bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the potential for AAV vector genotoxicity in a murine model
Authors: Li Hojun , Malani Nirav , Hamilton Shari R. , Schlachterman Alexander , Bussadori Giulio , Edmonson Shyrie E. , Shah Rachel , Arruda Valder R. , Mingozzi Federico , Fraser Wright J. , Bushman Frederic D. , High Katherine A. 
Published: November 2010

AbstractGene transfer using adeno-associated virus (AAV) vectors has great potential for treating human disease. Recently, questions have arisen about the safety of AAV vectors, specifically, whether integration of vector DNA in transduced cell genomes promotes tumor formation. This study addresses these questions with high-dose liver-directed AAV-mediated gene transfer in the adult mouse as a model (80 AAV-injected mice and 52 controls). After 18 months of follow-up, AAV-injected mice did not show a significantly higher rate of hepatocellular carcinoma compared with controls. Tumors in mice treated with AAV vectors did not have significantly different amounts of vector DNA compared with adjacent normal tissue. A novel high-throughput method for identifying AAV vector integration sites was developed and used to clone 1029 integrants. Integration patterns in tumor tissue and adjacent normal tissue were similar to each other, showing preferences for active genes, cytosine-phosphate-guanosine islands, and guanosine/cysteine-rich regions. Gene expression data showed that genes near integration sites did not show significant changes in expression patterns compared with genes more distal to integration sites. No integration events were identified as causing increased oncogene expression. Thus, we did not find evidence that AAV vectors cause insertional activation of oncogenes and subsequent tumor formation.
Autologous hematopoietic stem cell transplantation in chronic lymphocytic leukemia: results of European intergroup randomized trial comparing autografting versus observation
Authors: Michallet Mauricette , Dreger Peter , Sutton Laurent , Brand Ronald , Richards Sue , van Os Marleen , Sobh Mohamad , Choquet Sylvain , Corront Bernadette , Dearden Claire , Gratwohl Alois , Herr Wolfgang , Catovsky Daniel , Hallek Michael , de Witte Theo , Niederwieser Dietger , Leporrier Michel , Milligan Donald 
Published: November 2010

Abstract
We present results of a phase 3 randomized trial of autografting in chronic lymphocytic leukemia versus observation for responding patients after first- or second-line treatment. The primary objective was to demonstrate that autografting improves the 5-year event-free survival (EFS) from 30% to 50%. There were 223 enrolled patients, 72% men and 28% women, 83% after first and 17% after second-line treatment. Binet stages were progressive A 13%, B 67%, C 20%; at randomization, 59% were in complete remission, and 41% in less than complete remission. Patients were randomized between autografting (n = 112) and observation (n = 111). Median EFS was 24.4 months (range, 16.7-32 months) in the observation group and 51.2 months (39.8-62.5 months) in the autografting group; the 5-year EFS was 24% and 42%, respectively (P < .001). Accordingly, the 5-year relapse incidence was 76% versus 54% (P < .001). Median time to relapse requiring therapy or death was 40 months (25-56 months) in the observation arm and 65 months (59-71 months) after autografting (P = .002). Cox modeling confirmed that autografting significantly improved EFS (hazard ratio 0.44, 95% confidence interval 0.30-0.65; P < .001). At 5 years, the probability of OS was 85.5% and 84.3% for autografting and observation, respectively (P = .77). In chronic lymphocytic leukemia, consolidating autografting reduces the risk of progression by more than 50% but has no effect on overall survival.
Speeding up tandem mass spectrometry-based database searching by longest common prefix
Authors: Zhou Chen , Chi Hao , Wang Le-Heng , Li You , Wu Yan-Jie , Fu Yan , Sun Rui-Xiang , He Si-Min 
Published: November 2010

Abstract

Background
Tandem mass spectrometry-based database searching has become an important technology for peptide and protein identification. One of the key challenges in database searching is the remarkable increase in computational demand, brought about by the expansion of protein databases, semi- or non-specific enzymatic digestion, post-translational modifications and other factors. Some software tools choose peptide indexing to accelerate processing. However, peptide indexing requires a large amount of time and space for construction, especially for the non-specific digestion. Additionally, it is not flexible to use.

Results
We developed an algorithm based on the longest common prefix (ABLCP) to efficiently organize a protein sequence database. The longest common prefix is a data structure that is always coupled to the suffix array. It eliminates redundant candidate peptides in databases and reduces the corresponding peptide-spectrum matching times, thereby decreasing the identification time. This algorithm is based on the property of the longest common prefix. Even enzymatic digestion poses a challenge to this property, but some adjustments can be made to this algorithm to ensure that no candidate peptides are omitted. Compared with peptide indexing, ABLCP requires much less time and space for construction and is subject to fewer restrictions.

Conclusions
The ABLCP algorithm can help to improve data analysis efficiency. A software tool implementing this algorithm is available at http://pfind.ict.ac.cn/pfind2dot5/index.htm
Protogenin, a new member of the immunoglobulin superfamily, is implicated in the development of the mouse lower first molar
Authors: Takahashi Keiko F , Kiyoshima Tamotsu , Kobayashi Ieyoshi , Xie Ming , Yamaza Haruyoshi , Fujiwara Hiroaki , Ookuma Yukiko , Nagata Kengo , Wada Hiroko , Sakai Takako , Terada Yoshihiro , Sakai Hidetaka 
Published: November 2010

Abstract

Background

Protogenin (Prtg) has been identified as a gene which is highly expressed in the mouse mandible at embryonic day 10.5 (E10.5) by a cDNA subtraction method between mandibles at E10.5 and E12.0. Prtg is a new member of the deleted in colorectal carcinoma (DCC) family, which is composed of DCC, Neogenin, Punc and Nope. Although these members play an important role in the development of the embryonic central nervous system, recent research has also shed on the non-neuronal organization. However, very little is known regarding the fetal requirement of the non-neuronal organization for Prtg and how this may be associated with the tooth germ development. This study examined the functional implications of Prtg in the developing tooth germ of the mouse lower first molar.

Results
Ptrg is preferentially expressed in the early stage of organogenesis. Prtg mRNA and protein were widely expressed in the mesenchymal cells in the mandible at E10.5. The oral epithelial cells were also positive for Prtg. The expression intensity of Prtg after E12.0 was markedly reduced in the mesenchymal cells of the mandible, and was restricted to the area where the tooth bud was likely to be formed. Signals were also observed in the epithelial cells of the tooth germ. Weak signals were observed in the inner enamel epithelial cells at E16.0 and E18.0. An inhibition assay using a hemagglutinating virus of Japan-liposome containing Prtg antisense-phosphorothioated-oligodeoxynucleotide (AS-S-ODN) in cultured mandibles at E10.5 showed a significant growth inhibition in the tooth germ. The relationship between Prtg and the odontogenesis-related genes was examined in mouse E10.5 mandible, and we verified that the Bmp-4 expression had significantly been decreased in the mouse E10.5 mandible 24 hr after treatment with Prtg AS-S-ODN.

Conclusion
These results indicated that the Prtg might be related to the initial morphogenesis of the tooth germ leading to the differentiation of the inner enamel epithelial cells in the mouse lower first molar. A better understanding of the Prtg function might thus play a critical role in revealing a precious mechanism in tooth germ development.
Genetic constraints for thermal coadaptation in Drosophila subobscura
Authors: Dolgova Olga , Rego Carla , Calabria Gemma , Balanyà Joan , Pascual Marta , Rezende Enrico L , Santos Mauro 
Published: November 2010

AbstractBackgroundBehaviour has been traditionally viewed as a driver of subsequent evolution because behavioural adjustments expose organisms to novel environments, which may result in a correlated evolution on other traits. InDrosophila subobscura, thermal preference and heat tolerance are linked to chromosomal inversion polymorphisms that show parallel latitudinal clines worldwide, such that "cold-climate" ("warm-climate") chromosome arrangements collectively favour a coherent response to colder (warmer) settings as flies carrying them prefer colder (warmer) conditions and have lower (higher) knock out temperatures. Yet, it is not clear whether a genetic correlation between thermal preference and heat tolerance can partially underlie such response.ResultsWe have analyzed the genetic basis of thermal preference and heat tolerance using isochromosomal lines inD. subobscura. Chromosome arrangements on the O chromosome were known to have a biometrical effect on thermal preference in a laboratory temperature gradient, and also harbour several genes involved in the heat shock response; in particular, the genesHsp68andHsp70. Our results corroborate that arrangements on chromosome O affect adult thermal preference in a laboratory temperature gradient, with cold-climate Ostcarriers displaying a lower thermal preference than their warm-climate O3+4and O3+4+8counterparts. However, these chromosome arrangements did not have any effect on adult heat tolerance and, hence, we putatively discard a genetic covariance between both traits arising from linkage disequilibrium between genes affecting thermal preference and candidate genes for heat shock resistance. Nonetheless, a possible association of juvenile thermal preference and heat resistance warrants further analysis.ConclusionsThermal preference and heat tolerance in the isochromosomal lines ofD. subobscuraappear to be genetically independent, which might potentially prevent a coherent response of behaviour and physiology (i.e., coadaptation) to thermal selection. If this pattern is general to all chromosomes, then any correlation between thermal preference and heat resistance across latitudinal gradients would likely reflect a pattern of correlated selection rather than genetic correlation.
Genome sequence of adherent-invasive Escherichia coli and comparative genomic analysis with other E. coli pathotypes
Authors: Nash John HE , Villegas Andre , Kropinski Andrew M , Aguilar-Valenzuela Renan , Konczy Paulina , Mascarenhas Mariola , Ziebell Kim , Torres Alfredo G , Karmali Mohamed A , Coombes Brian K 
Published: November 2010

Abstract

Background
Adherent and invasive Escherichia coli (AIEC) are commonly found in ileal lesions of Crohn's Disease (CD) patients, where they adhere to intestinal epithelial cells and invade into and survive in epithelial cells and macrophages, thereby gaining access to a typically restricted host niche. Colonization leads to strong inflammatory responses in the gut suggesting that AIEC could play a role in CD immunopathology. Despite extensive investigation, the genetic determinants accounting for the AIEC phenotype remain poorly defined. To address this, we present the complete genome sequence of an AIEC, revealing the genetic blueprint for this disease-associated E. coli pathotype.

Results
We sequenced the complete genome of E. coli NRG857c (O83:H1), a clinical isolate of AIEC from the ileum of a Crohn's Disease patient. Our sequence data confirmed a phylogenetic linkage between AIEC and extraintestinal pathogenic E. coli causing urinary tract infections and neonatal meningitis. The comparison of the NRG857c AIEC genome with other pathogenic and commensal E. coli allowed for the identification of unique genetic features of the AIEC pathotype, including 41 genomic islands, and unique genes that are found only in strains exhibiting the adherent and invasive phenotype.

Conclusions
Up to now, the virulence-like features associated with AIEC are detectable only phenotypically. AIEC genome sequence data will facilitate the identification of genetic determinants implicated in invasion and intracellular growth, as well as enable functional genomic studies of AIEC gene expression during health and disease.
Novel Method of Monitoring Trace Cytokines and Activated STAT Molecules in the Paws of Arthritic Mice using Multiplex Bead Technology
Authors: Lu Lily D , Stump Kristine L , Seavey Matthew M 
Published: November 2010

Abstract

Background
The use of mouse models to study human disease provides useful data that can provide support for research projects or an existing drug discovery program. How well a model recapitulates the human condition and the ease and reproducibility of data collected will determine how much confidence a scientist can place on results obtained. Designing new treatments for rheumatic diseases, such as rheumatoid arthritis (RA), requires complex immunocompetent models that depend on intricate cytokine networks. Using local cytokines, signal transduction and transcription factor molecules as potential biomarkers to monitor disease and treatment efficacy is the best method to follow the progression of tissue damage and repair when testing an unknown compound or biologic. Described here in this report, a novel method for the non-enzymatic extraction and measurement of cytokines and signal transducers and activators of transcription (STAT) molecules using Luminex® bead array technology in two different mouse models for human RA - collagen antibody-dependent arthritis (CAIA) and collagen-induced arthritis (CIA).

Results
Dynamic expression of several pro-inflammatory cytokines responsible for promoting disease augmentation overtime were monitored, such as IL-1β, TNFα, IL-6 and IL-12, locally in the paws of affected animals directly ex vivo. Local cytokine responses could be matched with serum cytokine levels and joint pathology results. In addition, STAT1, 3, and 5a/b activation status could be monitored with confidence using specifically formulated extraction buffer that protected the phosphorylation site. STAT3 activation followed paw swelling and cytokine levels in both models and correlates of disease could be ablated upon treatment with dexamethasone. Here reported a novel method of extracting joint fluid from the paws of inflamed mice coupled with powerful multiplex bead technology allowing us to measure cytokine responses, pharmacodynamic markers such as STATs and pharmacokinetic analysis of dosed agent all from the same sample directly ex vivo.

Conclusions
This method is powerful in that it is applicable to multiple autoimmunity model types, streamlines ex vivo readouts in a high-throughput manner, and allows multiplexing providing the investigator with an array of options and possible analytes when developing preclinical animal models to support drug discovery efforts in the search for new treatments for rheumatic diseases.
Estimation of cancer incidence and mortality attributable to alcohol drinking in china
Authors: Liang Hao , Wang Jianbing , Xiao Huijuan , Wang Ding , Wei Wenqiang , Qiao Youlin , Boffetta Paolo 
Published: November 2010

AbstractBackgroundCancer constitutes a serious burden of disease worldwide and has become the second leading cause of death in China. Alcohol consumption is causally associated with the increased risk of certain cancers. Due to the current lack of data and the imperative need to guide policymakers on issues of cancer prevention and control, we aim to estimate the role of alcohol on the cancer burden in China in 2005.MethodsWe calculated the proportion of cancers attributable to alcohol use to estimate the burden of alcohol-related cancer. The population attributable fraction was calculated based on the assumption of no alcohol drinking. Data on alcohol drinking prevalence were from two large-scale national surveys of representative samples of the Chinese population. Data on relative risk were obtained from meta-analyses and large-scale studies.ResultsWe found that a total of 78,881 cancer deaths were attributable to alcohol drinking in China in 2005, representing 4.40% of all cancers (6.69% in men, 0.42% in women). The corresponding figure for cancer incidence was 93,596 cases (3.63% of all cancer cases). Liver cancer was the main alcohol-related cancer, contributing more than 60% of alcohol-related cancers.ConclusionsParticular attention needs to be paid to the harm of alcohol as well as its potential benefits when making public health recommendations on alcohol drinking.
Impact of air pollution on pulmonary function and respiratory symptoms in children. Longitudinal repeated-measures study
Authors: Linares Benigno , Guizar Juan M , Amador Norma , Garcia Alfonso , Miranda Victor , Perez Jose R , Chapela Rocío 
Published: November 2010

Abstract

Background
Salamanca, Mexico occupied fourth place nationally in contaminating emissions. The aim of the study was to determine the impact of air pollution on the frequency of pulmonary function alterations and respiratory symptoms in school-age children in a longitudinal repeated-measures study.

Methods
We recruited a cohort of 464 children from 6 to 14 years of age, from two schools differing in distance from the major stationary air pollution sources. Spirometry, respiratory symptoms and air pollutants (O3, SO2, NO, NO2, NOx, PM10,) were obtained for each season. Mixed models for continuous variables and multilevel logistic regression for respiratory symptoms were fitted taking into account seasonal variations in health effects according to air pollution levels.

Results
Abnormalities in lung function and frequency of respiratory symptoms were higher in the school closer to major stationary air pollution sources than in the distant school. However, in winter differences on health disappeared. The principal alteration in lung function was the obstructive type, which frequency was greater in those students with greater exposure (10.4% vs. 5.3%; OR = 1.95, 95% CI 1.0-3.7), followed by the mixed pattern also more frequent in the same students (4.1% vs. 0.9%; OR = 4.69, 95% CI, 1.0-21.1). PM10 levels were the most consistent factor with a negative relationship with FVC, FEV1 and PEF but with a positive relationship with FEV1/FVC coefficient according to its change per 3-month period.

Conclusions
Students from the school closer to major stationary air pollution sources had in general more respiratory symptoms than those from the distant school. However, in winter air pollution was generalized in this city and differences in health disappeared. PM10 levels were the most consistent factor related to pulmonary function according, to its change per 3-month period.
The Key Indicator Method for Manual Handling Operations (KIM-MHO) - evaluation of a new method for the assessment of working conditions within a cross-sectional study
Authors: Klussmann André , Steinberg Ulf , Liebers Falk , Gebhardt Hansjürgen , Rieger Monika A 
Published: November 2010

Abstract

Background
Upper extremity musculoskeletal symptoms and disorders are common in the working population. The economic and social impact of such disorders is considerable. Long-time, dynamic repetitive exposure of the hand-arm system during manual handling operations (MHO) alone or in combination with static and postural effort are recognised as causes of musculoskeletal symptoms and disorders. The assessment of these manual work tasks is crucial to estimate health risks of exposed employees. For these work tasks, a new method for the assessment of the working conditions was developed by the Federal Institute for Occupational Safety and Health (BAuA) and released as a draft in the year 2007. The draft of the so-called Key Indicator Method for Manual Handling Operations (KIM-MHO) was developed in analogy with the existing KIM for Lifting/Holding/Carrying (KIM-LHC) and Pulling/Pushing (KIM-PP) of loads. The KIM-MHO is designed to fill the gap existing in risk assessment of manual work processes, since the existing KIMs deal only with manual handling of loads.
This research project focused on the following:
- Examination of the validity of workplace assessment with the KIM-MHO comparing expert ratings with the results of the observations.
- Examination of the objectivity of workplace assessment with the KIM-MHO applied by different examiners.
- Examination of the criterion validity of the risk assessment provided by KIM-MHO with respect to the association between exposure and the occurrence and prevalence of health related outcomes.

Methods/Design
To determine the objectivity and validity of workplace assessment, the KIM-MHO is applied by occupational health and safety officers at different workplaces involving manual handling operations.
To determine the criterion validity of risk assessment, a survey of employees at different workplaces takes place with standardised questionnaires and interviews about symptoms in the neck and upper extremities. In addition, physical examinations of these employees following a standardised medical diagnostic procedure are also carried out.

Discussion
This research project will provide scientific evaluation of the new KIM-MHO and, if necessary, indicate areas for modification to improve this new method for assessment of the health risk of manual handling operations at diverse workplaces.
Inhibition of core gene of HCV 3a genotype using synthetic and vector derived siRNAs
Authors: Khaliq Saba , Jahan Shah , Ijaz Bushra , Ahmad Waqar , Asad Sultan , Pervaiz Asim , Samreen Baila , Khan Mahwish , Hassan Sajida 
Published: November 2010

Abstract

Background
Hepatitis C virus (HCV) is a major causative agent of liver associated diseases throughout the world, with genotype 3a responsible for most of the cases in Pakistan. Due to the limited efficiency of current therapy, RNA interference (RNAi) a novel regulatory and powerful silencing approach for molecular therapeutics through a sequence-specific RNA degradation process represents an alternative option.

Results
The current study was purposed to assess and explore the possibility of RNAi to silence the HCV-3a Core gene expression, which play complex role in regulation of cell growth and host genes expression essential for infectivity and disease progression. To identify the potent siRNA target sites, 5 small interfering RNAs (siRNAs) against Core gene were designed and in
vitro transcribed after consensus sequence analysis of different HCV-3a isolates. Antiviral effects of siRNAs showed upto 80% inhibition of Core gene expression by different siRNAs into Huh-7 cells as compared with Mock transfected and control siRNAs treated cells. For long lasting effect of siRNAs, vector based short hairpin siRNAs (shRNAs) were designed and tested against HCV-3a Core which resulted in a similar pattern of inhibition on RNA and protein expression of HCV Core as synthetic siRNAs. Furthermore, the efficacy of cell culture tested siRNA and shRNA, were evaluated for inhibition of HCV replication in HCV infected serum inoculated Huh-7 cells and a significant decrease in HCV viral copy number was observed.

Conclusions
Our results support the possibility of using consensus siRNA and shRNA-based molecular therapy as a promising strategy in effective inhibition of HCV-3a genotype.
Computed tomography imaging of subpleural lipoma in two men: two case reports
Authors: Karlo Christoph A , Stolzmann Paul , Frauenfelder Thomas , Donati Olivio F , Leschka Sebastian 
Published: November 2010

Abstract

Introduction
Subpleural lipomas are very rare pleural lesions and are often discovered incidentally in asymptomatic patients on conventional radiographs.

Case presentations
We report two cases of subpleural lipomas and describe their imaging characteristics on chest radiographs and computed tomography. We describe the cases of two Caucasian men, aged 77 and 62 years old.

Conclusions
For non-invasive diagnostic investigation, computed tomography enables the identification and quantification of these tumors due to their characteristic fat attenuation.