bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional and Survival Outcomes in Patients Undergoing Total Glossectomy Compared with Total Laryngoglossectomy
Authors: Sinclair Catherine F. , Carroll William R. , Desmond Renee A. , Rosenthal Eben L. 
Published: June 2011

ObjectiveTo compare functional and survival outcomes for patients undergoing total glossectomy (TG) or total glossectomy plus laryngectomy (TGL) for advanced squamous cell carcinoma (SCC) of the tongue.Study DesignCase series with chart review.SettingAcademic tertiary referral center.Subjects and MethodsThere were 30 included patients (20 TG, 10 TGL). Outcomes included tumor recurrence, disease‐free survival, and functional data (swallowing, gastrostomy tube dependence, speech, airway).ResultsMean patient age was 56 years with a male predominance (90%). Compared with TG, TGL was more commonly performed for recurrent tumors (90% vs 55%, P =. 06). Perineural invasion and extracapsular extension occurred more commonly in the TGL group (80% vs 50%, P =. 12). At 12 months postoperatively, 61% of TG patients had disease recurrence compared with 40% of TGL patients (P =. 43), and 12‐month disease‐free survival was 40% (TG) and 50% (TGL). Functionally, more TG patients were totally gastrostomy tube dependent (70% vs 30%, P =. 04), and 50% of TG patients were also tracheostomy dependent. Intelligible speech was achieved by 30% of TG and 10% of TGL patients (P =. 68).ConclusionPatients undergoing TGL had similar functional and survival outcomes to patients undergoing TG alone despite the presence of more locally advanced disease with greater adverse pathological features. Following TG alone, positive or close margins occurred most commonly at the inferior margin of resection (hyoid/valleculae), which could explain why TGL in patients with advanced tongue SCC may improve local disease control.
Patient characteristics and determinants of quality of life in an international population with multiple sclerosis: Assessment using the MusiQoL and SF-36 questionnaires
Authors: Fernández Oscar , Baumstarck-Barrau Karine , Simeoni Marie-Claude , Auquier Pascal ,   on behalf of the MusiQoL study group
Published: June 2011

Background: Multiple sclerosis (MS) can have psychological and socioeconomic consequences that affect patients’ health-related quality of life (HRQoL) as much as physical disability. Objective: To determine the clinical and sociodemographic factors affecting HRQoL in a large international study using the MS International QoL (MusiQoL) questionnaire. Methods: Patients aged >18 years with a diagnosis of MS for >6 months or clinically isolated syndrome (CIS) were enrolled. Sociodemographic and clinical data were recorded, and patients completed the MusiQoL and 36-item short form (SF-36) health survey questionnaires. Results: In total, 1992 patients from 15 countries were enrolled (mean [standard deviation] age: 42.3 [12.5] years; 70.5% women; 70.4% with relapsing–remitting MS). Multivariate multiple regression analyses identified lower educational level, higher Expanded Disability Status Scale (EDSS) score, cognitive impairment, being single and shorter time since last relapse as significant predictors of lower MusiQoL global index scores ( p < 0.05). Older age, female sex, higher EDSS score, shorter time since last relapse and receiving current MS treatment were significant predictors of lower SF-36 physical component summary scores ( p < 0.05). The SF-36 mental component summary score was linked to occupational status, inpatient/outpatient status, time since last relapse, and whether the patient was receiving MS treatment ( p < 0.05). Conclusion: Sociodemographic and clinical factors are linked to HRQoL in patients with MS. Interventions that affect these factors might be expected to influence HRQoL.
Certain investigations in enhancing power yield from wind farms
Authors: Jerome J , Mayurappriyan P S , Shanmugam K N 
Published: June 2011

India has moved up to the fourth position globally, following Germany, Spain, and USA with an installed capacity of 11 806.69 MW at the end of March 2010. India has some special requirements. The penalty for low power factor is severe, but European designs do not have provision for compensation to this level. In Tamil Nadu, the Tamil Nadu Electricity Board has introduced the penalty only in the late 1990s. Since most of the wind turbine generators are being imported from European countries and as the principals have failed to understand the problem and provide solution, most of the Indian subsidiaries have approached third parties. A wide range of reactive power compensation schemes are available today. The cheapest and easiest solution preferred was to add more contactors and more capacitor steps. This will reduce the reactive power consumption but results in other problems. There is no systematic study to evaluate losses and scope for improving productivity. This article is an attempt to make realistic evaluation of wind farms provided with different systems in Tamil Nadu, India. To enhance the power yield from the wind farms, several methodologies are proposed.
An experimental investigation in a diesel engine using carbon nanotubes blended water–diesel emulsion fuel
Authors: Basha J Sadhik , Anand R B 
Published: June 2011

An experimental investigation is carried out to establish the performance, emission, and combustion characteristics of a diesel engine using carbon nanotubes (CNT) blended water–diesel emulsion fuels. The investigation is carried out in three phases using an experimental set-up consisting of a single-cylinder diesel engine coupled with an electrical loading device, an AVL Di-gas analyser, an AVL smoke meter, and a data-acquisition system comprising a Kistler piezoelectric pressure transducer and a crank angle encoder: using neat diesel in the first phase, water–diesel emulsion fuel in the second phase, and CNT blended water–diesel emulsion fuels in the third phase. The water–diesel emulsion fuel is prepared in the proportion of 5 per cent water, 93 per cent diesel, and 2 per cent surfactants (Span 80 and Tween 80) by volume with a hydrophilic–lipophilic balance of 8. The CNT are blended with the water–diesel emulsion fuel in the mass fractions of 25 and 50 ppm with the aid of a mechanical homogenizer and an ultrasonicator. Subsequently, the stability characteristics of CNT blended water–diesel emulsion fuels are analysed under static conditions. All the experiments are conducted at a constant speed of 1500 r/min and the results revealed a considerable enhancement in the brake thermal efficiency and substantial reduction in the harmful pollutants due to the incorporation of CNT in the water–diesel emulsion fuel.
RANS–URANS in axial compressor, a design methodology
Authors: Montomoli F , Hodson H P , Lapworth L 
Published: June 2011

Turbomachinery flows are inherently unsteady. Until now during the design process, unsteadiness has been neglected, with resort merely to steady numerical simulations. Despite the assumption involved, the results obtained with steady simulations have been used with success. One of the questions arising in recent years is can unsteady simulations be used to improve the design of turbomachines? In this work the numerical simulation of a multi-stage axial compressor is carried out. Comparison of Reynolds averaged Navier-Stokes (RANS) and unsteady Reynolds averaged Navier-Stokes (URANS) calculation shows that the unsteadiness affects pressure losses and the prediction of stall limit. The unsteady inflow due to the wake passing mainly modifies the losses and whirl angle near the endwalls. The computational cost of the fully unsteady compared with a steady simulation is about four times in terms of mesh dimension and two orders of magnitude as number of iterations. A mixed RANS–URANS solution has been proposed to give the designer the possibility to simulate an unsteady stage embedded in a steady-state simulation. This method has been applied to the simulation of a four-stage axial compressor rig. The mixed RANS–URANS approach has been developed using sliding and mixing planes as interface conditions. The rotor–stator interaction has been captured physically while reducing the computational time and mesh size.
Economic and environmental evaluation of selected advanced power generation technologies
Authors: Kotowicz J , Skorek-Osikowska A , Bartela Ł 
Published: June 2011

In this article, the economic and ecological benefits of selected advanced technologies for electricity production based on coal and natural gas are evaluated. Among the analysed technologies are integrated gasification combined cycle (IGCC) systems, supercritical coal-fired power plants, multi-fuel hybrid cycles, and natural gas combined cycles. In addition, as a complement to coal technologies, CO2 capture and storage installations are adopted. The main indicators evaluated are the unit carbon dioxide emission and the break-even price of electricity. The analysis took into account, among other factors, the existing support mechanisms for ecological technologies, primarily in the form of the European Union (EU) Emissions Trading Scheme. The analysis shows that the systems integrated with CO2 capture can be competitive compared to systems without capture. Especially interesting in this context are IGCC systems integrated with carbon capture installations. The results are, however, affected by many factors, such as the fuel price, operational reliability, and auxiliary power need. The influence of these factors is evaluated in this article both qualitatively and quantitatively.
A critical role for SHP2 in STAT5 activation and growth factor–mediated proliferation, survival, and differentiation of human CD34+ cells
Authors: Li Liang , Modi Hardik , McDonald Tinisha , Rossi John , Yee Jiing-Kuan , Bhatia Ravi 
Published: June 2011

AbstractSHP2, a cytoplasmic protein-tyrosine phosphatase encoded by the PTPN11 gene, plays a critical role in developmental hematopoiesis in the mouse, and gain-of-function mutations of SHP2 are associated with hematopoietic malignancies. However, the role of SHP2 in adult hematopoiesis has not been addressed in previous studies. In addition, the role of SHP2 in human hematopoiesis has not been described. These questions are of considerable importance given the interest in development of SHP2 inhibitors for cancer treatment. We used shRNA-mediated inhibition of SHP2 expression to investigate the function of SHP2 in growth factor (GF) signaling in normal human CD34+ cells. SHP2 knockdown resulted in markedly reduced proliferation and survival of cells cultured with GF, and reduced colony-forming cell growth. Cells expressing gain-of-function SHP2 mutations demonstrated increased dependency on SHP2 expression for survival compared with cells expressing wild-type SHP2. SHP2 knockdown was associated with significantly reduced myeloid and erythroid differentiation with retention of CD34+ progenitors with enhanced proliferative capacity. Inhibition of SHP2 expression initially enhanced and later inhibited STAT5 phosphorylation and reduced expression of the antiapoptotic genes MCL1 and BCLXL. These results indicate an important role for SHP2 in STAT5 activation and GF-mediated proliferation, survival, and differentiation of human progenitor cells.
Notch1 inhibition targets the leukemia-initiating cells in a Tal1/Lmo2 mouse model of T-ALL
Authors: Tatarek Jessica , Cullion Kathleen , Ashworth Todd , Gerstein Rachel , Aster Jon C. , Kelliher Michelle A. 
Published: June 2011

Abstract
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy largely caused by aberrant activation of the TAL1/SCL, LMO1/2, and NOTCH1 oncogenes. Approximately 30% of T-ALL patients relapse, and evidence is emerging that relapse may result from a failure to eliminate leukemia-initiating cells (LICs). Thymic expression of the Tal1 and Lmo2 oncogenes in mice results in rapid development of T-ALL; and similar to T-ALL patients, more than half the leukemic mice develop spontaneous mutations in Notch1. Using this mouse model, we demonstrate that mouse T-ALLs are immunophenotypically and functionally heterogeneous with approximately 1 of 10 000 leukemic cells capable of initiating disease on transplantation. Our preleukemic studies reveal expansion of Notch-active double-negative thymic progenitors, and we find the leukemic DN3 population enriched in disease potential. To examine the role of Notch1 in LIC function, we measured LIC activity in leukemic mice treated with vehicle or with a γ-secretase inhibitor. In 4 of 5 leukemias examined, Notch inhibition significantly reduced or eliminated LICs and extended survival. Remarkably, in 2 mice, γ-secretase inhibitor treatment reduced LIC frequency below the limits of detection of this assay, and all transplanted mice failed to develop disease. These data support the continued development of Notch1 therapeutics as antileukemia agents.
Hypoxic induction of vascular endothelial growth factor regulates murine hematopoietic stem cell function in the low-oxygenic niche
Authors: Rehn Matilda , Olsson André , Reckzeh Kristian , Diffner Eva , Carmeliet Peter , Landberg Göran , Cammenga Jörg 
Published: June 2011

Abstract
Hypoxia is emerging as an important characteristic of the hematopoietic stem cell (HSC) niche, but the molecular mechanisms contributing to quiescence, self-renewal, and survival remain elusive. Vascular endothelial growth factor A (VEGFA) is a key regulator of angiogenesis and hematopoiesis. Its expression is commonly regulated by hypoxia-inducible factors (HIF) that are functionally induced in low-oxygen conditions and that activate transcription by binding to hypoxia-response elements (HRE). Vegfa is indispensable for HSC survival, mediated by a cell-intrinsic, autocrine mechanism. We hypothesized that a hypoxic HSC microenvironment is required for maintenance or up-regulation of Vegfa expression in HSCs and therefore crucial for HSC survival. We have tested this hypothesis in the mouse model Vegfaδ/δ, where the HRE in the Vegfa promoter is mutated, preventing HIF binding. Vegfa expression was reduced in highly purified HSCs from Vegfaδ/δ mice, showing that HSCs reside in hypoxic areas. Loss of hypoxia-regulated Vegfa expression increases the numbers of phenotypically defined hematopoietic stem and progenitor cells. However, HSC function was clearly impaired when assessed in competitive transplantation assays. Our data provide further evidence that HSCs reside in a hypoxic microenvironment and demonstrate a novel way in which the hypoxic niche affects HSC fate, via the hypoxia-VEGFA axis.
Cyclophosphamide, fludarabine, alemtuzumab, and rituximab as salvage therapy for heavily pretreated patients with chronic lymphocytic leukemia
Authors: Badoux Xavier C. , Keating Michael J. , Wang Xuemei , O'Brien Susan M. , Ferrajoli Alessandra , Faderl Stefan , Burger Jan , Koller Charles , Lerner Susan , Kantarjian Hagop , Wierda William G. 
Published: June 2011

AbstractPatients with relapsed chronic lymphocytic leukemia (CLL) and high-risk features, such as fludarabine refractoriness, complex karyotype, or abnormalities of chromosome 17p, experience poor outcomes after standard fludaradine-based regimens. Alemtuzumab is a chimeric CD52 monoclonal antibody with activity in CLL patients with fludarabine-refractory disease and 17p deletion. We report the outcome for 80 relapsed or refractory patients with CLL enrolled in a phase 2 study of cyclophosphamide, fludarabine, alemtuzumab, and rituximab (CFAR). All patients were assessed for response and progression according to the 1996 CLL-working group criteria. For the intention-to-treat analysis, the overall response rate was 65%, including 29% complete response. The estimated progression-free survival was 10.6 months and median overall survival was 16.7 months. Although we noted higher complete response in high-risk patients after CFAR compared with a similar population who had received fludarabine, cyclophosphamide, and rituximab as salvage therapy, there was no significant improvement in progression-free survival and overall survival appeared worse. CFAR was associated with a high rate of infectious complications with 37 patients (46%) experiencing a serious infection during therapy and 28% of evaluable patients experiencing late serious infections. Although CFAR produced good response rates in this highly pretreated high-risk group of patients, there was no benefit in survival outcomes.
How I treat Gaucher disease
Authors: Zimran Ari 
Published: June 2011

AbstractThis review presents a cohesive approach to treating patients with Gaucher disease. The spectrum of the clinical presentation of the disease is broad, yet heretofore there was only one disease-specific treatment. In the past 2 years, a global shortage of this product has resulted in reassessment of the “one enzyme–one disease–one therapy” mantra. It has also showcased the multiple levels that engage the patient, the treating physician, and the third-party insurer in providing adequate treatment to all symptomatic patients. The key points summarizing the way I manage my patients include accurate enzymatic diagnosis with mutation analysis (for some prognostication and better carrier detection in the family), a detailed follow-up every 6-12 months (with an option to see consultants and attention to comorbidities), and initiation of enzyme replacement therapy according to symptoms or deterioration in clinically significant features or both. I do not treat patients with very mild disease, but I consider presymptomatic therapy for patients at risk, including young women with poor obstetric history. I prefer the minimal-effective dose rather than the maximally tolerated dose, and when the difference between high-dose and lower-dose regimens is (merely statistically significant but) clinically meaningless, minimizing the burden on society by advocating less-expensive treatments is ethically justified.
Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome
Authors: Hsu Amy P. , Sampaio Elizabeth P. , Khan Javed , Calvo Katherine R. , Lemieux Jacob E. , Patel Smita Y. , Frucht David M. , Vinh Donald C. , Auth Roger D. , Freeman Alexandra F. , Olivier Kenneth N. , Uzel Gulbu , Zerbe Christa S. , Spalding Christine , Pittaluga Stefania , Raffeld Mark , Kuhns Douglas B. , Ding Li , Paulson Michelle L. , Marciano Beatriz E. , Gea-Banacloche Juan C. , Orange Jordan S. , Cuellar-Rodriguez Jennifer , Hickstein Dennis D. , Holland Steven M. 
Published: June 2011

Abstract
The syndrome of monocytopenia, B-cell and NK-cell lymphopenia, and mycobacterial, fungal, and viral infections is associated with myelodysplasia, cytogenetic abnormalities, pulmonary alveolar proteinosis, and myeloid leukemias. Both autosomal dominant and sporadic cases occur. We identified 12 distinct mutations in GATA2 affecting 20 patients and relatives with this syndrome, including recurrent missense mutations affecting the zinc finger-2 domain (R398W and T354M), suggesting dominant interference of gene function. Four discrete insertion/deletion mutations leading to frame shifts and premature termination implicate haploinsufficiency as a possible mechanism of action as well. These mutations were found in hematopoietic and somatic tissues, and several were identified in families, indicating germline transmission. Thus, GATA2 joins RUNX1 and CEBPA not only as a familial leukemia gene but also as a cause of a complex congenital immunodeficiency that evolves over decades and combines predisposition to infection and myeloid malignancy.
A minor role of CD4+ T lymphocytes in the control of a primary infection of cattle with Mycoplasma mycoides subsp. mycoides
Authors: Sacchini Flavio , Naessens Jan , Awino Elias , Heller Martin , Hlinak Andreas , Haider Wolfram , Sterner-Kock Anja , Jores Joerg 
Published: June 2011

Abstract
Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp. mycoides, is an important livestock disease in Africa. The current control measures rely on a vaccine with limited efficacy and occasional severe side effects. Knowledge of the protective arms of immunity involved in this disease will be beneficial for the development of an improved vaccine. In previous studies on cattle infected with M. mycoides subsp. mycoides, a correlation was detected between the levels of mycoplasma-specific IFN-γ-secreting CD4+ T lymphocytes and reduced clinical signs. However, no cause and effect has been established, and the role of such cells and of protective responses acquired during a primary infection is not known.
We investigated the role of CD4+ T lymphocytes in CBPP by comparing disease patterns and post mortem findings between CD4+ T cell depleted and non-depleted cattle. The depletion was carried out using several injections of BoCD4 specific murine monoclonal antibody on day 6 after experimental endotracheal infection with the strain Afadé. All cattle were monitored clinically daily and sacrificed 28-30 days post-infection. Statistically significant but small differences were observed in the mortality rate between the depleted and non-depleted animals. However, no differences in clinical parameters (fever, signs of respiratory distress) and pathological lesions were observed, despite elimination of CD4+ T cells for more than a week. The slightly higher mortality in the depleted group suggests a minor role of CD4+ T cells in control of CBPP.
Reconstructing genome-wide regulatory network of E. coli using transcriptome data and predicted transcription factor activities
Authors: Fu Yao , Jarboe Laura R , Dickerson Julie A 
Published: June 2011

Abstract

Background
Gene regulatory networks play essential roles in living organisms to control growth, keep internal metabolism running and respond to external environmental changes. Understanding the connections and the activity levels of regulators is important for the research of gene regulatory networks. While relevance score based algorithms that reconstruct gene regulatory networks from transcriptome data can infer genome-wide gene regulatory networks, they are unfortunately prone to false positive results. Transcription factor activities (TFAs) quantitatively reflect the ability of the transcription factor to regulate target genes. However, classic relevance score based gene regulatory network reconstruction algorithms use models do not include the TFA layer, thus missing a key regulatory element.

Results
This work integrates TFA prediction algorithms with relevance score based network reconstruction algorithms to reconstruct gene regulatory networks with improved accuracy over classic relevance score based algorithms. This method is called G ene expression and T ranscription factor activity based R elevance N etwork (GTRNetwork). Different combinations of TFA prediction algorithms and relevance score functions have been applied to find the most efficient combination. When the integrated GTRNetwork method was applied to E. coli data, the reconstructed genome-wide gene regulatory network predicted 381 new regulatory links. This reconstructed gene regulatory network including the predicted new regulatory links show promising biological significances. Many of the new links are verified by known TF binding site information, and many other links can be verified from the literature and databases such as EcoCyc. The reconstructed gene regulatory network is applied to a recent transcriptome analysis of E. coli during isobutanol stress. In addition to the 16 significantly changed TFAs detected in the original paper, another 7 significantly changed TFAs have been detected by using our reconstructed network.

Conclusions
The GTRNetwork algorithm introduces the hidden layer TFA into classic relevance score-based gene regulatory network reconstruction processes. Integrating the TFA biological information with regulatory network reconstruction algorithms significantly improves both detection of new links and reduces that rate of false positives. The application of GTRNetwork on E. coli gene transcriptome data gives a set of potential regulatory links with promising biological significance for isobutanol stress and other conditions.