bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination immunotherapy using adoptive T-cell transfer and tumor antigen vaccination on the basis of hTERT and survivin after ASCT for myeloma
Authors: Rapoport Aaron P. , Aqui Nicole A. , Stadtmauer Edward A. , Vogl Dan T. , Fang Hong-Bin , Cai Ling , Janofsky Stephen , Chew Anne , Storek Jan , Akpek Gorgun , Badros Ashraf , Yanovich Saul , Tan Ming T. , Veloso Elizabeth , Pasetti Marcela F. , Cross Alan , Philip Sunita , Murphy Heather , Bhagat Rita , Zheng Zhaohui , Milliron Todd , Cotte Julio , Cannon Andrea , Levine Bruce L. , Vonderheide Robert H. , June Carl H. 
Published: October 2010

AbstractIn a phase 1/2 two-arm trial, 54 patients with myeloma received autografts followed by ex vivo anti-CD3/anti-CD28 costimulated autologous T cells at day 2 after transplantation. Study patients positive for human leukocyte antigen A2 (arm A, n = 28) also received pneumococcal conjugate vaccine immunizations before and after transplantation and a multipeptide tumor antigen vaccine derived from the human telomerase reverse transcriptase and the antiapoptotic protein survivin. Patients negative for human leukocyte antigen A2 (arm B, n = 26) received the pneumococcal conjugate vaccine only. Patients exhibited robust T-cell recoveries by day 14 with supraphysiologic T-cell counts accompanied by a sustained reduction in regulatory T cells. The median event-free survival (EFS) for all patients is 20 months (95% confidence interval, 14.6-24.7 months); the projected 3-year overall survival is 83%. A subset of patients in arm A (36%) developed immune responses to the tumor antigen vaccine by tetramer assays, but this cohort did not exhibit better EFS. Higher posttransplantation CD4+ T-cell counts and a lower percentage of FOXP3+ T cells were associated with improved EFS. Patients exhibited accelerated polyclonal immunoglobulin recovery compared with patients without T-cell transfers. Adoptive transfer of tumor antigen vaccine-primed and costimulated T cells leads to augmented and accelerated cellular and humoral immune reconstitution, including antitumor immunity, after autologous stem cell transplantation for myeloma. This study was registered at www.clinicaltrials.gov as NCT00499577.
Acute myeloid leukemia with mutated nucleophosmin (NPM1): is it a distinct entity?
Authors: Falini Brunangelo , Martelli Maria Paola , Bolli Niccolò , Sportoletti Paolo , Liso Arcangelo , Tiacci Enrico , Haferlach Torsten 
Published: October 2010

Abstract
After the discovery of NPM1-mutated acute myeloid leukemia (AML) in 2005 and its subsequent inclusion as a provisional entity in the 2008 World Health Organization classification of myeloid neoplasms, several controversial issues remained to be clarified. It was unclear whether the NPM1 mutation was a primary genetic lesion and whether additional chromosomal aberrations and multilineage dysplasia had any impact on the biologic and prognostic features of NPM1-mutated AML. Moreover, it was uncertain how to classify AML patients who were double-mutated for NPM1 and CEBPA. Recent studies have shown that: (1) the NPM1 mutant perturbs hemopoiesis in experimental models; (2) leukemic stem cells from NPM1-mutated AML patients carry the mutation; and (3) the NPM1 mutation is usually mutually exclusive of biallelic CEPBA mutations. Moreover, the biologic and clinical features of NPM1-mutated AML do not seem to be significantly influenced by concomitant chromosomal aberrations or multilineage dysplasia. Altogether, these pieces of evidence point to NPM1-mutated AML as a founder genetic event that defines a distinct leukemia entity accounting for approximately one-third of all AML.
Increased epithelial permeability in pulmonary fibrosis in relation to disease progression
Authors: Goh N.S.L. , Desai S.R. , Anagnostopoulos C. , Hansell D.M. , Hoyles R.K. , Sato H. , Denton C.P. , Black C.M. , du Bois R.M. , Wells A.U. 
Published: October 2010

Epithelial injury contributes to pathogenesis in idiopathic pulmonary fibrosis (IPF) but its role in the interstitial lung disease (ILD) of systemic sclerosis (SSc) is uncertain. We quantified the prognostic significance of inhaled technetium-99m (99mTc)-labelled diethylene triamine pentacetate (DTPA) pulmonary clearance, a marker of the extent of epithelial injury, in both diseases.Baseline99mTc-DTPA pulmonary clearance was evaluated retrospectively in patients with SSc-ILD (n = 168) and IPF (n = 97) against mortality and disease progression.In SSc-ILD, the rapidity of total clearance (hazard ratio (HR) 1.02, 95% CI 1.01–1.03; p = 0.001) and the presence of abnormally rapid clearance (HR 2.10; 95% CI 1.25–3.53; p = 0.005) predicted a shorter time to forced vital capcity (FVC) decline, independent of disease severity. These associations were robust in both mild and severe disease. By contrast, in IPF, delayed clearance of the slow component, an expected consequence of honeycomb change, was an independent predictor of a shorter time to FVC decline (HR 1.01, 95% CI 1.00–1.02; p<0.01).Epithelial injury should be incorporated in pathogenetic models in SSc-ILD. By contrast, outcome is not linked to the overall extent of epithelial injury in IPF, apart from abnormalities ascribable to honeycombing, suggesting that core pathogenetic events may be more spatially focal in that disease.
Exposure to combustion of solid fuel and tuberculosis: a matched case–control study
Authors: Gninafon M. , Ade G. , Aït-Khaled N. , Enarson D.A. , Chiang C-Y. 
Published: October 2010

The present study was conducted in Benin to ascertain the association between exposure to combustion of solid fuel (coal and biomass) and tuberculosis.Cases were consecutive, sputum smear-positive tuberculosis patients never previously treated for tuberculosis for as long as 1 month. Two controls were selected from the neighbourhood of each case, matched by age and sex by a predefined procedure.A total of 200 new smear-positive cases and 400 neighbourhood controls were enrolled. In univariate analysis, using solid fuel for cooking (OR 1.7, 95% CI 1.1–2.8), ever smoking (OR 5.5, 95% CI 3.1–9.8), male sex (OR 10.5, 95% CI 1.6–71.1), daily use of alcoholic beverages (OR 2.3, 95% CI 1.2–4.2) and having a family member with tuberculosis in the previous 5 yrs (OR 30.5, 95% CI 10.8–85.8) were all significantly associated with tuberculosis cases. When all significant variables were entered into a multivariate conditional logistic regression model, the association between using solid fuel for cooking and tuberculosis cases was no longer statistically significant (adjusted OR 1.4, 95% CI 0.7–2.7).In conclusion, the association between exposure to combustion of solid fuel and tuberculosis was relatively weak and not statistically significant.
Interferon-γ release assays for the diagnosis of latentMycobacterium tuberculosisinfection: a systematic review and meta-analysis
Authors: Diel R. , Goletti D. , Ferrara G. , Bothamley G. , Cirillo D. , Kampmann B. , Lange C. , Losi M. , Markova R. , Migliori G.B. , Nienhaus A. , Ruhwald M. , Wagner D. , Zellweger J.P. , Huitric E. , Sandgren A. , Manissero D. 
Published: October 2010

We conducted a systematic review and meta-analysis to compare the accuracy of the QuantiFERON-TB® Gold In-Tube (QFT-G-IT) and the T-SPOT®.TBassays with the tuberculin skin test (TST) for the diagnosis of latentMycobacterium tuberculosisinfection (LTBI).The Medline, Embase and Cochrane databases were explored for relevant articles in November 2009. Specificities, and negative (NPV) and positive (PPV) predictive values of interferon-γ release assays (IGRAs) and the TST, and the exposure gradient influences on test results among bacille Calmette–Guérin (BCG) vaccinees were evaluated.Specificity of IGRAs varied 98–100%. In immunocompetent adults, NPV for progression to tuberculosis within 2 yrs were 97.8% for T-SPOT®.TBand 99.8% for QFT-G-IT. When test performance of an immunodiagnostic test was not restricted to prior positivity of another test, progression rates to tuberculosis among IGRA-positive individuals followed for 19–24 months varied 8–15%, exceeding those reported for the TST (2–3%). In multivariate analyses, the odd ratios for TST positivity following BCG vaccination varied 3–25, whereas IGRA results remained uninfluenced and IGRA positivity was clearly associated with exposure to contagious tuberculosis cases.IGRAs may have a relative advantage over the TST in detecting LTBI and allow the exclusion ofM. tuberculosisinfection with higher reliability.
Influence of hay and animal feed exposure on respiratory status: a longitudinal study
Authors: Thaon I. , Thiebaut A. , Jochault L. , Lefebvre A. , Laplante J.J. , Dalphin J.C. 
Published: October 2010

Our aim was to study respiratory symptoms and lung function decline in farmers, with particular attention to the influence of handling hay, straw and animal feed.From a cohort recruited in 1993–1994, 219 (82.6%) dairy farmers, 130 (62.5%) nondairy agricultural workers and 99 (66.4%) controls were re-evaluated in 2006. They answered medical and occupational questionnaires, underwent spirometric tests at both evaluations and pulse oximetry in 2006.Dairy and nondairy agricultural workers showed an increased risk for usual morning phlegm (adjusted OR 4.27 (95% CI 1.41–12.95) and 3.59 (95% CI 1.16–11.10), respectively). Animal feed handling was associated with increased risks of wheezing (p = 0.01) and usual morning phlegm (p = 0.04); hay or straw handling was associated with increased risk of wheezing (p = 0.008). Adjusting for smoking, age, height, sex and altitude, dairy farmers had greater declines in forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio (p = 0.01) than controls. An increased decline in FEV1for all agricultural workers was associated with animal feed handling, both measured as a categorical (currentlyversusnever handling; p = 0.05) or quantitative value (years of exposure during the survey period; p = 0.03).Hay, straw or animal feed handling represents a risk factor of bronchial symptoms and, for animal feed only, of accelerated decline in expiratory flows.
Genetic profiling and epidermal growth factor receptor-directed therapy in nonsmall cell lung cancer
Authors: Cadranel J. , Zalcman G. , Sequist L. 
Published: October 2010

The principle of preferentially selecting patients most likely to benefit from therapy according to their genetic profile has led to substantial clinical benefit in some tumour types, and has potential to considerably refine treatment in advanced nonsmall cell lung cancer (NSCLC). Effective, reliable use of molecular biomarkers to inform clinical practice requires the standardisation of testing methods and careful assessment of biomarkers’ predictive and prognostic value.Although a number of studies have shown that patients with activating mutations in exons 18–21 of the epidermal growth factor receptor (EGFR) gene respond particularly well to gefitinib and erlotinib, a prospective, randomised study was needed to differentiate between the prognostic and predictive value ofEGFRmutations. From one such study, it appeared that mutational testing should become standard at diagnosis, at least for adenocarcinoma patients with a never or low smoking history, as clinical predictors are insufficient to optimise treatment.However, outstanding questions remain: what are the treatment options for patients with tumours resistant to erlotinib/gefitinib? What conclusions about treatment can we draw fromEGFRcopy number orKRASmutation status? What role should anti-EGFR antibodies play in NSCLC treatment, and in which patients?This review considers current evidence linking biomarker profile to efficacy of EGFR-targeted therapy in NSCLC, and clinical implications of recent findings.
Contrasting population genetic patterns within the white-throated sparrow genome (Zonotrichia albicollis)
Authors: Huynh Lynn Y , Maney Donna L , Thomas James W 
Published: October 2010

Abstract

Background
The level of nucleotide diversity observed across the genome is positively correlated with the local rate of recombination. Avian karyotypes are typified by large variation in chromosome size and the rate of recombination in birds has been shown to be negatively correlated with chromosome size. It has thus been predicted that nucleotide diversity is negatively correlated with chromosome size in aves. However, there is limited empirical evidence to support this prediction.

Results
Here we sequenced 27 autosomal and 12 sex chromosome-linked loci in the white-throated sparrow (Zonotrichia albicollis) to quantify and compare patterns of recombination, linkage disequilibrium (LD), and genetic diversity across the genome of this North American songbird. Genetic diversity on the autosomes varied up to 8-fold, with the lowest diversity observed on the macrochromosomes and the highest diversity on the microchromosomes. Genetic diversity on the sex chromosomes was reduced compared to the autosomes, the most extreme difference being a ~300-fold difference between the W chromosome and the microchromosomes. LD and population structure associated with a common inversion polymorphism (ZAL2/2m) in this species were found to be atypical compared to other macrochromosomes, and nucleotide diversity within this inversion on the two chromosome arrangements was more similar to that observed on the Z chromosome.

Conclusions
A negative correlation between nucleotide diversity and autosome size was observed in the white-throated sparrow genome, as well as low levels of diversity on the sex chromosomes comparable to those reported in other birds. The population structure and extended LD associated with the ZAL2/2m chromosomal polymorphism are exceptional compared to the rest of the white-throated sparrow genome.
Rhomboid homologs in mycobacteria: insights from phylogeny and genomic analysis
Authors: Kateete David P , Okee Moses , Katabazi Fred A , Okeng Alfred , Asiimwe Jeniffer , Boom Henry W , Eisenach Kathleen D , Joloba Moses L 
Published: October 2010

AbstractBackgroundRhomboids are ubiquitous proteins with diverse functions in all life kingdoms, and are emerging as important factors in the biology of some pathogenic apicomplexa andProvidencia stuartii. Although prokaryotic genomes contain one rhomboid, actinobacteria can have two or more copies whose sequences have not been analyzed for the presence putative rhomboid catalytic signatures. We report detailed phylogenetic and genomic analyses devoted to prokaryotic rhomboids of an important genus,Mycobacterium.ResultsMany mycobacterial genomes contained two phylogenetically distinct active rhomboids orthologous to Rv0110 (rhomboid protease 1) and Rv1337 (rhomboid protease 2) ofMycobacterium tuberculosisH37Rv, which were acquired independently. There was a genome-wide conservation and organization of the orthologs of Rv1337 arranged in proximity with glutamate racemase (mur1), while the orthologs of Rv0110 appeared evolutionary unstable and were lost inMycobacterium lepraeand theMycobacterium aviumcomplex. The orthologs of Rv0110 clustered with eukaryotic rhomboids and contained eukaryotic motifs, suggesting a possible common lineage. A novel nonsense mutation at the Trp73 codon split the rhomboid ofMycobacterium aviumsubsp.Paratuberculosisinto two hypothetical proteins (MAP2425c and MAP2426c) that are identical to MAV_1554 ofMycobacterium avium. Mycobacterial rhomboids contain putative rhomboid catalytic signatures, with the protease active site stabilized by Phenylalanine. The topology and transmembrane helices of the Rv0110 orthologs were similar to those of eukaryotic secretase rhomboids, while those of Rv1337 orthologs were unique. Transcription assays indicated that both mycobacterial rhomboids are possibly expressed.ConclusionsMycobacterial rhomboids are active rhomboid proteases with different evolutionary history. The Rv0110 (rhomboid protease 1) orthologs represent prokaryotic rhomboids whose progenitor may be the ancestors of eukaryotic rhomboids. The Rv1337 (rhomboid protease 2) orthologs appear more stable and are conserved nearly in all mycobacteria, possibly alluding to their importance in mycobacteria. MAP2425c and MAP2426c provide the first evidence for a split homologous rhomboid, contrasting whole orthologs of genetically related species. Although valuable insights to the roles of rhomboids are provided, the data herein only lays a foundation for future investigations for the roles of rhomboids in mycobacteria.
Plasma concentrations of osteopontin, but not thrombin-cleaved osteopontin, are associated with the presence and severity of nephropathy and coronary artery disease in patients with type 2 diabetes mellitus
Authors: Yan Xiaoxiang , Sano Motoaki , Lu Lin , Wang Wei , Zhang Qi , Zhang Ruiyan , Wang Lingjie , Chen Qiujing , Fukuda Keiichi , Shen Weifeng 
Published: October 2010

Abstract

Background
The aim of the present cross-sectional study was to assess possible associations between osteopontin (OPN), and thrombin-cleaved (N-half) OPN, and nephropathy and coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM).

Methods
Plasma levels of OPN, N-half OPN, and high-sensitivity C-reactive protein (hsCRP) were determined in 301 diabetic patients with (n = 226) or without (n = 75) angiographically documented CAD (luminal diameter narrowing >50%), as well as in 75 non-diabetic controls with normal angiography. The estimated glomerular filtration rate (eGFR) was calculated in all patients.

Results
Plasma levels of OPN and hsCRP were significantly higher in patients with T2DM compared with controls. In addition, there was a higher occurrence of moderate renal insufficiency and lower eGFR in patients with T2DM (all P < 0.01). T2DM patients in whom OPN levels were greater than the median value had higher serum creatinine levels, a greater prevalence of mild or moderate renal insufficiency, a higher incidence of CAD, and lower eGFR (all P < 0.05) than T2DM patients in whom OPN levels were the same as or lower than the median value. However, there were no differences in these parameters when patients were stratified according to plasma N-half OPN levels. Furthermore, there was a significant correlation between OPN, but not N-half OPN, and the severity of nephropathy and CAD in diabetes. After adjustment for potential confounders and treatments, multiple linear regression analysis demonstrated an independent association between OPN, but not N-half OPN, and eGFR. Multivariate logistic regression revealed that higher OPN levels conferred a fourfold greater risk of renal insufficiency and CAD in patients with T2DM.

Conclusions
The results of the present study demonstrate that there is an independent association between plasma levels of OPN, but not N-half OPN, and the presence and severity of nephropathy and CAD in diabetes.
Penalized likelihood and multi-objective spatial scans for the detection and inference of irregular clusters
Authors: Cançado André LF , Duarte Anderson R , Duczmal Luiz H , Ferreira Sabino J , Fonseca Carlos M , Gontijo Eliane CDM 
Published: October 2010

Abstract

Background
Irregularly shaped spatial clusters are difficult to delineate. A cluster found by an algorithm often spreads through large portions of the map, impacting its geographical meaning. Penalized likelihood methods for Kulldorff's spatial scan statistics have been used to control the excessive freedom of the shape of clusters. Penalty functions based on cluster geometry and non-connectivity have been proposed recently. Another approach involves the use of a multi-objective algorithm to maximize two objectives: the spatial scan statistics and the geometric penalty function.

Results & Discussion
We present a novel scan statistic algorithm employing a function based on the graph topology to penalize the presence of under-populated disconnection nodes in candidate clusters, the disconnection nodes cohesion function. A disconnection node is defined as a region within a cluster, such that its removal disconnects the cluster. By applying this function, the most geographically meaningful clusters are sifted through the immense set of possible irregularly shaped candidate cluster solutions. To evaluate the statistical significance of solutions for multi-objective scans, a statistical approach based on the concept of attainment function is used. In this paper we compared different penalized likelihoods employing the geometric and non-connectivity regularity functions and the novel disconnection nodes cohesion function. We also build multi-objective scans using those three functions and compare them with the previous penalized likelihood scans. An application is presented using comprehensive state-wide data for Chagas' disease in puerperal women in Minas Gerais state, Brazil.

Conclusions
We show that, compared to the other single-objective algorithms, multi-objective scans present better performance, regarding power, sensitivity and positive predicted value. The multi-objective non-connectivity scan is faster and better suited for the detection of moderately irregularly shaped clusters. The multi-objective cohesion scan is most effective for the detection of highly irregularly shaped clusters.
Cyanidin-3-Glucoside inhibits ethanol-induced invasion of breast cancer cells overexpressing ErbB2
Authors: Xu Mei , Bower Kimberly A , Wang Siying , Frank Jacqueline A , Chen Gang , Ding Min , Wang Shiow , Shi Xianglin , Ke Zunji , Luo Jia 
Published: October 2010

Abstract

Background
Ethanol is a tumor promoter. Both epidemiological and experimental studies suggest that ethanol may enhance the metastasis of breast cancer cells. We have previously demonstrated that ethanol increased the migration/invasion of breast cancer cells expressing high levels of ErbB2. Amplification of ErbB2 is found in 20-30% of breast cancer patients and is associated with poor prognosis. We sought to identify agents that can prevent or ameliorate ethanol-induced invasion of breast cancer cells. Cyanidin-3-glucoside (C3G), an anthocyanin present in many vegetables and fruits, is a potent natural antioxidant. Ethanol exposure causes the accumulation of intracellular reactive oxygen species (ROS). This study evaluated the effect of C3G on ethanol-induced breast cancer cell migration/invasion.

Results
C3G attenuated ethanol-induced migration/invasion of breast cancer cells expressing high levels of ErbB2 (BT474, MDA-MB231 and MCF7ErbB2) in a concentration dependent manner. C3G decreased ethanol-mediated cell adhesion to the extracellular matrix (ECM) as well as the amount of focal adhesions and the formation of lamellipodial protrusion. It inhibited ethanol-stimulated phosphorylation of ErbB2, cSrc, FAK and p130Cas, as well as interactions among these proteins. C3G abolished ethanol-mediated p130Cas/JNK interaction.

Conclusions
C3G blocks ethanol-induced activation of the ErbB2/cSrc/FAK pathway which is necessary for cell migration/invasion. C3G may be beneficial in preventing/reducing ethanol-induced breast cancer metastasis.