bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between 25 Lung Cancer Risk–Related SNPs and Polycyclic Aromatic Hydrocarbon–Induced Genetic Damage in Coke Oven Workers
Authors: Dai Xiayun , Deng Siyun , Wang Tian , Qiu Gaokun , Li Jun , Yang Binyao , Feng Wei , He Xiaosheng , Deng Qifei , Ye Jian , Zhang Wangzhen , He Meian , Zhang Xiaomin , Guo Huan , Wu Tangchun 
Published: April 2014

Abstract
Background: Genome-wide association studies (GWAS) have identified multiple single-nucleotide polymorphisms (SNP) associated with lung cancer. However, whether these SNPs are associated with genetic damage, a crucial event in cancer initiation and evolution, is still unknown. We aimed to establish associations between these SNPs and genetic damage caused by the ubiquitous carcinogens, polycyclic aromatic hydrocarbons (PAH).
Methods: We cross-sectionally investigated the associations between SNPs from published GWAS for lung cancer in Asians and PAH-induced genetic damage in 1,557 coke oven workers in China. Urinary PAH metabolites, plasma benzo[a]pyrene-r-7,t-8,c-10-tetrahydrotetrol-albumin (BPDE-Alb) adducts, urinary 8-hydroxydeoxyguanosine (8-OHdG), and micronuclei (MN) frequency were determined by gas chromatography-mass spectrometry, sandwich ELISA, high-performance liquid chromatography, and cytokinesis-block micronucleus assay, respectively.
Results: 13q12.12-rs753955C was suggestively associated with elevated 8-OHdG levels (P = 0.003). Higher 8-OHdG levels were observed in individuals with rare allele homozygotes (CC) than in TT homozygotes (β, 0.297; 95% confidence interval, 0.124–0.471; P = 0.001). 9p21-rs1333040C, 10p14-rs1663689G, and 15q25.1-rs3813572G were significantly associated with lower MN frequency (P values were 0.002, 0.001, and 0.005, respectively). 10p14-rs1663689G polymorphism downregulated the relationship of the total concentration of PAH metabolites to 8-OHdG levels (Pinteraction = 0.002). TERT-rs2736100G and VTI1A-rs7086803A aggravated the relationship of BPDE-Alb adducts to MN frequency, whereas BPTF-rs7216064G attenuated that correlation (all Pinteraction &lt; 0.001).
Conclusions: Lung cancer risk–associated SNPs and their correlations with PAH exposure were associated with 8-OHdG levels and MN frequency.
Impact: Lung cancer risk–associated SNPs might influence one's susceptibility to genetic damage caused by PAHs. Cancer Epidemiol Biomarkers Prev; 23(6); 986–96. ©2014 AACR.
Warfarin Versus Aspirin for Prevention of Cognitive Decline in Atrial Fibrillation
Authors: Mavaddat Nahal , Roalfe Andrea , Fletcher Kate , Lip Gregory Y.H. , Hobbs F.D. Richard , Fitzmaurice David , Mant Jonathan 
Published: April 2014

Background and Purpose—
Atrial fibrillation is associated with decline of cognitive function. Observational evidence suggests that anticoagulation might protect against this decline. We report the first randomized controlled trial evidence on the effect of anticoagulation on cognitive function in elderly patients with atrial fibrillation.

Methods—
A total of 973 patients aged ≥75 years with atrial fibrillation were recruited from primary care and randomly assigned to warfarin (n=488; target international normalized ratio, 2–3) or aspirin (n=485; 75 mg/d). Neither participants nor investigators were masked to group assignment. Follow-up was for a mean of 2.7 years (SD, 1.2). Cognitive outcome was assessed using the Mini-Mental State Examination at 9-, 21-, and 33-month follow-up. Participants who had a stroke were censored from the analysis, which was by intention to treat with imputation for missing data.

Results—
There was no difference between mean Mini-Mental State Examination scores in people assigned to warfarin or aspirin at 9 or 21 months. At 33-month follow-up, there was a nonsignificant difference of 0.56 in favor of warfarin that decreased to 0.49 (95% confidence interval, –0.01 to 0.98) after imputation.

Conclusions—
We found no evidence that anticoagulation confers clinically important protection over aspirin against cognitive decline as measured by the Mini-Mental State Examination in atrial fibrillation in the first 33 months of treatment other than that provided by preventing clinical stroke.

Clinical Trial Registration—

URL:
http://www.controlled-trials.com
. Unique identifier: ISRCTN89345269.
An Improved Weak Pressure Gradient Scheme for Single-Column Modeling
Authors: Edman Jacob P. , Romps David M. 
Published: April 2014

Abstract
A new formulation of the weak pressure gradient approximation (WPG) is introduced for parameterizing large-scale dynamics in limited-domain atmospheric models. This new WPG is developed in the context of the one-dimensional, linearized, damped, shallow-water equations and then extended to Boussinesq and compressible fluids. Unlike previous supradomain-scale parameterizations, this formulation of WPG correctly reproduces both steady-state solutions and first baroclinic gravity waves. In so doing, this scheme eliminates the undesirable gravity wave resonance in previous versions of WPG. In addition, this scheme can be extended to accurately model the emission of gravity waves with arbitrary vertical wavenumber.
Interannual Variability and Long-Term Changes of Atmospheric Circulation over the Chukchi and Beaufort Seas
Authors: Wu Qigang , Zhang Jing , Zhang Xiangdong , Tao Wei 
Published: April 2014

The Beaufort Sea high (BSH) plays an important role in forcing Arctic sea ice and the Beaufort Gyre. This study examines the variability and long-term trends of atmospheric circulation over the Chukchi and Beaufort Seas using the ECMWF Interim Re-Analysis (ERA-Interim) for the period 1979–2012. Because of the mobility of the BSH through the year, EOF analysis is applied to the sea level pressure (SLP) field in order to investigate the principal patterns of BSH variability. In each season, the three leading EOF modes explain nearly 90% of the total variance and reflect a strengthened or weakened BSH centered over the western Arctic Ocean (EOF1), a north–south dipole-like SLP anomaly (EOF2), and a west–east dipole-like SLP anomaly (EOF3), respectively. These three EOF modes offer distinct influences on local climate in each season and have different connections with the large-scale climate variability modes in winter. In particular, the second principal component (PC2) associated with EOF2 in the autumn exhibits a tendency toward high-index polarity significant at the 5% level, and is related to strongly reduced sea ice extent. Further, the authors have detected significant anticyclonic trends among surface wind fields associated with a strengthened BSH during summer and autumn, but significant cyclonic trends associated with a weakened BSH during early midwinter, consistent with significant trends in SLP gradients between western Arctic Ocean and the adjoining landmass. Comparison with forced trends of surface winds from various simulations from the IPCC Fifth Assessement Report (AR5) indicates that summertime changes in atmospheric circulation cannot be explained by natural external forcing or lower boundary forcings and may instead be attributable to external anthropogenic forcing.
Far infrared study of K+ , Rb+ and Cs+ during their exchange with Na+ and Ca2+ in vermiculite
Authors: Badreddine R. , Le Dred R. , Prost R. 
Published: April 2014

AbstractAll the exchange isotherms of Na+ or Ca2+ in vermiculite for K+, Rb+ or Cs+ show two kinds of exchanges sites: the first corresponds to sites located in phlogopite-like interlamellar spaces and the second to sites located in smectite-like interlamellar spaces. During the exchange, three mineralogical phases are formed: Na- or Ca-vermiculite; K-, Rb- or Cs-vermiculite and a mixed-layer phase. Far infrared absorption bands of K+, Rb+ and Cs+ located in the phlogopite-like interlamellar spaces are at 72, 59 and 53 cm–1, respectively. These frequencies are characteristic of a trioctahedral mixed-layer phase. Selectivity is greater for cations with a low hydration energy (K+, Rb+, Cs+) than for cations with a high hydration energy (Na+, Ca2+). On the other hand, for cations with a low hydration energy, structural parameters such as the tetrahedral rotation angle, α, have to be taken into account.
Genome-wide variations in a natural isolate of the nematode Caenorhabditis elegans
Authors: Vergara Ismael A , Tarailo-Graovac Maja , Frech Christian , Wang Jun , Qin Zhaozhao , Zhang Ting , She Rong , Chu Jeffrey SC , Wang Ke , Chen Nansheng 
Published: April 2014

AbstractBackgroundIncreasing genetic and phenotypic differences found among natural isolates ofC. eleganshave encouraged researchers to explore the natural variation of this nematode species.ResultsHere we report on the identification of genomic differences between the reference strain N2 and the Hawaiian strain CB4856, one of the most genetically distant strains from N2. To identify both small- and large-scale genomic variations (GVs), we have sequenced the CB4856 genome using both Roche 454 (~400 bps single reads) and Illumina GA DNA sequencing methods (101 bps paired-end reads). Compared to previously described variants (available in WormBase), our effort uncovered twice as many single nucleotide variants (SNVs) and increased the number of small InDels almost 20-fold. Moreover, we identified and validated large insertions, most of which range from 150 bps to 1.2 kb in length in the CB4856 strain. Identified GVs had a widespread impact on protein-coding sequences, including 585 single-copy genes that have associated severe phenotypes of reduced viability in RNAi and genetics studies. Sixty of these genes are homologs of human genes associated with diseases. Furthermore, our work confirms previously identified GVs associated with differences in behavioural and biological traits between the N2 and CB4856 strains.ConclusionsThe identified GVs provide a rich resource for future studies that aim to explain the genetic basis for other trait differences between the N2 and CB4856 strains.
Functional polymorphism in aldehyde dehydrogenase-2 gene associated with risk of tuberculosis
Authors: Park Seung Kyu , Park Choon-Sik , Lee Hyo-Suk , Park Kyong Soo , Park Byung Lae , Cheong Hyun Sub , Shin Hyoung Doo 
Published: April 2014

Abstract

Background
The well-known genetic polymorphisms in ADH1B(His47Arg) and ALDH2(Glu487Lys) have dramatic effects on the rate of metabolizing alcohol and acetaldehyde. We investigated possible involvement of these functional polymorphisms in other common complex-trait diseases.

Methods
The genetic effects of these two polymorphisms on hepatitis, asthma, type-2 diabetes mellitus (T2DM), and tuberculosis (TB) were examined in a Korean population.

Results
We demonstrated that the well-known functional polymorphism of a primary alcohol-metabolizing enzyme (ALDH2 Glu487Lys) has a strong genetic association with the risk of TB. The frequency of the minor allele (ALDH2*487Lys) was found to be much lower in TB patients (freq. = 0.099/n = 477) than among controls (freq. = 0.162/n = 796) (P = 0.00001, OR (95% confidential interval) = 0.57 (0.45-0.74)). Our data may indicate that TB was once an endemic disease, which exerted selection pressure for higher frequencies of ALDH2*487Lys in Asian populations. In addition, the calculated attributable fraction (AF) indicates that 39.5% of TB patients can attribute their disease to the detrimental effects of ALDH2Glu487Glu.

Conclusion
Our results suggest that this polymorphism is one of the genetic components of TB, at least in the Korean population.
A hierarchical classification method for finger knuckle print recognition
Authors: Kong Tao , Yang Gongping , Yang Lu 
Published: April 2014

Abstract
Finger knuckle print has recently been seen as an effective biometric technique. In this paper, we propose a hierarchical classification method for finger knuckle print recognition, which is rooted in traditional score-level fusion methods. In the proposed method, we firstly take Gabor feature as the basic feature for finger knuckle print recognition and then a new decision rule is defined based on the predefined threshold. Finally, the minor feature speeded-up robust feature is conducted for these users, who cannot be recognized by the basic feature. Extensive experiments are performed to evaluate the proposed method, and experimental results show that it can achieve a promising performance.
Engagement of immune effector cells by trastuzumab induces HER2/ERBB2 downregulation in cancer cells through STAT1 activation
Authors: Shi Yun , Fan Xuejun , Meng Weixu , Deng Hui , Zhang Ningyan , An Zhiqiang 
Published: April 2014

Abstract
Introduction
Trastuzumab has been widely used for the treatment of human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer for more than a decade. However, reports on the involvement of HER2 downregulation in trastuzumab’s mechanism of action are inconsistent. The aim of this study is to investigate if the dependence of trastuzumab-mediated cancer cell HER2 downregulation on immune effector cells represents a novel mechanism of action for trastuzumab.

Methods
HER2 expression was evaluated by Western blotting, flow cytometry, and real-time polymerase chain reaction (PCR) in cell lysates from co-cultures of multiple cancer cell lines with peripheral blood mononuclear cells (PBMCs) in the presence or absence of trastuzumab. The engagement of immune cells by trastuzumab through Fc gamma receptors (FcγRs) was tested using three trastuzumab variants with compromised or no Fc (fragment crystallizable) functions and FcγRs blocking experiments. The engagement of immune cells by trastuzumab in HER2 downregulation was also evaluated in in vivo mouse xenograft tumor models.

Results
HER2 downregulation of cancer cells by trastuzumab occurred only when trastuzumab was actively engaged with immune cells and cancer cells, as demonstrated consistently in co-cultures of cancer cell lines with PBMCs and in vivo mouse xenograft tumor models. We further demonstrated that HER2 downregulation in cancer cells by immune-cell-engaged trastuzumab was at the transcriptional level, not through the HER2 degradation pathway. Activation of signal transducer and activator of transcription 1 (STAT1) in cancer cells by the increased interferon gamma (IFN-γ) production in immune cells played an important role in downregulating HER2 in cancer cells upon engagement of immune cells by trastuzumab. Furthermore, HER2 downregulation in cancer cells induced by trastuzumab engagement of immune cells was correlated with the antibody’s antitumor efficacy in vivo.

Conclusions
This study reveals that engagement of immune effector cells by trastuzumab induces HER2 downregulation in HER2-expressing cancer cells, which represents a new function of immune cells in trastuzumab-mediated antitumor efficacy and serves as a novel mechanism of action for trastuzumab. Our results imply that HER2 downregulation in cancer cells treated by trastuzumab may predict active engagement of immune effector cells in tumor microenvironment.
Hypermethylation in the ZBTB20 gene is associated with major depressive disorder
Authors: Davies Matthew N , Krause Lutz , Bell Jordana T , Gao Fei , Ward Kirsten J , Wu Honglong , Lu Hanlin , Liu Yuan , Tsai Pei-Chein , Collier David A , Murphy Therese , Dempster Emma , Mill Jonathan ,   UK Brain Expression Consortium, Battle Alexis , Mostafavi Sara , Zhu Xiaowei , Henders Anjali , Byrne Enda , Wray Naomi R , Martin Nicholas G , Spector Tim D , Wang Jun 
Published: April 2014

Abstract
Background
Although genetic variation is believed to contribute to an individual’s susceptibility to major depressive disorder, genome-wide association studies have not yet identified associations that could explain the full etiology of the disease. Epigenetics is increasingly believed to play a major role in the development of common clinical phenotypes, including major depressive disorder.

Results
Genome-wide MeDIP-Sequencing was carried out on a total of 50 monozygotic twin pairs from the UK and Australia that are discordant for depression. We show that major depressive disorder is associated with significant hypermethylation within the coding region of ZBTB20, and is replicated in an independent cohort of 356 unrelated case-control individuals. The twins with major depressive disorder also show increased global variation in methylation in comparison with their unaffected co-twins. ZBTB20 plays an essential role in the specification of the Cornu Ammonis-1 field identity in the developing hippocampus, a region previously implicated in the development of major depressive disorder.

Conclusions
Our results suggest that aberrant methylation profiles affecting the hippocampus are associated with major depressive disorder and show the potential of the epigenetic twin model in neuro-psychiatric disease.
Associations Between Insulin Resistance, Free Fatty Acids, and Oocyte Quality in Polycystic Ovary Syndrome During In Vitro Fertilization
Authors: Niu Zhihong , Lin Nan , Gu Ruihuan , Sun Yijuan , Feng Yun 
Published: April 2014

Context:
Both polycystic ovary syndrome (PCOS) and obesity are associated with specific reproductive health complications, including lower oocyte quality and clinical pregnancy rates in assisted conception cycles, which may be a result of metabolism-induced changes in the oocyte through the microenvironment of follicular fluid. Free fatty acids (FFAs) are important biomedical indicators of abnormal lipid metabolism and have pronounced effects on cells, leading to changes in metabolism, cell growth, and differentiation

Objective:
Our objective was to determine the effect of FFA metabolism in plasma and follicular fluid on oocyte quality in the women with PCOS undergoing in vitro fertilization.

Design and Setting:
Ninety-three women undergoing in vitro fertilization treatment, including 55 with PCOS and 38 age-matched controls, were recruited. PCOS patients were divided into obese and nonobese subgroups on the basis of their body mass index.

Main Outcome Measures:
Embryo quality was morphologically assessed, and serum sex hormone and insulin levels were measured. FFAs in plasma and follicular fluid were measured using gas chromatography-mass spectrometry.

Results:
PCOS was found to be associated with significantly higher LH/FSH, total T, free androgen index (FAI), and lower SHBG levels, independent of obesity(P &lt; .05). Obese women with PCOS had a significantly higher total T level, FAI, fasting insulin, insulin resistance index as determined by homeostasis model assessment for insulin resistance, and lower SHBG levels than the nonobese women with PCOS (P &lt; .05). The embryo fragmentation score was significantly positively correlated with the oleic acid concentration in all PCOS patients (r = 0.22, P = .04, for nonobese patients and r = 0.25, P = .03, for obese patients).

Conclusions:
Our findings clearly demonstrated that PCOS is associated with significantly higher FAI and insulin resistance levels and decreased plasma SHBG levels, independent of body mass index. Obese PCOS patients had higher palmitoleic acid and oleic acid levels in both the plasma and follicular fluid than did the control subject and nonobese PCOS patients. Our results indicated that developmental competence is associated with oleic and stearic acid concentrations, which may contribute to the poor pregnancy outcomes in patients with PCOS.
Effects of Long-term Growth Hormone Replacement in Adults With Growth Hormone Deficiency Following Cure of Acromegaly: A KIMS Analysis
Authors: Tritos Nicholas A. , Johannsson Gudmundur , Korbonits Márta , Miller Karen K. , Feldt-Rasmussen Ulla , Yuen Kevin C. J. , King Donna , Mattsson Anders F. , Jonsson Peter J. , Koltowska-Haggstrom Maria , Klibanski Anne , Biller Beverly M. K. 
Published: April 2014

Context:GH deficiency (GHD) may occur in adults with cured acromegaly (acroGHD).Objective:Our objective was to examine the effectiveness and safety of GH replacement in acroGHD.Design:This study was a retrospective analysis of data from KIMS (Pfizer International Metabolic Database).Setting:Data were extracted from a pharmaco-epidemiological survey of &gt;16 000 GHD adults from 31 countries.Patients:The effectiveness population included 115 adults with acroGHD and 142 age-, gender-, and body mass index-matched GHD adults with nonfunctioning pituitary adenoma (NFPA) followed up to 5 years on GH. The safety population included 164 adults with acroGHD and 2469 with NFPA, all GH-replaced. Both acroGHD and NFPA were compared with several cohorts from the general population (including the World Health Organization Global Burden of Disease).Outcome Measures:Outcome measures included quality of life (QoL-AGHDA), lipids, serious adverse events, and additional safety endpoints.Results:Median GH dose was 0.3 mg/d in acroGHD and NFPA at 5 years. There were comparable improvements in QoL-AGHDA and total and low-density lipoprotein cholesterol in acroGHD and NFPA. High-density lipoprotein cholesterol increased only in acroGHD. Cardiovascular mortality was increased in acroGHD vs NFPA (standardized mortality ratio = 3.03, P = .02). All-cause mortality was similar in acroGHD (ratio between observed/expected cases [95% confidence interval] = 1.32 [0.70–2.25]) and lower in NFPA [observed/expected = 0.58 [0.48–0.70]) in comparison with the general population. There was no difference in incidence of all cancers, benign or malignant brain tumors, or diabetes mellitus between acroGHD and NFPA.Conclusions:GH replacement has comparable effects on quality of life and lipids in acroGHD and NFPA. Further investigation is needed to examine whether the increased cardiovascular mortality may be attributed to the history of previous GH excess in acroGHD.
Commissions and Sales Targets Under Competition
Authors: Gallego Guillermo , Talebian Masoud 
Published: April 2014

We consider a game between two capacity providers that compete for customers through a broker who earns commissions on sales and sells to both loyal and nonloyal customers. The providers compete by selecting commission margins and sales targets above which the margins on total sales increase. We study the contract form in equilibrium and the effect that sales targets have on the profit split between the providers and the broker. We show that in equilibrium, contracts require positive sales targets that can be best described as a mechanism for the larger provider to profit at the expense of the smaller provider. The effect of sales targets is different when commission margins are exogenous and the providers compete by setting targets. In this case, it is the low-margin provider who benefits from sales targets at the expense of the broker, who in this context resists the imposition of targets. This paper was accepted by Yossi Aviv, operations management.