bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioterrorism: Lessons Learned Since the Anthrax Mailings
Authors: Imperiale Michael J. , Casadevall Arturo 
Published: October 2011

ABSTRACT

In the fall of 2001,
Bacillus anthracis
spores were spread through letters mailed in the United States. Twenty-two people are known to have been infected, and five of these individuals died. Together with the September 11 attacks, this resulted in a reevaluation of the risks and benefits of life science research with the potential for misuse. In this editorial, we review some of the results of these discussions and their implications for the future.
A decompositional analysis of the relative contribution of age, sex and methods of suicide to the changing patterns of suicide in Taipei City, 2004–2006
Authors: Yip Paul S F , Caine Eric D , Kwok Raymond C L , Chen Ying-Yeh 
Published: October 2011

BackgroundTaipei has seen a substantial increase in suicide rates during the past decade, with a significant rise between 2004 and 2006, the time of this study period.MethodsA decompositional analytic method was used to quantify the relative contributions of age, sex and case fatality of methods to attempts and suicides.ResultsFrom 2004 to 2006, the rate of fatal and non-fatal suicide attempts combined for population aged 15 years or above in Taipei increased by 37.3%, while the suicide rate increased by 29.2%. Three factors in these analyses contributed to the increase in suicide rates: (1) an increase in number of attempts, (2) a greater proportion of men among fatal and non-fatal attempts and (3) an increase in the use of a lethal method—burning of charcoal to produce carbon monoxide. The authors estimated that 74.5% and 25.6% among men and women, respectively, of the overall increased suicide mortality were attributable to increased ‘charcoal burning suicides.’ConclusionsThe rise in suicide rate reflected an increase in attempts and an influx of working-age men joining the pool of people attempting suicide. The much larger size of the attempter pool had the effect of reducing the case fatality even as the suicide rate climbed. The increase in the number of suicide attempts and the rise in the suicide rate were age-, sex-, and method-specific. These results strongly support the concept that reducing the total number of attempts is a central element to curbing suicides.
p53-Responsive miR-194 Inhibits Thrombospondin-1 and Promotes Angiogenesis in Colon Cancers
Authors: Sundaram Prema , Hultine Stacy , Smith Lauren M. , Dews Michael , Fox Jamie L. , Biyashev Dauren , Schelter Janell M. , Huang Qihong , Cleary Michele A. , Volpert Olga V. , Thomas-Tikhonenko Andrei 
Published: October 2011

Abstract
Thrombospondin-1 (TSP-1) is an endogenous inhibitor of angiogenesis encoded by the THBS1 gene, whose promoter is activated by p53. In advanced colorectal cancers (CRC), its expression is sustained or even slightly increased despite frequent loss of p53. Here, we determined that in HCT116 CRC cells, p53 activates the THBS1 primary transcript, but fails to boost THBS1 mRNA or protein levels, implying posttranscriptional regulation by microRNAs (miRNA). In a global miRNA gain-of-function screen done in the Dicer-deficient HCT116 variant, several miRNAs negatively regulated THBS1 mRNA and protein levels, one of them being miR-194. Notably, in agreement with published data, p53 upregulated miR-194 expression in THBS1 retrovirus-transduced HCT116 cells, leading to decreased TSP-1 levels. This negative effect was mediated by a single miR-194 complementary site in the THBS1 3′-untranslated region, and its elimination resulted in TSP-1 reactivation, impaired angiogenesis in Matrigel plugs, and reduced growth of HCT116 xenografts. Conversely, transient overexpression of miR-194 in HCT116/THBS1 cells boosted Matrigel angiogenesis, and its stable overexpression in Ras-induced murine colon carcinomas increased microvascular densities and vessel sizes. Although the overall contribution of miR-194 to neoplastic growth is context dependent, p53-induced activation of this GI tract–specific miRNA during ischemia could promote angiogenesis and facilitate tissue repair. Cancer Res; 71(24); 7490–501. ©2011 AACR.
Dendritic Cell Internalization of α-Galactosylceramide from CD8 T Cells Induces Potent Antitumor CD8 T-cell Responses
Authors: Choi Dong Hoon , Kim Kwang Soon , Yang Se Hwan , Chung Doo Hyun , Song Boyeong , Sprent Jonathan , Cho Jae Ho , Sung Young Chul 
Published: October 2011

AbstractDendritic cells (DC) present α-galactosylceramide (αGalCer) to invariant T-cell receptor–expressing natural killer T cells (iNKT) activating these cells to secrete a variety of cytokines, which in turn results in DC maturation and activation of other cell types, including NK cells, B cells, and conventional T cells. In this study, we showed that αGalCer-pulsing of antigen-activated CD8 T cells before adoptive transfer to tumor-bearing mice caused a marked increase in donor T-cell proliferation, precursor frequency, and cytotoxic lymphocyte activity. This effect was interleukin (IL)-2 dependent and involved both natural killer T cells (NKT) and DCs, as mice lacking IL-2, NKTs, and DCs lacked any enhanced response to adoptively transferred αGalCer-loaded CD8 T cells. iNKT activation was mediated by transfer of αGalCer from the cell membrane of the donor CD8 T cells onto the αGalCer receptor CD1d which is present on host DCs. αGalCer transfer was increased by prior activation of the donor CD8 T cells and required AP-2–mediated endocytosis by host DCs. In addition, host iNKT cell activation led to strong IL-2 synthesis, thereby increasing expansion and differentiation of donor CD8 T cells. Transfer of these cells led to improved therapeutic efficacy against established solid tumors in mice. Thus, our findings illustrate how αGalCer loading of CD8 T cells after antigen activation in vitro may leverage the therapeutic potential of adoptive T-cell therapies. Cancer Res; 71(24); 7442–51. ©2011 AACR.
Dasatinib as a Single Agent in Triple-Negative Breast Cancer: Results of an Open-Label Phase 2 Study
Authors: Finn Richard S. , Bengala Carmelo , Ibrahim Nuhad , Roché Henri , Sparano Joseph , Strauss Lewis C. , Fairchild Justin , Sy Oumar , Goldstein Lori J. 
Published: October 2011

Abstract
Purpose: Dasatinib is a potent, oral SRC-family kinase inhibitor with preclinical antiproliferative, antimetastatic, and antiosteoclastic activity suggesting dasatinib sensitivity in triple-negative, or basal-like, breast cancer cell lines. This phase 2 trial assessed efficacy and safety of single-agent dasatinib in patients with advanced triple-negative breast cancer (TNBC).
Experimental Design: Female patients with measurable, locally advanced or metastatic TNBC initially received dasatinib 100 mg twice daily (BID); to improve tolerability, the protocol was amended and subsequent patients received 70 mg BID. Primary endpoint was Response Evaluation Criteria in Solid Tumors–defined objective response rate (ORR); secondary endpoints included progression-free survival (PFS), disease control rate (DCR), safety, and limited pharmacokinetics.
Results: Of the 44 treated patients, 43 were response evaluable. ORR was 4.7%: two patients had confirmed partial responses lasting 14 and 58 weeks, respectively. Of 11 patients with stable disease, two continued for more than 16 weeks, thus protocol-defined DCR was 9.3%. Median PFS was 8.3 weeks (95% CI: 7.3–15.3). Five patients discontinued before first tumor assessment. No grade 4 adverse events (AE) were reported; grade 3 AEs occurring in more than 5% of patients were fatigue (9.1%), diarrhea, pleural effusion, and dyspnea (all 6.8%). Laboratory abnormalities were uncommon. Dasatinib at 100 mg BID was not well tolerated; rates of treatment interruption, dose reduction, and serious AEs were lower with dasatinib 70 mg BID.
Conclusions: Single-agent dasatinib has limited activity in unselected patients with TNBC. Dasatinib 70 mg BID was better tolerated than 100 mg BID. Future studies will investigate dasatinib in other breast cancer settings, including chemotherapy combinations. Clin Cancer Res; 17(21); 6905–13. ©2011 AACR.
Identification of Docetaxel Resistance Genes in Castration-Resistant Prostate Cancer
Authors: Marín-Aguilera Mercedes , Codony-Servat Jordi , Kalko Susana G. , Fernández Pedro L. , Bermudo Raquel , Buxo Elvira , Ribal María José , Gascón Pedro , Mellado Begoña 
Published: October 2011

AbstractDocetaxel-based chemotherapy is the standard first-line therapy in metastatic castration-resistant prostate cancer (CRPC). However, most patients eventually develop resistance to this treatment. In this study, we aimed to identify key molecular genes and networks associated with docetaxel resistance in two models of docetaxel-resistant CRPC cell lines and to test for the most differentially expressed genes in tumor samples from patients with CRPC. DU-145 and PC-3 cells were converted to docetaxel-resistant cells, DU-145R and PC-3R, respectively. Whole-genome arrays were used to compare global gene expression between these four cell lines. Results showed differential expression of 243 genes (P &lt; 0.05, Bonferroni-adjusted P values and log ratio &gt; 1.2) that were common to DU-145R and PC-3R cells. These genes were involved in cell processes like growth, development, death, proliferation, movement, and gene expression. Genes and networks commonly deregulated in both DU-145R and PC-3R cells were studied by Ingenuity Pathways Analysis. Exposing parental cells to TGFB1 increased their survival in the presence of docetaxel, suggesting a role of the TGF-β superfamily in conferring drug resistance. Changes in expression of 18 selected genes were validated by real-time quantitative reverse transcriptase PCR in all four cell lines and tested in a set of 11 FFPE and five optimal cutting temperature tumor samples. Analysis in patients showed a noteworthy downexpression of CDH1 and IFIH1, among others, in docetaxel-resistant tumors. This exploratory analysis provides information about potential gene and network involvement in docetaxel resistance in CRPC. Further clinical validation of these results is needed to develop targeted therapies in patients with CRPC that can circumvent such resistance to treatment. Mol Cancer Ther; 11(2); 329–39. ©2011 AACR.
Nicotine Does Not Enhance Tumorigenesis in MutantK-Ras–Driven Mouse Models of Lung Cancer
Authors: Maier Colleen R. , Hollander M. Christine , Hobbs Evthokia A. , Dogan Irem , Linnoila R. Ilona , Dennis Phillip A. 
Published: October 2011

AbstractSmoking is the leading cause of preventable cancer deaths in the United States. Nicotine replacement therapies (NRT) have been developed to aid in smoking cessation, which decreases lung cancer incidence. However, the safety of NRT is controversial because numerous preclinical studies have shown that nicotine enhances tumor cell growth in vitro and in vivo. We modeled NRT in mice to determine the effects of physiologic levels of nicotine on lung tumor formation, tumor growth, or metastasis. Nicotine administered in drinking water did not enhance lung tumorigenesis after treatment with the tobacco carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Tumors that develop in this model have mutations in K-ras, which is commonly observed in smoking-related, human lung adenocarcinomas. In a transgenic model of mutant K-ras–driven lung cancer, nicotine did not increase tumor number or size and did not affect overall survival. Likewise, in a syngeneic model using lung cancer cell lines derived from NNK-treated mice, oral nicotine did not enhance tumor growth or metastasis. These data show that nicotine does not enhance lung tumorigenesis when given to achieve levels comparable with those of NRT, suggesting that nicotine has a dose threshold, below which it has no appreciable effect. These studies are consistent with epidemiologic data showing that NRT does not enhance lung cancer risk in former smokers. Cancer Prev Res; 4(11); 1743–51. ©2011 AACR.
Electrocardiographic Characteristics and
SCN5A
Mutations in Idiopathic Ventricular Fibrillation Associated With Early Repolarization
Authors: Watanabe Hiroshi , Nogami Akihiko , Ohkubo Kimie , Kawata Hiro , Hayashi Yuka , Ishikawa Taisuke , Makiyama Takeru , Nagao Satomi , Yagihara Nobue , Takehara Naofumi , Kawamura Yuichiro , Sato Akinori , Okamura Kazuki , Hosaka Yukio , Sato Masahito , Fukae Satoki , Chinushi Masaomi , Oda Hirotaka , Okabe Masaaki , Kimura Akinori , Maemura Koji , Watanabe Ichiro , Kamakura Shiro , Horie Minoru , Aizawa Yoshifusa , Shimizu Wataru , Makita Naomasa 
Published: October 2011

Background—
Recently, we and others reported that early repolarization (J wave) is associated with idiopathic ventricular fibrillation. However, its clinical and genetic characteristics are unclear.

Methods and Results—

This study included 50 patients (44 men; age, 45±17 years) with idiopathic ventricular fibrillation associated with early repolarization, and 250 age- and sex-matched healthy controls. All of the patients had experienced arrhythmia events, and 8 (16%) had a family history of sudden death. Ventricular fibrillation was inducible by programmed electric stimulation in 15 of 29 patients (52%). The heart rate was slower and the PR interval and QRS duration were longer in patients with idiopathic ventricular fibrillation than in controls. We identified nonsynonymous variants in
SCN5A
(resulting in A226D, L846R, and R367H) in 3 unrelated patients. These variants occur at residues that are highly conserved across mammals. His-ventricular interval was prolonged in all of the patients carrying an
SCN5A
mutation. Sodium channel blocker challenge resulted in an augmentation of early repolarization or development of ventricular fibrillation in all of 3 patients, but none was diagnosed with Brugada syndrome. In heterologous expression studies, all of the mutant channels failed to generate any currents. Immunostaining revealed a trafficking defect in A226D channels and normal trafficking in R367H and L846R channels.

Conclusions—

We found reductions in heart rate and cardiac conduction and loss-of-function mutations in
SCN5A
in patients with idiopathic ventricular fibrillation associated with early repolarization. These findings support the hypothesis that decreased sodium current enhances ventricular fibrillation susceptibility.
SYNTAX Score Reproducibility and Variability Between Interventional Cardiologists, Core Laboratory Technicians, and Quantitative Coronary Measurements
Authors: Généreux Philippe , Palmerini Tullio , Caixeta Adriano , Cristea Ecaterina , Mehran Roxana , Sanchez Raquel , Lazar Dana , Jankovic Ivana , Corral Maria D. , Dressler Ovidiu , Fahy Martin P. , Parise Helen , Lansky Alexandra J. , Stone Gregg W. 
Published: October 2011

Background—
In the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) trial, the SYNTAX score was useful in risk stratifying patients with complex coronary artery disease. The reproducibility of this score may affect its clinical utility. We therefore assessed SYNTAX score interobserver and intraobserver variability among a group of interventional cardiologists (ICs) and an experienced group of angiographic core laboratory (ACL) technicians.

Methods and Results—

After basic training from the SYNTAX score website, 3 ICs and 4 ACL technicians, each working independently, assessed the SYNTAX score of 30 multivessel disease angiograms. The ICs then underwent an intensive training session with ACL technicians, after which the SYNTAX score from 50 additional angiograms were assessed independently by both groups. Interobserver Fleiss κ statistic values were determined. A third assessment was performed using quantitative coronary angiography (QCA). The ACL technician interobserver strength of agreement from both periods was substantial or greater (k=0.82; 95% CI [0.72, 1.00] and 0.84 [0.76, 1.00]) and not different than QCA. The IC interobserver agreement was initially estimated to be at least slight (k=0.33 [0.18, 0.44]), improving to substantial or greater after advanced training (k=0.76 [0.64, 1.00]). Despite advanced training, ICs underscored the number of lesions, bifurcations, and small-vessel disease (
P
<0.001), resulting in a lower score than ACL technicians (mean difference=7.5,
P
<0.001).

Conclusions—
Highly reproducible SYNTAX score measurements were quickly achieved by experienced ACL technicians. In contrast, agreement among ICs after the basic tutorial was initially poor but improved considerably after further training with the ACL, although differences still remained in interpretation of several lesion types. These findings have important implications for adoption of SYNTAX score methodology in routine practice and future clinical trials.
Thermal and mechanical properties of ultrasonically treated wool
Authors: Li Qing , Hurren Christopher J , Yu Hengxing , Ding Cailing , Wang Xungai 
Published: October 2011

Wool fabrics, ultrasonically treated in various chemical conditions and for different time durations, were analysed for thermal properties by thermo-gravimetric analysis and differential scanning calorimeter, in comparison with the untreated fabric. Fabric mechanical properties, such as bending and tensile performance, and changes in fibre morphology were also evaluated before and after ultrasonic treatment. It is found that wool treated with ultrasonics at the appropriate time, has less mass loss and a higher thermal degradation temperature than that without ultrasonic treatment or with prolonged ultrasonic treatment. Resistance to thermal degradation is reduced when wool is ultrasonically treated in the presence of alkali. Differential scanning calorimeter analysis shows that while ultrasonic treatment has little effect on fibre crystallinity, an appropriate treatment can provide wool with increased water absorption. Ultrasonic treatment stiffens wool fabric to some extent when the treatment time is prolonged. The addition of detergent alone to the ultrasonic bath has little effect on fabric tensile behaviour, whereas a treatment with both detergent and alkali produces severe fibre damage and significant loss of fabric tensile strength.
Hair nicotine/cotinine concentrations as a method of monitoring exposure to tobacco smoke among infants and adults
Authors: Tzatzarakis MN , Vardavas CI , Terzi I , Kavalakis M , Kokkinakis M , Liesivuori J , Tsatsakis AM 
Published: October 2011

In this pilot study, we examined the validity and usefulness of hair nicotine–cotinine evaluation as a biomarker of monitoring exposure to tobacco. Head hair samples were collected from 22 infants (<2 years of age) and 44 adults with different exposures to tobacco (through either active or passive smoking) and analyzed by liquid chromatography–mass spectrometry (LC-MS) for nicotine and cotinine. Hair samples were divided into three groups, infants, passive smoker adults and active smoker adults, and into eight subgroups according to the degree of exposure. The limit of quantification (LOQ) was 0.1 ng/mg for nicotine and 0.05 ng/mg for cotinine. Mean recovery was 69.15% for nicotine and 72.08% for cotinine. The within- and between-day precision for cotinine and nicotine was calculated at different concentrations. Moreover, hair nicotine and cotinine concentrations were highly correlated among adult active smokers ( R2 = 0.710, p < 0.001), among adult nonsmokers exposed to secondhand smoke (SHS; R2 = 0.729, p < 0.001) and among infants ( R2 = 0.538, p = 0.01). Among the infants exposed to SHS from both parents the noted correlations were even stronger ( R2 = 0.835, p = 0.02). The above results identify the use of hair samples as an effective method for assessing exposure to tobacco, with a high association between nicotine and cotinine especially among infants heavily exposed to SHS.
Synergistic effects of parabens on the induction of calbindin-D9k gene expression act via a progesterone receptor-mediated pathway in GH3 cells
Authors: Yang H , Nguyen T-T , An B-S , Choi K-C , Jeung E-B 
Published: October 2011

Although the endocrine-disrupting bioactivity of parabens is weakly estrogenic (parabens are xenoestrogens), their combined synergistic effect is unknown. The aim of this study was to investigate the effects of methyl paraben (MP), ethyl paraben (EP), propyl paraben (PP), isopropyl paraben (IPP), butyl paraben (BP), and isobutyl paraben (IBP), either alone or in combination (MP + EP + PP + BP; PP + IPP; and BP + IBP) on the induction of the estrogenic biomarker gene, calbindin-D9k( CaBP-9k), in rat pituitary lactosomatotrophic GH3 cells. The expression of CaBP-9k mRNA and protein was analyzed using real-time PCR and Western blot analysis, respectively. After 24 h of treatment, a significant increase in CaBP-9k expression was observed. This was dependent upon the length of the paraben alkyl chains (shortest in MP and longest in IBP). Interestingly, the synergistic effects of these paraben combinations were observed at a dose (10−5 M) of these parabens, which induced the highest expression of CaBP-9k mRNA and protein. To investigate the involvement of estrogen receptors (ERs) and progesterone receptors (PRs), through which parabens exert their effects, the expression levels of ERα and PR-B were also examined. The expression of ERα mRNA and protein fluctuated after paraben treatment in GH3 cells, which was not significant. However, the expression level of ERα gene was induced when cotreated with 17β-estradiol (E2) and ICI 182, 780 (estrogen receptor antagonist). The different combinations of parabens induced the expression of the PR-B gene, which was abolished by cotreatment with ICI 182,780. The expression patterns of CaBP-9k and PR-B genes appeared to be similar in response to paraben treatments. This implied that CaBP-9k expression in GH3 cells may be induced by parabens via a PR-mediated pathway. Taken together, these results suggest that exposure to multiple parabens at low concentrations may increase their synergistic estrogenic activities in GH3 cells through a PR-mediated pathway.
Expression and methylation analysis of p15 and p16 in mouse bone marrow cells exposed to 1,4-benzoquinone
Authors: Tian J-F , Peng C-H , Yu X-Y , Yang X-J , Yan H-T 
Published: October 2011

Benzene is an important industrial chemical. It is also an environmental pollutant recognized as a human carcinogen. Both prenatal and adult exposures to benzene are associated with the development of leukemia. To understand the mechanism of benzene-induced epigenetic variations, we investigated the expression and methylation patterns of CpG (phosphodiester bond between cytosine and guanine) islands in p15 and p16 promoter regions in 1,4-benzoquinone (1,4-BQ)-treated primary cultivated C57BL/6J mouse bone marrow cells in vitro. The cell toxicity of 1,4-BQ was evaluated by cell viability test, real-time PCR was used to measure the mRNA expression levels, and bisulfite sequencing PCR (BSP) was used to look into the methylation patterns. The cell viability test indicates that 1,4-BQ exhibited a dose-dependent toxicity to mouse bone marrow cells. After a 24-h exposure to 1,4-BQ at final concentrations of 0, 0.1, 1, and 10 μmol/L, the mRNA expression of p15 and p16 decreased with the increase in 1,4-BQ concentration. The BSP results gathered from the exposure and the control groups were the same. In summary, despite the observation that short-term exposure to 1,4-BQ primary cultivated mouse bone marrow cells decreased the p15 and p16 transcripts, with no influence by their gene promoter methylation.