bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaccinia virus-mediated intra-tumoral expression of matrix metalloproteinase 9 enhances oncolysis of PC-3 xenograft tumors
Authors: Schäfer Simon , Weibel Stephanie , Donat Ulrike , Zhang Qian , Aguilar Richard J , Chen Nanhai G , Szalay Aladar A 
Published: August 2012

Abstract

Background
Oncolytic viruses, including vaccinia virus (VACV), are a promising alternative to classical mono-cancer treatment methods such as surgery, chemo- or radiotherapy. However, combined therapeutic modalities may be more effective than mono-therapies. In this study, we enhanced the effectiveness of oncolytic virotherapy by matrix metalloproteinase (MMP-9)-mediated degradation of proteins of the tumoral extracellular matrix (ECM), leading to increased viral distribution within the tumors.

Methods
For this study, the oncolytic vaccinia virus GLV-1h255, containing the mmp-9 gene, was constructed and used to treat PC-3 tumor-bearing mice, achieving an intra-tumoral over-expression of MMP-9. The intra-tumoral MMP-9 content was quantified by immunohistochemistry in tumor sections. Therapeutic efficacy of GLV-1h255 was evaluated by monitoring tumor growth kinetics and intra-tumoral virus titers. Microenvironmental changes mediated by the intra-tumoral MMP-9 over-expression were investigated by microscopic quantification of the collagen IV content, the blood vessel density (BVD) and the analysis of lymph node metastasis formation.

Results
GLV-1h255-treatment of PC-3 tumors led to a significant over-expression of intra-tumoral MMP-9, accompanied by a marked decrease in collagen IV content in infected tumor areas, when compared to GLV-1h68-infected tumor areas. This led to considerably elevated virus titers in GLV-1h255 infected tumors, and to enhanced tumor regression. The analysis of the BVD, as well as the lumbar and renal lymph node volumes, revealed lower BVD and significantly smaller lymph nodes in both GLV-1h68- and GLV-1h255- injected mice compared to those injected with PBS, indicating that MMP-9 over-expression does not alter the metastasis-reducing effect of oncolytic VACV.

Conclusions
Taken together, these results indicate that a GLV-1h255-mediated intra-tumoral over-expression of MMP-9 leads to a degradation of collagen IV, facilitating intra-tumoral viral dissemination, and resulting in accelerated tumor regression. We propose that approaches which enhance the oncolytic effect by increasing the intra-tumoral viral load, may be an effective way to improve therapeutic outcome.
Spatial clusters of suicide in the municipality of São Paulo 1996–2005: an ecological study
Authors: Bando Daniel H , Moreira Rafael S , Pereira Julio CR , Barrozo Ligia V 
Published: August 2012

AbstractBackgroundIn a classical study, Durkheim mapped suicide rates, wealth, and low family density and realized that they clustered in northern France. Assessing others variables, such as religious society, he constructed a framework for the analysis of the suicide, which still allows international comparisons using the same basic methodology. The present study aims to identify possible significantly clusters of suicide in the city of São Paulo, and then, verify their statistical associations with socio-economic and cultural characteristics.MethodsA spatial scan statistical test was performed to analyze the geographical pattern of suicide deaths of residents in the city of São Paulo by Administrative District, from 1996 to 2005. Relative risks and high and/or low clusters were calculated accounting for gender and age as co-variates, were analyzed using spatial scan statistics to identify geographical patterns. Logistic regression was used to estimate associations with socioeconomic variables, considering, the spatial cluster of high suicide rates as the response variable. Drawing from Durkheim’s original work, current World Health Organization (WHO) reports and recent reviews, the following independent variables were considered: marital status, income, education, religion, and migration.ResultsThe mean suicide rate was 4.1/100,000 inhabitant-years. Against this baseline, two clusters were identified: the first, of increased risk (RR = 1.66), comprising 18 districts in the central region; the second, of decreased risk (RR = 0.78), including 14 districts in the southern region. The downtown area toward the southwestern region of the city displayed the highest risk for suicide, and though the overall risk may be considered low, the rate climbs up to an intermediate level in this region. One logistic regression analysis contrasted the risk cluster (18 districts) against the other remaining 78 districts, testing the effects of socioeconomic-cultural variables. The following categories of proportion of persons within the clusters were identified as risk factors: singles (OR = 2.36), migrants (OR = 1.50), Catholics (OR = 1.37) and higher income (OR = 1.06). In a second logistic model, likewise conceived, the following categories of proportion of persons were identified as protective factors: married (OR = 0.49) and Evangelical (OR = 0.60).ConclusionsThis risk/ protection profile is in accordance with the interpretation that, as a social phenomenon, suicide is related to social isolation. Thus, the classical framework put forward by Durkheim seems to still hold, even though its categorical expression requires re-interpretation.
A set of dual promoter vectors for high throughput cloning, screening, and protein expression in eukaryotic and prokaryotic systems from a single plasmid
Authors: Sinah Namita , Williams Charlotte A , Piper Robert C , Shields S Brookhart 
Published: August 2012

Abstract

Background
The ability to produce the same recombinant protein in both prokaryotic and eukaryotic cells offers many experimental opportunities. However, the cloning of the same gene into multiple plasmids is required, which is time consuming, laborious and still may not produce soluble, stable protein in sufficient quantities. We have developed a set of expression vectors that allows for ligation-independent cloning and rapid functional screening for protein expression in both E. coli and S. cerevisiae.

Results
A set of expression vectors was made that can express the same open reading frame in E. coli (via the T7 phage promoter) and in S. cerevisiae (via the CUP1 or MET25 promoter). These plasmids also contain the essential elements for replication and selection in both cell types and have several advantages: they allow for cloning of genes by homologous recombination in yeast, protein expression can be determined before plasmid isolation and sequencing, and a GST-fusion tag is added to aid in soluble expression and purification. We have also included a TEV recognition site that allows for the specific cleavage of the fusion proteins to yield native proteins.

Conclusions
The dual promoter vectors can be used for rapid cloning, expression, and purification of target proteins from both prokaryotic and eukaryotic systems with the ability to study post-translation modifications.
Clinicians’ and patients’ views of metrics of change derived from patient reported outcome measures (PROMs) for comparing providers’ performance of surgery
Authors: Hildon Zoe , Neuburger Jenny , Allwood Dominique , van der Meulen Jan , Black Nick 
Published: August 2012

Abstract

Background
Patient reported outcome measures (PROMs) are increasingly being used to compare the performance of health care providers. Our objectives were to determine the relative frequency of use of different metrics that can be derived from PROMs, explore clinicians’ and patients’ views of the options available, and make recommendations.

Methods
First a rapid review of the literature on metrics derived from two generic (EQ-5D and EQ-VAS) and three disease-specific (Oxford Hip Score; Oxford Knee Score; Aberdeen Varicose Vein Questionnaire) PROMs was conducted. Next, the findings of the literature review were mapped onto our typology of metrics to determine their relative frequency of use, Finally, seven group meetings with surgical clinicians (n = 107) and six focus groups with patients (n = 45) were held which were audio-taped, transcribed and analysed thematically.

Results
Only nine studies (9.3% of included papers) used metrics for comparing providers. These were derived from using either the follow-up PROM score (n = 3) or the change in score as an outcome (n = 5), both adjusted for pre-intervention score. There were no recorded uses of the proportion reaching a specified (‘good’) threshold and only two studies used the proportion reaching a minimally important difference (MID).
Surgical clinicians wanted multiple outcomes, with most support expressed for the mean change in score, perceiving it to be more interpretable; there was also some support for the MID. For patients it was apparent that rather than the science behind these measures, the most important aspects were the use of language that would make the metrics personally meaningful and linking the metric to a familiar scale.

Conclusions
For clinicians the recommended metrics are the mean change in score and the proportion achieving a MID, both adjusted for pre-intervention score. Both need to be clearly described and explained. For patients we recommend the proportion achieving a MID or proportion achieving a significant improvement in hip function, both adjusted for pre-intervention score.
Rituximab and new regimens for indolent lymphoma: a brief update from 2012 ASCO Annual Meeting
Authors: Zhao Jiangning , Xu Zhenshu , Liu Delong , Lu Quanyi 
Published: August 2012

Abstract
Indolent lymphoma (IL), the second most common lymphoma, remains incurable with chemotherapy alone. While R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) remains the standard frontline regimen for diffuse Large B –cell lymphoma, the optimal chemotherapy regimen for frontline therapy of advanced IL remains uncertain. FCR (fludarabine, cyclophosphamide, rituximab) has been shown to be better than fludarabine alone and fludarabine plus cyclophosphamide for IL. In FOLL05 trial, R-CHOP was compared with R-CVP (cyclophosphamide, vincristine, prednisone) and R-FM (fludarabine, mitoxantrone). The study showed that R-CHOP appears to have the best risk-benefit ratio for IL. The StiL NHL1 trial showed that BR (bendamustine, rituximab) has longer progression free survival and is better tolerated than R-CHOP. Long-term complications with secondary malignancies between the two regimens appear to be comparable. In this review, new combination regimens reported at 2012 ASCO annual meeting were evaluated for frontline and salvage therapy of indolent lymphoma.
Single blood-Hg samples can result in exposure misclassification: temporal monitoring within the Japanese community (United States)
Authors: Tsuchiya Ami , Duff Rob , Stern Alan H , White Jim W , Krogstad Finn , Burbacher Thomas M , Faustman Elaine M , Mariën Koenraad 
Published: August 2012

Abstract

Background
The most prominent non-occupational source of exposure to methylmercury is the consumption of fish. In this study we examine a fish consuming population to determine the extent of temporal exposure and investigate the extent to which single time estimates of methylmercury exposure based on blood-Hg concentration can provide reliable estimates of longer-term average exposure.

Methods
Blood-mercury levels were obtained from a portion of the Arsenic Mercury Intake Biometric Study (AMIBS) cohort. Specifically, 56 Japanese women residing in the Puget Sound area of Washington State, US were sampled on three occasions across a one-year period.

Results
An average of 135 days separated samples, with mean blood-mercury levels for the visits being 5.1, 6.6 and 5.0 μg/l and geometric means being 2.7, 4.5 and 3.1 μg/l. The blood-mercury levels in this group exceed national averages with geometric means for two of the visits being between the 90th and 95th percentiles of nationally observed levels and the lowest geometric mean being between the 75th and 90th percentile. Group means were not significantly different across sampling periods suggesting that exposure of combined subjects remained relatively constant. Comparing intra-individual results over time did not reveal a strong correlation among visits (r = 0.19, 0.50, 0.63 between 1st and 2nd, 2nd and 3rd, and 1st and 3rd sample results, respectively). In comparing blood-mercury levels across two sampling interval combinations (1st and 2nd, 2nd and 3rd, and 1st and 3rd visits, respectively), 58% (n = 34), 53% (n = 31) and 29% (n = 17) of the individuals had at least a 100% difference in blood-Hg levels.

Conclusions
Point estimates of blood-mercury, when compared with three sample averages, may not reflect temporal variability and individual exposures estimated on the basis of single blood samples should be treated with caution as indicators of long-term exposure. Reliance on single blood samples can make predicting ongoing methylmercury exposure highly speculative due to the large intra-individual variability.
Association between type 2 diabetes and chronic arsenic exposure in drinking water: A cross sectional study in Bangladesh
Authors: Islam Md Rafiqul , Khan Ismail , Hassan Sheikh Md Nazmul , McEvoy Mark , D’Este Catherine , Attia John , Peel Roseanne , Sultana Munira , Akter Shahnaz , Milton Abul Hasnat 
Published: August 2012

AbstractBackgroundChronic exposure to high level of inorganic arsenic in drinking water has been associated with Type 2 Diabetes (T2D). Most research has been ecological in nature and has focused on high levels of arsenic exposure with few studies directly measuring arsenic levels in drinking water as an index of arsenic exposure. The effect of low to moderate levels of arsenic exposure on diabetes risk is largely unknown thus our study is adding further knowledge over previous works.MethodsThis cross sectional study was conducted in 1004 consenting women and men from 1682 eligible participants yielding a participation rate of 60%. These participants are aged>30 years and were living in Bangladesh and had continuously consumed arsenic-contaminated drinking water for at least 6 months. T2D cases were diagnosed using glucometer following the new diagnostic criteria (Fasting Blood Glucose>126 mg/dl) from the WHO guideline (WHO 2006), or a self-reported physician diagnosis of type 2 diabetes. Association between T2D and chronic arsenic exposure was estimated by multiple logistic regression with adjustment for age, sex, education, Body Mass Index (BMI) and family history of T2D.ResultsA total of 1004 individuals participated in the study. The prevalence of T2D was 9% (95% CI 7-11%). After adjustment for diabetes risk factors, an increased risk of type 2 diabetes was observed for arsenic exposure over 50 μg/L with those in the highest category having almost double the risk of type 2 diabetes (OR=1.9 ; 95% CI 1.1-3.5). For most levels of arsenic exposure, the risk estimates are higher with longer exposure; a dose–response pattern was also observed.ConclusionsThese findings suggest an association between chronic arsenic exposure through drinking water and T2D. Risks are generally higher with longer duration of arsenic exposure. The risk of T2D is highest among those who were exposed to the highest concentration of arsenic for more than 10 years.
Environmental exposure to arsenic may reduce human semen quality: associations derived from a Chinese cross-sectional study
Authors: Xu Weipan , Bao Huaqiong , Liu Feng , Liu Liangpo , Zhu Yong-Guan , She Jianwen , Dong Sijun , Cai Min , Li Lianbing , Li Chuanhai , Shen Heqing 
Published: August 2012

Abstract

Background
Recent observations in in vitro and in vivo models suggest that arsenic (As) is an endocrine disruptor at environmentally-relevant levels. When exposed to As, male rats and mice show steroidogenic dysfunction that can lead to infertility. However, the possible effects of As on human male semen quality remain obscure.

Methods
We monitored the profile of As species in the urine of a reproductive-age human cohort and assessed its association with semen quality. Men (n = 96) were recruited in an infertility clinic from July 2009 to August 2010 in the Affiliated Hospital of Chongqing Institute for Population and Family Planning. Five urinary As species were analyzed by high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry (HPLC-ICP-MS). Clinical information on the semen volume, sperm concentration and motility was employed to catalogue and evaluate semen quality according to WHO guidelines. As species concentrations in addition to other continuous variables were dichotomized by the medians and modelled as categorical variables in order to explore using the binary logistic regression possible associations between As exposure and semen quality.

Results
Urinary concentrations (geometric mean ± SD, μg g-1 creatinine) of different As species were 7.49 (±24.8) for AsB, 20.9 (±13.7) for DMA, 2.77 (±3.33) for MMA, and 4.03 (±3.67) for Asi (Asi
III and Asi
V). DMA concentrations above the median were significantly associated with below-reference sperm concentrations (P =0.02) after adjusting for age, body mass index (BMI), abstinence, smoking and drinking habits. In addition, smoking was positively associated with MMA.

Conclusion
Reduced parameters in human semen quality are positively associated with As exposure in a reproductive-age Chinese cohort.
Nanoparticles in the environment: assessment using the causal diagram approach
Authors: Smita Suchi , Gupta Shailendra K , Bartonova Alena , Dusinska Maria , Gutleb Arno C , Rahman Qamar 
Published: August 2012

Abstract
Nanoparticles (NPs) cause concern for health and safety as their impact on the environment and humans is not known. Relatively few studies have investigated the toxicological and environmental effects of exposure to naturally occurring NPs (NNPs) and man-made or engineered NPs (ENPs) that are known to have a wide variety of effects once taken up into an organism.
A review of recent knowledge (between 2000-2010) on NP sources, and their behaviour, exposure and effects on the environment and humans was performed. An integrated approach was used to comprise available scientific information within an interdisciplinary logical framework, to identify knowledge gaps and to describe environment and health linkages for NNPs and ENPs.
The causal diagram has been developed as a method to handle the complexity of issues on NP safety, from their exposure to the effects on the environment and health. It gives an overview of available scientific information starting with common sources of NPs and their interactions with various environmental processes that may pose threats to both human health and the environment. Effects of NNPs on dust cloud formation and decrease in sunlight intensity were found to be important environmental changes with direct and indirect implication in various human health problems. NNPs and ENPs exposure and their accumulation in biological matrices such as microbiota, plants and humans may result in various adverse effects. The impact of some NPs on human health by ROS generation was found to be one of the major causes to develop various diseases.
A proposed cause-effects diagram for NPs is designed considering both NNPs and ENPs. It represents a valuable information package and user-friendly tool for various stakeholders including students, researchers and policy makers, to better understand and communicate on issues related to NPs.
Cytochrome c oxidase is activated by the oncoprotein Ras and is required for A549 lung adenocarcinoma growth
Authors: Telang Sucheta , Nelson Kristin K , Siow Deanna L , Yalcin Abdullah , Thornburg Joshua M , Imbert-Fernandez Yoannis , Klarer Alden C , Farghaly Hanan , Clem Brian F , Eaton John W , Chesney Jason 
Published: August 2012

Abstract

Background
Constitutive activation of Ras in immortalized bronchial epithelial cells increases electron transport chain activity, oxygen consumption and tricarboxylic acid cycling through unknown mechanisms. We hypothesized that members of the Ras family may stimulate respiration by enhancing the expression of the Vb regulatory subunit of cytochrome c oxidase (COX).

Results
We found that the introduction of activated H-RasV12 into immortalized human bronchial epithelial cells increased eIF4E-dependent COX Vb protein expression simultaneously with an increase in COX activity and oxygen consumption. In support of the regulation of COX Vb expression by the Ras family, we also found that selective siRNA-mediated inhibition of K-Ras expression in A549 lung adenocarcinoma cells reduced COX Vb protein expression, COX activity, oxygen consumption and the steady-state concentration of ATP. We postulated that COX Vb-mediated activation of COX activity may be required for the anchorage-independent growth of A549 cells as soft agar colonies or as lung xenografts. We transfected the A549 cells with COX Vb small interfering or shRNA and observed a significant reduction of their COX activity, oxygen consumption, ATP and ability to grow in soft agar and as poorly differentiated tumors in athymic mice.

Conclusion
Taken together, our findings indicate that the activation of Ras increases COX activity and mitochondrial respiration in part via up-regulation of COX Vb and that this regulatory subunit of COX may have utility as a Ras effector target for the development of anti-neoplastic agents.
Effect of the anodization voltage on the pore-widening rate of nanoporous anodic alumina
Authors: Rahman Mohammad Mahbubur , Garcia-Caurel Enric , Santos Abel , Marsal Lluis F , Pallarès Josep , Ferré-Borrull Josep 
Published: August 2012

Abstract
A detailed study of the pore-widening rate of nanoporous anodic alumina layers as a function of the anodization voltage was carried out. The study focuses on samples produced under the same electrolyte and concentration but different anodization voltages within the self-ordering regime. By means of ellipsometry-based optical characterization, it is shown that in the pore-widening process, the porosity increases at a faster rate for lower anodization voltages. This opens the possibility of obtaining three-dimensional nanostructured nanoporous anodic alumina with controlled thickness and refractive index of each layer, and with a refractive index difference of up to 0.24 between layers, for samples produced with oxalic acid electrolytes.
Performance enhancement of IEEE 802.11 DCF using novel backoff algorithm
Authors: Kuo Chao-Yu , Huang Yi-Hung , Lin Kuan-Cheng 
Published: August 2012

Abstract
In the IEEE 802.11 distributed coordination function (DCF), the binary exponential backoff algorithm selects a random backoff number from a uniform probability distribution to avoid the problem of packet collision. In this article, we present a novel backoff algorithm that uses a binominal distribution rather than a uniform distribution to determine the backoff value. Simulation results show that the proposed algorithm outperforms the original IEEE 802.11 DCF algorithm.