bluuebunny/crossref_metadata_2025_split huggingface dataset:
First report of phase 2 study of dasatinib with hyper-CVAD for the frontline treatment of patients with Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia
Authors: Ravandi Farhad , O'Brien Susan , Thomas Deborah , Faderl Stefan , Jones Dan , Garris Rebecca , Dara Samuel , Jorgensen Jeffrey , Kebriaei Partow , Champlin Richard , Borthakur Gautam , Burger Jan , Ferrajoli Alessandra , Garcia-Manero Guillermo , Wierda William , Cortes Jorge , Kantarjian Hagop 
Published: May 2010

AbstractThe combination of cytotoxic chemotherapy and imatinib has improved the outcome for patients with Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL). Dasatinib has significant clinical activity in patients with imatinib resistance. We examined the efficacy and safety of combining chemotherapy with dasatinib for patients with Ph+ ALL. Newly diagnosed patients received dasatinib 50 mg by mouth twice per day (or 100 mg daily) for the first 14 days of each of 8 cycles of alternating hyper-CVAD, and high-dose cytarabine and methotrexate. Patients in complete remission received maintenance daily dasatinib and monthly vincristine and prednisone for 2 years, followed by dasatinib indefinitely. Thirty-five patients with untreated Ph+ ALL with a median age of 53 years (range, 21-79 years) were treated; 33 patients (94%) achieved complete remission. Two patients died of infections before response assessment. Grade 3 and 4 adverse events included hemorrhage and pleural and pericardial effusions. With a median follow-up of 14 months (range, 4-37 months), the median disease-free survival and median overall survival have not been reached, with an estimated 2-year survival of 64%. The combination of chemotherapy with dasatinib is effective in achieving long-term remissions in patients with newly diagnosed Ph+ ALL. This study was registered at www.ClinicalTrials.gov as NCT00390793.
Genome-wide estimation of firing efficiencies of origins of DNA replication from time-course copy number variation data
Authors: Luo Huaien , Li Juntao , Eshaghi Majid , Liu Jianhua , Karuturi R Krishna Murthy 
Published: May 2010

Abstract

Background
DNA replication is a fundamental biological process during S phase of cell division. It is initiated from several hundreds of origins along whole chromosome with different firing efficiencies (or frequency of usage). Direct measurement of origin firing efficiency by techniques such as DNA combing are time-consuming and lack the ability to measure all origins. Recent genome-wide study of DNA replication approximated origin firing efficiency by indirectly measuring other quantities related to replication. However, these approximation methods do not reflect properties of origin firing and may lead to inappropriate estimations.

Results
In this paper, we develop a probabilistic model - Spanned Firing Time Model (SFTM) to characterize DNA replication process. The proposed model reflects current understandings about DNA replication. Origins in an individual cell may initiate replication randomly within a time window, but the population average exhibits a temporal program with some origins replicated early and the others late. By estimating DNA origin firing time and fork moving velocity from genome-wide time-course S-phase copy number variation data, we could estimate firing efficiency of all origins. The estimated firing efficiency is correlated well with the previous studies in fission and budding yeasts.

Conclusions
The new probabilistic model enables sensitive identification of origins as well as genome-wide estimation of origin firing efficiency. We have successfully estimated firing efficiencies of all origins in S.cerevisiae, S.pombe and human chromosomes 21 and 22.
Gene bi-targeting by viral and human miRNAs
Authors: Veksler-Lublinsky Isana , Shemer-Avni Yonat , Kedem Klara , Ziv-Ukelson Michal 
Published: May 2010

Abstract

Background
MicroRNAs (miRNAs) are an abundant class of small noncoding RNAs (20-24 nts) that can affect gene expression by post-transcriptional regulation of mRNAs. They play important roles in several biological processes (e.g., development and cell cycle regulation). Numerous bioinformatics methods have been developed to identify the function of miRNAs by predicting their target mRNAs. Some viral organisms also encode miRNAs, a fact that contributes to the complex interactions between viruses and their hosts. A need arises to understand the functional relationship between viral and host miRNAs and their effect on viral and host genes. Our approach to meet this challenge is to identify modules where viral and host miRNAs cooperatively regulate host gene expression.

Results
We present a method to identify groups of viral and host miRNAs that cooperate in post-transcriptional gene regulation, and their target genes that are involved in similar biological processes. We call these groups (genes and miRNAs of human and viral origin) - modules. The modules are found in a new two-stage procedure, which we call bi-targeting, and is presented in this paper. The stages are (i) a new and efficient target prediction, and (ii) a new method for clustering objects of three different data types. In this work we integrate multiple information sources, including miRNA-target binding information, miRNA expression profiles, and GO annotations. Our hypotheses and the methods have been tested on human and Epstein Barr virus (EBV) miRNAs and human genes, for which we found 34 modules. We provide supporting evidence from biological and medical literature for two of our modules. Our code and data are available at http://www.cs.bgu.ac.il/~vaksler/BiTargeting.htm

Conclusions
The presented algorithm, which makes use of diverse biological data, is demonstrated to be an efficient approach for finding bi-targeting modules of viral and human miRNAs. These modules can contribute to a better understanding of viral-host interactions and the role that miRNAs play in them.
The gene transformer-2 of Anastrephafruit flies (Diptera, Tephritidae) and its evolution in insects
Authors: Sarno Francesca , Ruiz María F , Eirín-López José M , Perondini André LP , Selivon Denise , Sánchez Lucas 
Published: May 2010

AbstractBackgroundIn the tephritidsCeratitis,BactroceraandAnastrepha, the genetransformerprovides the memory device for sex determination via its auto-regulation; only in females is functional Tra protein produced. To date, the isolation and characterisation of the genetransformer-2in the tephritids has only been undertaken inCeratitis, and it has been shown that its function is required for the female-specific splicing ofdoublesexandtransformerpre-mRNA. It therefore participates intransformerauto-regulatory function. In this work, the characterisation of this gene in eleven tephritid species belonging to the less extensively analysed genusAnastrephawas undertaken in order to throw light on the evolution oftransformer-2.ResultsThe genetransformer-2produces a protein of 249 amino acids in both sexes, which shows the features of the SR protein family. No significant partially spliced mRNA isoform specific to the male germ line was detected, unlike inDrosophila. It is transcribed in both sexes during development and in adult life, in both the soma and germ line. The injection ofAnastrepha transformer-2dsRNA intoAnastrephaembryos caused a change in the splicing pattern of the endogenoustransformeranddoublesexpre-mRNA of XX females from the female to the male mode. Consequently, these XX females were transformed into pseudomales. The comparison of the elevenAnastrephaTransformer-2 proteins among themselves, and with the Transformer-2 proteins of other insects, suggests the existence of negative selection acting at the protein level to maintain Transformer-2 structural features.ConclusionsThese results indicate thattransformer-2is required for sex determination inAnastrephathrough its participation in the female-specific splicing oftransformeranddoublesexpre-mRNAs. It is therefore needed for the auto-regulation of the genetransformer. Thus, thetransformer/transfomer-2 > doublesexelements at the bottom of the cascade, and their relationships, probably represent the ancestral state (which still exists in the Tephritidae, Calliphoridae and Muscidae lineages) of the extant cascade found in the Drosophilidae lineage (in whichtrais just another component of the sex determination gene cascade regulated bySex-lethal). In the phylogenetic lineage that gave rise to the drosophilids, evolution co-opted forSex-lethal, modified it, and converted it into the key gene controlling sex determination.
Duplication, concerted evolution and purifying selection drive the evolution of mosquito vitellogenin genes
Authors: Chen Song , Armistead Jennifer S , Provost-Javier Katie N , Sakamoto Joyce M , Rasgon Jason L 
Published: May 2010

Abstract

Background
Mosquito vitellogenin (Vtg) genes belong to a small multiple gene family that encodes the major yolk protein precursors required for egg production. Multiple Vtg genes have been cloned and characterized from several mosquito species, but their origin and molecular evolution are poorly understood.

Results
Here we used in silico and molecular cloning techniques to identify and characterize the evolution of the Vtg gene family from the genera Culex, Aedes/Ochlerotatus, and Anopheles. We identified the probable ancestral Vtg gene among different mosquito species by its conserved association with a novel gene approximately one kilobase upstream of the start codon. Phylogenetic analysis indicated that the Vtg gene family arose by duplication events, but that the pattern of duplication was different in each mosquito genera. Signatures of purifying selection were detected in Culex, Aedes and Anopheles. Gene conversion is a major driver of concerted evolution in Culex, while unequal crossover is likely the major driver of concerted evolution in Anopheles. In Aedes, smaller fragments have undergone gene conversion events.

Conclusions
The study shows concerted evolution and purifying selection shaped the evolution of mosquito Vtg genes following gene duplication. Additionally, similar evolutionary patterns were observed in the Vtg genes from other invertebrate and vertebrate organisms, suggesting that duplication, concerted evolution and purifying selection may be the major evolutionary forces driving Vtg gene evolution across highly divergent taxa.
Massively parallel pyrosequencing-based transcriptome analyses of small brown planthopper (Laodelphax striatellus), a vector insect transmitting rice stripe virus (RSV)
Authors: Zhang Fujie , Guo Hongyan , Zheng Huajun , Zhou Tong , Zhou Yijun , Wang Shengyue , Fang Rongxiang , Qian Wei , Chen Xiaoying 
Published: May 2010

Abstract

Background
The small brown planthopper (Laodelphax striatellus) is an important agricultural pest that not only damages rice plants by sap-sucking, but also acts as a vector that transmits rice stripe virus (RSV), which can cause even more serious yield loss. Despite being a model organism for studying entomology, population biology, plant protection, molecular interactions among plants, viruses and insects, only a few genomic sequences are available for this species. To investigate its transcriptome and determine the differences between viruliferous and naïve L. striatellus, we employed 454-FLX high-throughput pyrosequencing to generate EST databases of this insect.

Results
We obtained 201,281 and 218,681 high-quality reads from viruliferous and naïve L. striatellus, respectively, with an average read length as 230 bp. These reads were assembled into contigs and two EST databases were generated. When all reads were combined, 16,885 contigs and 24,607 singletons (a total of 41,492 unigenes) were obtained, which represents a transcriptome of the insect. BlastX search against the NCBI-NR database revealed that only 6,873 (16.6%) of these unigenes have significant matches. Comparison of the distribution of GO classification among viruliferous, naïve, and combined EST databases indicated that these libraries are broadly representative of the L. striatellus transcriptomes. Functionally diverse transcripts from RSV, endosymbiotic bacteria Wolbachia and yeast-like symbiotes were identified, which reflects the possible lifestyles of these microbial symbionts that live in the cells of the host insect. Comparative genomic analysis revealed that L. striatellus encodes similar innate immunity regulatory systems as other insects, such as RNA interference, JAK/STAT and partial Imd cascades, which might be involved in defense against viral infection. In addition, we determined the differences in gene expression between vector and naïve samples, which generated a list of candidate genes that are potentially involved in the symbiosis of L. striatellus and RSV.

Conclusions
To our knowledge, the present study is the first description of a genomic project for L. striatellus. The identification of transcripts from RSV, Wolbachia, yeast-like symbiotes and genes abundantly expressed in viruliferous insect, provided a starting-point for investigating the molecular basis of symbiosis among these organisms.
Primary gamma-herpesviral infection in Zambian children
Authors: Minhas Veenu , Brayfield Brad P , Crabtree Kay L , Kankasa Chipepo , Mitchell Charles D , Wood Charles 
Published: May 2010

Abstract

Background
HHV-8 is closely related to Epstein-Barr virus (EBV), but the clinical presentations of these two infections in early childhood are not well understood. Also, it is not known whether infection by one virus correlates with another. Here, we compare the natural history of infection by these two viruses along with the clinical manifestations and risk factors that are associated with early childhood infection in Zambia, which is an endemic area for HHV-8.

Methods
This study was conducted in a cohort of 12 month old Zambian children (N = 677). Data on socio-economic status and a wide range of clinical manifestations were collected. Logistic regression was used to test for significant associations between the collected variables and HHV-8 or EBV serostatus at 12 months of age.

Results
We observed a significantly higher seroprevalence for EBV (58.9%) as compared to HHV-8 (13.4%). HIV-1 infected children had at a significantly higher risk of being infected with HHV-8 (Odds ratio [OR] 3.69, 95% confidence interval [CI] 1.64 - 8.32). HIV-1 infection of the mothers was a significant risk factor for increased acquisition of EBV but not HHV-8 by children (OR 1.86, 05% CI 1.20 - 2.87). Self reported rash was marginally associated with primary infection for HHV-8 and EBV.

Conclusions
These results suggest that there is no correlation between EBV and HHV-8 infections. Infection by one does not increase the susceptibility for the second virus. Primary HHV-8 and EBV infection in early childhood may clinically present as rash but remains largely asymptomatic and may remain undetected in this population. HIV infection in the mother or child are important risk factors that contribute to EBV or HHV-8 infection.
A long-term follow-up of the imatinib mesylate treatment for the patients with recurrent gastrointestinal stromal tumor (GIST): the liver metastasis and the outcome
Authors: Zhu Jiang , Yang Yu , Zhou Lin , Jiang Ming , Hou Mei 
Published: May 2010

Abstract

Background
About 80% of patients with GIST would experience tumor recurrence or metastasis after radical resection. The most common site of the metastasis is the liver. Imatinib mesylate has been proved effective for advanced GIST. The present study was designed to further observe the effectiveness of the imatinib mesylate treatment on the recurrent GIST and the correlation between the liver metastasis and the outcome.

Methods
Forty-two patients who had recurrent GIST after the first radical resection were enrolled. According to the recurrent sites, the patients were divided into 3 groups: group LG (recurrent liver GISTs), group AG (recurrent abdominal GISTs) and group ALG (recurrent abdominal and liver GISTs). All the patients were given imatinib mesylate at an initial dose of 400 mg per day. Their clinical data was prospectively collected. A follow-up over 3 years was conducted. Tumor response, time to progression and survival were evaluated.

Results
The long-term Imatinib mesylate treatment was safe and well tolerated. At a median follow-up time for 39.5 months, the 3-year survival rate was 66.7%. Median TTP and OS were 37 months (95% CI: 28.2~45.8 months) and 48 months (95% CI: 37.0~58.9 months), respectively. There was no statistical difference in tumor response among the 3 groups. The similar TTP (P = 0.291) and OS (P = 0.160) were observed in the 3 groups.

Conclusions
The imatinib mesylate treatment could prolong the survival of the patients who have recurrent GIST after the radical surgery in spite of an existence of the liver metastasis. Survival was not significantly affected by liver metastasis when imatinib mesylate was warranted.
Seladin-1 expression is regulated by promoter methylation in adrenal cancer
Authors: Simi Lisa , Malentacchi Francesca , Luciani Paola , Gelmini Stefania , Deledda Cristiana , Arvia Rosaria , Mannelli Massimo , Peri Alessandro , Orlando Claudio 
Published: May 2010

AbstractBackgroundSeladin-1 overexpression exerts a protective mechanism against apoptosis. Seladin-1 mRNA is variably expressed in normal human tissues. Adrenal glands show the highest levels of seladin-1 expression, which are significantly reduced in adrenal carcinomas (ACC). Since up to now seladin-1 mutations were not described, we investigated whether promoter methylation could account for the down-regulation of seladin-1 expression in ACC.MethodsA methylation sensitive site was identified in the seladin-1 gene. We treated DNA extracted from two ACC cell lines (H295R and SW13) with the demethylating agent 5-Aza-2-deoxycytidine (5-Aza). Furthermore, to evaluate the presence of an epigenetic regulation also 'in vivo', seladin-1 methylation and its mRNA expression were measured in 9 ACC and in 5 normal adrenal glands.ResultsThe treatment of cell lines with 5-Aza induced a significant increase of seladin-1 mRNA expression in H295R (fold increase, F.I. = 1.8; p = 0.02) and SW13 (F.I. = 2.9; p = 0.03). In ACC, methylation density of seladin-1 promoter was higher (2682 ± 686) than in normal adrenal glands (362 ± 97; p = 0.02). Seladin-1 mRNA expression in ACC (1452 ± 196) was significantly lower than in normal adrenal glands (3614 ± 949; p = 0.01).ConclusionOn this basis, methylation could be involved in the altered pattern of seladin-1 gene expression in ACC.
From design to implementation - The Joint Asia Diabetes Evaluation (JADE) program: A descriptive report of an electronic web-based diabetes management program
Authors: Ko Gary T , So Wing-Yee , Tong Peter C , Le Coguiec Francois , Kerr Debborah , Lyubomirsky Greg , Tamesis Beaver , Wolthers Troels , Nan Jennifer , Chan Juliana 
Published: May 2010

Abstract

Background
The Joint Asia Diabetes Evaluation (JADE) Program is a web-based program incorporating a comprehensive risk engine, care protocols, and clinical decision support to improve ambulatory diabetes care.

Methods
The JADE Program uses information technology to facilitate healthcare professionals to create a diabetes registry and to deliver an evidence-based care and education protocol tailored to patients' risk profiles. With written informed consent from participating patients and care providers, all data are anonymized and stored in a databank to establish an Asian Diabetes Database for research and publication purpose.

Results
The JADE electronic portal (e-portal: http://www.jade-adf.org) is implemented as a Java application using the Apache web server, the mySQL database and the Cocoon framework. The JADE e-portal comprises a risk engine which predicts 5-year probability of major clinical events based on parameters collected during an annual comprehensive assessment. Based on this risk stratification, the JADE e-portal recommends a care protocol tailored to these risk levels with decision support triggered by various risk factors. Apart from establishing a registry for quality assurance and data tracking, the JADE e-portal also displays trends of risk factor control at each visit to promote doctor-patient dialogues and to empower both parties to make informed decisions.

Conclusions
The JADE Program is a prototype using information technology to facilitate implementation of a comprehensive care model, as recommended by the International Diabetes Federation. It also enables health care teams to record, manage, track and analyze the clinical course and outcomes of people with diabetes.
A nuclear targeting system in Plasmodium falciparum
Authors: Wittayacom Kanjana , Uthaipibull Chairat , Kumpornsin Krittikorn , Tinikul Ruchanok , Kochakarn Theerarat , Songprakhon Pucharee , Chookajorn Thanat 
Published: May 2010

AbstractBackgroundThe distinct differences in gene control mechanisms acting in the nucleus betweenPlasmodium falciparumand the human host could lead to new potential drug targets for anti-malarial development. New molecular toolkits are required for dissecting molecular machineries in theP. falciparumnucleus. One valuable tool commonly used in model organisms is protein targeting to specific sub-cellular locations. Targeting proteins to specified locations allows labeling of organelles for microscopy, or testing of how the protein of interest modulates organelle function. In recent years, this approach has been developed for various malaria organelles, such as the mitochondrion and the apicoplast. A tool for targeting a protein of choice to theP. falciparumnucleus using an exogenous nuclear localization sequence is reported here.MethodsTo develop a nuclear targeting system, a putative nuclear localization sequence was fused with green fluorescent protein (GFP). The nuclear localization sequence from the yeast transcription factor Gal4 was chosen because of its well-defined nuclear localization signal. A series of truncated Gal4 constructs was also created to narrow down the nuclear localization sequence necessary forP. falciparumnuclear import. Transfected parasites were analysed by fluorescent and laser-scanning confocal microscopy.ResultsThe nuclear localization sequence of Gal4 is functional inP. falciparum. It effectively transported GFP into the nucleus, and the first 74 amino acid residues were sufficient for nuclear localization.ConclusionsThe Gal4 fusion technique enables specific transport of a protein of choice into theP. falciparumnucleus, and thus provides a tool for labeling nuclei without using DNA-staining dyes. The finding also indicates similarities between the nuclear transport mechanisms of yeast andP. falciparum. Since the nuclear transport system has been thoroughly studied in yeast, this could give clues to research on the same mechanism inP. falciparum.