bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Dual Role for the Nonreceptor Tyrosine Kinase Pyk2 during the Intracellular Trafficking of Human Papillomavirus 16
Authors: Gottschalk Elinor Y. , Meneses Patricio I. 
Published: June 2015

ABSTRACT

The infectious process of human papillomaviruses (HPVs) has been studied considerably, and many cellular components required for viral entry and trafficking continue to be revealed. In this study, we investigated the role of the nonreceptor tyrosine kinase Pyk2 during HPV16 pseudovirion infection of human keratinocytes. We found that Pyk2 is necessary for infection and appears to be involved in the intracellular trafficking of the virus. Small interfering RNA-mediated reduction of Pyk2 resulted in a significant decrease in infection but did not prevent viral entry at the plasma membrane. Pyk2 depletion resulted in altered endolysosomal trafficking of HPV16 and accelerated unfolding of the viral capsid. Furthermore, we observed retention of the HPV16 pseudogenome in the
trans
-Golgi network (TGN) in Pyk2-depleted cells, suggesting that the kinase could be required for the viral DNA to exit the TGN. While Pyk2 has previously been shown to function during the entry of enveloped viruses at the plasma membrane, the kinase has not yet been implicated in the intracellular trafficking of a nonenveloped virus such as HPV. Additionally, these data enrich the current literature on Pyk2's function in human keratinocytes.

IMPORTANCE
In this study, we investigated the role of the nonreceptor tyrosine kinase Pyk2 during human papillomavirus (HPV) infection of human skin cells. Infections with high-risk types of HPV such as HPV16 are the leading cause of cervical cancer and a major cause of genital and oropharyngeal cancer. As a nonenveloped virus, HPV enters cells by interacting with cellular receptors and established cellular trafficking routes to ensure that the viral DNA reaches the nucleus for productive infection. This study identified Pyk2 as a cellular component required for the intracellular trafficking of HPV16 during infection. Understanding the infectious pathways of HPVs is critical for developing additional preventive therapies. Furthermore, this study advances our knowledge of intracellular trafficking processes in keratinocytes.
Impaired Epstein-Barr Virus-Specific Neutralizing Antibody Response during Acute Infectious Mononucleosis Is Coincident with Global B-Cell Dysfunction
Authors: Panikkar Archana , Smith Corey , Hislop Andrew , Tellam Nick , Dasari Vijayendra , Hogquist Kristin A. , Wykes Michelle , Moss Denis J. , Rickinson Alan , Balfour Henry H. , Khanna Rajiv 
Published: June 2015

ABSTRACT
Here we present evidence for previously unappreciated B-cell immune dysregulation during acute Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM). Longitudinal analyses revealed that patients with acute IM have undetectable EBV-specific neutralizing antibodies and gp350-specific B-cell responses, which were associated with a significant reduction in memory B cells and no evidence of circulating antibody-secreting cells. These observations correlate with dysregulation of tumor necrosis factor family members BAFF and APRIL and increased expression of FAS on circulating B cells.
Traumatic episodes and mental health effects in young men and women in Rwanda, 17 years after the genocide
Authors: Rugema Lawrence , Mogren Ingrid , Ntaganira Joseph , Krantz Gunilla 
Published: June 2015

ObjectivesTo investigate mental health effects associated with exposure to trauma in Rwanda during the 1994 genocide period, and over the lifetime, in Rwandan men and women aged 20–35 years.SettingThis was a cross-sectional population-based study conducted in the southern province of Rwanda. Data was collected during December 2011 to January 2012.ParticipantsA total population of 917 individuals were included, 440 (48%) men and 477 (52%) women aged 20–35 years. Number of households for inclusion in each village was selected proportional to the total number of households in each selected village. The response rate was 99.8%. Face-to-face interviewing was done by experienced and trained clinical psychologists, following a structured questionnaire.ResultsWomen were slightly less exposed during the genocide period (women 35.4% and men 37.5%; p=0.537), but more women than men were exposed to traumatic episodes over their lifetime (women 83.6%, n=399; men 73.4%, n=323; p<0.001). Current major depressive episodes (MDE) were twice as prevalent in women as in men. Traumatic episodes experienced in the genocide period severely affected men's current mental health status with relative risk (RR) 3.02 (95% CI 1.59 to 5.37) for MDE past and with RR 2.15 (95% CI 1.21 to 3.64) for suicidality. Women's mental health was also affected by trauma experienced in the genocide period but to an even higher extent, by similar trauma experienced in the lifetime with RR 1.91 (95% CI 1.03 to 3.22) for suicidality and RR 1.90 (95% CI 1.34 to 2.42) for generalised anxiety disorder, taking spousal physical/sexual violence into consideration.ConclusionsDepression, post-traumatic stress disorder, anxiety and suicidal attempts are prevalent in Rwanda, with rates twice as high in women compared with men. For women, exposure to physical and sexual abuse was independently associated with all these disorders. Early detection of gender-based violence through homes and community interventions is important.
Enduring health effects of asbestos use in Belgian industries: a record-linked cohort study of cause-specific mortality (2001–2009)
Authors: Van den Borre Laura , Deboosere Patrick 
Published: June 2015

ObjectiveTo investigate cause-specific mortality among asbestos workers and potentially exposed workers in Belgium and evaluate potential excess in mortality due to established and suspected asbestos-related diseases.DesignThis cohort study is based on an individual record linkage between the 1991 Belgian census and cause-specific mortality information for Flanders and Brussels (2001–2009).SettingBelgium (Flanders and Brussels region).ParticipantsThe study population consists of 1 397 699 male workers (18–65 years) with 72 074 deaths between 1 October 2001 and 31 December 2009. Using a classification of high-risk industries, mortality patterns between 2056 asbestos workers, 385 046 potentially exposed workers and the working population have been compared.Outcome measuresStandardised mortality ratios (SMRs) and 95% CIs are calculated for manual and non-manual workers.ResultsOur findings show clear excess in asbestos-related mortality in the asbestos industry with SMRs for mesothelioma of 4071 (CI 2327 to 6611) among manual workers and of 4489 (CI 1458 to 10 476) among non-manual workers. Excess risks in asbestos-related mortality are also found in the chemical industry, the construction industry, the electrical generation and distribution industry, the basic metals manufacturing industry, the metal products manufacturing industry, the railroad industry, and the shipping industry. Oral cancer mortality is significantly higher for asbestos workers (SMR 383; CI 124 to 894), railroad workers (SMR 192; CI 112 to 308), shipping workers (SMR 172; CI 102 to 271) and construction workers (SMR 125; CI 100 to 153), indicating a possible association with occupational asbestos exposure. Workers in all four industries have elevated mortality rates for cancer of the mouth. Only construction workers experience significantly higher pharyngeal cancer mortality (SMR 151; CI 104 to 212).ConclusionsThe study identifies vulnerable groups of Belgian asbestos workers, demonstrating the current-day health repercussions of historical asbestos use. Results support the hypothesis of a possible association between the development of oral cancer and occupational asbestos exposure.
Exposure to traffic and lung function in adults: a general population cohort study
Authors: Carlsen Hanne Krage , Modig Lars , Levinsson Anna , Kim Jeong-Lim , Toren Kjell , Nyberg Fredrik , Olin Anna-Carin 
Published: June 2015

ObjectivesTo investigate the association between living near dense traffic and lung function in a cohort of adults from a single urban region.DesignCross-sectional results from a cohort study.SettingThe adult-onset asthma and exhaled nitric oxide (ADONIX) cohort, sampled during 2001–2008 in Gothenburg, Sweden. Exposure was expressed as the distance from participants’ residential address to the nearest road with dense traffic (>10 000 vehicles per day) or very dense traffic (>30 000 vehicles per day). The exposure categories were: low (>500 m; reference), medium (75–500 m) or high (<75 m).ParticipantsThe source population was a population-based cohort of adults (n=6153). The study population included 5441 participants of European descent with good quality spirometry and information about all outcomes and covariates.Outcome measuresForced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were measured at a clinical examination. The association with exposure was examined using linear regression adjusting for age, gender, body mass index, smoking status and education in all participants and stratified by sex, smoking status and respiratory health status.ResultsWe identified a significant dose–response trend between exposure category and FEV1(p=0.03) and borderline significant trend for FVC (p=0.06) after adjusting for covariates. High exposure was associated with lower FEV1(−1.0%, 95% CI −2.5% to 0.5%) and lower FVC (−0.9%, 95% CI −2.2% to 0.4%). The effect appeared to be stronger in women. In highly exposed individuals with current asthma or chronic obstructive pulmonary disease, FVC was lower (−4.5%, 95% CI −8.8% to −0.1%).ConclusionsHigh traffic exposure at the residential address was associated with lower than predicted FEV1and FVC lung function compared with living further away in a large general population cohort. There were particular effects on women and individuals with obstructive disease.
Socioeconomic status and self-reported health among middle-aged Japanese men: results from a nationwide longitudinal study
Authors: Wada Koji , Higuchi Yoshiyuki , Smith Derek R 
Published: June 2015

ObjectiveTo examine potential associations between socioeconomic factors and self-rated health among a national sample of Japanese men aged 50–59 years between 2005 and 2010, including the 2008 global financial crisis.DesignProspective cohort study.SettingRandomly selected 2515 census areas from a total of 1.8 million census areas in Japan.ParticipantsThis study utilised data from a national, longitudinal survey conducted by the Ministry of Health, Labour and Welfare. Starting in 2005, 16 738 Japanese men aged 50–59 years were recruited and sent a questionnaire each year. We analysed data for the 6-year period (2005–2010) from participants who had worked for over 20 years in the same industry (n=9727).Main outcome measuresWe focused on worsening self-rated health status by occupation, education and employment contract.ResultsWorking in the manufacturing industry was associated with worsening self-rated health scores when compared to those working in management (HR=1.19; 95% CI 1.04 to 1.37). A relationship between education level and worsening self-rated health was also identified as follows: junior high school (HR=1.49; 95% CI 1.31 to 1.69), high school (HR=1.29; 95% CI 1.17 to 1.42), and vocational college (HR=1.25; 95% CI 1.07 to 1.46), when compared with those holding university-level qualifications. Precarious employment (HR=1.17; 95% CI 1.00 to 1.37) was also associated with worsening self-rated health status in the current study.ConclusionsThis study suggests that working in manufacturing for more than 20 years and having lower education levels may have a significant impact on the self-rated health of middle-aged Japanese men. This may reflect a progressive decline in Japanese working conditions following the global financial crisis and/or the impact of lower socioeconomic status.
Relationship between low response to clopidogrel and periprocedural ischemic events with coil embolization for intracranial aneurysms
Authors: Asai Takumi , Miyachi Shigeru , Izumi Takashi , Matsubara Noriaki , Haraguchi Kenichi , Yamanouchi Takashi , Ota Keisuke , Shintai Kazunori , Tajima Hayato , Wakabayashi Toshihiko 
Published: June 2015

ObjectivesLow response to antiplatelet drugs is one of the risk factors for ischemic events. We examined the influence of low response to clopidogrel on symptomatic ischemic events and new ischemic MRI lesions with endovascular intracranial aneurysmal coil embolization.Materials and methodsBetween August 2010 and July 2013, 189 procedures in 181 consecutive patients who underwent endovascular coiling and received clopidogrel before treatment were investigated retrospectively. Platelet aggregation activity was examined by VerifyNow analysis. Low response to clopidogrel was defined as P2Y12 reaction units ≥230 in this study. Symptomatic ischemic complications within 30 days and postoperative new ischemic lesions on MRI–diffusion weighted imaging were evaluated.Results66 of 189 (34.9%) cases were low responders to clopidogrel. Ischemic complications occurred in 2 of 66 (3.0%) low responders compared with 6 of 123 (4.9%) responders (p=0.72). A new high intensity spot larger than 5 mm was significantly more frequent in low responders (26 of 66; 39.4%) than in responders (26 of 121; 21.2%; p=0.01). On multivariate analysis, independent risk factors for larger new ischemic lesions were low response to clopidogrel, smokers, posterior location, and aneurysms with a larger neck.ConclusionsLow response to clopidogrel had little effect on clinical outcome although it increased asymptomatic large ischemic lesions in this cohort.
Effective vaccination against rabies in puppies in rabies endemic regions
Authors: Morters M. K. , McNabb S. , Horton D. L. , Fooks A. R. , Schoeman J. P. , Whay H. R. , Wood J. L. N. , Cleaveland S. 
Published: June 2015

In rabies endemic regions, a proportionally higher incidence of rabies is often reported in dogs younger than 12 months of age, which includes puppies less than 3 months of age; this presents a serious risk to public health. The higher incidence of rabies in young dogs may be the effect of low vaccination coverage in this age class, partly as a result of the perception that immature immune systems and maternal antibodies inhibit seroconversion to rabies vaccine in puppies less than three months of age. Therefore, to test this perception, the authors report the virus neutralising antibody titres from 27 dogs that were vaccinated with high quality, inactivated rabies vaccine aged three months of age and under as part of larger serological studies undertaken in Gauteng Province, South Africa, and the Serengeti District, Tanzania. All of these dogs seroconverted to a single dose of vaccine with no adverse reactions reported and with postvaccinal peak titres ranging from 2.0 IU/ml to 90.5 IU/ml. In light of these results, and the risk of human beings contracting rabies from close contact with puppies, the authors recommend that all dogs in rabies endemic regions, including those less than three months of age, are vaccinated with high quality, inactivated vaccine.
Constraining magmatic fluxes through thermal modelling of contact metamorphism
Authors: Floess David , Baumgartner Lukas P. 
Published: June 2015

Abstract
The thermal evolution of a contact aureole is strongly dependent on the emplacement mode of the intrusion that is causing the thermal anomaly. Inferences on the emplacement mode can be made if solid temperature estimates are available. The contact aureole of the Western Adamello Tonalite provides a unique combination of magma ascent close to the host rock and suitable rock chemistry. We use three mineral reactions at different distances in the aureole in combination with phase petrology to estimate temperatures. These temperatures are not reproducible by thermal models considering the emplacement of the intrusion as a single batch. The external zone of the intrusion represents a feeder conduit in which magma was transported. We investigated the thermal effect of the conduit on the host rocks using thermal models. Different thermal profiles for the aureole are obtained by varying flow/no-flow times, conduit thickness and magma temperature. We show that only a few combinations match the temperature constraints in the aureole, and that the amount of magma transported through the conduit can be calculated. A comparison with time-averaged fluxes of recent volcanoes and the presence of reworked volcanic sediments in the surroundings of the Adamello batholith indicate that the calculated rates and volumes are plausible.

Supplementary material:

Tables comparing sample compositions with literature experimental data are available at
http://www.geolsoc.org.uk/SUP18847
High-Throughput Logic Timing Simulation on GPGPUs
Authors: Holst Stefan , Imhof Michael E. , Wunderlich Hans-Joachim 
Published: June 2015

Many EDA tasks such as test set characterization or the precise estimation of power consumption, power droop and temperature development, require a very large number of time-aware gate-level logic simulations. Until now, such characterizations have been feasible only for rather small designs or with reduced precision due to the high computational demands.
The new simulation system presented here is able to accelerate such tasks by more than two orders of magnitude and provides for the first time fast and comprehensive timing simulations for industrial-sized designs. Hazards, pulse-filtering, and pin-to-pin delay are supported for the first time in a GPGPU accelerated simulator, and the system can easily be extended to even more realistic delay models and further applications.
A sophisticated mapping with efficient memory utilization and access patterns as well as minimal synchronizations and control flow divergence is able to use the full potential of GPGPU architectures. To provide such a mapping, we combine for the first time the versatility of event-based timing simulation and multi-dimensional parallelism used in GPU-based gate-level simulators. The result is a throughput-optimized timing simulation algorithm, which runs many simulation instances in parallel and at the same time fully exploits gate-parallelism within the circuit.
Greedy-Bayes for Targeted News Dissemination
Authors: Massoulié Laurent , Ohannessian Mesrob I. , Proutière Alexandre 
Published: June 2015

This work addresses user targeting for news content delivery. Specifically, we wish to disseminate a fresh news content, whose topic is yet unknown, to all interested users, while "spamming" a minimum number of uninterested users. We formulate this as an online stochastic optimization problem that extends in several ways the classical multi-armed bandit problem.
We introduce Greedy-Bayes, a policy with appealing robustness properties. We establish optimal scaling of a suitably defined regret measure in various scenarios of interest. To that end we develop an original proof technique based on martingale concentration inequalities. Numerical experiments show that Greedy-Bayes improves upon Thompson sampling, the state-of-the-art algorithm for bandit problems.
Our analysis further implies that low regret can only be achieved if the assessment of content relevance for one user leverages feedback from users with widely distinct tastes. This impacts the design of efficient news dissemination platforms: existing systems typically do not leverage such negative feedback and could hence be improved upon with adequate extensions.
microRNA Biomarker Discovery and High-Throughput DNA Sequencing Are Possible Using Long-term Archived Serum Samples
Authors: Rounge Trine B. , Lauritzen Marianne , Langseth Hilde , Enerly Espen , Lyle Robert , Gislefoss Randi E. 
Published: June 2015

Abstract
Background: The impacts of long-term storage and varying preanalytical factors on the quality and quantity of DNA and miRNA from archived serum have not been fully assessed. Preanalytical and analytical variations and degradation may introduce bias in representation of DNA and miRNA and may result in loss or corruption of quantitative data.
Methods: We have evaluated DNA and miRNA quantity, quality, and variability in samples stored up to 40 years using one of the oldest prospective serum collections in the world, the Janus Serumbank, a biorepository dedicated to cancer research.
Results: miRNAs are present and stable in archived serum samples frozen at −25°C for at least 40 years. Long-time storage did not reduce miRNA yields; however, varying preanalytical conditions had a significant effect and should be taken into consideration during project design. Of note, 500 μL serum yielded sufficient miRNA for qPCR and small RNA sequencing and on average 650 unique miRNAs were detected in samples from presumably healthy donors. Of note, 500 μL serum yielded sufficient DNA for whole-genome sequencing and subsequent SNP calling, giving a uniform representation of the genomes.
Conclusions: DNA and miRNA are stable during long-term storage, making large prospectively collected serum repositories an invaluable source for miRNA and DNA biomarker discovery.
Impact: Large-scale biomarker studies with long follow-up time are possible utilizing biorepositories with archived serum and state-of-the-art technology. Cancer Epidemiol Biomarkers Prev; 24(9); 1381–7. ©2015 AACR.
High Cholesterol Awareness, Treatment, and Control Among Hispanic/Latinos: Results From the Hispanic Community Health Study/Study of Latinos
Authors: Rodriguez Carlos J. , Cai Jianwen , Swett Katrina , González Hector M. , Talavera Gregory A. , Wruck Lisa M. , Wassertheil‐Smoller Sylvia , Lloyd‐Jones Donald , Kaplan Robert , Daviglus Martha L. 
Published: June 2015

Background

We assessed high cholesterol (
HC
) awareness, treatment, and control rates among
US
Hispanic/Latino adults and describe factors associated with
HC
awareness and management.

Methods and Results

Baseline data (collected 2008–2011) from a multisite probability sample of Hispanic/Latino adults in the Hispanic Community Health Study/Study of Latinos (18 to 74 years old; N=16 207) were analyzed.
HC
was defined as low‐density lipoprotein‐cholesterol ≥130 mg/dL and/or total cholesterol ≥240 mg/dL or use of cholesterol‐lowering medication. Among Hispanic/Latino adults with
HC
, almost half (49.3%) were not aware of their condition and only 29.5% were receiving treatment. Men had a higher
HC
prevalence than women (44.0% versus 40.5%) but a lower rate of treatment (28.1% versus 30.6%). Younger adults were significantly less likely to be
HC
aware compared to those who were older. Those with hypertension, diabetes, and high socioeconomic position were more likely to be
HC
aware.
US
‐born Hispanic/Latino were more likely to be
HC
unaware than foreign‐born Hispanics/Latinos, but longer
US
residency was significantly associated with being
HC
aware, treated, and controlled. Cholesterol control was achieved among 64.3% of those who were
HC
treated. However, younger adults, women, those with lower income, those uninsured, and more recent immigrants were less likely to be
HC
controlled. Individuals of Puerto Rican or Dominican background were most likely to be
HC
aware and treated, whereas those of Mexican or Central American background were least likely to be
HC
treated. Individuals of Cuban and South American background had the lowest rates of
HC
control, whereas Puerto Ricans had the highest.

Conclusions

Understanding gaps in
HC
awareness, treatment, and control among
US
Hispanic/Latino adults can help inform physicians and policymakers to improve disease management and patient education programs.