bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prolonged use of extracorporeal membrane oxygenation combined with prone positioning in patients with acute respiratory distress syndrome and invasive Aspergillosis
Authors: Otterspoor LC , Smit FH , van Laar TJ , Kesecioglu J , van Dijk D 
Published: March 2012

Extracorporeal membrane oxygenation (ECMO) is increasingly being used in patients with severe acute respiratory distress syndrome. In two large cohorts of such patients, the median duration of treatment with ECMO was 9 and 10 days. We describe two patients, both with H1N1 pneumonia complicated by invasive Aspergillosis, who required ECMO support significantly longer at 45 and 52 days, but eventually made a full recovery. In both patients, prone positioning was used during ECMO treatment.
Preparation and properties of dynamically cured polypropylene (PP)/maleic anhydride–grafted polypropylene (MAH-g-PP)/calcium carbonate (CaCO3)/epoxy composites
Authors: Jiang Xueliang , Fan Yihong , Li Fan 
Published: March 2012

In this study, an epoxy resin was dynamically cured in a polypropylene (PP)/maleic anhydride–grafted polypropylene (MAH-g-PP)/calcium carbonate (CaCO3) matrix to prepare dynamically cured PP/MAH-g-PP/CaCO3/epoxy composites. The torque measurement shows that the addition of epoxy resin into the PP/MAH-g-PP/CaCO3 composites results in a slight increase in the torque at equilibrium, and epoxy resin in the composites has been cured by 2-ethylene-4-methane-imidazole (EMI-2,4). Scanning electron microscopic analysis shows that dual compatibilizers composed of MAH-g-PP and an epoxy resin were demonstrated to effectively compatibilize the immiscible PP/CaCO3 composites. MAH-g-PP with a low MAH content is miscible with PP to make it quasi-functionalized, while the epoxy resin can react with MAH-g-PP and hydroxyl groups at the CaCO3 surface. Thus the formed MAH-g-PP-co-epoxy-co-CaCO3 copolymer at the interface is able to anchor along the interface and serve as an efficient compatibilizer. Dynamic cure of the epoxy resin can further increase the interaction adhesion in the PP/CaCO3 composites. The epoxy resin does not show compatibilization effects for the PP/CaCO3 composites without the presence of MAH-g-PP. The shift of crystallization peaks to the higher temperature suggests that the CaCO3 filler in the composites can act as a nucleating agent, accelerating the crystallization of PP component, and the PP/CaCO3 composites compatibilized by MAH-g-PP and the epoxy resin have higher crystallization peaks. This shows that an increase in the interaction adhesion between the CaCO3 and PP matrix, improving the nucleating activity of the filler and promoting crystallization of PP. Thermogravimetric analysis shows that the incorporation of the CaCO3 into the PP could improve the thermal stability of PP, and the addition of MAH-g-PP and the epoxy resin into the composites obviously could further improve the thermal stability. The mechanical properties of PP/MAH-g-PP/CaCO3 and PP/MAH-g-PP/CaCO3/epoxy composites are better than that of the PP/CaCO3 composites. The PP/MAH-g-PP/CaCO3/epoxy/EMI-2,4 composites have the best mechanical properties in all the PP/CaCO3 composites, which is attributed to the better interaction adhesion. The suitable content of epoxy resin is about 5 wt% in the presence of MAH-g-PP in the PP/CaCO3 composites, while an excess epoxy resin of above 5 wt% acts as an organic filler for PP.
The Utility of a Forehead-to-Inion Derivation in Recording the Subcortical Far-Field Potential (P14) During Median Nerve Somatosensory-Evoked Potential Testing
Authors: Fried Stephen J. , Legatt Alan D. 
Published: March 2012

American Clinical Neurophysiology Society (ACNS) guidelines recommend recording P14 between an ipsilateral centroparietal electrode (CPi) and a noncephalic reference, typically the contralateral Erb’s point (EPc) (American Clinical Neurophysiology Society. Guideline 9D: guidelines on short-latency somatosensory evoked potentials. J Clin Neurophysiol. 2006;23(2):168-179). We investigated the utility of a forehead (Fpz)-to-inion derivation for recording P14. We analyzed 74 median nerve somatosensory-evoked potential (SEP) studies (148 nerves) with bilaterally normal peripheral and central conductions. The presence of an identifiable P14 and its amplitude and latency were assessed in both the CPi-EPc and Fpz-inion derivations. In 7 of the 148 recordings, P14 was not identifiable in either derivation. The P14 was only identifiable in CPi-EPc in 9 recordings, and only identifiable in Fpz-inion in 4 recordings. In the remaining 128 recordings, the mean P14 latency was 13.2 ± 1.1 ms in both derivations. The mean P14 amplitude using CPi-EPc was 2.0 ± 0.6 µV, significantly larger than that using Fpz-inion, 1.2 ± 0.6 µV ( P < .001). In conclusion, the CPi-EPc derivation and the Fpz-inion derivation both record the same P14 component, and latency norms based on either derivation are interchangeable. Although the CPi-EPc derivation typically yields a larger and more identifiable P14, occasionally Fpz-inion yields a larger P14, and rarely P14 is only identifiable using Fpz-inion. Thus, recording of the Fpz-inion derivation may be a useful adjunct during median nerve SEP testing.
Social networking research opportunities: the example of ‘Netmums’
Authors: Russell Sally 
Published: March 2012

This paper describes how the Netmums social network has been used over recent years as a source of research and discusses whether this type of research has the potential to influence policy. Online social networks are a new phenomenon, but as they have increased in scale their potential to reflect the interests and experiences of real communities is starting to be recognised. While there is significant awareness of the ways in which social networks have recently been able to further democratic processes, there has been less focus on the opportunities that they provide to change local services and government policies. The research opportunities available through the Netmums social network are diverse and the website provides access to a rich resource, but there are a number of limitations to the research that can be conducted. As yet there is little evidence to demonstrate the influence that research based on the network might have, but a comparison of research methods shows that, despite these limitations, the use of communities such as Netmums should provide researchers and policy makers with cost-effective and powerful tools of influence in the future.
Preventing and treating postpartum depression in women – a municipality model
Authors: Glavin Kari 
Published: March 2012

Objective: The objective of this paper is to describe and discuss a municipal model for prevention, identification and treatment of postpartum depression (PPD). Major findings: The changed care in the municipality was associated with a significant difference in Edinburgh Postnatal Depression Scale scores between the intervention municipality and the usual care municipality at 6 weeks, 3, 6 and 12 months postpartum. The women who had been depressed at least once during the first postpartum year reported significantly higher levels of parenting stress at 12 months. The public health nurses found the scale easy to score and easy for the mothers to complete, and they were confident that they identified PPD more frequently than before. Conclusion: The results of the present study suggest a basis for a municipality model that gives the primary health care system better possibilities to help women with mental health problems in the postpartum period. The changed care consisted of several elements considered important for the result of this study. The results can be incorporated in a descriptive model for prevention, identification and treatment in municipalities. The components are (1) preconditions in the municipality, (2) initiatives to prevent PPD, (3) identification of women with PPD, (4) treatment of PPD and (5) follow-up.
Adult patients with acute lymphoblastic leukemia and molecular failure display a poor prognosis and are candidates for stem cell transplantation and targeted therapies
Authors: Gökbuget Nicola , Kneba Michael , Raff Thorsten , Trautmann Heiko , Bartram Claus-Rainer , Arnold Renate , Fietkau Rainer , Freund Mathias , Ganser Arnold , Ludwig Wolf-Dieter , Maschmeyer Georg , Rieder Harald , Schwartz Stefan , Serve Hubert , Thiel Eckhard , Brüggemann Monika , Hoelzer Dieter 
Published: March 2012

Abstract
Quantification of minimal residual disease (MRD) by real-time PCR directed to TCR and Ig gene rearrangements allows a refined evaluation of response in acute lymphoblastic leukemia (ALL). The German Multicenter Study Group for Adult ALL prospectively evaluated molecular response after induction/consolidation chemotherapy according to standardized methods and terminology in patients with Philadelphia chromosome-negative ALL. The cytologic complete response (CR) rate was 89% after induction phases 1 and 2. At this time point the molecular CR rate was 70% in 580 patients with cytologic CR and evaluable MRD. Patients with molecular CR after consolidation had a significantly higher probability of continuous complete remission (CCR; 74% vs 35%; P < .0001) and of overall survival (80% vs 42%; P = .0001) compared with patients with molecular failure. Patients with molecular failure without stem cell transplantation (SCT) in first CR relapsed after a median time of 7.6 months; CCR and survival at 5 years only reached 12% and 33%, respectively. Quantitative MRD assessment identified patients with molecular failure as a new high-risk group. These patients display resistance to conventional drugs and are candidates for treatment with targeted, experimental drugs and allogeneic SCT. Molecular response was shown to be highly predictive for outcome and therefore constitutes a relevant study end point. The studies are registered at www.clinicaltrials.gov as NCT00199056 and NCT00198991.
5-azacytidine and decitabine exert proapoptotic effects on neoplastic mast cells: role of FAS-demethylation and FAS re-expression, and synergism with FAS-ligand
Authors: Ghanim Viviane , Herrmann Harald , Heller Gerwin , Peter Barbara , Hadzijusufovic Emir , Blatt Katharina , Schuch Karina , Cerny-Reiterer Sabine , Mirkina Irina , Karlic Heidrun , Pickl Winfried F. , Zöchbauer-Müller Sabine , Valent Peter 
Published: March 2012

Abstract
Aggressive systemic mastocytosis (ASM) and mast cell leukemia (MCL) are advanced hematopoietic neoplasms with poor prognosis. In these patients, neoplastic mast cells (MCs) are resistant against various drugs. We examined the effects of 2 demethylating agents, 5-azacytidine and decitabine on growth and survival of neoplastic MCs and the MC line HMC-1. Two HMC-1 subclones were used, HMC-1.1 lacking KIT D816V and HMC-1.2 exhibiting KIT D816V. Both agents induced apoptosis in HMC-1.1 and HMC-1.2 cells. Decitabine, but not 5-azacytidine, also produced a G2/M cell-cycle arrest in HMC-1 cells. Drug-induced apoptosis was accompanied by cleavage of caspase-8 and caspase-3 as well as FAS-demethylation and FAS–re-expression in neoplastic MCs. Furthermore, both demethylating agents were found to synergize with the FAS-ligand in inducing apoptosis in neoplastic MCs. Correspondingly, siRNA against FAS was found to block drug-induced expression of FAS and drug-induced apoptosis in HMC-1 cells. Neither 5-azacytidine nor decitabine induced substantial apoptosis or growth arrest in normal MCs or normal bone marrow cells. Together, 5-azacytidine and decitabine exert growth-inhibitory and proapoptotic effects in neoplastic MCs. These effects are mediated through “FAS–re-expression” and are augmented by the FAS-ligand. Whether epigenetic drugs produce antineoplastic effects in vivo in patients with ASM and MCL remains to be determined.
A targeted complement-dependent strategy to improve the outcome of mAb therapy, and characterization in a murine model of metastatic cancer
Authors: Elvington Michelle , Huang Yuxiang , Morgan B. Paul , Qiao Fei , van Rooijen Nico , Atkinson Carl , Tomlinson Stephen 
Published: March 2012

Abstract
Complement inhibitors expressed on tumor cells provide an evasion mechanism against mAb therapy and may modulate the development of an acquired antitumor immune response. Here we investigate a strategy to amplify mAb-targeted complement activation on a tumor cell, independent of a requirement to target and block complement inhibitor expression or function, which is difficult to achieve in vivo. We constructed a murine fusion protein, CR2Fc, and demonstrated that the protein targets to C3 activation products deposited on a tumor cell by a specific mAb, and amplifies mAb-dependent complement activation and tumor cell lysis in vitro. In syngeneic models of metastatic lymphoma (EL4) and melanoma (B16), CR2Fc significantly enhanced the outcome of mAb therapy. Subsequent studies using the EL4 model with various genetically modified mice and macrophage-depleted mice revealed that CR2Fc enhanced the therapeutic effect of mAb therapy via both macrophage-dependent FcγR-mediated antibody-dependent cellular cytotoxicity, and by direct complement-mediated lysis. Complement activation products can also modulate adaptive immunity, but we found no evidence that either mAb or CR2Fc treatment had any effect on an antitumor humoral or cellular immune response. CR2Fc represents a potential adjuvant treatment to increase the effectiveness of mAb therapy of cancer.
Multilineage dysplasia does not influence prognosis in CEBPA-mutated AML, supporting the WHO proposal to classify these patients as a unique entity
Authors: Bacher Ulrike , Schnittger Susanne , Macijewski Katja , Grossmann Vera , Kohlmann Alexander , Alpermann Tamara , Kowarsch Andreas , Nadarajah Niroshan , Kern Wolfgang , Haferlach Claudia , Haferlach Torsten 
Published: March 2012

Abstract
In 2008, the World Health Organization introduced CEBPA (encoding the CCAAT/enhancer binding protein)–mutated acute myeloid leukemia (AML) as a provisional entity. However, the classification of CEBPA-mutated AML with multilineage dysplasia (MLD; ≥ 50% dysplastic cells in 2-3 lineages) remains to be clarified. In the present study, we investigated 108 CEBPA-mutated AML patients for the impact of MLD, karyotype, and additional mutations. MLD+ patients differed from MLD− patients only by lower mean WBC counts, not by biologic characteristics, cytogenetic risk profiles, or additional mutations. Survival was better for female patients, patients < 60 years of age, for intermediate versus adverse karyotypes, and, in the case of FLT3-ITD negativity, biallelic versus monoallelic/homozygous CEBPA mutations. In contrast, 2-year overall survival and event-free survival did not differ significantly between MLD+ and MLD− patients. By univariable Cox regression analysis, sex, age, WBC count, and cytogenetic risk category were related to overall survival, but MLD was not. Therefore, because dysplasia is not relevant for this subtype, CEBPA-mutated AML patients should be characterized only according to mutation status, cytogenetic risk group, or additional mutations.
Dynamic HoxB4-regulatory network during embryonic stem cell differentiation to hematopoietic cells
Authors: Fan Rong , Bonde Sabrina , Gao Peng , Sotomayor Brendan , Chen Changya , Mouw Tyler , Zavazava Nicholas , Tan Kai 
Published: March 2012

Abstract
Efficient in vitro generation of hematopoietic stem cells (HSCs) from embryonic stem cells (ESCs) holds great promise for cell-based therapies to treat hematologic diseases. To date, HoxB4 remains the most effective transcription factor (TF) the overexpression of which in ESCs confers long-term repopulating ability to ESC-derived HSCs. Despite its importance, the components and dynamics of the HoxB4 transcriptional regulatory network is poorly understood, hindering efforts to develop more efficient protocols for in vitro derivation of HSCs. In the present study, we performed global gene-expression profiling and ChIP coupled with deep sequencing at 4 stages of the HoxB4-mediated ESC differentiation toward HSCs. Joint analyses of ChIP/deep sequencing and gene-expression profiling unveiled several global features of the HoxB4 regulatory network. First, it is highly dynamic and gradually expands during the differentiation process. Second, HoxB4 functions as a master regulator of hematopoiesis by regulating multiple hematopoietic TFs and chromatin-modification enzymes. Third, HoxB4 acts in different combinations with 4 other hematopoietic TFs (Fli1, Meis1, Runx1, and Scl) to regulate distinct sets of pathways. Finally, the results of our study suggest that down-regulation of mitochondria and lysosomal genes by HoxB4 plays a role in the impaired lymphoid lineage development from ESC-derived HSCs.
A neutrophil elastase inhibitor prevents bleomycin-induced pulmonary fibrosis in mice
Authors: Takemasa Akihiro , Ishii Yoshiki , Fukuda Takeshi 
Published: March 2012

Neutrophil elastase plays pivotal roles in the pathogenesis of pulmonary fibrosis. The neutrophil elastase inhibitor, sivelestat, could alleviate pulmonary fibrosis; however, the antifibrotic mechanisms have not yet been clarified. We examined the antifibrotic mechanisms, mainly focusing on a key fibrotic cytokine, transforming growth factor (TGF)-β1, in this study.To elucidate the antifibrotic mechanisms of sivelestat, we examined a murine model of bleomycin-induced early-stage pulmonary fibrosis. After intratracheal instillation of bleomycin, sivelestat was administered intraperitoneally once a day for 7 or 14 days. Bronchoalveolar lavage fluid and lung samples were examined on day 7 or day 14 after bleomycin instillation.In the bleomycin-induced early-stage pulmonary fibrosis model, the neutrophil elastase level was increased in the lungs. Sivelestat significantly inhibited the increase in lung collagen content, fibrotic changes, the numbers of total cells (including macrophages, neutrophils and lymphocytes), the levels of the active form of TGF-β1 and phospho-Smad2 in bleomycin-induced early-stage pulmonary fibrosis. The total TGF-β1 levels and relative changes of TGF-β1 mRNA expression, however, were not decreased significantly by sivelestat.These results suggest that sivelestat alleviated bleomycin-induced pulmonary fibrosisviainhibition of both TGF-β activation and inflammatory cell recruitment in the lung.
Codon Deviation Coefficient: a novel measure for estimating codon usage bias and its statistical significance
Authors: Zhang Zhang , Li Jun , Cui Peng , Ding Feng , Li Ang , Townsend Jeffrey P , Yu Jun 
Published: March 2012

Abstract

Background
Genetic mutation, selective pressure for translational efficiency and accuracy, level of gene expression, and protein function through natural selection are all believed to lead to codon usage bias (CUB). Therefore, informative measurement of CUB is of fundamental importance to making inferences regarding gene function and genome evolution. However, extant measures of CUB have not fully accounted for the quantitative effect of background nucleotide composition and have not statistically evaluated the significance of CUB in sequence analysis.

Results
Here we propose a novel measure--Codon Deviation Coefficient (CDC)--that provides an informative measurement of CUB and its statistical significance without requiring any prior knowledge. Unlike previous measures, CDC estimates CUB by accounting for background nucleotide compositions tailored to codon positions and adopts the bootstrapping to assess the statistical significance of CUB for any given sequence. We evaluate CDC by examining its effectiveness on simulated sequences and empirical data and show that CDC outperforms extant measures by achieving a more informative estimation of CUB and its statistical significance.

Conclusions
As validated by both simulated and empirical data, CDC provides a highly informative quantification of CUB and its statistical significance, useful for determining comparative magnitudes and patterns of biased codon usage for genes or genomes with diverse sequence compositions.
Molecular diversity, population structure, and linkage disequilibrium in a worldwide collection of tobacco (Nicotiana tabacum L.) germplasm
Authors: Fricano Agostino , Bakaher Nicolas , Corvo Marcello Del , Piffanelli Pietro , Donini Paolo , Stella Alessandra , Ivanov Nikolai V , Pozzi Carlo 
Published: March 2012

Abstract

Background
The goals of our study were to assess the phylogeny and the population structure of tobacco accessions representing a wide range of genetic diversity; identify a subset of accessions as a core collection capturing most of the existing genetic diversity; and estimate, in the tobacco core collection, the extent of linkage disequilibrium (LD) in seven genomic regions using simple sequence repeat (SSR) markers. To this end, a collection of accessions were genotyped with SSR markers. Molecular diversity was evaluated and LD was analyzed across seven regions of the genome.

Results
A genotyping database for 312 tobacco accessions was profiled with 49 SSR markers. Principal Coordinate Analysis (PCoA) and Bayesian cluster analysis revealed structuring of the tobacco population with regard to commercial classes and six main clades were identified, which correspond to "Oriental", Flue-Cured", "Burley", "Dark", "Primitive", and "Other" classes. Pairwise kinship was calculated between accessions, and an overall low level of co-ancestry was observed. A set of 89 genotypes was identified that captured the whole genetic diversity detected at the 49 loci. LD was evaluated on these genotypes, using 422 SSR markers mapping on seven linkage groups. LD was estimated as squared correlation of allele frequencies (r

2
). The pattern of intrachromosomal LD revealed that in tobacco LD extended up to distances as great as 75 cM with r

2
> 0.05 or up to 1 cM with r

2
> 0.2. The pattern of LD was clearly dependent on the population structure.

Conclusions
A global population of tobacco is highly structured. Clustering highlights the accessions with the same market class. LD in tobacco extends up to 75 cM and is strongly dependent on the population structure.
Individual patient data meta-analysis of survival data using Poisson regression models
Authors: Crowther Michael J , Riley Richard D , Staessen Jan A , Wang Jiguang , Gueyffier Francois , Lambert Paul C 
Published: March 2012

AbstractBackgroundAn Individual Patient Data (IPD) meta-analysis is often considered the gold-standard for synthesising survival data from clinical trials. An IPD meta-analysis can be achieved by either a two-stage or a one-stage approach, depending on whether the trials are analysed separately or simultaneously. A range of one-stage hierarchical Cox models have been previously proposed, but these are known to be computationally intensive and are not currently available in all standard statistical software. We describe an alternative approach using Poisson based Generalised Linear Models (GLMs).MethodsWe illustrate, through application and simulation, the Poisson approach both classically and in a Bayesian framework, in two-stage and one-stage approaches. We outline the benefits of our one-stage approach through extension to modelling treatment-covariate interactions and non-proportional hazards. Ten trials of hypertension treatment, with all-cause death the outcome of interest, are used to apply and assess the approach.ResultsWe show that the Poisson approach obtains almost identical estimates to the Cox model, is additionally computationally efficient and directly estimates the baseline hazard. Some downward bias is observed in classical estimates of the heterogeneity in the treatment effect, with improved performance from the Bayesian approach.ConclusionOur approach provides a highly flexible and computationally efficient framework, available in all standard statistical software, to the investigation of not only heterogeneity, but the presence of non-proportional hazards and treatment effect modifiers.