bluuebunny/crossref_metadata_2025_split huggingface dataset:
COI is better than 16S rRNA for DNA barcoding Asiatic salamanders (Amphibia: Caudata: Hynobiidae)
Authors: XIA YUN , GU HAI‐FENG , PENG RUI , CHEN QIN , ZHENG YU‐CHI , MURPHY ROBERT W. , ZENG XIAO‐MAO 
Published: August 2011

AbstractThe 5′ region of the mitochondrial DNA (mtDNA) gene cytochrome c oxidase I (COI) is the standard marker for DNA barcoding. However, because COI tends to be highly variable in amphibians, sequencing is often challenging. Consequently, another mtDNA gene, 16S rRNA gene, is often advocated for amphibian barcoding. Herein, we directly compare the usefulness of COI and 16S in discriminating species of hynobiid salamanders using 130 individuals. Species identification and classification of these animals, which are endemic to Asia, are often based on morphology only. Analysis of Kimura 2‐parameter genetic distances (K2P) documents the mean intraspecific variation for COI and 16S rRNA genes to be 1.4% and 0.3%, respectively. Whereas COI can always identify species, sometimes 16S cannot. Intra‐ and interspecific genetic divergences occasionally overlap in both markers, thus reducing the value of a barcoding gap to identify genera. Regardless, COI is the better DNA barcoding marker for hynobiids. In addition to the comparison of two potential markers, high levels of intraspecific divergence in COI (>5%) suggest that both Onychodactylus fischeri and Salamandrella keyserlingii might be composites of cryptic species.
Melanotic neuroectodermal tumor of infancy: a histopathological and immunohistochemical study
Authors: Mendis Balapuwaduge Ranjit Rigobert Nihal , Lombardi Tommaso , Tilakaratne Wanninayake Mudiyanselage 
Published: August 2011

AbstractMelanotic neuroectodermal tumor of infancy is an uncommon neoplasm that normally occurs in the anterior maxilla of children less than 1 year of age. This is a tumor with controversial origin, although neural crest origin is proposed. This case report presents an analysis of histopathological and immunohistochemical findings in this rare tumor.
Recent success in the discovery of coronary artery disease genes
Authors: Roberts Robert , Chen Li , Wells George A. , Stewart Alexandre F.R. 
Published: August 2011

For more than 50 years, epidemiological studies have indicated that genetic predisposition accounts for approximately 50% of the susceptibility to coronary artery disease (CAD) and its sequelae, including myocardial infarction. Since common diseases such as CAD are caused by multiple genes, the age-old method of linkage analysis used to map monogenic Mendelian disorders in families unfortunately lacks the required sensitivity. The technology to identify genes predisposing individuals to CAD and other common diseases did not become available until 2005. This technology provided computerized arrays containing hundreds of thousands of DNA markers in the form of single-nucleotide polymorphisms (SNPs). This made it possible to pursue an unbiased approach referred to as genome-wide association studies. The first gene for CAD was simultaneously identified by 2 independent groups in 2007. In a very short interval, a total of 23 loci were mapped that were linked to increased risk for CAD. The results of these studies confirm that CAD is caused by multiple genes, each contributing minimal risk. The most exciting and novel findings are that these loci do not act through known risk factors for CAD and that the loci are more likely to be in DNA regions that regulate transcription rather than being in coding regions for protein.
M-CAT element mediates mechanical stretch-activated transcription of B-type natriuretic peptide via ERK activation
Authors: Koivisto Elina , Karkkola Laura , Majalahti Theresa , Aro Jani , Tokola Heikki , Kerkelä Risto , Ruskoaho Heikki 
Published: August 2011

The muscle-CAT (M-CAT) promoter element is found on promoters of most muscle-specific cardiac genes, but its role in cardiac pathology is poorly understood. Here we studied whether the M-CAT element is involved in hypertrophic process activated by mechanical stretch, and identified the intracellular pathways mediating the response. When an in vitro stretch model of cultured neonatal rat cardiomyocytes and luciferase reporter construct driven by rat B-type natriuretic peptide (BNP) promoter were used, mutation of M-CAT element inhibited not only the basal reporter activity (88%), but also the stretch-activated BNP transcription (58%, p < 0.001). Stretch-induced BNP promoter activation was associated with an increase in transcriptional enhancer factor-1 (TEF-1) binding activity after 24 h mechanical stretch (p < 0.05). Inhibition of mitogen-activated protein kinases ERK, JNK, or p38 attenuated stretch-induced BNP activation. Interestingly, as opposed to p38 and JNK, inhibition of ERK had no additional effect on transcriptional activity of BNP promoter harboring the M-CAT mutation, suggesting a pivotal role for ERK in regulating stretch-induced BNP transcription via M-CAT binding site. Finally, immunoprecipitation studies showed that mechanical stretch induced myocyte enhancer factor-2 (MEF-2) binding to TEF-1. These data suggest a central role for M-CAT element in regulation of mechanical stretch-induced hypertrophic response via ERK activation.
Genetically Lowered Microsomal Epoxide Hydrolase Activity and Tobacco-Related Cancer in 47,000 Individuals
Authors: Lee Julie , Dahl Morten , Nordestgaard Børge G. 
Published: August 2011

Abstract
Background: Two functional polymorphisms of the microsomal epoxide hydrolase (mEH) gene (EPHX1), Tyr113His (rs1051740) and His139Arg (rs2234922), have variably been found to influence susceptibility to various cancer forms. We tested whether genetically lowered mEH activity affects risk of developing cancer in the general population.
Methods: We genotyped 47,089 individuals from the Danish general population for the Tyr113His and His139Arg polymorphisms in the EPHX1 gene and divided them into groups with predicted fast, intermediate, and slow mEH activity. Using Cox proportional hazards models, we calculated HRs for 26 individual cancer diagnoses and for groups of any cancer, tobacco-related cancers, estrogen-related female cancers, and other cancers.
Results: Of the 47,089 individuals, 7,590 experienced a cancer event, and of these, 1,466 were tobacco-related. After multifactorial adjustment, the HRs (95% CI) for tobacco-related cancer were 1.1 (0.8–1.5) and 1.5 (1.1–2.0) in individuals with intermediate and slow mEH activity versus individuals with the fast phenotype (Ptrend = 0.003). The corresponding HRs among ever-smokers were 1.1 (0.8–1.5) and 1.5 (1.1–2.0; Ptrend = 0.003), whereas HRs among never-smokers did not differ from 1.0.
Conclusions: Our results indicate that genetically lowered mEH activity is associated with increased risk of developing tobacco-related cancer among smokers in the general population; however, additional studies are needed to confirm our findings.
Impact: To our knowledge, this is the largest study to investigate the association of mEH phenotype and genotype with tobacco-related cancers combined in the general population. Cancer Epidemiol Biomarkers Prev; 20(8); 1673–82. ©2011 AACR.
The Handling of Missing Data in Molecular Epidemiology Studies
Authors: Desai Manisha , Kubo Jessica , Esserman Denise , Terry Mary Beth 
Published: August 2011

Abstract
Molecular epidemiology studies face a missing data problem, as biospecimen or imaging data are often collected on only a proportion of subjects eligible for study. We investigated all molecular epidemiology studies published as Research Articles, Short Communications, or Null Results in Brief in Cancer Epidemiology, Biomarkers & Prevention from January 1, 2009, to March 31, 2010, to characterize the extent that missing data were present and to elucidate how the issue was addressed. Of 278 molecular epidemiology studies assessed, most (95%) had missing data on a key variable (66%) and/or used availability of data (often, but not always the biomarker data) as inclusion criterion for study entry (45%). Despite this, only 10% compared subjects included in the analysis with those excluded from the analysis and 88% with missing data conducted a complete-case analysis, a method known to yield biased and inefficient estimates when the data are not missing completely at random. Our findings provide evidence that missing data methods are underutilized in molecular epidemiology studies, which may deleteriously affect the interpretation of results. We provide practical guidelines for the analysis and interpretation of molecular epidemiology studies with missing data. Cancer Epidemiol Biomarkers Prev; 20(8); 1571–9. ©2011 AACR.
Age-Period-Cohort Analysis of Primary Bone Cancer Incidence Rates in the United States (1976–2005)
Authors: Anfinsen Kristin P. , Devesa Susan S. , Bray Freddie , Troisi Rebecca , Jonasdottir Thora J. , Bruland Oyvind S. , Grotmol Tom 
Published: August 2011

Abstract
Background: Primary bone cancer comprises three major histologic types: osteosarcoma (OS), Ewing sarcoma (ES), and chondrosarcoma (CS). Given the limited knowledge about the etiology of primary bone cancer, we undertook an age-period-cohort (APC) analysis to determine whether incidence varied by birth cohort or calendar period. The purpose was to examine the temporal development of each bone cancer type and generate etiologic hypotheses via the observed birth cohort-related changes.
Methods: An APC model was fitted to incidence data for U.S. whites for OS, ES, and CS obtained from nine registries of the Surveillance, Epidemiology, and End Results program, which covers about 10% of the U.S. population, 1976–2005.
Results: The incidence of OS decreased between 1976 and 2005 among those aged over 60 years, a decline that occurred among patients with OS as their primary malignancy only. From 1986–1995 to 1996–2005, the incidence rate of CS among females of 20 to 69 years rose by about 50%, with rates increasing among consecutive cohorts born during 1935–1975. CS rates among males were stable, as were rates of ES.
Conclusion: The risk reduction in OS as a primary malignancy at older ages could possibly be related to diminished exposure over time to bone-seeking radionuclides. The CS increase among females corresponds to birth cohorts with rising exposures to oral contraceptives and menopausal hormonal therapy.
Impact: As the estrogen signaling pathway has been shown to stimulate proliferation of normal and malignant chondrocytes, estrogen exposure may increase the risk for CS. Further studies are warranted to clarify its possible etiological significance. Cancer Epidemiol Biomarkers Prev; 20(8); 1770–7. ©2011 AACR.
Tobacco Smoking and Cutaneous Squamous Cell Carcinoma: A 16-Year Longitudinal Population-Based Study
Authors: McBride Penelope , Olsen Catherine M. , Green Adèle C. 
Published: August 2011

Abstract
Background: Although tobacco smoking is commonly cited as a risk factor for cutaneous squamous cell carcinoma (SCC), the evidence from previous clinical and case–control studies is conflicting. We therefore aimed to prospectively examine the role of tobacco smoking in the development of SCC of the skin in a population-based study.
Methods: Study participants were 1,287 adults aged 25 to 75 years in 1992, randomly selected from the Nambour community, with no previous history of SCC. Standard skin pigment and sun-sensitivity profiles were obtained at baseline. Detailed prospective information on sun exposure, smoking, and skin cancer occurrence (histologically confirmed) was collected over a 16-year period, 1992 to 2007.
Results: Of 1,287 participants, 43% were male and average age was 48 years. A total of 188 first cutaneous SCCs were identified during the study period. After adjustment for other known risk factors, neither former nor current smokers were at raised risk of SCC: relative risk (RR) = 1.1, 95% CI: 0.8–1.5 and RR = 1.1, 95% CI: 0.7–1.5, respectively, compared with lifelong nonsmokers, nor were there any dose–response relationships with amount smoked or duration of smoking and risk of SCC.
Conclusions: In this Australian follow-up study, tobacco smoking did not increase the risk of SCC of the skin.
Impact: These prospective adjusted data provide strong evidence which suggests that cutaneous SCC should not be on the list of tobacco-related cancers. Cancer Epidemiol Biomarkers Prev; 20(8); 1778–83. ©2011 AACR.
Gender Disparities in the Tumor Genetics and Clinical Outcome of Multiple Myeloma
Authors: Boyd Kevin D. , Ross Fiona M. , Chiecchio Laura , Dagrada GianPaolo , Konn Zoe J. , Tapper William J. , Walker Brian A. , Wardell Christopher P. , Gregory Walter M. , Szubert Alex J. , Davies Faith E. , Morgan Gareth J. 
Published: August 2011

AbstractBackground: Several cancer types have differences in incidence and clinical outcome dependent on gender, but these are not well described in myeloma. The aim of this study was to characterize gender disparities in myeloma.Methods: We investigated the association of gender with the prevalence of tumor genetic lesions and the clinical outcome of 1,960 patients enrolled in the phase III clinical trial MRC Myeloma IX. Genetic lesions were characterized by FISH.Results: Disparities were found in the prevalence of primary genetic lesions with immunoglobulin heavy chain gene (IGH) translocations being more common in women (50% of female patients vs. 38% of male patients, P &lt; 0.001) and hyperdiploidy being more common in men (50% female vs. 62% male, P &lt; 0.001). There were also differences in secondary genetic events with del(13q) (52% female vs. 41% male, P &lt; 0.001) and +1q (43% female vs. 36% male, P = 0.042) being found more frequently in female myeloma patients. Female gender was associated with inferior overall survival (median: 44.8 months female vs. 49.9 months male, P = 0.020).Conclusions: We found gender-dependent differences in the prevalence of the primary genetic events of myeloma, with IGH translocations being more common in women and hyperdiploidy more common in men. This genetic background may impact subsequent genetic events such as +1q and del(13q), which were both more frequent in women. The higher prevalence of lesions associated with poor prognosis in the female myeloma population, such as t(4;14), t(14;16) and +1q, may adversely affect clinical outcome.Impact: These differences suggest that gender influences the primary genetic events of myeloma. Cancer Epidemiol Biomarkers Prev; 20(8); 1703–7. ©2011 AACR.
Sex Disparities in Cancer Mortality and Survival
Authors: Cook Michael B. , McGlynn Katherine A. , Devesa Susan S. , Freedman Neal D. , Anderson William F. 
Published: August 2011

Abstract
Background: Previous research has noted higher cancer mortality rates and lower survival among males than females. However, systematic comparisons of these two metrics by sex have been limited.
Methods: We extracted U.S. vital rates and survival data from the Surveillance, Epidemiology and End Results Database for 36 cancers by sex and age for the period 1977 to 2006. We compared sex-specific mortality rates and examined male-to-female mortality rate ratios (MRR). We also extracted case data which included age and date of diagnosis, sex, primary cancer site, tumor stage and grade, survival time, vital status, and cause of death. Relative cancer-specific HRs for death in the 5-year period following diagnosis were estimated with Cox proportional hazards models, adjusted for covariates.
Results: For the vast majority of cancers, age-adjusted mortality rates were higher among males than females with the highest male-to-female MRR for lip (5.51), larynx (5.37), hypopharynx (4.47), esophagus (4.08), and urinary bladder (3.36). Cancer-specific survival was, for most cancers, worse for males than females, but such disparities were drastically less than corresponding MRRs [e.g., lip (HR = 0.93), larynx (HR = 1.09), hypopharynx (HR = 0.98), esophagus (HR = 1.05), and urinary bladder (HR = 0.83)].
Conclusions: Male-to-female MRRs differed markedly while cancer survival disparities were much less pronounced. This suggests that sex-related cancer disparities are more strongly related to etiology than prognosis.
Impact: Future analytic studies should attempt to understand causes of observed sex disparities in cancer. Cancer Epidemiol Biomarkers Prev; 20(8); 1629–37. ©2011 AACR.
Do Community Health Worker Interventions Improve Rates of Screening Mammography in the United States? A Systematic Review
Authors: Wells Kristen J. , Luque John S. , Miladinovic Branko , Vargas Natalia , Asvat Yasmin , Roetzheim Richard G. , Kumar Ambuj 
Published: August 2011

Abstract
Background: Community health workers (CHW) are lay individuals who are trained to serve as liaisons between members of their communities and health care providers and services.
Methods: A systematic review was conducted to synthesize evidence from all prospective controlled studies on effectiveness of CHW programs in improving screening mammography rates. Studies reported in English and conducted in the United States were included if they: (i) evaluated a CHW intervention designed to increase screening mammography rates in women 40 years of age or older without a history of breast cancer; (ii) were a randomized controlled trial (RCT), case–controlled study, or quasi-experimental study; and (iii) evaluated a CHW intervention outside of a hospital setting.
Results: Participation in a CHW intervention was associated with a statistically significant increase in receipt of screening mammography [risk ratio (RR): 1.06 (favoring intervention); 95% CI: 1.02–1.11, P = 0.003]. The effect remained when pooled data from only RCTs were included in meta-analysis (RR: 1.07; 95% CI: 1.03–1.12, P = 0.0005) but was not present using pooled data from only quasi-experimental studies (RR: 1.03; 95% CI: 0.89–1.18, P = 0.71). In RCTs, participants recruited from medical settings (RR: 1.41; 95% CI: 1.09–1.82, P = 0.008), programs conducted in urban settings (RR: 1.23; 95% CI: 1.09, 1.39, P = 0.001), and programs where CHWs were matched to intervention participants on race or ethnicity (RR: 1.58, 95% CI: 1.29–1.93, P = 0.0001) showed stronger effects on increasing mammography screening rates.
Conclusions: CHW interventions are effective for increasing screening mammography in certain settings and populations.
Impact: CHW interventions are especially associated with improvements in rate of screening mammography in medical settings, urban settings, and in participants who are racially or ethnically concordant with the CHW. Cancer Epidemiol Biomarkers Prev; 20(8); 1580–98. ©2011 AACR.
Vitamin D-Related Genetic Variants, Interactions with Vitamin D Exposure, and Breast Cancer Risk among Caucasian Women in Ontario
Authors: Anderson Laura N. , Cotterchio Michelle , Cole David E. C. , Knight Julia A. 
Published: August 2011

Abstract
Background: Vitamin D, from diet and sunlight exposure, may be associated with reduced breast-cancer risk. This study investigated if candidate gene variants in vitamin D pathways are associated with breast cancer risk, or modify the associations between breast cancer and vitamin D exposure.
Methods: Breast cancer cases aged 25 to 74 years were identified from the Ontario Cancer Registry (histopathologically confirmed and diagnosed 2002–2003) and population-based controls were identified through random digit dialing of Ontario households. Saliva (DNA) was available for 1,777 cases and 1,839 controls. Multivariate logistic regression was used to evaluate associations between 19 single nucleotide polymorphisms (SNP) in vitamin D related genes, including vitamin D binding protein (GC), vitamin D receptor (VDR), and cytochrome P450 type 24A1 (CYP24A1). Statistical interactions were assessed using the likelihood ratio test.
Results: Some SNPs were found to be significantly associated with breast cancer risk. For example, breast cancer risk was associated with the GC rs7041 TT genotype (age-adjusted odds ratio (OR) = 1.23; 95% CI: 1.01, 1.51) and inversely with the VDR Fok1 (rs2228570) ff genotype (OR = 0.71; 95% CI: 0.57, 0.88). Few significant gene-environment interactions were observed between dietary vitamin D and genetic variants.
Conclusion: Our study suggests certain vitamin D related genetic variants may influence breast-cancer risk and we found limited evidence that genetic variants modify the associations between vitamin D exposure and breast cancer risk.
Impact: Variation in vitamin D-related genotypes may help to explain inconsistent results from previous epidemiologic studies and may lead to targeted prevention strategies. Cancer Epidemiol Biomarkers Prev; 20(8); 1708–17. ©2011 AACR.
Biomarkers Related to One-Carbon Metabolism as Potential Risk Factors for Distal Colorectal Adenomas
Authors: de Vogel Stefan , Schneede Jörn , Ueland Per Magne , Vollset Stein Emil , Meyer Klaus , Fredriksen Åse , Midttun Øivind , Bjørge Tone , Kampman Ellen , Bretthauer Michael , Hoff Geir 
Published: August 2011

Abstract
Background: Efficient one-carbon metabolism, which requires adequate supply of methyl group donors and B-vitamins, may protect against colorectal carcinogenesis. However, plasma folate and vitamins B2 and B12 have inconsistently been associated with colorectal cancer risk, and there have been no previous studies relating plasma concentrations of methionine, choline, and betaine to this outcome.
Methods: This study comprised 10,601 individuals, 50 to 64 years of age, participating in the Norwegian Colorectal Cancer Prevention (NORCCAP) screening study. Using logistic regression analyses, we crosssectionally investigated associations between distal colorectal adenoma occurrence–potential precursor lesions of colorectal carcinomas–and plasma concentrations of methyl group donors and B-vitamins, and polymorphisms of genes related to one-carbon metabolism.
Results: Screening revealed 1,809 subjects (17.1%) with at least one adenoma. The occurrence of high-risk adenomas (observed in 421 subjects) was inversely associated with plasma concentrations of methionine (highest versus lowest quartile: odds ratio (OR) = 0.61; 95% confidence interval (CI) = 0.45–0.83), betaine: OR = 0.74; 95% CI = 0.54–1.02, the vitamin B2 form flavin-mononucleotide (FMN): OR = 0.65; 95% CI = 0.49–0.88, and the vitamin B6 form pyridoxal 5′-phosphate (PLP): OR = 0.69; 95% CI = 0.51–0.95, but not with folate, choline, vitamin B12 concentrations, or with the studied polymorphisms. High methionine concentration in combination with high vitamin B2 or B6 concentrations was associated with lower occurrence of high-risk adenomas compared with these factors individually.
Conclusions: High plasma concentrations of methionine and betaine, and vitamins B2 and B6 may reduce risk of developing colorectal adenomas.
Impact: In addition to B-vitamins, methyl group donors such as methionine and betaine may play a role in colorectal carcinogenesis. Cancer Epidemiol Biomarkers Prev; 20(8); 1726–35. ©2011 AACR.
Incomplete Data: What You Don't Know Might Hurt You
Authors: Heitjan Daniel F. 
Published: August 2011

Abstract
Molecular epidemiology studies commonly exhibit missing observations. Methods for extracting correct and efficient analyses from incomplete data are well known in statistics, but relatively few such methods have diffused into applications. I review some areas of incomplete data research that are relevant to molecular epidemiology and appeal for greater efforts by statisticians to translate their methods into practice. Cancer Epidemiol Biomarkers Prev; 20(8); 1567–70. ©2011 AACR.