bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-agent arsenic trioxide in the treatment of children with newly diagnosed acute promyelocytic leukemia
Authors: Zhou Jin , Zhang Yingmei , Li Jinmei , Li Xiaoxia , Hou Jinxiao , Zhao Yanqiu , Liu Xiuhua , Han Xueying , Hu Longhu , Wang Shuye , Zhao Yanhong , Zhang Ying , Fan Shengjin , Lv Chengfang , Li Limin , Zhu Lingling 
Published: December 2009

Abstract
The aim of this study was to determine the efficacy and safety of treatment of pediatric acute promyelocytic leukemia (APL) with single-agent arsenic trioxide (ATO). A total of 19 children (≤ 15 years of age) with newly diagnosed APL were treated with single-agent ATO for remission induction and postremission therapy. Seventeen of the children (89.5%) achieved complete hematologic remission, and 2 early deaths occurred from intracranial hemorrhage. ATO-induced leukocytosis was observed in 13 (68.4%) patients. Other ATO-related toxicities were minimal and transient. Postremission ATO therapy continued for 3 years; the most common side effect was ATO-induced neutropenia. With a median follow-up of 53 months (range, 23-76 months), the calculated 5-year overall survival and event-free survival were 83.9% and 72.7%, respectively, which are comparable with results achieved by the use of ATRA plus chemotherapy, which is the standard therapy for APL. No chronic arsenic toxicity or second malignancies were found during the follow-up period, and arsenic retention was not significant in patients off treatment more than 24 months. ATO resistance was observed in only 1 patient with a complex karyotype. The results indicate the high efficacy and safety of single-agent ATO regimens in the treatment of children with de novo APL.
A new permutation strategy of pathway-based approach for genome-wide association study
Authors: Guo Yan-Fang , Li Jian , Chen Yuan , Zhang Li-Shu , Deng Hong-Wen 
Published: December 2009

Abstract

Background
Recently introduced pathway-based approach is promising and advantageous to improve the efficiency of analyzing genome-wide association scan (GWAS) data to identify disease variants by jointly considering variants of the genes that belong to the same biological pathway. However, the current available pathway-based approaches for analyzing GWAS have limited power and efficiency.

Results
We proposed a new and efficient permutation strategy based on SNP randomization for determining significance in pathway analysis of GWAS. The developed permutation strategy was evaluated and compared to two previously available methods, i.e. sample permutation and gene permutation, through simulation studies and a study on a real dataset. Results showed that the proposed permutation strategy is more powerful and efficient with greatly reducing the computational complexity.

Conclusion
Our findings indicate the improved performance of SNP permutation and thus render pathway-based analysis of GWAS more applicable and attractive.
Complete reversal of epithelial to mesenchymal transition requires inhibition of both ZEB expression and the Rho pathway
Authors: Das Shreyas , Becker Bryan N , Hoffmann F Michael , Mertz Janet E 
Published: December 2009

Abstract

Background
Epithelial to Mesenchymal Transition (EMT) induced by Transforming Growth Factor-β (TGF-β) is an important cellular event in organogenesis, cancer, and organ fibrosis. The process to reverse EMT is not well established. Our purpose is to define signaling pathways and transcription factors that maintain the TGF-β-induced mesenchymal state.

Results
Inhibitors of five kinases implicated in EMT, TGF-β Type I receptor kinase (TβRI), p38 mitogen-activated protein kinase (p38 MAPK), MAP kinase kinase/extracellular signal-regulated kinase activator kinase (MEK1), c-Jun NH-terminal kinase (JNK), and Rho kinase (ROCK), were evaluated for reversal of the mesenchymal state induced in renal tubular epithelial cells. Single agents did not fully reverse EMT as determined by cellular morphology and gene expression. However, exposure to the TβRI inhibitor SB431542, combined with the ROCK inhibitor Y27632, eliminated detectable actin stress fibers and mesenchymal gene expression while restoring epithelial E-cadherin and Kidney-specific cadherin (Ksp-cadherin) expression. A second combination, the TβRI inhibitor SB431542 together with the p38 MAPK inhibitor SB203580, was partially effective in reversing EMT. Furthermore, JNK inhibitor SP600125 inhibits the effectiveness of the TβRI inhibitor SB431542 to reverse EMT. To explore the molecular basis underlying EMT reversal, we also targeted the transcriptional repressors ZEB1 and ZEB2/SIP1. Decreasing ZEB1 and ZEB2 expression in mouse mammary gland cells with shRNAs was sufficient to up-regulate expression of epithelial proteins such as E-cadherin and to re-establish epithelial features. However, complete restoration of cortical F-actin required incubation with the ROCK inhibitor Y27632 in combination with ZEB1/2 knockdown.

Conclusions
We demonstrate that reversal of EMT requires re-establishing both epithelial transcription and structural components by sustained and independent signaling through TβRI and ROCK. These findings indicate that combination small molecule therapy targeting multiple kinases may be necessary to reverse disease conditions.
Developmental dynamics of cone photoreceptors in the eel
Authors: Cottrill Phillippa B , Davies Wayne L , Semo Ma'ayan , Bowmaker James K , Hunt David M , Jeffery Glen 
Published: December 2009

Abstract

Background
Many fish alter their expressed visual pigments during development. The number of retinal opsins expressed and their type is normally related to the environment in which they live. Eels are known to change the expression of their rod opsins as they mature, but might they also change the expression of their cone opsins?

Results
The Rh2 and Sws2 opsin sequences from the European Eel were isolated, sequenced and expressed in vitro for an accurate measurement of their λmax values. In situ hybridisation revealed that glass eels express only rh2 opsin in their cone photoreceptors, while larger yellow eels continue to express rh2 opsin in the majority of their cones, but also have <5% of cones which express sws2 opsin. Silver eels showed the same expression pattern as the larger yellow eels. This observation was confirmed by qPCR (quantitative polymerase chain reaction).

Conclusions
Larger yellow and silver European eels express two different cone opsins, rh2 and sws2. This work demonstrates that only the Rh2 cone opsin is present in younger fish (smaller yellow and glass), the sws2 opsin being expressed additionally only by older fish and only in <5% of cone cells.
Phylogenomics of the oxidative phosphorylation in fungi reveals extensive gene duplication followed by functional divergence
Authors: Marcet-Houben Marina , Marceddu Giuseppe , Gabaldón Toni 
Published: December 2009

Abstract

Background
Oxidative phosphorylation is central to the energy metabolism of the cell. Due to adaptation to different life-styles and environments, fungal species have shaped their respiratory pathways in the course of evolution. To identify the main mechanisms behind the evolution of respiratory pathways, we conducted a phylogenomics survey of oxidative phosphorylation components in the genomes of sixty fungal species.

Results
Besides clarifying orthology and paralogy relationships among respiratory proteins, our results reveal three parallel losses of the entire complex I, two of which are coupled to duplications in alternative dehydrogenases. Duplications in respiratory proteins have been common, affecting 76% of the protein families surveyed. We detect several instances of paralogs of genes coding for subunits of respiratory complexes that have been recruited to other multi-protein complexes inside and outside the mitochondrion, emphasizing the role of evolutionary tinkering.

Conclusions
Processes of gene loss and gene duplication followed by functional divergence have been rampant in the evolution of fungal respiration. Overall, the core proteins of the respiratory pathways are conserved in most lineages, with major changes affecting the lineages of microsporidia, Schizosaccaromyces and Saccharomyces/Kluyveromyces due to adaptation to anaerobic life-styles. We did not observe specific adaptations of the respiratory metabolism common to all pathogenic species.
Phylogenetic analysis and temporal diversification of mosquitoes (Diptera: Culicidae) based on nuclear genes and morphology
Authors: Reidenbach Kyanne R , Cook Shelley , Bertone Matthew A , Harbach Ralph E , Wiegmann Brian M , Besansky Nora J 
Published: December 2009

Abstract

Background
Phylogenetic analyses provide a framework for examining the evolution of morphological and molecular diversity, interpreting patterns in biogeography, and achieving a stable classification. The generic and suprageneric relationships within mosquitoes (Diptera: Culicidae) are poorly resolved, making these subjects difficult to address.

Results
We carried out maximum parsimony and maximum likelihood, including Bayesian, analyses on a data set consisting of six nuclear genes and 80 morphological characters to assess their ability to resolve relationships among 25 genera. We also estimated divergence times based on sequence data and fossil calibration points, using Bayesian relaxed clock methods. Strong support was recovered for the basal position and monophyly of the subfamily Anophelinae and the tribes Aedini and Sabethini of subfamily Culicinae. Divergence times for major culicid lineages date to the early Cretaceous.

Conclusions
Deeper relationships within the family remain poorly resolved, suggesting the need for additional taxonomic sampling. Our results support the notion of rapid radiations early in the diversification of mosquitoes.
Pre-radiotherapy plasma carotenoids and markers of oxidative stress are associated with survival in head and neck squamous cell carcinoma patients: a prospective study
Authors: Sakhi Amrit K , Russnes Kjell M , Thoresen Magne , Bastani Nasser E , Karlsen Anette , Smeland Sigbjørn , Blomhoff Rune 
Published: December 2009

Abstract

Background
The purpose of this study was to compare plasma levels of antioxidants and oxidative stress biomarkers in head and neck squamous cell carcinoma (HNSCC) patients with healthy controls. Furthermore, the effect of radiotherapy on these biomarkers and their association with survival in HNSCC patients were investigated.

Methods
Seventy-eight HNSCC patients and 100 healthy controls were included in this study. Follow-up samples at the end of radiotherapy were obtained in 60 patients. Fifteen antioxidant biomarkers (6 carotenoids, 4 tocopherols, ascorbic acid, total antioxidant capacity, glutathione redox potential, total glutathione and total cysteine) and four oxidative stress biomarkers (total hydroperoxides, γ-glutamyl transpeptidase, 8-isoprostagladin F2α and ratio of oxidized/total ascorbic acid) were measured in plasma samples. Analysis of Covariance was used to compare biomarkers between patients and healthy controls. Kaplan-Meier plots and Cox' proportional hazards models were used to study survival among patients.

Results
Dietary antioxidants (carotenoids, tocopherols and ascorbic acid), ferric reducing antioxidant power (FRAP) and modified FRAP were lower in HNSCC patients compared to controls and dietary antioxidants decreased during radiotherapy. Total hydroperoxides (d-ROMs), a marker for oxidative stress, were higher in HNSCC patients compared to controls and increased during radiotherapy. Among the biomarkers analyzed, high levels of plasma carotenoids before radiotherapy are associated with a prolonged progression-free survival (hazard rate ratio: 0.42, 95% CI: 0.20-0.91, p = 0.03). Additionally, high relative increase in plasma levels of d-ROMs (hazard rate ratio: 0.31, 95% CI: 0.13-0.76, p = 0.01) and high relative decrease in FRAP (hazard rate ratio: 0.42, 95% CI: 0.17-0.998, p = 0.05) during radiotherapy are also positively associated with survival.

Conclusions
Biomarkers of antioxidants and oxidative stress are unfavourable in HNSCC patients compared to healthy controls, and radiotherapy affects many of these biomarkers. Increasing levels of antioxidant biomarkers before radiotherapy and increasing oxidative stress during radiotherapy may improve survival indicating that different factors/mechanisms may be important for survival before and during radiotherapy in HNSCC patients. Thus, the therapeutic potential of optimizing antioxidant status and oxidative stress should be explored further in these patients.
RNA degradation compromises the reliability of microRNA expression profiling
Authors: Ibberson David , Benes Vladimir , Muckenthaler Martina U , Castoldi Mirco 
Published: December 2009

Abstract

Background
MicroRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression and their expression is frequently altered in human diseases, including cancer. To correlate clinically relevant parameters with microRNA expression, total RNA is frequently prepared from samples that were archived for various time periods in frozen tissue banks but, unfortunately, RNA integrity is not always preserved in these frozen tissues. Here, we investigate whether experimentally induced RNA degradation affects microRNA expression profiles.

Results
Tissue samples were maintained on ice for defined time periods prior to total RNA extraction, which resulted in different degrees of RNA degradation. MicroRNA expression was then analyzed by microarray analysis (miCHIP) or microRNA-specific real-time quantitative PCR (miQPCR). Our results demonstrate that the loss of RNA integrity leads to in unpredictability of microRNA expression profiles for both, array-based and miQPCR assays.

Conclusion
MicroRNA expression cannot be reliably profiled in degraded total RNA. For the profiling of microRNAs we recommend use of RNA samples with a RNA integrity number equal to or above seven.
Identification and verification of ultrafine particle affinity zones in urban neighbourhoods: sample design and data pre-processing
Authors: Harris Paul , Lindley Sarah , Gallagher Martin , Agius Raymond 
Published: December 2009

AbstractA methodology is presented and validated through which long-term fixed site air quality measurements are used to characterise and remove temporal signals in sample-based measurements which have good spatial coverage but poor temporal resolution. The work has been carried out specifically to provide a spatial dataset of atmospheric ultrafine particle (UFP < 100 nm) data for ongoing epidemiologic cohort analysis but the method is readily transferable to wider epidemiologic investigations and research into the health effects of other pollutant species.
Comparative proteomic analysis of pathogenic and non-pathogenic strains from the swine pathogen Mycoplasma hyopneumoniae
Authors: Pinto Paulo M , Klein Cátia S , Zaha Arnaldo , Ferreira Henrique B 
Published: December 2009

AbstractBackgroundMycoplasma hyopneumoniaeis a highly infectious swine pathogen and is the causative agent of enzootic pneumonia (EP). Following the previous report of a proteomic survey of the pathogenic 7448 strain of swine pathogen,Mycoplasma hyopneumoniae, we performed comparative protein profiling of threeM. hyopneumoniaestrains, namely the non-pathogenic J strain and the two pathogenic strains 7448 and 7422.ResultsIn 2DE comparisons, we were able to identify differences in expression levels for 67 proteins, including the overexpression of some cytoadherence-related proteins only in the pathogenic strains. 2DE immunoblot analyses allowed the identification of differential proteolytic cleavage patterns of the P97 adhesin in the three strains. For more comprehensive protein profiling, an LC-MS/MS strategy was used. Overall, 35% of theM. hyopneumoniaegenome coding capacity was covered. Partially overlapping profiles of identified proteins were observed in the strains with 81 proteins identified only in one strain and 54 proteins identified in two strains. Abundance analysis of proteins detected in more than one strain demonstrates the relative overexpression of 64 proteins, including the P97 adhesin in the pathogenic strains.ConclusionsOur results indicate the physiological differences between the non-pathogenic strain, with its non-infective proliferate lifestyle, and the pathogenic strains, with its constitutive expression of adhesins, which would render the bacterium competent for adhesion and infection prior to host contact.
Race and ancestry in biomedical research: exploring the challenges
Authors: Caulfield Timothy , Fullerton Stephanie M , Ali-Khan Sarah E , Arbour Laura , Burchard Esteban G , Cooper Richard S , Hardy Billie-Jo , Harry Simrat , Hyde-Lay Robyn , Kahn Jonathan , Kittles Rick , Koenig Barbara A , Lee Sandra SJ , Malinowski Michael , Ravitsky Vardit , Sankar Pamela , Scherer Stephen W , Séguin Béatrice , Shickle Darren , Suarez-Kurtz Guilherme , Daar Abdallah S 
Published: December 2009

AbstractThe use of race in biomedical research has, for decades, been a source of social controversy. However, recent events, such as the adoption of racially targeted pharmaceuticals, have raised the profile of the race issue. In addition, we are entering an era in which genomic research is increasingly focused on the nature and extent of human genetic variation, often examined by population, which leads to heightened potential for misunderstandings or misuse of terms concerning genetic variation and race. Here, we draw together the perspectives of participants in a recent interdisciplinary workshop on ancestry and health in medicine in order to explore the use of race in research issue from the vantage point of a variety of disciplines. We review the nature of the race controversy in the context of biomedical research and highlight several challenges to policy action, including restrictions resulting from commercial or regulatory considerations, the difficulty in presenting precise terminology in the media, and drifting or ambiguous definitions of key terms.
Intensive Loading Dose of Trastuzumab Achieves Higher-Than-Steady–State Serum Concentrations and Is Well Tolerated
Authors: Leyland-Jones Brian , Colomer Ramon , Trudeau Maureen E. , Wardley Andrew , Latreille Jean , Cameron David , Cubedo Ricardo , Al-Sakaff Nedal , Feyereislova Andrea , Catalani Olivier , Fukushima Yumi , Brewster Michael , Cortés Javier 
Published: December 2009

Purpose Pharmacokinetics (PKs) and safety results from phase II/III trials suggest that, if high trastuzumab serum concentrations are reached early during treatment for human epidermal growth factor receptor 2 (HER2)–positive breast cancer, patients will gain clinical benefit, and the synergistic effects of trastuzumab and chemotherapy will be maximized. This phase I/II study evaluated the PKs, efficacy, and safety of a novel, intensive loading regimen of trastuzumab in women with HER2-positive metastatic breast cancer (MBC). Patients and Methods An intensive loading regimen of trastuzumab was given (6 mg/kg intravenously on days 1, 8, and 15 followed by 6 mg/kg every 3 weeks from day 22) to women age 18 years or older with HER2-positive MBC who may have received previous surgery, radiotherapy, and/or chemotherapy. Study medication was continued until disease progression or withdrawal occurred. Results All eligible women (N = 72) received at least one dose of trastuzumab. Median estimated trough concentration of trastuzumab at the end of 3 weeks of the intensive loading regimen (total of 18 mg/kg of trastuzumab administered) of cycle 1 was 119 mg/L, which is higher than steady-state trough concentrations with a conventional weekly or every-3-week regimen (64.9 or 47.3 mg/L, respectively). No new or unexpected adverse events or increased cardiotoxicity were reported during the study. In patients with measurable disease (n = 47), response rate was 23.4%. Median time to progression was 7.7 months (in all patients). Conclusion An intensive loading regimen of trastuzumab achieved higher-than-steady–state serum concentrations during cycle 1, was well tolerated, and had a good efficacy profile.
Pandemic influenza A (H1N1) 2009: the experience of the first six months
Authors: Maritz Jean , Maree Leana , Preiser Wolfgang 
Published: December 2009

Abstract
After a break of 41 years, 2009 saw the first influenza pandemic of the 21st century caused by a triple-reassortant influenza A (H1N1) virus. The current estimated case fatality rate is lower than that of previous influenza pandemics, but this may change as the pandemic evolves. Illness frequently occurs in previously healthy, young adults with a wide range of clinical presentations. The majority of circulating pandemic viruses remain susceptible to neuraminidase inhibitors, although all strains are intrinsically resistant to the adamantanes. Monovalent vaccines against the pandemic strain are available in both live attenuated and inactivated forms. This review aims to summarise important virological, epidemiological and clinical aspects of the pandemic influenza A (H1N1) virus for physicians and other clinical personnel.
Clin Chem Lab Med 2010;48:11–21.
Natural Variation in Odorant Recognition Among Odorant-Binding Proteins in Drosophila melanogaster
Authors: Wang Ping , Lyman Richard F , Mackay Trudy F C , Anholt Robert R H 
Published: December 2009

Abstract
Chemical recognition is essential for survival and reproduction. Adaptive evolution has resulted in diverse chemoreceptor families, in which polymorphisms contribute to individual variation in chemosensation. To gain insights into the genetic determinants of individual variation in odorant recognition, we measured olfactory responses to two structurally similar odorants in a population of wild-derived inbred lines of Drosophila melanogaster. Odorant-binding proteins (OBPs) are the first components of the insect olfactory system to encounter odorants. Previously four single-nucleotide polymorphisms (SNPs) in the Obp99 group were associated with variation in olfactory responses to benzaldehyde. Here, we identify six different SNPs that are associated with variation in responses to a structurally similar odorant, acetophenone, in the same Obp genes. Five SNPs are in coding regions of Obp99b and Obp99d and one SNP is in the 3′-untranslated region of Obp99a (A610G). We found that the 610G allele is associated with higher response scores to acetophenone than the 610A allele, but with lower expression of Obp99a, suggesting that binding of acetophenone to Opb99a might limit rather than facilitate access to odorant receptors. Our results show that overlapping sets of OBPs contribute to odorant recognition for structurally similar odorants, but that different SNPs are associated with odorant-specific individual variation. Thus, dual olfactory recognition where OBPs regulate odorant access to receptors may enhance olfactory discrimination.
An Algebraic Approach to Weakly Symmetric Finsler Spaces
Authors: Deng Shaoqiang 
Published: December 2009

AbstractIn this paper, we introduce a new algebraic notion, weakly symmetric Lie algebras, to give an algebraic description of an interesting class of homogeneous Riemann-Finsler spaces, weakly symmetric Finsler spaces. Using this new definition, we are able to give a classification of weakly symmetric Finsler spaces with dimensions 2 and 3. Finally, we show that all the non-Riemannian reversible weakly symmetric Finsler spaces we find are non-Berwaldian and with vanishing S-curvature. Thismeans that reversible non-Berwaldian Finsler spaces with vanishing S-curvaturemay exist at large. Hence the generalized volume comparison theorems due to Z. Shen are valid for a rather large class of Finsler spaces.