe two self-reported health surveys underestimated the population incidence of injury among Ontario children by at least 49% and 53%, respectively. Systematic errors exist in survey data capture such that injuries in infants and preschoolers (<4 years of age) and urban residents were most likely to be missed by the population health surveys.ConclusionInjury incidence estimated through self-report is not representative of the population burden and experience of paediatric injury for Ontario children, and may produce biased estimates of risk when analysed as independent sources of data.
Memory Type 2 Helper T Cells Induce Long-Lasting Antitumor Immunity by Activating Natural Killer Cells
Authors: Kitajima Masayuki , Ito Toshihiro , Tumes Damon J. , Endo Yusuke , Onodera Atsushi , Hashimoto Kahoko , Motohashi Shinichiro , Yamashita Masakatsu , Nishimura Takashi , Ziegler Steven F. , Nakayama Toshinori 
Published: June 2011

AbstractFunctionally polarized helper T cells (Th cells) play crucial roles in the induction of tumor immunity. There is considerable knowledge about the contributions of IFN-producing Th1 cells that supports the role of cytotoxic cluster of differentiation (CD8) T cells and natural killer (NK) cells, but much less is known about how IL-4–producing Th2 cells contribute to tumor immunity. In this study, we investigated the cellular and molecular mechanisms employed by memory Th2 cells in sustaining tumor immunity by using a mouse model system wherein ovalbumin (OVA) is used as a specific tumor antigen. In this model, we found that OVA-specific memory Th2 cells exerted potent and long-lasting antitumor effects against NK-sensitive OVA-expressing tumor cells, wherein antitumor effects were mediated by NK cells. Specifically, NK cell cytotoxic activity and expression of perforin and granzyme B were dramatically enhanced by the activation of memory Th2 cells. Interleukin 4 (IL-4) produced by memory Th2 cells in vivo was critical for the antitumor effects of the NK cells, which IL-4 directly stimulated to induce their perforin- and granzyme-B–dependent cytotoxic activity. Our findings show that memory Th2 cells can induce potent antitumor immunity through IL-4–induced activation of NK cells, suggesting potential applications in cellular therapy for cancer patients. Cancer Res; 71(14); 4790–8. ©2011 AACR.
Sequential Activation of Snail1 and N-Myc Modulates Sonic Hedgehog–Induced Transformation of Neural Cells
Authors: Wanshura Leah E. Colvin , Galvin Katherine E. , Ye Hong , Fernandez-Zapico Martin E. , Wetmore Cynthia 
Published: June 2011

Abstract
Activation of the Sonic hedgehog (Shh) pathway and increased expression of Gli1 play an important role in proliferation and transformation of granule cell progenitors (GCP) in the developing cerebellum. Medulloblastomas arising from cerebellar GCPs are frequently driven by Shh pathway–activating mutations; however, molecular mechanisms of Shh pathway dysregulation and transformation of neural progenitors remain poorly defined. We report that the transcription factor and oncogene Snail1 (Sna1) is directly induced by Shh pathway activity in GCPs, murine medulloblastomas, and human medulloblastoma cells. Enforced expression of Sna1 was sufficient to induce GCPs and medulloblastoma cell proliferation in the absence of Shh/Gli1 exposure. In addition, enforced expression of Sna1 increased transformation of medulloblastoma cells in vitro and in vivo. Analysis of potential Sna1 targets in neural cells revealed a novel Sna1 target, N-Myc, a transcription factor known to play a role in Shh-mediated GCP proliferation and medulloblastoma formation. We found that Sna1 directly induced transcription of N-Myc in human medulloblastoma cells and that depletion of N-Myc ablated the Sna1-induced proliferation and transformation. Taken together, these results provide further insight into the mechanism of Shh-induced transformation of neural progenitor cells and suggest that induction of Sna1 may serve to amplify the oncogenic potential of Shh pathway activation through N-Myc induction. Cancer Res; 71(15); 5336–45. ©2011 AACR.
Dissecting the Oncogenic and Tumorigenic Potential of Differentiated Human Induced Pluripotent Stem Cells and Human Embryonic Stem Cells
Authors: Ghosh Zhumur , Huang Mei , Hu Shijun , Wilson Kitchener D. , Dey Devaveena , Wu Joseph C. 
Published: June 2011

Abstract
Pluripotent stem cells, both human embryonic stem cells (hESC) and human-induced pluripotent stem cells (hiPSC), can give rise to multiple cell types and hence have tremendous potential for regenerative therapies. However, the tumorigenic potential of these cells remains a great concern, as reflected in the formation of teratomas by transplanted pluripotent cells. In clinical practice, most pluripotent cells will be differentiated into useful therapeutic cell types such as neuronal, cardiac, or endothelial cells prior to human transplantation, drastically reducing their tumorigenic potential. Our work investigated the extent to which these differentiated stem cell derivatives are truly devoid of oncogenic potential. In this study, we analyzed the gene expression patterns from three sets of hiPSC- and hESC-derivatives and the corresponding primary cells, and compared their transcriptomes with those of five different types of cancer. Our analysis revealed a significant gene expression overlap of the hiPSC- and hESC-derivatives with cancer, whereas the corresponding primary cells showed minimum overlap. Real-time quantitative PCR analysis of a set of cancer-related genes (selected on the basis of rigorous functional and pathway analyses) confirmed our results. Overall, our findings suggested that pluripotent stem cell derivatives may still bear oncogenic properties even after differentiation, and additional stringent functional assays to purify these cells should be done before they can be used for regenerative therapy. Cancer Res; 71(14); 5030–9. ©2011 AACR.
Following Cancer Prevention Guidelines Reduces Risk of Cancer, Cardiovascular Disease, and All-Cause Mortality
Authors: McCullough Marjorie L. , Patel Alpa V. , Kushi Lawrence H. , Patel Roshni , Willett Walter C. , Doyle Colleen , Thun Michael J. , Gapstur Susan M. 
Published: June 2011

AbstractBackground: Few studies have evaluated the combined impact of following recommended lifestyle behaviors on cancer, cardiovascular disease (CVD) and all-cause mortality, and most included tobacco avoidance. Because 80% of Americans are never or former smokers, it is important to consider the impact of other recommended behaviors.Methods: In 1992 and 1993, 111,966 nonsmoking men and women in the Cancer Prevention Study-II Nutrition Cohort completed diet and lifestyle questionnaires. A score ranging from 0 to 8 points was computed to reflect adherence to the American Cancer Society cancer prevention guidelines on body mass index, physical activity, diet, and alcohol consumption, with 8 points representing optimal adherence. Multivariable-adjusted relative risks (RR) of death and 95% CI were computed by Cox proportional hazard regression.Results: During 14 years of follow-up, 10,369 men and 6,613 women died. The RR of all-cause mortality was lower for participants with high (7, 8) versus low (0–2) scores (men, RR = 0.58, 95% CI: 0.53–0.62; women, RR = 0.58, 95% CI: 0.52–0.64). Inverse associations were found with CVD mortality (men, RR = 0.52, 95% CI: 0.45–0.59; women, RR = 0.42, 95% CI: 0.35–0.51) and cancer mortality (men, RR = 0.70, 95% CI: 0.61–0.80; women, RR = 0.76, 95% CI: 0.65–0.89). Similar associations, albeit not all statistically significant, were observed for never and former smokers.Conclusion: Adherence to cancer prevention guidelines for obesity, diet, physical activity, and alcohol consumption is associated with lower risk of death from cancer, CVD, and all causes in nonsmokers.Impact: Beyond tobacco avoidance, following other cancer prevention guidelines may substantially lower risk of premature mortality in older adults. Cancer Epidemiol Biomarkers Prev; 20(6); 1089–97. ©2011 AACR.
PSA Quo Vadis? It Is Reasonable to Start with Prostate-Specific Antigen Testing at the Age of 40!
Authors: Börgermann Christof , vom Dorp Frank , Swoboda Andreas , Ketteniß Oskar , Becker Markus , Rübben Herbert 
Published: June 2011

Abstract
Background: It is common to start with PSA (prostate-specific antigen)-testing at the age of 50. If patients with a PSA value greater than 4 ng/mL should be considered for prostate biopsy, approximately 20% of all men undergoing test are considered for biopsy at the time of first early-detection examination.
Methods: We have screened 2,592 asymptomatic men younger than 45 years. With a short questionnaire, we assessed age, body mass index (BMI), concomitant diseases, last sexual intercourse, and last bicycle riding. We compared this cohort with a group of 11,656 men aged 45–75 years from a nationwide prostate cancer screening trial.
Results: In this cohort, only 4 men with a PSA value greater than 4 ng/mL and 10 with a PSA greater than 3 ng/mL were identified. More than 99% of all men younger than 45 years had a PSA lesser than 4 ng/mL. Sexual intercourse, bicycle riding, or BMI had a significant but minimal influence on the PSA value.
Conclusions: It is reasonable to start with PSA testing at the age of 40 years. The advantage of screening younger patients is that almost no one should be considered for biopsy at the time of first early-detection examination. We identified a baseline value at which only a minimal influence was exerted by benign prostatic hypertrophy. In comparison with many current guidelines, we gained a lead time of 10 years for observation of PSA dynamics.
Impact: The importance of PSA velocity for stratification of patients at risk for development of significant prostate cancer will grow. Cancer Epidemiol Biomarkers Prev; 20(6); 1190–5. ©2011 AACR.
A Computational Method to Classify Variants of Uncertain Significance Using Functional Assay Data with Application to BRCA1
Authors: Iversen Edwin S. , Couch Fergus J. , Goldgar David E. , Tavtigian Sean V. , Monteiro Alvaro N.A. 
Published: June 2011

Abstract
Background: Besides revealing cancer predisposition variants or the absence of any changes, genetic testing for cancer predisposition genes can also identify variants of uncertain clinical significance (VUS). Classifying VUSs is a pressing problem, as ever more patients seek genetic testing for disease syndromes and receive noninformative results from those tests. In cases such as the breast and ovarian cancer syndrome in which prophylactic options can be severe and life changing, having information on the disease relevance of the VUS that a patient harbors can be critical.
Methods: We describe a computational approach for inferring the disease relevance of VUSs in disease genes from data derived from an in vitro functional assay. It is based on a Bayesian hierarchical model that accounts for sources of experimental heterogeneity.
Results: The functional data correlate well with the pathogenicity of BRCA1 BRCT VUSs, thus providing evidence regarding pathogenicity when family and genetic data are absent or uninformative.
Conclusions: We show the utility of the model by using it to classify 76 VUSs located in the BRCT region of BRCA1. The approach is both sensitive and specific when evaluated on variants previously classified using independent sources of data. Although the functional data are very informative, they will need to be combined with other forms of data to meet the more stringent requirements of clinical application.
Impact: Our work will lead to improved classification of VUSs and will aid in the clinical decision making of their carriers. Cancer Epidemiol Biomarkers Prev; 20(6); 1078–88. ©2011 AACR.
Serum 25-Hydroxyvitamin D and Risk of Oropharynx and Larynx Cancers in Finnish Men
Authors: Arem Hannah , Weinstein Stephanie J. , Horst Ronald L. , Virtamo Jarmo , Yu Kai , Albanes Demetrius , Abnet Christian C. 
Published: June 2011

Abstract
Background: Published studies suggesting a relationship between vitamin D and some common cancers sparked interest in the association of vitamin D with head and neck cancers. Prolonged darker months in Finland are associated with lower levels of ultraviolet B radiation, raising concerns about low vitamin D levels.
Methods: We used a nested case–control study in the prospective Alpha-Tocopherol Beta Carotene (ATBC) Study of male smokers in Finland, to examine the relationship between serum 25(OH)D and risk of developing squamous cancers of the head and neck. Using conditional logistic regression, we calculated the multivariate adjusted ORs and CIs comparing those with serum 25(OH)D adequate levels of 50 to &lt;75 nmol/L to those &lt;25.0.
Results: We identified incident cancers of the oral cavity (n = 134), pharynx (n = 48), and larynx (n = 158). Median serum vitamin D was 31 nmol/L (interquartile range: 21–48), which is below the 50 nmol/L cutoff point was considered adequate for bone and overall health. Comparing those with serum 25(OH)D below 25 nmol/L to those 50 to &lt;75 nmol/L as the referent, the OR was 1.35 (95% CI: 0.53–3.43, Ptrend = 0.65) for overall head and neck cancers. Stratification by cancer subsites of the oral cavity, pharynx, and larynx (Ptrend = 0.93, 0.78, 0.26, respectively) or by season of blood draw also showed no association.
Conclusions: Our study showed no association between serum 25(OH)D and risk of head and neck cancers.
Impact: This study does not support the hypothesis that greater vitamin D exposure would reduce the risk of developing head and neck squamous cancers. Cancer Epidemiol Biomarkers Prev; 20(6); 1178–84. ©2011 AACR.
Inflammation-Related Gene Variants as Risk Factors for Pancreatic Cancer
Authors: Reid-Lombardo Kaye M. , Fridley Brooke L. , Bamlet William R. , Cunningham Julie M. , Sarr Michael G. , Petersen Gloria M. 
Published: June 2011

Abstract
Background: Recent reports support an association between chronic inflammation and progression to pancreatic cancer (PC).
Methods: This case–control, candidate gene association study evaluated 1,354 Caucasian patients with pancreatic ductal adenocarcinoma and 1,189 healthy Caucasian controls. We genotyped 1,538 single nucleotide polymorphism (SNP) in 102 genes from inflammatory pathways involving NF-κB. Primary tests of association assumed a multiplicative (log-additive) genotype effect; secondary analyses examined dominant, additive, and recessive SNP effects.
Results: After adjusting for known risk factors for PC, single SNP analysis revealed an association between four SNPs in NOS1 and one in the CD101 gene with PC risk. These results, however, were not replicated in a PC case–control and cohort population.
Conclusion:NOS1 and CD101 may be associated with a risk of PC; however, these findings did not replicate in other PC populations. Future research is needed into the possible role of NOS1 and CD101 for PC.
Impact: This research shows a lack of association between genetic variation in 102 inflammation-related genes and PC. Future research is needed into the possible role of other inflammation-related genes and PC risk. Cancer Epidemiol Biomarkers Prev; 20(6); 1251–4. ©2011 AACR.
Levels of p27 Sensitize to Dual PI3K/mTOR Inhibition
Authors: Lee Misu , Theodoropoulou Marily , Graw Jochen , Roncaroli Federico , Zatelli Maria Chiara , Pellegata Natalia S. 
Published: June 2011

Abstract
Constitutive activation of the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling cascade occurs in a variety of human malignancies, where it sustains tumor cell proliferation and survival. Pharmacologic blockade of this pathway exerts antineoplastic activity by triggering apoptosis and/or cell-cycle arrest. Pituitary adenomas show activation of the PI3K/AKT/mTOR pathway, but only a fraction of them respond in vitro to the antiproliferative action of rapamycin and RAD001 (mTOR inhibitors), possibly because of the described negative feedback loop on AKT which reactivates the signaling cascade. Rats affected by the multiple endocrine neoplasia-like syndrome (MENX) develop pituitary adenomas showing increased activated AKT. In this study, we comparatively investigated the antitumor potential of the novel dual PI3K/mTOR inhibitor NVP-BEZ235 and the single mTOR inhibitor RAD001 on rat pituitary adenoma cells in primary culture. NVP-BEZ235 inhibits the PI3K pathway both upstream and downstream of AKT, thereby preventing the negative feedback loop. NVP-BEZ235 was more effective than RAD001 in reducing cell viability of pituitary adenomas. Consistently, NVP-BEZ235 treatment decreased Akt and S6 phosphorylation and triggered apoptosis. Because MENX is caused by a germline loss-of-function mutation in the cell-cycle inhibitor p27Kip1, we investigated the relationship between this defect and response to NVP-BEZ235 treatment. The levels of p27Kip1 positively correlate with the response to NVP-BEZ235 treatment. Combined treatment with NVP-BEZ235 and the proteasome inhibitor bortezomib, which increases p27Kip1 amount, shows synergistic antiproliferative effects on pituitary adenoma cells. Our data suggest that NVP-BEZ235 may represent an effective therapeutic modality for pituitary adenomas and that p27Kip1 levels represent a potential predictor of response to dual PI3K/mTOR inhibition. Mol Cancer Ther; 10(8); 1450–9. ©2011 AACR.
Cortactin and Focal Adhesion Kinase as Predictors of Cancer Risk in Patients with Laryngeal Premalignancy
Authors: Rodrigo Juan P. , Álvarez-Alija Gustavo , Menéndez Sofía Tirados , Mancebo Gonzalo , Allonca Eva , García-Carracedo Darío , Fresno Manuel Florentino , Suárez Carlos , García-Pedrero Juana María 
Published: June 2011

Abstract
Novel markers are needed to accurately predict the risk of malignant transformation in laryngeal premalignancies. We therefore investigated the clinical significance of cortactin (CTTN) and focal adhesion kinase (FAK) during laryngeal tumorigenesis and their potential utility as cancer risk markers. CTTN and FAK protein expression and gene amplification were assessed in 82 patients with laryngeal dysplasia and correlated with clinicopathologic parameters and laryngeal cancer risk. Increased CTTN and FAK expression was found respectively in 41 (50%) and 40 (49%) of 82 laryngeal dysplasias; protein expression was maintained or further augmented in the corresponding patient-matched invasive tumors subsequently developed. CTTN and FAK/PTK2 gene amplifications were respectively detected in 10 (12%) and 26 (32%) laryngeal dysplasias. Both CTTN and FAK protein expression increased with the grade of dysplasia; however, CTTN and FAK expression but not histology correlated significantly with increased laryngeal cancer risk (P = 0.009 and P = 0.002, respectively). Patients carrying strong CTTN- or FAK-expressing dysplastic lesions experienced a significantly higher cancer incidence (P = 0.006 and P = 0.001, respectively; log-rank test). Furthermore, FAK expression was an independent predictor of laryngeal cancer development (HR = 3.706, 95% CI: 1.735–7.916; P = 0.001) and the combination of FAK and CTTN showed superior predictive value (HR = 5.042, 95% CI: 2.255–11.274; P &lt; 0.001). Taken together, our findings support the involvement of CTTN and FAK in malignant transformation and provide original evidence for their potential clinical utility as biomarkers for the risk of developing laryngeal cancer. Cancer Prev Res; 4(8); 1333–41. ©2011 AACR.
Five-Year Clinical and Angiographic Outcomes of a Randomized Comparison of Sirolimus-Eluting and Paclitaxel-Eluting Stents
Authors: Räber Lorenz , Wohlwend Lea , Wigger Mathias , Togni Mario , Wandel Simon , Wenaweser Peter , Cook Stéphane , Moschovitis Aris , Vogel Rolf , Kalesan Bindu , Seiler Christian , Eberli Franz , Lüscher Thomas F. , Meier Bernhard , Jüni Peter , Windecker Stephan 
Published: June 2011

Background—
Long-term comparative data of first-generation drug-eluting stents are scarce. We investigated clinical and angiographic outcomes of sirolimus-eluting (SES) and paclitaxel-eluting stents (PES) at 5 years as part of the Sirolimus-Eluting Versus Paclitaxel-Eluting Stents for Coronary Revascularization (SIRTAX) LATE study.

Methods and Results—

A total of 1012 patients were randomly assigned to SES or PES. Repeat angiography was completed in 444 of 1012 patients (43.8%) at 5 years. Major adverse cardiac events occurred in 19.7% of SES- and 21.4% of PES-treated patients (hazard ratio, 0.89; 95% confidence interval, 0.68 to 1.17;
P
=0.39) at 5 years. There were no differences between SES and PES in terms of cardiac death (5.8% versus 5.7%;
P
=0.35), myocardial infarction (6.6% versus 6.9%;
P
=0.51), and target lesion revascularization (13.1% versus 15.1%;
P
=0.29). Between 1 and 5 years, the annual rate of target lesion revascularization was 2.0% (95% confidence interval, 1.4% to 2.6%) for SES and 1.4% (95% confidence interval, 0.9% to 2.0%) for PES. Among patients undergoing paired angiography at 8 months and 5 years, delayed lumen loss amounted to 0.37±0.73 mm for SES and 0.29±0.59 mm for PES (
P
=0.32). The overall rate of definite stent thrombosis was 4.6% for SES and 4.1% for PES (
P
=0.74), and very late definite stent thrombosis occurred at an annual rate of 0.65% (95% confidence interval, 0.40% to 0.90%).

Conclusions—
Long-term follow-up of first-generation drug-eluting stents shows no significant differences in clinical and angiographic outcomes between SES and PES. The continuous increase in late lumen loss in conjunction with the ongoing risk of very late stent thrombosis suggests that vascular healing remains incomplete up to 5 years after implantation of first-generation drug-eluting stents.

Clinical Trial Registration—

http://www.clinicaltrials.gov
. Unique identifier: NCT00297661.