bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non‐total body irradiation myeloablative conditioning with intravenous busulfan and cyclophosphamide in hematopoietic stem cell transplantation for malignant infantile osteopetrosis
Authors: Behfar Maryam , Dehghani S. Sharareh , Hosseini Ashraf Sadat , Jalali Arash , Hamidieh Amir Ali , Ghavamzadeh Ardeshir 
Published: April 2015

AbstractHSCT is the only curative treatment for MIOP. We prospectively investigated the outcome of HSCT using intravenous busulfan‐based conditioning regimen from 2008 to 2013. Nineteen patients (median age = 17 months) underwent transplantation from HLA‐matched related donors (n = 14), HLA‐haploidentical related donors (n = 2), partially matched cord blood donors (n = 2), and HLA‐matched unrelated donor (n = 1). Bone marrow (n = 9), peripheral blood (n = 8), and cord blood (n = 2) were used as stem cell sources. All but one patient demonstrated primary engraftment. Two patients experienced secondary graft failure. During the follow‐up period, three patients showed mixed chimerism (45%, 45%, and 70% of donor cells were engrafted in each one of these patients) but are disease free. Two‐yr OS and DFS were 84.2% and 73.7%, respectively. Improvement of visual acuity and partial reversal of mild conductive hearing loss occurred in two and four patients, respectively. The causes of death among three patients were infection, GvHD, and disease progression. In conclusion, due to major side effects of MIOP such as visual and hearing loss, early treatment using myeloablative conditioning without irradiation HSCT is suggested. The use of an HLA‐matched related donor seems to be highly successful in this regard. Also, according to results of our study, mixed chimerism may be sufficient to resolve symptoms of disease.
Impact of socioeconomic deprivation on the development of diabetic retinopathy: a population-based, cross-sectional and longitudinal study over 12 years
Authors: Low Liying , Law Jonathan P , Hodson James , McAlpine Ritchie , O'Colmain Una , MacEwen Caroline 
Published: April 2015

ObjectiveTo study the association between socioeconomic deprivation and prevalence of diabetic retinopathy (DR).DesignPopulation-based, cross-sectional observational study and retrospective longitudinal analysis over 12 years.SettingPrimary care, East of Scotland.MethodsOutcome data from DR screening examinations (digital retinal photography) were collected from the Scottish regional diabetes electronic record from inception of database to December 2012. The overall Scottish Index of Multiple Deprivation (SIMD) 2012 score for each patient was obtained using their residential postcode. Multiple binary logistic regression was used to analyse the relationship between overall SIMD score and prevalence of DR, adjusting for other variables: age, gender, glycated haemoglobin, cholesterol levels and duration of disease.Primary outcomeAny retinopathy (R1 and above) in either eye.ResultsA total of 1861 patients with type 1 diabetes mellitus (DM) and 18 197 patients with type 2 DM were included in the study. Prevalence of DR in type 1 and type 2 DM were 56.3% and 25.5%, respectively. Increased prevalence of DR in type 1 DM was associated with higher overall SIMD score (p=0.002), with an OR for the most deprived relative to the least deprived of 2.40 (95% CI 1.36 to 4.27). In type 2 DM, the overall SIMD score was not significantly associated with increased prevalence of DR, with an OR for the most deprived relative to the least deprived of 0.85 (95% CI 0.71 to 1.02, p=0.07).ConclusionsSocioeconomic deprivation is associated with increased prevalence of DR in patients with type 1 DM and this occurs earlier. This highlights the need for targeted interventions to address inequalities in eye healthcare.
Cobas 4800 HPV detection in the cervical, vaginal and urine samples of women with high-grade CIN before and after treatment
Authors: Stanczuk Grazyna A , Currie Heather , Baxter Gwen , Foster Adele , Gibson Lindsay , Graham Catriona , Cuschieri Kate 
Published: April 2015

AimsTo assess the performance of a clinically validated human papillomavirus (HPV) test (the Cobas 4800 HPV test) in urine and self-taken vaginal specimens within a colposcopy population and to assess HPV prevalence before and after treatment across the different biospecimens.MethodsA total of 100 women attending a colposcopy clinic provided three biospecimens (a clinician-taken liquid-based cytology sample (LBC), a self-taken vaginal sample and a urine sample) for HPV testing. HPV prevalence and concordance was compared across the biospecimens and clinical performance relative to the detection of cervical intraepithelial neoplasia (CIN)2+ and CIN3+ was assessed. A total of 39 women retuned at 6 months for a post-treatment follow-up appointment, and HPV concordance in all biospecimens was measured relative to their original HPV status.Results65 cases of CIN2+ were detected in the baseline population; sensitivity for CIN2+ was 92% (82 to 97) for the vaginal and the LBC sample and 80.0 (68% to 88%) for the urine sample. In the follow-up (post treatment) population, women were twice as likely to be HPV positive in their urine or vaginal sample compared with the equivalent LBC sample.ConclusionsVaginal and LBC samples showed very similar performance for the detection of CIN2+ in this population using the Cobas HPV test; further validation of these findings in screening contexts will be of value. Self-taken samples may have less utility in a ‘test of cure’ setting—given the higher prevalence of HPV relative to LBC.
Genomic and Functional Analysis of the E3 Ligase PARK2 in Glioma
Authors: Lin De-Chen , Xu Liang , Chen Ye , Yan Haiyan , Hazawa Masaharu , Doan Ngan , Said Jonathan W. , Ding Ling-Wen , Liu Li-Zhen , Yang Henry , Yu Shizhu , Kahn Michael , Yin Dong , Koeffler H. Phillip 
Published: April 2015

AbstractPARK2 (PARKIN) is an E3 ubiquitin ligase whose dysfunction has been associated with the progression of Parkinsonism and human malignancies, and its role in cancer remains to be explored. In this study, we report that PARK2 is frequently deleted and underexpressed in human glioma, and low PARK2 expression is associated with poor survival. Restoration of PARK2 significantly inhibited glioma cell growth both in vitro and in vivo, whereas depletion of PARK2 promoted cell proliferation. PARK2 attenuated both Wnt- and EGF-stimulated pathways through downregulating the intracellular level of β-catenin and EGFR. Notably, PARK2 physically interacted with both β-catenin and EGFR. We further found that PARK2 promoted the ubiquitination of these two proteins in an E3 ligase activity-dependent manner. Finally, inspired by these newly identified tumor-suppressive functions of PARK2, we tested and proved that combination of small-molecule inhibitors targeting both Wnt–β-catenin and EGFR–AKT pathways synergistically impaired glioma cell viability. Together, our findings uncover novel cancer-associated functions of PARK2 and provide a potential therapeutic approach to treat glioma. Cancer Res; 75(9); 1815–27. ©2015 AACR.
Aurora A Kinase Inhibition Selectively Synergizes with Histone Deacetylase Inhibitor through Cytokinesis Failure in T-cell Lymphoma
Authors: Zullo Kelly M. , Guo Yige , Cooke Laurence , Jirau-Serrano Xavier , Mangone Michael , Scotto Luigi , Amengual Jennifer E. , Mao Yinghui , Nandakumar Renu , Cremers Serge , Duong Jimmy , Mahadevan Daruka , O'Connor Owen A. 
Published: April 2015

Abstract
Purpose: Aurora A kinase (AAK) is expressed exclusively during mitosis, and plays a critical role in centrosome duplication and spindle formation. Alisertib is a highly selective AAK inhibitor that has demonstrated marked clinical activity of alisertib across a spectrum of lymphomas, though particularly in patients with T-cell lymphoma (TCL). We sought to compare and contrast the activity of alisertib in preclinical models of B-cell lymphoma (BCL) and TCL, and identify combinations worthy of clinical study. High-throughput screening of pralatrexate, the proteasome inhibitor (ixazomib), and the histone deacetylase (HDAC) inhibitor (romidepsin) revealed that only romidepsin synergized with alisertib, and only in models of TCL. We discovered that the mechanism of synergy between AAK inhibitors and HDAC inhibitors appears to be mediated through cytokinesis failure.
Experimental Design: A high-throughput screening approach was used to identify drugs that were potentially synergistic in combination with alisertib. Live-cell imaging was used to explore the mechanistic basis for the drug: drug interaction between alisertib and romidepsin. An in vivo xenograft TCL model was used to confirm in vitro results.
Results: In vitro, alisertib exhibited concentration-dependent cytotoxicity in BCL and TCL cell lines. Alisertib was synergistic with romidepsin in a T-cell–specific fashion that was confirmed in vivo. Live-cell imaging demonstrated that the combination treatment resulted in profound cytokinesis failure.
Conclusions: These data strongly suggest that the combination of alisertib and romidepsin is highly synergistic in TCL through modulation of cytokinesis and merits clinical development. Clin Cancer Res; 21(18); 4097–109. ©2015 AACR.
Fibronectin extra domain A stabilises atherosclerotic plaques in apolipoprotein E and in LDL-receptor-deficient mice
Authors: Venu Vivek Krishna Pulakazhi , Uboldi Patrizia , Dhyani Ashish , Patrini Alessandro , Baetta Roberta , Ferri Nicola , Corsini Alberto , Muro Andrés F. , Catapano Alberico Luigi , Norata Giuseppe Danilo 
Published: April 2015

SummaryThe primary transcript of fibronectin undergoes alternative splicing in the cassette-type EDA and EDB exons and in the IIICs segment to generate different protein isoforms. Human carotid atherosclerotic plaques with a more stable phenotype are enriched with EDA containing fibronectin (FN-EDA). The aim of this study was to investigate the role of EDA containing fibronectin during atherogenesis. Mice constitutively expressing or lacking the EDA domain of fibronectin (EDA+/+ or EDA-/-) were crossed with ApoE-/- or LDL-R-/- mice and fed with a western type diet for 12 weeks. Lack of FN-EDA resulted in reduced atherosclerosis and in a plaque phenotype characterised by decreased calponin positive VSMC’s (-15 %) and increased macrophages (+20 %). This was paralleled by increased MMP2, MMP9, and reduced TIMP2, collagen 1A1, 1A2 and 3A1 gene expression compared to that of wild-type and EDA+/+ mice. In vitro, VSMCs and macrophages isolated from EDA-/- mice showed increased MMPs expression and activity compared to wild-type or EDA+/+ mice. Albumin-Cre recombinase/ EDA+/+/ApoE-/- mice, which produce EDA containing FN only in peripheral tissues, presented an extension, a composition and a gene expression pattern in the atherosclerotic lesions similar to that of controls. The inclusion of EDA in FN results in larger atherosclerotic plaques compared to mice lacking EDA but with a more favourable phenotype in two animals models of atherosclerosis. This effect depends on the EDA-containing fibronectin produced by cells in the vasculature but not in the liver. These observations set the stage for investigating the properties of circulating EDA containing FN in improving plaque stability.
Inhibitors in nonsevere haemophilia A: outcome and eradication strategies
Authors: van Velzen Alice S. , Eckhardt Corien L. , Hart Daniel P. , Peters Marjolein , Rangarajan Savita , Mancuso Maria Elisa , Smiers Frans J. , Khair Kate , Petrini Pia , Jimenez-Yuste Victor , Hay Charles R. M. , van der Bom Johanna G. , Yee Thynn T. , Fijnvandraat Karin ,   for the INSIGHT study group
Published: April 2015

SummaryIn nonsevere haemophilia A (HA) patients the presence of an inhibitor may exacerbate the bleeding phenotype dramatically. There are very limited data on the optimal therapeutic approach to eradicate inhibitors in these patients. We aimed to describe inhibitor eradication treatment in a large cohort of unselected nonsevere HA patients with inhibitors. We included 101 inhibitor patients from a source population of 2,709 nonsevere HA patients (factor VIII 2–40 IU/dl), treated in Europe and Australia (median age 37 years, interquartile range (IQR) 15–60; median peak titre 7 BU/ml, IQR 2–30). In the majority of the patients (71 %; 72/101) the inhibitor disappeared; either spontaneously (70 %, 51/73) or after eradication treatment (75 %, 21/28). Eradication treatment strategies varied widely, including both immune tolerance induction and immunosuppression. Sustained success (no inhibitor after rechallenge with factor VIII concentrate after inhibitor disappearance) was achieved in 64 % (30/47) of those patients rechallenged with FVIII concentrate. In high-titre inhibitor patients sustained success was associated with eradication treatment (unadjusted relative risk 2.3, 95 % confidence interval 1.3–4.3), compared to no eradication treatment. In conclusion, in nonsevere HA patients most inhibitors disappear spontaneously. However, in 35 % (25/72) of these patients an anamnestic response still can occur when rechallenged, thus disappearance in these patients does not always equal sustained response. Treatment for those requiring eradication has to be decided case by case, as one single approach is unlikely to be appropriate for all.Study was carried out in: Emma Children’s Hospital, Academic Medical Center, Amsterdam, the Netherlands.
Gesto, Oralidade, Escritura e Tradução: A emergência das línguas de sinais e o primado fonológico dos estudos linguísticos.
Authors: Schramm Junior Roberto Mário 
Published: April 2015

<p>Este ensaio pretende refletir acerca de certos problemas decorrentes do primado da fala e da oralidade na constituição da ciência Linguística. Partimos da consideração das línguas gestuais e tentamos demonstrar o quão desconfortáveis podem parecer alguns dos conceitos da ciência da linguagem que expressam o privilégio da fala fonética no estabelecimento dos conceitos-chave da Linguística estrutural. Para tanto, discutiremos esses conceitos no âmbito da passagem do modelo semiológico do século XX para um paradigma multimodal que emerge no século XXI. Ademais, confrontaremos as abordagens 'oralistas' e 'textualistas' com as questões que emergem do estudo das linguagens gestuais. Nossa tese: a dimensão gestual é uma modalidade constituinte do discurso tanto quanto a fala e a escrita; de modo que a discursividade plena se resolve num modelo tradutivo, onde cada modalidade se refere, esclarece e complementa a seguinte.</p>
Association Between Perioperative Dexmedetomidine and Arrhythmias After Surgery for Congenital Heart Disease
Authors: Shuplock Jacqueline M. , Smith Andrew H. , Owen Jill , Van Driest Sara L. , Marshall Matt , Saville Benjamin , Xu Meng , Radbill Andrew E. , Fish Frank A. , Kannankeril Prince J. 
Published: April 2015

Background—
Dexmedetomidine is commonly used after congenital heart surgery and may be associated with a decreased incidence of postoperative tachyarrhythmias. Using a large cohort of patients undergoing congenital heart surgery, we examined for an association between dexmedetomidine use in the immediate postoperative period and subsequent arrhythmia development.

Methods and Results—

A total of 1593 surgical procedures for congenital heart disease were performed. Dexmedetomidine was administered in the immediate postoperative period after 468 (29%) surgical procedures. When compared with 1125 controls, the group receiving dexmedetomidine demonstrated significantly fewer tachyarrhythmias (29% versus 38%;
P
<0.001), tachyarrhythmias receiving intervention (14% versus 23%;
P
<0.001), bradyarrhythmias (18% versus 22%;
P
=0.03), and bradyarrhythmias receiving intervention (12% versus 16%;
P
=0.04). After propensity score matching with 468 controls, the arrhythmia incidence between groups became similar: tachyarrhythmias (29% versus 31%;
P
=0.66), tachyarrhythmias receiving intervention (14% versus 17%;
P
=0.16), bradyarrhythmias (18% versus 15%;
P
=0.44), and bradyarrhythmias receiving intervention (12% versus 9%;
P
=0.17). After excluding controls exposed to dexmedetomidine at a later time in the hospitalization, dexmedetomidine was associated with increased odds of bradyarrhythmias receiving intervention (odds ratio, 2.18; 95% confidence interval, 1.02–4.65). Furthermore, there was a dose-dependent increase in the odds of bradyarrhythmias (odds ratio, 1.04; 95% confidence interval, 1.01–1.07) and bradyarrhythmias receiving intervention (odds ratio, 1.05; 95% confidence interval, 1.01–1.08).

Conclusions—
Although dexmedetomidine exposure in the immediate postoperative period is not associated with a clinically meaningful difference in the incidence of tachyarrhythmias after congenital heart surgery, it may be associated with increased odds of bradyarrhythmias.
Improved Low-Cloud Simulation from the Community Atmosphere Model with an Advanced Third-Order Turbulence Closure
Authors: Cheng Anning , Xu Kuan-Man 
Published: April 2015

Abstract
In this study, a simplified intermediately prognostic higher-order turbulence closure (IPHOC) is implemented in the Community Atmosphere Model, version 5 (CAM5), to provide a consistent treatment of subgrid-scale cloud processes, except for deep convection. The planetary boundary layer (PBL) height is prognosticated to better resolve the discontinuity of temperature and moisture above the PBL top. Single-column model tests show that fluxes of liquid water potential temperature and total water, cloud fraction, and liquid water content are improved with this approach. The simplified IPHOC package replaces the boundary layer dry and moist turbulence parameterizations, the shallow convection parameterization, and the liquid-phase part of the cloud macrophysics parameterization in CAM5. CAM5-IPHOC improves the simulation of the low-level clouds off the west coasts of continents and the storm track region in the Southern Hemisphere (SH). The transition from stratocumulus to cumulus clouds is more gradual. There are also improvements on the cloud radiative forcing, especially shortwave, in the subsidence regime. The improvements in the relationships among low cloud amount, surface relative humidity, lower tropospheric stability, and PBL depth are seen in some stratocumulus regions. CAM5-IPHOC, however, produces weaker precipitation at the South Pacific convergence zone than CAM5 because of less energy flux into the SH atmosphere. The more downward surface shortwave radiative cooling and the less top-of-the-atmosphere longwave cloud radiative heating in the SH relative to the Northern Hemisphere explains the anomalous cooling and the lesser energy flux into the SH, which is related to the underestimate of extratropical middle/high clouds in the SH.
The biocompatibility of calcium phosphate cements containing alendronate-loaded PLGA microparticlesin vitro
Authors: Li Yu-Hua , Wang Zhen-Dong , Wang Wei , Ding Chang-Wei , Zhang Hao-Xuan , Li Jian-Min 
Published: April 2015

The composite of poly-lactic- co-glycolic acid (PLGA) and calcium phosphate cements (CPC) are currently widely used in bone tissue engineering. However, the properties and biocompatibility of the alendronate-loaded PLGA/CPC (APC) porous scaffolds have not been characterized. APC scaffolds were prepared by a solid/oil/water emulsion solvent evaporation method. The morphology, porosity, and mechanical strength of the scaffolds were characterized. Bone marrow mesenchymal stem cells (BMSCs) from rabbit were cultured, expanded and seeded on the scaffolds, and the cell morphology, adhesion, proliferation, cell cycle and osteogenic differentiation of BMSCs were determined. The results showed that the APC scaffolds had a porosity of 67.43 ± 4.2% and pore size of 213 ± 95 µm. The compressive strength for APC was 5.79 ± 1.21 MPa, which was close to human cancellous bone. The scanning electron microscopy, cell counting kit-8 assay, flow cytometry and ALP activity revealed that the APC scaffolds had osteogenic potential on the BMSCs in vitro and exhibited excellent biocompatibility with engineered bone tissue. APC scaffolds exhibited excellent biocompatibility and osteogenesis potential and can potentially be used for bone tissue engineering.
Amine-immobilized Three-dimensional Wormhole Mesostructured MSU-J Silica for CO2 Adsorption: Effect of Amine Loading and Temperature on the Adsorption Capacity
Authors: Jiao Jian , Cao Jing , Lv Pan P 
Published: April 2015

Abstract
Large-pore mesoporous silica (MSU-J) with wormhole framework structure was prepared and modified with triethylenetetramine (TETA) by wet-impregnation. It was used as adsorbent for CO2. The hydrolyzing mesoporous silica was prepared by boiling the MSU-J in distilled water. CO2 adsorption capacity was investigated at different temperatures and TETA loadings. The results showed that adsorption capacity decreased with increase of adsorption temperature. Increase of TETA content increased CO2 adsorption. Repeated adsorption/desorption cycles showed that amine-impregnated materials were efficient in CO2 adsorption.
Synthesis of Fluorescent Hollow Silica Nanoparticles and Application in Detecting Hypochlorite
Authors: Wang Gang , Zhu Yue-Hong , Zhou Guang-Gai , Liu Wei-Liang , Zhang Xian , Cai Xiao-Xia , Liu Qin-Ze , Wang Xin-Qiang 
Published: April 2015

Abstract
In this paper, fluorescent hollow silica nanoparticles (FHSNs) have been used for the detection of hypochlorite by monitoring fluorescence intensity changes. The fluorescent and sensing properties of the FHSNs were dramatically improved compared to those of the corresponding free probes. With unique hollow structure and strong fluorescence, the FHSNs have potential applications in the fields of biology and medicine.
Particle-dressed, Silica Shell-isolated Cavity Architectures for Surface-enhanced Raman Scattering
Authors: Du Yuanchun , Yang Sen , Li Huanhuan , Chen Shu , Hu Jiawen 
Published: April 2015

Abstract
Particle-dressed, SiO2 shell-isolated cavity architectures were fabricated. These architectures, owing to their structured surface and substantial hot spots created by particle–cavity interaction, showed reproducible, improved surface-enhanced Raman scattering activity relative to Au nanoparticles immobilized on a glass slide.
The Lifelong Learning in the Field of Employment Policy in Slovakia
Authors: Hužovičová Mária , Jakúbek Peter 
Published: April 2015

Abstract
The rate of employment (or vice versa the rate of unemployment) is an important indicator of economic maturity and quality of life in a particular country. Compared to other countries of the European Union, unemployment in the Slovak Republic is a serious problem. Improving the quality and the efficiency of Slovak educational institutions can be one of the ways how to struggle with this problem. The Slovak economy has been transformed from planned economy to market economy, and, therefore, retraining, re-educations and improvement (in the field of industry and services) have been required. The Institute of Lifelong Learning is very helpful in this field. The article deals with shortcomings of the Institute of Lifelong Learning and it points out the reality leading to drawbackks. It also concerns the following possibilities, which might improve the current situation. In a theoretical analysis of the current state, we define the basic terms and problems in this field.