bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of tax and price policies in tobacco control: Table 1
Authors: Chaloupka Frank J , Straif Kurt , Leon Maria E 
Published: November 2010

ObjectiveOver 20 experts on economics, epidemiology, public policy and tobacco control were asked by the International Agency for Research on Cancer (IARC) to evaluate the strength of the available evidence on the effects of tax and price policies to prevent and reduce tobacco use.MethodsDraft papers presenting and assessing the evidence on the following topics were developed by the experts in an 8-month period prior to the meeting: tobacco industry pricing strategies and tax related lobbying; tax, price and aggregate demand for tobacco; tax, price and adult tobacco use, use among young people and use among the poor; tax avoidance and tax evasion; and the economic and health impact of tobacco taxation. Subsequently, papers were peer reviewed, revised and resubmitted for final discussion at a 6-day meeting at IARC in Lyon, France, where a consensus evaluation of 18 concluding statements using the pre-established criteria of the IARC Cancer Prevention Handbooks took place. Studies published (or accepted for publication) in the openly available scientific literature were the main source of evidence for the review and evaluation; other types of publications were included when appropriate.ResultsIn support of 12 of the 18 conclusions, the experts agreed that there was sufficient evidence of effectiveness of increased tobacco excise taxes and prices in reducing overall tobacco consumption and prevalence of tobacco use and improvement of public health, including by preventing initiation and uptake among young people, promoting cessation among current users and lowering consumption among those who continue to use. For the remaining six concluding statements the evidence was strong (four statements) or limited (two statements).ConclusionsThe evidence presented and assessed in IARC Handbook volume 14 documents the effectiveness of tax and price policies in the control of tobacco use and improvement of public health.
Consistent normal interpolation
Authors: Reshetov Alexander , Soupikov Alexei , Mark William R. 
Published: December 2010

Rendering a polygonal surface with Phong normal interpolation allows shading to appear as it would for a true curved surface while maintaining the efficiency and simplicity of coarse polygonal geometry. However, this approximation fails in certain situations, especially for grazing viewing directions. Well-known problems include physically impossible reflections and implausible illumination. Some of these artifacts can be mitigated through special-case processing, although no universal or generally accepted approaches are available. In particular, all known solutions that guarantee that reflected rays will always point outward from the surface also create discontinuities in the reflection ray direction.
We present a simple modification of Phong normal interpolation that allows physically plausible reflections and creates an appearance of a smooth surface. We introduce an additional scalar parameter that characterizes the deviation between per-vertex normals and per face normals and use it to adjust linearly interpolated normals. The proposed technique eliminates perceptually objectionable artifacts caused by inconsistencies between the shading and geometric normals while retaining most of the practical advantages and simplicity of the original Phong formulation.
Genetic Variants in MicroRNA Biosynthesis Pathways and Binding Sites Modify Ovarian Cancer Risk, Survival, and Treatment Response
Authors: Liang Dong , Meyer Larissa , Chang David W. , Lin Jie , Pu Xia , Ye Yuanqing , Gu Jian , Wu Xifeng , Lu Karen 
Published: December 2010

Abstract
MicroRNAs (miRNA) play important roles in tumorigenesis. Genetic variations in miRNA processing genes and miRNA binding sites may affect the biogenesis of miRNA and the regulatory effect of miRNAs to their target genes, hence promoting tumorigenesis. This study analyzed 226 single nucleotide polymorphisms (SNP) in miRNA processing genes and miRNA binding sites in 339 ovarian cancer cases and 349 healthy controls to assess association with cancer risk, overall survival, and treatment response. Thirteen polymorphisms were found to have significant association with risk. The most significant were 2 linked SNPs (r2 = 0.99), rs2740351 and rs7813 in GEMIN4 [odds ratio (OR) = 0.71; 95% confidence interval (CI), 0.57–0.87 and OR = 0.71; 95% CI, 0.57–0.88, respectively]. Unfavorable genotype analysis showed the cumulative effect of these 13 SNPs on risk (P for trend &lt; 0.0001). Potential higher order gene–gene interactions were identified, which categorized patients into different risk groups according to their genotypic signatures. In the clinical outcome study, 24 SNPs exhibited significant association with overall survival and 17 SNPs with treatment response. Notably, patients carrying a rare homozygous genotype of rs1425486 in PDGFC had poorer overall survival [hazard ratio (HR) = 2.69; 95% CI, 1.67–4.33] and worse treatment response (OR = 3.38; 95% CI, 1.39–8.19), compared to carriers of common homozygous and heterozygous genotypes. Unfavorable genotype analyses also showed a strong gene-dosage effect with decreased survival and increased risk of treatment nonresponse in patients with greater number of unfavorable genotypes (P for trend &lt; 0.0001). Taken together, miRNA-related genetic polymorphisms may impact ovarian cancer predisposition and clinical outcome both individually and jointly. Cancer Res; 70(23); 9765–76. ©2010 AACR.
Sp100 as a Potent Tumor Suppressor: Accelerated Senescence and Rapid Malignant Transformation of Human Fibroblasts through Modulation of an Embryonic Stem Cell Program
Authors: Negorev Dmitri G. , Vladimirova Olga V. , Kossenkov Andrew V. , Nikonova Elena V. , Demarest Renee M. , Capobianco Anthony J. , Showe Michael K. , Rauscher Frank J. , Showe Louise C. , Maul Gerd G. 
Published: December 2010

Abstract
Identifying the functions of proteins, which associate with specific subnuclear structures, is critical to understanding eukaryotic nuclear dynamics. Sp100 is a prototypical protein of ND10/PML nuclear bodies, which colocalizes with Daxx and the proto-oncogenic PML. Sp100 isoforms contain SAND, PHD, Bromo, and HMG domains and are highly sumoylated, all characteristics suggestive of a role in chromatin-mediated gene regulation. A role for Sp100 in oncogenesis has not been defined previously. Using selective Sp100 isoform-knockdown approaches, we show that normal human diploid fibroblasts with reduced Sp100 levels rapidly senesce. Subsequently, small rapidly dividing Sp100 minus cells emerge from the senescing fibroblasts and are found to be highly tumorigenic in nude mice. The derivation of these tumorigenic cells from the parental fibroblasts is confirmed by microsatellite analysis. The small rapidly dividing Sp100 minus cells now also lack ND10/PML bodies, and exhibit genomic instability and p53 cytoplasmic sequestration. They have also activated MYC, RAS, and TERT pathways and express mesenchymal to epithelial transdifferentiation (MET) markers. Reintroduction of expression of only the Sp100A isoform is sufficient to maintain senescence and to inhibit emergence of the highly tumorigenic cells. Global transcriptome studies, quantitative PCR, and protein studies, as well as immunolocalization studies during the course of the transformation, reveal that a transient expression of stem cell markers precedes the malignant transformation. These results identify a role for Sp100 as a tumor suppressor in addition to its role in maintaining ND10/PML bodies and in the epigenetic regulation of gene expression. Cancer Res; 70(23); 9991–10001. ©2010 AACR.
Genome-Wide Interrogation IdentifiesYAP1Variants Associated with Survival of Small-Cell Lung Cancer Patients
Authors: Wu Chen , Xu Binghe , Yuan Peng , Miao Xiaoping , Liu Yu , Guan Yin , Yu Dianke , Xu Jian , Zhang Tongwen , Shen Hongbing , Wu Tangchun , Lin Dongxin 
Published: December 2010

AbstractAlthough most patients with small-cell lung cancer respond to chemotherapy, the survival time is highly diverse. We conducted a genome-wide analysis to examine whether germline genetic variations are prognostic factors in small-cell lung cancer patients treated with the same chemotherapy regimen. Genome-wide scan of single nucleotide polymorphisms (SNP) was performed using blood DNA to identify genotypes associated with overall survival in 245 patients treated with platinum-based chemotherapy, and the results were replicated in another independent set of 305 patients. Associations were estimated by Cox models and function of the variants was examined by biochemical assays. We found that rs1820453 T&gt;G SNP within the promoter region of YAP1 on chromosome 11q22 and rs716274 A&gt;G SNP in the region of downstream of DYNC2H1 on chromosome 11q22.3 are associated with small-cell lung cancer survival. In pooled analysis of 2 independent cohorts, the adjusted hazard ratio for patients with the rs1820453 TG or GG genotype was 1.49 (95% CI, 1.19–1.85; P = 0.0004) and 1.65 (95% CI, 1.36–2.01; P = 4.76 × 10−7), respectively, compared with the TT genotype; and for patients with the rs716274 AG or GG genotype was 1.83 (95% CI, 1.47–2.29; P = 8.74 × 10−8) and 2.96 (95% CI, 1.90–4.62; P = 1.59 × 10−6), respectively, compared with the AA genotype. Functional analysis showed that the rs1820453 T&gt;G change creates a transcriptional factor binding site and results in downregulation of YAP1 expression. These results suggest that YAP1 may play an important role in prognosis of small-cell lung cancer patients treated with platinum-based chemotherapy. Cancer Res; 70(23); 9721–9. ©2010 AACR.
MicroRNA miR-183 Functions as an Oncogene by Targeting the Transcription FactorEGR1and Promoting Tumor Cell Migration
Authors: Sarver Aaron L. , Li Lihua , Subramanian Subbaya 
Published: December 2010

AbstractThe transcription factor EGR1 is a tumor suppressor gene that is downregulated in many cancer types. Clinically, loss of EGR1 translates to increased tumor transformation and subsequent patient morbidity and mortality. In synovial sarcoma, the SS18-SSX fusion protein represses EGR1 expression through a direct association with the EGR1 promoter. However, the mechanism through which EGR1 becomes downregulated in other tumor types is unclear. Here, we report that EGR1 is regulated by microRNA (miR)-183 in multiple tumor types including synovial sarcoma, rhabdomyosarcoma (RMS), and colon cancer. Using an integrative network analysis, we identified that miR-183 is significantly overexpressed in these tumor types as well as in corresponding tumor cell lines. Bioinformatic analyses suggested that miR-183 could target EGR1 mRNA and this specific interaction was validated in vitro. miR-183 knockdown in synovial sarcoma, RMS, and colon cancer cell lines revealed deregulation of a miRNA network composed of miR-183–EGR1–PTEN in these tumors. Integrated miRNA- and mRNA-based genomic analyses indicated that miR-183 is an important contributor to cell migration in these tumor types and this result was functionally validated to be occurring via an EGR1-based mechanism. In conclusion, our findings have significant implications in the mechanisms underlying EGR1 regulation in cancers. miR-183 has a potential oncogenic role through the regulation of 2 tumor suppressor genes, EGR1 and PTEN, and the deregulation of this fundamental miRNA regulatory network may be central to many tumor types. Cancer Res; 70(23); 9570–80. ©2010 AACR.
Phase 1 Study of Valproic Acid in Pediatric Patients with Refractory Solid or CNS Tumors: A Children's Oncology Group Report
Authors: Su Jack M. , Li Xiao-Nan , Thompson Patrick , Ou Ching-Nan , Ingle Ashish M. , Russell Heidi , Lau Ching C. , Adamson Peter C. , Blaney Susan M. 
Published: November 2010

Abstract
Purpose: The primary purpose of this trial was to define and describe the toxicities of oral valproic acid (VPA) at doses required to maintain trough concentrations of 100 to 150 mcg/mL or 150 to 200 mcg/mL in children with refractory solid or central nervous system (CNS) tumors. Secondary objectives included assessment of free and total VPA pharmacokinetics (PKs) and histone acetylation in peripheral blood mononuclear cells (PBMC) at steady state.
Patients and Methods: Oral VPA, initially administered twice daily and subsequently three times daily, was continued without interruption to maintain trough concentrations of 100 to 150 mcg/mL. First-dose and steady-state PKs were studied. Histone H3 and H4 acetylation in PBMCs was evaluated using an ELISA technique.
Results: Twenty-six children, sixteen of whom were evaluable for toxicity, were enrolled. Dose-limiting somnolence and intratumoral hemorrhage were associated with VPA troughs of 100 to 150 mcg/mL. Therefore, the final cohort of six children received VPA to maintain troughs of 75 to 100 mcg/mL and did not experience any dose-limiting toxicity. First-dose and steady-state VPA PK parameters were similar to values previously reported in children with seizures. Increased PBMC histone acetylation was documented in 50% of patients studied. One confirmed partial response (glioblastoma multiforme) and one minor response (brainstem glioma) were observed.
Conclusions: VPA administered three times daily to maintain trough concentrations of 75 to 100 mcg/mL was well tolerated in children with refractory solid or CNS tumors. Histone hyperacetylation in PBMCs was observed in half of the patients at steady state. Future trials combining VPA with chemotherapy and/or radiation therapy should be considered, especially for CNS tumors. Clin Cancer Res; 17(3); 589–97. ©2010 AACR.
Impact of Global Ocean Surface Warming on Seasonal-to-Interannual Climate Prediction
Authors: Luo Jing-Jia , Behera Swadhin K. , Masumoto Yukio , Yamagata Toshio 
Published: November 2010

Abstract
Surface air temperature (SAT) over the globe, particularly the Northern Hemisphere continents, has rapidly risen over the last 2–3 decades, leading to an abrupt shift toward a warmer climate state after 1997/98. Whether the terrestrial warming might be caused by local response to increasing greenhouse gas (GHG) concentrations or by sea surface temperature (SST) rise is recently in dispute. The SST warming itself may be driven by both the increasing GHG forcing and slowly varying natural processes. Besides, whether the recent global warming might affect seasonal-to-interannual climate predictability is an important issue to be explored. Based on the Japan Agency for Marine-Earth Science and Technology (JAMSTEC) climate prediction system in which only observed SSTs are assimilated for coupled model initialization, the present study shows that the historical SST rise plays a key role in driving the intensified terrestrial warming over the globe. The SST warming trend, while negligible for short lead predictions, has substantial impact on the climate predictability at long lead times (&gt;1 yr) particularly in the extratropics. The tropical climate predictability, however, is little influenced by global warming. Given a perfect warming trend and/or a perfect model, global SAT and precipitation could be predicted beyond two years in advance with an anomaly correlation skill above ∼0.6.
Without assimilating ocean subsurface observations, model initial conditions show a strong spurious cooling drift of subsurface temperature; this is caused by large negative surface heat flux damping arising from the SST-nudging initialization. The spurious subsurface cooling drift acts to weaken the initial SST warming trend during model forecasts, leading to even negative trends of global SAT and precipitation at long lead times and hence deteriorating the global climate predictability. Concerning the important influence of the subsurface temperature on the global SAT trend, future efforts are required to develop a good scheme for assimilating subsurface information particularly in the extratropical oceans.
Water Storage, Net Precipitation, and Evapotranspiration in the Mackenzie River Basin from October 2002 to September 2009 Inferred from GRACE Satellite Gravity Data
Authors: Morrow E. , Mitrovica J. X. , Fotopoulos G. 
Published: November 2010

Abstract
Gravity Recovery and Climate Experiment (GRACE) satellite gravity data are used to determine the variability of terrestrial water storage within the Mackenzie River basin from October 2002 to September 2009. During that period, it is estimated that there is no significant (7 yr) linear trend in the water storage after having accounted for postglacial rebound using the ICE-5G (VM2) ice sheet and Earth viscosity model. Errors in this model may alter this conclusion. The GRACE gravity data are also combined with precipitation and river discharge datasets to estimate trends in net precipitation and evapotranspiration in the basin. Net precipitation is seen to have a significant trend with a corresponding increase in river discharge. Evapotranspiration was found to be constant over the study period.
The tumor suppressor gene WWOX links the canonical and noncanonical NF-κB pathways in HTLV-I Tax-mediated tumorigenesis
Authors: Fu Jing , Qu Zhaoxia , Yan Pengrong , Ishikawa Chie , Aqeilan Rami I. , Rabson Arnold B. , Xiao Gutian 
Published: November 2010

Abstract
Both the canonical and noncanonical nuclear factor κB (NF-κB) pathways have been linked to tumorigenesis. However, it remains unknown whether and how the 2 signaling pathways cooperate during tumorigenesis. We report that inhibition of the noncanonical NF-κB pathway significantly delays tumorigenesis mediated by the viral oncoprotein Tax. One function of noncanonical NF-κB activation was to repress expression of the WWOX tumor suppressor gene. Notably, WWOX specifically inhibited Tax-induced activation of the canonical, but not the noncanonical NF-κB pathway. Mechanistic studies indicated that WWOX blocked Tax-induced inhibitors of κB kinaseα (IKKα) recruitment to RelA and subsequent RelA phosphorylation at S536. In contrast, WWOX Y33R, a mutant unable to block the IKKα recruitment and RelA phosphorylation, lost the ability to inhibit Tax-mediated tumorigenesis. These data provide one important mechanism by which Tax coordinates the 2 NF-κB pathways for tumorigenesis. These data also suggest a novel role of WWOX in NF-κB regulation and viral tumorigenesis.
CCL3 (MIP-1α) plasma levels and the risk for disease progression in chronic lymphocytic leukemia
Authors: Sivina Mariela , Hartmann Elena , Kipps Thomas J. , Rassenti Laura , Krupnik Diana , Lerner Susan , LaPushin Ruth , Xiao Lianchun , Huang Xuelin , Werner Lillian , Neuberg Donna , Kantarjian Hagop , O'Brien Susan , Wierda William G. , Keating Michael J. , Rosenwald Andreas , Burger Jan A. 
Published: November 2010

AbstractB-cell receptor (BCR) signaling has been inferred as an important mechanism for disease progression in chronic lymphocytic leukemia (CLL) and other B-cell malignancies. In response to BCR activation, CLL cells secrete the chemokine CCL3, which fosters interactions between CLL cells and the leukemia microenvironment. CCL3 secretion correlates with expression of the 70-kDa ζ-associated protein (ZAP-70) and responsiveness of the CLL clone to BCR stimulation. Here, we measured CCL3 plasma levels by enzyme-linked immunosorbent assay (ELISA) in 351 CLL patients and examined CCL3 levels for associations with established prognostic markers and time from diagnosis to initial therapy. We found that CCL3 plasma concentrations were strongly associated with established prognostic markers. In a Cox proportional hazards regression model, CCL3 as well as established prognostic markers (immunoglobulin heavy chain variable-region mutation status, CD38 or ZAP-70 cytogenetics, clinical stage) were significantly associated with time to treatment. Multivariable analysis revealed that CCL3 (hazard ratio [HR] = 2.33, P < .0001), advanced clinical stage (HR = 2.75, P = .0025), poor risk cytogenetics (del 17p, HR = 2.38; del11q, HR = 2.36, P = .001), and CD38 expression (HR = 1.43, P = .023) were independent prognostic markers. Collectively, CCL3 is a novel, robust, and independent prognostic marker in CLL that can easily and reliably be measured by ELISA. CCL3 therefore should become useful for risk assessment in patients with CLL.
Efficacy of L-asparaginase with methotrexate and dexamethasone (AspaMetDex regimen) in patients with refractory or relapsing extranodal NK/T-cell lymphoma, a phase 2 study
Authors: Jaccard Arnaud , Gachard Nathalie , Marin Benoit , Rogez Sylvie , Audrain Marie , Suarez Felipe , Tilly Hervé , Morschhauser Franck , Thieblemont Catherine , Ysebaert Loic , Devidas Alain , Petit Barbara , de Leval Laurence , Gaulard Philippe , Feuillard Jean , Bordessoule Dominique , Hermine Olivier ,   for the GELA and GOELAMS Intergroup
Published: December 2010

Abstract
Extranodal NK/T-cell lymphoma, nasal type, is a rare and highly aggressive disease with a grim prognosis. No therapeutic strategy is currently identified in relapsing patients. We report the results of a French prospective phase II trial of an L-asparaginase-containing regimen in 19 patients with relapsed or refractory disease treated in 13 centers. Eleven patients were in relapse and 8 patients were refractory to their first line of treatment. L-Asparaginase–based treatment yielded objective responses in 14 of the 18 evaluable patients after 3 cycles. Eleven patients entered complete remission (61%), and only 4 of them relapsed. The median overall survival time was 1 year, with a median response duration of 12 months. The main adverse events were hepatitis, cytopenia, and allergy. The absence of antiasparaginase antibodies and the disappearance of Epstein-Barr virus serum DNA were significantly associated with a better outcome. These data confirm the excellent activity of L-asparaginase–containing regimens in extranodal NK/T-cell lymphoma. L-Asparaginase–based treatment should thus be considered for salvage therapy, especially in patients with disseminated disease. First-line L-asparaginase combination therapy for extranodal NK/T-cell lymphoma warrants evaluation in prospective trials. This trial is registered at www.clinicaltrials.gov as #NCT00283985.
Chromosome 4q31 locus in COPD is also associated with lung cancer
Authors: Young R.P. , Whittington C.F. , Hopkins R.J. , Hay B.A. , Epton M.J. , Black P.N. , Gamble G.D. 
Published: December 2010

Chronic obstructive pulmonary disease (COPD) is the single greatest risk factor for lung cancer in smokers and is found in 50–90% of lung cancer cases. The link between COPD and lung cancer may stem in part from the matrix remodelling and repair processes underlying COPD, and the development of epithelial–mesenchymal transition (EMT) that underlies lung carcinogenesis. The Hedgehog-interacting protein (HHIP), which mediates the epithelial response (EMT) to smoking, has been implicated in COPD and lung cancer. Recent genome-wide and candidate gene studies of COPD implicate genetic variants on the chromosomal 4q31 (HHIP/glycophorin A (GYPA)) locus.In a case–control study of smokers with normal lung function, COPD and lung cancer (subphenotyped for COPD), we show the GG genotype of the rs 1489759HHIPsingle-nucleotide polymorphism (SNP) and the CC genotype of the rs 2202507 GYPA SNP confers a “protective” effect on COPD (OR 0.59, p = 0.006 forHHIPand OR = 0.65, p = 0.006 forGYPA) and lung cancer (OR = 0.70 (p = 0.05) forHHIPand OR 0.70 (p = 0.02) forGYPA).This study suggests that, in smokers, genetic variants of the 4q31 locus conferring a protective effect for COPD are also protective in lung cancer. We conclude that genetic susceptibility to lung cancer includes COPD-related gene variants.