bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Variation in the TGF-β Signaling Pathway and Colon and Rectal Cancer Risk
Authors: Slattery Martha L. , Herrick Jennifer S. , Lundgreen Abbie , Wolff Roger K. 
Published: January 2011

Abstract
Background: The TGF-β signaling pathway is an essential regulator of many cellular process involved in carcinogenesis. Smad proteins are central to the function of TGF-β signaling. In this study, we evaluated genetic variation in TGFβ1, TGFβR1, Smad1, Smad2, Smad3, and Smad4 and risk of colon and rectal cancer.
Methods: Data are from a large case–control study of colon (n = 1,444 cases, 1,841 controls) and rectal (n = 754 cases, 856 controls) cancer participants with DNA.
Results: Both TGFβ1 rs1800469 and rs4803455 were associated with colon cancer [odds ratio (OR) = 0.65 and 1.43, 95% CI = 0.51–0.84 and 1.18–1.73, respectively) but not rectal cancer. Likewise, 1 of 3 tagSNPs for TGFβR1, 2 of the 4 tagSNPs for Smad2, and 4 of 37 Smad3 tagSNPs were associated with colon cancer. Fewer significant associations were observed for rectal cancer, with only 1 tagSNP in Smad2 and 3 tagSNP in Smad3 having 95% CIs excluding 1.0. Several Smad3 tagSNPs were only associated with CpG island methylator phenotype. We observed several statistically significant interactions between genetic variation in the TGF-β signaling pathway and NFκB1, further illustrating its involvement in proposed mechanisms. In addition, we observed statistically significant interaction between TGFβ1, TGFβR1, and Smad3 and cigarette smoking, aspirin use, and estrogen status for both colon and rectal cancers. Variation in TGFβ1, TGFβR1, and Smad3 seemed to influence survival after diagnosis of colon and rectal cancer.
Conclusions: These findings provide further support for genetic variation in the TGF-β signaling pathway and risk of developing both colon and rectal cancers.
Impact: Insight into biological pathways is provided. Cancer Epidemiol Biomarkers Prev; 20(1); 57–69. ©2011 AACR.
Generalizability and Epidemiologic Characterization of Eleven Colorectal Cancer GWAS Hits in Multiple Populations
Authors: He Jing , Wilkens Lynne R. , Stram Daniel O. , Kolonel Laurence N. , Henderson Brian E. , Wu Anna H. , Le Marchand Loic , Haiman Christopher A. 
Published: January 2011

Abstract
Background: Genome-wide association studies (GWAS) in populations of European ancestry have identified several loci that confer an increased risk of colorectal cancer (CRC).
Methods: We studied the generalizability of the associations with 11 risk variants for CRC on 8q23 (rs16892766), 8q24 (rs6983267), 9p24 (rs719725), 10p14 (rs10795668), 11q23 (rs3802842), 14q22 (rs4444235), 15q13 (rs4779584), 16q22 (rs9929218), 18q21 (rs4939827), 19q13 (rs10411210), and 20p12 (rs961253) in a multiethnic sample of 2,472 CRC cases, 839 adenoma cases and 4,466 controls comprised of European American, African American, Native Hawaiian, Japanese American, and Latino men and women. Because findings for CRC and adenoma were similar, we combined both groups in the analyses.
Results: We confirmed the associations with an increased risk of CRC/adenoma for the 8q24, 11q23 and 15q13 loci in European Americans, and observed significant associations between the 8q24 and 20p12 loci with CRC/adenoma risk in African Americans. Moreover, we found statistically significant cumulative effects of risk alleles on CRC/adenoma risk in all populations (odds ratio [OR] per allele = 1.07–1.09, P ≤ 0.039) except in Japanese Americans (OR = 1.01, P = 0.52). We found heterogeneity in the associations by tumor subsite, age of CRC/adenoma onset, sex, body mass index (BMI), and smoking status for some of the variants.
Conclusions: These results provide evidence that the known variants are in aggregate significantly associated with CRC/adenoma risk in multiple populations except Japanese Americans, and the influences may differ across groups defined by clinicopathological characteristics for some variants.
Impact: These results underline the importance of studying the epidemiologic architecture of these genetic effects in large and diverse populations. Cancer Epidemiol Biomarkers Prev; 20(1); 70–81. ©2011 AACR.
Race-Specific Impact of Natural History, Mammography Screening, and Adjuvant Treatment on Breast Cancer Mortality Rates in the United States
Authors: van Ravesteyn Nicolien T. , Schechter Clyde B. , Near Aimee M. , Heijnsdijk Eveline A.M. , Stoto Michael A. , Draisma Gerrit , de Koning Harry J. , Mandelblatt Jeanne S. 
Published: January 2011

Abstract
Background: U.S. Black women have higher breast cancer mortality rates than White women despite lower incidence. The aim of this study is to investigate how much of the mortality disparity can be attributed to racial differences in natural history, uptake of mammography screening, and use of adjuvant therapy.
Methods: Two simulation models use common national race, and age-specific data for incidence, screening and treatment dissemination, stage distributions, survival, and competing mortality from 1975 to 2010. Treatment effectiveness and mammography sensitivity are assumed to be the same for both races. We sequentially substituted Black parameters into the White model to identify parameters that drive the higher mortality for Black women in the current time period.
Results: Both models accurately reproduced observed breast cancer incidence, stage and tumor size distributions, and breast cancer mortality for White women. The higher mortality for Black women could be attributed to differences in natural history parameters (26–44%), use of adjuvant therapy (11–19%), and uptake of mammography screening (7–8%), leaving 38% to 46% unexplained.
Conclusion: Black women appear to have benefited less from cancer control advances than White women, with a greater race-related gap in the use of adjuvant therapy than screening. However, a greater portion of the disparity in mortality appears to be due to differences in natural history and undetermined factors.
Impact: Breast cancer mortality may be reduced substantially by ensuring that Black women receive equal adjuvant treatment and screening as White women. More research on racial variation in breast cancer biology and treatment utilization is needed. Cancer Epidemiol Biomarkers Prev; 20(1); 112–22. ©2011 AACR.
Joint Effects of Dietary Vitamin D and Sun Exposure on Breast Cancer Risk: Results from the French E3N Cohort
Authors: Engel Pierre , Fagherazzi Guy , Mesrine Sylvie , Boutron-Ruault Marie-Christine , Clavel-Chapelon Francoise 
Published: January 2011

Abstract
Background: Ecological studies have suggested that vitamin D production through ultraviolet (UV) solar irradiance could reduce breast cancer (BC) risk. Although studies restricted to dietary vitamin D intake have provided inconsistent results, little is known about the relationship between pre- and postmenopausal BC and combined intakes from diet, supplements, and sun exposure.
Methods: Cox proportional hazards regression models evaluated the association between vitamin D intakes, mean daily ultraviolet radiation dose (UVRd) at the place of residence and risk of BC among 67,721 women of the French E3N cohort. All analyses were stratified on menopausal status taking into account important confounders including calcium consumption.
Results: During 10 years of follow-up, a total of 2,871 BC cases were diagnosed. Dietary and supplemental vitamin D intakes were not associated with BC risk; however, in regions with the highest UVRd, postmenopausal women with high dietary or supplemental vitamin D intake had a significantly lower BC risk as compared with women with the lowest vitamin D intake (HR = 0.68, 95% CI: 0.54–0.85, and HR = 0.57, 95% CI: 0.36–0.90, respectively).
Conclusion: Our results suggest that a threshold of vitamin D exposure from both sun and diet is required to prevent BC and this threshold is particularly difficult to reach in postmenopausal women at northern latitudes where quality of sunlight is too poor for adequate vitamin D production.
Impact: Prospective studies should further investigate associations between BC risk, vitamin D status and sunlight exposure. Cancer Epidemiol Biomarkers Prev; 20(1); 187–98. ©2011 AACR.
Spliceosome-Mediated RNA Trans-Splicing Facilitates Targeted Delivery of Suicide Genes to Cancer Cells
Authors: Gruber Christina , Gratz Iris K. , Murauer Eva M. , Mayr Elisabeth , Koller Ulrich , Bruckner-Tuderman Leena , Meneguzzi Guerrino , Hintner Helmut , Bauer Johann W. 
Published: January 2011

Abstract
Patients suffering from recessive dystrophic epidermolysis bullosa (RDEB), a hereditary blistering disease of epithelia, show susceptibility to develop highly aggressive squamous cell carcinoma (SCC). Tumors metastasize early and are associated with mortality in the 30th–40th years of life in this patient group. So far, no adequate therapy is available for RDEB SCC. An approach is suicide gene therapy, in which a cell death-inducing agent is introduced to cancer cells. However, lack of specificity has constrained clinical application of this modality. Therefore, we used spliceosome-mediated RNA trans-splicing technology, capable of replacing a tumor-specific transcript with one encoding a cell death-inducing peptide/toxin, to provide tumor-restricted expression. We designed 3′ pre–trans-splicing molecules (PTM) and evaluated their efficiency to trans-splice an RDEB SCC-associated target gene, the matrix metalloproteinase-9 (MMP9), in a fluorescence-based test system. A highly efficient PTM was further adapted to insert the toxin streptolysin O (SLO) of Streptococcus pyogenes into the MMP9 gene. Transfection of RDEB SCC cells with the SLO-PTM resulted in cell death and induction of toxin function restricted to RDEB SCC cells. Thus, RNA trans-splicing is a suicide gene therapy approach with increased specificity to treat highly malignant SCC tumors. Mol Cancer Ther; 10(2); 233–41. ©2011 AACR.
Heme Iron from Meat and Risk of Colorectal Cancer: A Meta-analysis and a Review of the Mechanisms Involved
Authors: Bastide Nadia M. , Pierre Fabrice H.F. , Corpet Denis E. 
Published: January 2011

Abstract
Red meat and processed meat intake is associated with a risk of colorectal cancer, a major cause of death in affluent countries. Epidemiological and experimental evidence supports the hypothesis that heme iron present in meat promotes colorectal cancer. This meta-analysis of prospective cohort studies of colon cancer reporting heme intake included 566,607 individuals and 4,734 cases of colon cancer. The relative risk of colon cancer was 1.18 (95% CI: 1.06–1.32) for subjects in the highest category of heme iron intake compared with those in the lowest category. Epidemiological data thus show a suggestive association between dietary heme and risk of colon cancer. The analysis of experimental studies in rats with chemically-induced colon cancer showed that dietary hemoglobin and red meat consistently promote aberrant crypt foci, a putative precancer lesion. The mechanism is not known, but heme iron has a catalytic effect on (i) the endogenous formation of carcinogenic N-nitroso compounds and (ii) the formation of cytotoxic and genotoxic aldehydes by lipoperoxidation. A review of evidence supporting these hypotheses suggests that both pathways are involved in heme iron toxicity. Cancer Prev Res; 4(2); 177–84. ©2011 AACR.
Estrogen Receptor Expression in Atypical Hyperplasia: Lack of Association with Breast Cancer
Authors: Barr Fritcher Emily G. , Degnim Amy C. , Hartmann Lynn C. , Radisky Derek C. , Boughey Judy C. , Anderson Stephanie S. , Vierkant Robert A. , Frost Marlene H. , Visscher Daniel W. , Reynolds Carol 
Published: January 2011

Abstract
Estrogen receptor (ER) is expressed in normal and malignant breast epithelium, and expression levels have been found to increase with age in normal breast epithelium but not in atypical hyperplasia (AH) and carcinoma in situ. Here we assess ER expression in AH and its association with later breast cancer. ER expression was assessed immunohistochemically in archival sections from 246 women with AH who had open benign breast biopsy from 1967 to 1991. The ACIS III (Dako) was utilized to calculate ER expression in all atypical foci. Using multivariate linear regression, we examined associations of ER expression with age at biopsy, indication for biopsy, type of atypia, number of atypical foci, involution status, and family history. Breast cancer risk across levels of ER expression was also assessed compared with the Iowa SEER control population. Among 246 women, 87 (35%) had atypical ductal hyperplasia (ADH), 141 (57%) had atypical lobular hyperplasia (ALH), and 18 (7%) had both. Forty-nine (20%) developed breast cancer (median follow-up of 14.4 years). Multivariate analysis indicated that type of atypia and age at diagnosis were significantly associated with ER percent staining and intensity (P &lt; 0.05). ER expression was increased in women with ADH and/or those over age 55. ER expression did not significantly impact breast cancer risk in patients diagnosed with atypia. We found increasing ER expression in AH with increasing age. ER expression in AH does not further discriminate breast cancer risk in women with atypia. Cancer Prev Res; 4(3); 435–44. ©2011 AACR.
Intramyocardial Bone Marrow–Derived Mononuclear Cell Injection for Chronic Myocardial Ischemia
Authors: van Ramshorst Jan , Antoni M. Louisa , Beeres Saskia L.M.A. , Roes Stijntje D. , Delgado Victoria , Rodrigo Sander F. , de Roos Albert , Holman Eduard R. , Fibbe Willem E. , Lamb Hildo J. , Zwaginga Jaap J. , Boersma Eric , van der Wall Ernst E. , Schalij Martin J. , Atsma Douwe E. , Bax J.J. 
Published: January 2011

Background—
The present substudy of a recently published randomized trial aimed to investigate the effect of intramyocardial bone marrow cell injection on diastolic function in patients with chronic myocardial ischemia.

Methods and Results—

In a total of 50 patients, diastolic function was evaluated before and 3 months after bone marrow cell injection using standard echocardiography and strain analysis. In addition, MRI-derived transmitral flow measurements were obtained in a subset of 36 patients. Left ventricular ejection fraction increased from 50±5% to 54±7% in the bone marrow cell group, which was a significant improvement as compared with the placebo group (52±5% versus 51±7%,
P
=0.001). Filling pressure estimate E/E′ ratio improved from 14±5 at baseline to 12±4 at 3 months in the bone marrow cell group, whereas no improvement was observed in the placebo group (13±4 versus 13±5). The improvement in E/E′ ratio was significantly larger in the bone marrow cell group (
P
=0.008). Furthermore, the E/A peak flow ratio as assessed by MRI showed a significant increase in the bone marrow cell group as compared with the placebo group (+0.16±0.25 versus −0.04±0.21,
P
=0.01), which was mainly related to an increase in the early (E) peak flow rate in the bone marrow cell group (from 407±96 mL/s to 468±110 mL/s,
P
=0.009 as compared with the placebo group).

Conclusions—
The current study demonstrates that intramyocardial bone marrow cell injection is associated with a beneficial effect on myocardial relaxation and filling pressures in patients with chronic myocardial ischemia.

Clinical Trial Registration—

URL:
http://www.trialregister.nl
. Unique identifier: NTR400/ISRCTN58194927.
Assessment of a New Anemometry System for the Met Office’s Moored Buoy Network
Authors: Turton Jon , Pethica Charlie 
Published: January 2011

Abstract
Since the late 1980s the Met Office has operated a network of Marine Automatic Weather Stations (MAWS) around the United Kingdom. The network includes a number of instrumented moored buoys, which are mainly in exposed open-ocean locations. The anemometry is usually the first component to degrade or fail, often after 6–9 months at sea. Because the buoys are normally serviced on an annual basis, there is a need for a more durable wind system. This paper presents results from the initial deployments of a new anemometry system based on the Gill WindSonic on some of the Met Office’s moored buoys, where the new wind system has been deployed alongside a conventional cup-and-vane system for comparison. The results suggest that the new wind system has shown no evidence of deterioration in its measurement accuracy, even after 8–11 months at sea. However, there is evidence of degradation in the quality of the wind data from the collocated cup-and-vane system. As a result, the new wind system will be deployed across the network to improve wind measurement reliability.
Rapid Estimation of Column-Averaged CO2 Concentration Using a Correlation Algorithm
Authors: Polonsky Igor , O’Brien D. M. 
Published: January 2011

Abstract
Measurement of XCO2, the column-averaged mole fraction of CO2, using reflected sunlight in the near-infrared bands of CO2, is strongly influenced by photons that are scattered in the atmosphere because scattering can either decrease or increase the mean pathlength compared with the direct path from the sun to the surface to the satellite. A very simple algorithm that can be used to compensate for the errors introduced by scattering is presented. The algorithm is based on the observation that the apparent optical path differences in selected pairs of channels in the weak CO2 band at 1.6 μm and the O2 A band at 0.76 μm are tightly correlated for large ensembles of scattering atmospheres. The number of tightly correlated pairs of channels is many hundreds for the bands measured by NASA’s Orbiting Carbon Observatory (OCO). The physical reasons for the correlation are that the mean photon pathlengths are comparable for the members of each pair of channels, and that the extinction profiles vary similarly with height. For atmospheres with modest scattering optical thickness (less than 0.3), the slope and the intercept of the linear correlation for any pair depends weakly on the surface reflectance, the surface pressure, and the viewing geometry. Through numerical simulations the slope and intercept may be parameterized simply in terms of these variables. Thereafter, the task of retrieving XCO2 from measured spectra may be reduced to linear interpolation in precomputed tables of slopes and intercepts. Results with simulated data for NASA’s OCO satellite are presented, and random errors and biases are investigated. Although OCO did not reach orbit, the method is applicable to any instrument that operates using similar principles [such as those on the Greenhouse Gases Observing Satellite (GOSAT) and the replacement satellite OCO-2].
Community Radiative Transfer Model for Stratospheric Sounding Unit
Authors: Chen Yong , Han Yong , Liu Quanhua , Van Delst Paul , Weng Fuzhong 
Published: January 2011

AbstractTo better use the Stratospheric Sounding Unit (SSU) data for reanalysis and climate studies, issues associated with the fast radiative transfer (RT) model for SSU have recently been revisited and the results have been implemented into the Community Radiative Transfer Model version 2. This study revealed that the spectral resolution for the sensor’s spectral response functions (SRFs) calculations is very important, especially for channel 3. A low spectral resolution SRF results, on average, in 0.6-K brightness temperature (BT) errors for that channel. The variations of the SRFs due to the CO2 cell pressure variations have been taken into account. The atmospheric transmittance coefficients of the fast RT model for the Television and Infrared Observation Satellite (TIROS)-N, NOAA-6, NOAA-7, NOAA-8, NOAA-9, NOAA-11, and NOAA-14 have been generated with CO2 and O3 as variable gases. It is shown that the BT difference between the fast RT model and line-by-line model is less than 0.1 K, but the fast RT model is at least two orders of magnitude faster. The SSU measurements agree well with the simulations that are based on the atmospheric profiles from the Earth Observing System Aura Microwave Limb Sounding product and the Sounding of the Atmosphere using Broadband Emission Radiometry on the Thermosphere Ionosphere Mesosphere Energetics and Dynamics satellite. The impact of the CO2 cell pressures shift for SSU has been evaluated by using the Committee on Space Research (COSPAR) International Reference Atmosphere (CIRA) model profiles. It is shown that the impacts can be on an order of 1 K, especially for SSU NOAA-7 channel 2. There are large brightness temperature gaps between observation and model simulation using the available cell pressures for NOAA-7 channel 2 after June 1983. Linear fittings of this channel’s cell pressures based on previous cell leaking behaviors have been studied, and results show that the new cell pressures are reasonable. The improved SSU fast model can be applied for reanalysis of the observations. It can also be used to address two important corrections in deriving trends from SSU measurements: CO2 cell leaking correction and atmospheric CO2 concentration correction.
An Extensive Comparison of Commercial Pyrheliometers under a Wide Range of Routine Observing Conditions
Authors: Michalsky Joseph , Dutton Ellsworth G. , Nelson Donald , Wendell James , Wilcox Stephen , Andreas Afshin , Gotseff Peter , Myers Daryl , Reda Ibrahim , Stoffel Thomas , Behrens Klaus , Carlund Thomas , Finsterle Wolfgang , Halliwell David 
Published: January 2011

Abstract
In the most comprehensive pyrheliometer comparison known to date, 33 instruments were deployed to measure direct normal solar radiation over a 10-month period in Golden, Colorado. The goal was to determine their performance relative to four electrical-substitution cavity radiometers that were calibrated against the World Radiometric Reference (WRR) that is maintained at the World Radiation Center in Davos, Switzerland. Because of intermittent cabling problems with one of the cavity radiometers, the average of three windowed, electrical-substitution cavity radiometers served as the reference irradiance for 29 test instruments during the 10-month study. To keep the size of this work manageable, comparisons are limited to stable sunny conditions, passing clouds, calm and windy conditions, and hot and cold temperatures. Other variables could have been analyzed, or the conditions analyzed could have employed higher resolution. A more complete study should be possible now that the instruments are identified; note that this analysis was performed without any knowledge on the part of the analyst of the instruments’ manufacturers or models. Apart from the windowed cavities that provided the best measurements, two categories of performance emerged during the comparison. All instruments exceeded expectations in that they measured with lower uncertainties than the manufacturers’ own specifications. Operational 95% uncertainties for the three classes of instruments, which include the uncertainties of the open cavities used for calibration, were about 0.5%, 0.8%, and 1.4%. The open cavities that were used for calibration of all pyrheliometers have an estimated 95% uncertainty of 0.4%–0.45%, which includes the conservative estimate of 0.3% uncertainty for the WRR.