bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subnetwork-based analysis of chronic lymphocytic leukemia identifies pathways that associate with disease progression
Authors: Chuang Han-Yu , Rassenti Laura , Salcedo Michelle , Licon Kate , Kohlmann Alexander , Haferlach Torsten , Foà Robin , Ideker Trey , Kipps Thomas J. 
Published: July 2012

Abstract
The clinical course of patients with chronic lymphocytic leukemia (CLL) is heterogeneous. Several prognostic factors have been identified that can stratify patients into groups that differ in their relative tendency for disease progression and/or survival. Here, we pursued a subnetwork-based analysis of gene expression profiles to discriminate between groups of patients with disparate risks for CLL progression. From an initial cohort of 130 patients, we identified 38 prognostic subnetworks that could predict the relative risk for disease progression requiring therapy from the time of sample collection, more accurately than established markers. The prognostic power of these subnetworks then was validated on 2 other cohorts of patients. We noted reduced divergence in gene expression between leukemia cells of CLL patients classified at diagnosis with aggressive versus indolent disease over time. The predictive subnetworks vary in levels of expression over time but exhibit increased similarity at later time points before therapy, suggesting that degenerate pathways apparently converge into common pathways that are associated with disease progression. As such, these results have implications for understanding cancer evolution and for the development of novel treatment strategies for patients with CLL.
How I treat plasma cell leukemia
Authors: van de Donk Niels W. C. J. , Lokhorst Henk M. , Anderson Kenneth C. , Richardson Paul G. 
Published: July 2012

AbstractPrimary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell proliferative disorder with a very poor prognosis and with distinct biologic, clinical, and laboratory features. Compared with multiple myeloma, pPCL presents more often with extramedullary involvement, anemia, thrombocytopenia, hypercalcemia, elevated serum β2-microglobulin and lactate dehydrogenase levels, as well as impaired renal function. Many of the genetic aberrations observed in newly diagnosed pPCL are typically found in advanced multiple myeloma. These cytogenetic abnormalities and mutations lead to increased proliferation, enhanced inhibition of apoptosis, escape from immune surveillance, and independence from the BM microenvironment, with changes in expression of adhesion molecules or chemokine receptors. The outcome of pPCL has improved with the introduction of autologous stem cell transplantation and combination approaches with novel agents, including bortezomib and immunomodulatory drugs, such as lenalidomide. In this review, we provide an overview of currently available therapeutic options with recommendations of how these treatment modalities can best be used to improve outcome for plasma cell leukemia patients.
Tissue factor–positive neutrophils bind to injured endothelial wall and initiate thrombus formation
Authors: Darbousset Roxane , Thomas Grace M. , Mezouar Soraya , Frère Corinne , Bonier Rénaté , Mackman Nigel , Renné Thomas , Dignat-George Françoise , Dubois Christophe , Panicot-Dubois Laurence 
Published: July 2012

AbstractFor a long time, blood coagulation and innate immunity have been viewed as interrelated responses. Recently, the presence of leukocytes at the sites of vessel injury has been described. Here we analyzed interaction of neutrophils, monocytes, and platelets in thrombus formation after a laser-induced injury in vivo. Neutrophils immediately adhered to injured vessels, preceding platelets, by binding to the activated endothelium via leukocyte function antigen-1–ICAM-1 interactions. Monocytes rolled on a thrombus 3 to 5 minutes postinjury. The kinetics of thrombus formation and fibrin generation were drastically reduced in low tissue factor (TF) mice whereas the absence of factor XII had no effect. In vitro, TF was detected in neutrophils. In vivo, the inhibition of neutrophil binding to the vessel wall reduced the presence of TF and diminished the generation of fibrin and platelet accumulation. Injection of wild-type neutrophils into low TF mice partially restored the activation of the blood coagulation cascade and accumulation of platelets. Our results show that the interaction of neutrophils with endothelial cells is a critical step preceding platelet accumulation for initiating arterial thrombosis in injured vessels. Targeting neutrophils interacting with endothelial cells may constitute an efficient strategy to reduce thrombosis.
Oropharyngeal dysphagia is a risk factor for community-acquired pneumonia in the elderly
Authors: Almirall Jordi , Rofes Laia , Serra-Prat Mateu , Icart Roser , Palomera Elisabet , Arreola Viridiana , Clavé Pere 
Published: July 2012

The aim of this study was to explore whether oropharyngeal dysphagia is a risk factor for community-acquired pneumonia (CAP) in the elderly and to assess the physiology of deglutition of patients with pneumonia.In the case–control study, 36 elderly patients (aged ≥70 years) hospitalised with pneumonia were matched by age and sex with two independently living controls. All subjects were given the volume–viscosity swallow test to identify signs of oropharyngeal dysphagia. In the pathophysiological study, all cases and 10 healthy elderly subjects were examined using videofluoroscopy.Prevalence of oropharyngeal dysphagia in the case–control study was 91.7% in cases and 40.3% in controls (p<0.001). Adjusting for functionality and comorbidities, dysphagia showed an independent effect on pneumonia (OR 11.9, 95% CI 3.03–46.9). Among cases in the pathophysiological study, 16.7% showed safe swallow, 30.6% high penetrations, 36.1% severe penetrations and 16.7% silent aspirations during videofluoroscopy, while in the healthy elderly subjects these percentages were 80%, 20%, 0% and 0%, respectively (p<0.001). A delay in closure of the laryngeal vestibule (0.414±0.029 sversus0.200±0.059 s, p<0.01) was the main mechanism of impaired airway protection.In elderly subjects, oropharyngeal dysphagia is strongly associated with CAP, independently of functionality and comorbidities. Elderly patients with pneumonia presented a severe impairment of swallow and airway protection mechanisms. We recommend universal screening of dysphagia in older persons with pneumonia.
Effect of urbanisation on the relationship between total serum IgE and asthma
Authors: Checkley William , Robinson Colin L. , Baumann Lauren M. , Romero Karina , Combe Juan M. , Gilman Robert H. , Wise Robert A. , Hamilton Robert G. , Gonzalvez Guillermo , Cama Vitaliano , Hansel Nadia N. ,   the PURA study investigators
Published: July 2012

It is unclear if the relationship of total serum IgE with asthma varies with degree of urbanisation. We hypothesised that the relationship of total serum IgE to asthma is more pronounced in an urbanversusa rural environment.We enrolled 1441 children aged 13–15 years in a peri-urban shanty town in Lima, Peru (n=725) and 23 villages in rural Tumbes, Peru (n=716). We asked participants about asthma and allergy symptoms, environmental exposures and sociodemographics; and performed spirometry, and exhaled nitric oxide and allergy skin testing. We obtained blood for total serum IgE in 1143 (79%) participants.Geometric means for total serum IgE were higher in LimaversusTumbes (262versus192 kU·L−1; p<0.001). The odds of asthma increased by factors of 1.6 (95% CI 1.3–2.0)versus1.4 (95% CI 0.9–2.1) per log unit increase in total serum IgE in LimaversusTumbes, respectively. Atopy was an effect modifier of the relationship of total serum IgE on asthma. Among atopics and non-atopics, the odds of asthma increased by a factor of 2.0 (95% CI 1.5–2.7) and 1.0 (95% CI 0.7–1.4) per log unit increase in total serum IgE, respectively.Total serum IgE was associated with atopic asthma but not with non-atopic asthma. Urbanisation did not appear to be an effect modifier of this relationship.
Radial probe EBUSversusCT-guided needle biopsy for evaluation of peripheral pulmonary lesions: an economic analysis
Authors: Steinfort Daniel P. , Liew Danny , Irving Louis B. 
Published: July 2012

Selection of the optimal procedure for minimally invasive diagnosis of peripheral pulmonary lesions (PPLs) may be based on clinical factors; however, selection of diagnostic strategy may also be influenced by cost. Economic analysis of minimally invasive diagnosis of PPL has not been performed previously.Decision-tree analysis was applied to compare downstream costs of endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB) with computed tomography-guided percutaneous needle biopsy (CT-PNB). Calculations were based on real costs derived from patient data. Sensitivity analyses and probabilistic sensitivity analysis were undertaken to identify the more cost-beneficial approach for varying input parameter values. Cost-effectiveness calculations were based on estimated disutility, according to the wait-trade-off technique.For base-case analysis, initial evaluation with CT-PNB was cost-beneficial (AU$2,724versusEBUS-TBLB AU$2,748). The variable which exerted the most influence on cost-benefit outcomes was the cost of managing complications. CT-PNB remained the more cost-effective procedure at base-case parameters, although thresholds were identified during sensitivity analysis where EBUS-TBLB became more cost-effective.The costs of EBUS-TBLB and CT-PNB to evaluate PPL appear to be equivalent, but specific clinical-radiologic factors known to influence procedural outcomes will influence cost-benefit outcomes. Further evaluation of patient preferences and their influence on cost-effectiveness are required.
The role of bronchodilator treatment in the prevention of exacerbations of COPD
Authors: Wedzicha Jadwiga A. , Decramer Marc , Seemungal Terence A.R. 
Published: July 2012

Exacerbations of chronic obstructive pulmonary disease (COPD) are natural events in the progression of the disease, and are characterised by acute worsening of symptoms, especially dyspnoea. These heterogeneous events follow increased airway inflammation, often due to infection, and lead to decreased airflow and increased lung hyperinflation relative to stable COPD. Although exacerbation frequency generally increases as COPD progresses, some patients experience frequent exacerbations (≥2 per year) independently of disease severity. Exacerbations, especially frequent exacerbations, are associated with impaired health-related quality of life, reduced physical activity and poor disease prognosis.The cornerstone of pharmacotherapy for stable COPD is long-acting bronchodilators, including the long-acting β2-agonists (LABAs) and long-acting anti-muscarinic agents (LAMAs) alone or combined with inhaled corticosteroids (ICS). While ICS treatment can potentially reduce the risk of exacerbations, clinical studies have demonstrated the efficacy of LABAs and LAMAs in reducing COPD symptoms, primarily by reducing lung hyperinflation secondary to reduced airway resistance. Sustained reduction in lung hyperinflation may in turn lessen dyspnoea during an exacerbation. Indeed, recent studies suggest that bronchodilators may also reduce the incidence of, or prevent, exacerbations.Using data from recent studies, this review explores the evidence and possible mechanisms through which bronchodilators may prevent exacerbations.
Use of continuous positive airway pressure reduces airway reactivity in adults with asthma
Authors: Busk Michael , Busk Nancy , Puntenney Paula , Hutchins Janet , Yu Zhangsheng , Gunst Susan J. , Tepper Robert S. 
Published: July 2012

Asthma is characterised by airway hyperreactivity, which is primarily treated with β-adrenergic bronchodilators and anti-inflammatory agents. However, mechanical strain during breathing is an important modulator of airway responsiveness and we have previously demonstrated in animal models that continuous positive airway pressure (CPAP) resulted in lowerin vivoairway reactivity. We now evaluated whether using nocturnal CPAP decreased airway reactivity in clinically-stable adults with asthma.Adults with stable asthma and normal spirometry used nocturnal CPAP (8–10 cmH2O) or sham treatment (0–2 cmH2O) for 7 days. Spirometry and bronchial challenges were obtained before and after treatment. The primary outcome was the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 s (PC20).The CPAP group (n=16) had a significant decrease in airway reactivity (change in (Δ)logPC200.406, p<0.0017) while the sham group (n=9) had no significant change in airway reactivity (ΔlogPC200.003, p=0.9850). There was a significant difference in the change in airway reactivity for the CPAPversusthe sham group (ΔlogPC200.41, p<0.043).Our findings indicate that chronic mechanical strain of the lungs produced using nocturnal CPAP for 7 days reduced airway reactivity in clinically stable asthmatics. Future studies of longer duration are required to determine whether CPAP can also decrease asthma symptoms and/or medication usage.
Membrane damage and repair in primary monocytes exposed to human β-defensin-3
Authors: Lioi Anthony B , Reyes Rodriguez Angel L , Funderburg Nicholas T , Feng Zhimin , Weinberg Aaron , Sieg Scott F 
Published: July 2012

Abstract
Human beta defensin-3 damages cell membranes of monocytes, potentially affecting these cellsˈ survival and activity at inflammation sites.
Interactions of AMPs with plasma membranes of primary human immune cells are poorly characterized. Analysis of PI exclusion as a measure of membrane integrity indicated that hBD-3 caused membrane perturbations in monocytes but not T or B cells at concentrations typically used to kill bacteria or to induce activation of APCs. Bleb-like structures were observed in monocytes exposed to hBD-3. These cells also increased surface expression of LAMP1, a membrane repair marker after exposure to hBD-3. Furthermore, cell death was enhanced by adding an inhibitor of membrane repair. Removal of cholesterol from membranes resulted in greater susceptibility of cells to hBD-3, but cholesterol content was not different between the cell types, as assessed by filipin staining. Freshly isolated monocytes expressed higher levels of the negatively charged phospholipid, PS, on their outer leaflet compared with B or T cells. Preincubation of monocytes with molecules that bind PS protected these cells from hBD-3-induced membrane damage, suggesting that outer-membrane PS expression can at least partially explain monocyte susceptibility to hBD-3. The potential for membrane disruption caused by AMPs should be evaluated in various cell types when considering these molecules for therapeutic applications in humans.
Cigarette smoking as a risk factor for other substance misuse: 10-year study of individuals with and without attention-deficit hyperactivity disorder
Authors: Biederman Joseph , Petty Carter R. , Hammerness Paul , Batchelder Holly , Faraone Stephen V. 
Published: July 2012

BackgroundWe previously documented that cigarette smoking is a risk factor for subsequent alcohol and drug misuse and dependence in adolescent girls with attention-deficit hyperactivity disorder (ADHD).AimsTo revisit this hypothesis with a large longitudinal sample of both genders followed up for 10 years into young adulthood.MethodWe used data from two identically designed, longitudinal, case–control family studies of boys and girls with and without ADHD ascertained from psychiatric and paediatric sources. We studied 165 individuals with ADHD and 374 controls followed up longitudinally and masked for 10 years. We assessed ADHD, smoking and substance use status using structured diagnostic interviews. We tested the association between cigarette smoking and subsequent substance use outcomes using Cox proportional hazard regression models.ResultsYouth with ADHD who smoked cigarettes (n= 27) were significantly more likely to subsequently develop drug misuse and dependence compared with youth with ADHD who did not smoke (n= 138,P<0.05).ConclusionsThese results confirm that cigarette smoking increases the risk for subsequent drug and alcohol use disorders among individuals with ADHD. These findings have important public health implications, and underscore the already pressing need to prevent smoking in children with ADHD.
Ethnic density as a buffer for psychotic experiences: findings
from a national survey (EMPIRIC)
Authors: Das-Munshi Jayati , Bécares Laia , Boydell Jane E. , Dewey Michael E. , Morgan Craig , Stansfeld Stephen A. , Prince Martin J. 
Published: July 2012

BackgroundAetiological mechanisms underlying ethnic density associations with
psychosis remain unclear.AimsTo assess potential mechanisms underlying the observation that minority
ethnic groups experience an increased risk of psychosis when living in
neighbourhoods of lower own-group density.MethodMultilevel analysis of nationally representative community-level data
(from the Ethnic Minorities Psychiatric Illness Rates in the Community
survey), which included the main minority ethnic groups living in
England, and a White British group. Structured instruments assessed
discrimination, chronic strains and social support. The Psychosis
Screening Questionnaire ascertained psychotic experiences.ResultsFor every ten percentage point reduction in own-group density, the
relative odds of reporting psychotic experiences increased 1.07 times
(95% CI 1.01–1.14, P = 0.03 (trend)) for the total
minority ethnic sample. In general, people living in areas of lower
own-group density experienced greater social adversity that was in turn
associated with reporting psychotic experiences.ConclusionsPeople resident in neighbourhoods of higher own-group density experience
‘buffering’ effects from the social risk factors for psychosis.
Adsorption of Toluene on Alkali Metal Ion-Exchanged ZSM-5 and β-Zeolites under Humid Conditions
Authors: Takamitsu Yasuyuki , Ariga Ko , Yoshida Satoshi , Ogawa Hiroshi , Sano Tsuneji 
Published: July 2012

Abstract
Alkali metal ion-exchanged ZSM-5 and β-zeolites were tested as hydrocarbon traps for reducing cold-start emissions. The hydrocarbon trap performances were investigated by temperature-programmed desorption employing toluene as a probe molecule both in the presence and absence of water. Toluene adsorption was significantly inhibited in the presence of water. The extent of this inhibitory effect was strongly dependent on the nature of the alkali metal cation. The Cs cation was the most effective in suppressing the inhibition. The suppression of the inhibition is likely due to an enhancement of the interaction between the toluene molecules and zeolite-framework oxygens bearing high negative charge. Having investigated hydrocarbon trap performances of alkali metal ion-exchanged Y and mordenite zeolites as well as ZSM-5 and β, it was concluded that both the type of alkali metal cation employed and the Si/Al ratio of zeolite were the major factors that affected the hydrocarbon trap performance rather than the nature of framework structure of zeolite. On the other hand, the durability was influenced by the type of framework structure used. The stability decreased in the order: Cs/ZSM-5 &gt; Cs/β &gt; Cs/Y ≈ Cs/mordenite. The adsorption capacity of Cs/ZSM-5 was preserved even after thermal treatment at 900 °C.
Response Modification Factors of Steel Moment Frames Equipped with Completely Closed Ribbed Bracing System (CC-RBS)
Authors: Tabeshpour Mohammad Reza , Golafshani Ali Akbar , Shalmani Armin Masroor 
Published: July 2012

In this paper completely closed RBS (CC-RBS) is proposed as a function of a new ribbed bracing system (RBS). RBS is an innovative system which has capacity of performing variable stiffness that can be used for controlling structural deformations and frequency shifting to compensate seismic energy. The overstrength, ductility, and response modification factors of steel moment frames equipped with CC-RBS was evaluated by performing pushover analysis of model structures with various stories and compared with those which Iranian seismic code of practice, Standard No. 2800 is supposed for steel moment frame equipped with ordinary brace. The results were compared with those from nonlinear incremental dynamic analyses (IDA). According to the analysis results, the response modification factors of model structures computed from static pushover analysis (SPO) were generally smaller than the values given by incremental dynamic analysis, but both SPA and IDA lead to response modification factors larger than the value given in Iranian code, standard 2800, for steel moment frame equipped with ordinary brace.
Nothing Is Not Enough: Fix the Absurd Post-Booker Federal Sentencing System
Authors: III Frank O. Bowman, 
Published: July 2012

This article contends that the advisory guidelines system created by the Supreme Court's 200 decision in United States v. Booker should be replaced. It advances three arguments:
First, the post-Booker advisory system is conceptually indefensible. It retains virtually every feature excoriated by critics of the original sentencing guidelines. Its extreme 'advisoriness,' while partially ameliorating some problems with the original guidelines, reintroduces the very concerns about unreviewable judicial arbitrariness that spawned the structured sentencing movement in the first place. More importantly, the post-Booker system does not solve the biggest problem with the pre-Booker system — that its architecture and institutional arrangements predisposed the Commission's rule-making process to become a one-way upward ratchet which raised sentences often and lowered them virtually never. Its sole relative advantage — that of conferring additional (and effectively unreviewable) discretion on sentencing judges — is insufficient to justify its retention as a permanent system.
Second, there exist a number of constitutionally permissible alternatives to the court-created Booker system, one of which — that originally proposed by the Constitution Project and more recently endorsed by Judge William Sessions, former Chair of the U.S. Sentencing Commission — is markedly superior to the present system.
Third, the difficult problem is not designing a sentencing mechanism better than either the pre- or post-Booker guidelines, but ensuring that such a system, once in place, does not replicate pre-Booker experience and become a one-way upward ratchet prescribing ever higher sentences. The article offers suggestions about how this difficulty might be solved, while conceding both the difficulty of this problem and the justice of the concern that, however imperfect the advisory system, it may be the best that can be achieved given the present constellation of institutional and political forces.