bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nutritional and Global Indexes of Progression in Dementia
Authors: Coin Alessandra , Bolzetta Francesco , Rui Marina De , Veronese Nicola , Granziera Serena , Girardi Agostino , Manzato Enzo , Sergi Giuseppe 
Published: August 2012

Background: To assess the influence of body mass index (BMI) on the progression of dementia. Methods: Sixty elderly outpatients with untreated dementia followed for 12 months. All patients underwent clinical, cognitive, functional, and nutritional assessment at the baseline and after 12 months. Patients were divided into 2 groups by baseline BMI (< or ≥25 kg/m2). Results: Participants with a baseline BMI ≥25 kg/m2 had significantly higher Mini-Mental State Examination (MMSE) scores (21 ± 5.1 vs 15.9 ± 5.5; P < .001), while clinical dementia rating (CDR) and multidimensional prognostic index (MPI) scores were similar in the 2 groups. After 12 months, the MMSE score decreased significantly in both groups compared to the baseline, while the CDR and MPI scores increased significantly for patients with a baseline BMI <25 kg/m2. Conclusion: A BMI cutoff of 25 kg/m2 could be useful for identifying frail patients with dementia who will experience a more rapid global impairment, which could be assessed adequately using multidimensional evaluation tools.
BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia
Authors: Ott Christopher J. , Kopp Nadja , Bird Liat , Paranal Ronald M. , Qi Jun , Bowman Teresa , Rodig Scott J. , Kung Andrew L. , Bradner James E. , Weinstock David M. 
Published: August 2012

Abstract
We investigated the therapeutic potential of JQ1, an inhibitor of the BET class of human bromodomain proteins, in B-cell acute lymphoblastic leukemia (B-ALL). We show that JQ1 potently reduces the viability of B-ALL cell lines with high-risk cytogenetics. Among the most sensitive were lines with rearrangements of CRLF2, which is overexpressed in ∼ 10% of B-ALL. CRLF2 heterodimerizes with the IL7 receptor (IL7R) and signals through JAK2, JAK1, and STAT5 to drive proliferation and suppress apoptosis. As previously observed, JQ1 induced the down-regulation of MYC transcription, the loss of BRD4 at the MYC promoter, and the reduced expression of c-Myc target genes. Strikingly, JQ1 also down-regulated IL7R transcription, depleted BRD4 from the IL7R promoter, and reduced JAK2 and STAT5 phosphorylation. Genome-wide expression profiling demonstrated a restricted effect of JQ1 on transcription, with MYC and IL7R being among the most down-regulated genes. Indeed, IL7R was the only cytokine receptor in CRLF2-rearranged B-ALL cells significantly down-regulated by JQ1 treatment. In mice xenografted with primary human CRLF2-rearranged B-ALL, JQ1 suppressed c-Myc expression and STAT5 phosphorylation and significantly prolonged survival. Thus, bromodomain inhibition is a promising therapeutic strategy for B-ALL as well as other conditions dependent on IL7R signaling.
Specific lipid mediator signatures of human phagocytes: microparticles stimulate macrophage efferocytosis and pro-resolving mediators
Authors: Dalli Jesmond , Serhan Charles N. 
Published: August 2012

AbstractPhagocytes orchestrate acute inflammation and host defense. Here we carried out lipid mediator (LM) metabololipidomics profiling distinct phagocytes: neutrophils (PMN), apoptotic PMN, and macrophages. Efferocytosis increased specialized pro-resolving mediator (SPM) biosynthesis, including Resolvin D1 (RvD1), RvD2, and RvE2, which were further elevated by PMN microparticles. Apoptotic PMN gave elevated prostaglandin E2, lipoxin B4 and RvE2, whereas zymosan-stimulated PMN showed predominantly leukotriene B4 and 20-OH-leukotriene B4, as well as lipoxin marker 5,15-diHETE. Using deuterium-labeled precursors (d8-arachidonic acid, d5-eicosapentaenoic acid, and d5-docosahexaenoic acid), we found that apoptotic PMN and microparticles contributed to SPM biosynthesis during efferocytosis. M2 macrophages produced SPM including maresin-1 (299 ± 8 vs 45 ± 6 pg/2.5 × 105 cells; P < .01) and lower amounts of leukotriene B4 and prostaglandin than M1. Apoptotic PMN uptake by both macrophage subtypes led to modulation of their LM profiles. Leukotriene B4 was down-regulated in M2 (668 ± 81 vs 351 ± 39 pg/2.5 × 105 cells; P < .01), whereas SPM including lipoxin A4 (977 ± 173 vs 675 ± 167 pg/2.5 × 105 cells; P < .05) were increased. Conversely, uptake of apoptotic PMN by M2 macrophages reduced (∼ 25%) overall LM. Together, these results establish LM signature profiles of human phagocytes and related subpopulations. Moreover, they provide evidence for microparticle regulation of specific endogenous LM during defined stages of the acute inflammatory process and their dynamic changes in human primary phagocytes.
Reawakening fetal hemoglobin: prospects for new therapies for the β-globin disorders
Authors: Bauer Daniel E. , Kamran Sophia C. , Orkin Stuart H. 
Published: August 2012

AbstractThe level of fetal hemoglobin (HbF) modifies the severity of the common β-globin disorders. Knowledge of the normal mechanisms that repress HbF in the adult stage has remained limited until recently despite nearly 3 decades of molecular investigation, in part because of imperfect model systems. Recent studies have provided new insights into the developmental regulation of globin genes and identified specific transcription factors and epigenetic regulators responsible for physiologic silencing of HbF. Most prominent among these regulators is BCL11A, a transcriptional repressor that inhibits adult-stage HbF expression. KLF1 and c-Myb are additional critical HbF-regulating erythroid transcription factors more broadly involved in erythroid gene expression programs. Chromatin modifiers, including histone deacetylases and DNA methyltransferases, also play key roles in orchestrating appropriate globin gene expression. Taken together, these discoveries present novel therapeutic targets for further consideration. Although substantial hurdles remain, opportunities are now rich for the rational design of HbF inducers.
Differences between asthmatics and nonasthmatics hospitalised with influenza A infection
Authors: Myles Puja , Nguyen-Van-Tam Jonathan S. , Semple Malcolm G. , Brett Stephen J. , Bannister Barbara , Read Robert C. , Taylor Bruce L. , McMenamin Jim , Enstone Joanne E. , Nicholson Karl G. , Openshaw Peter J. , Lim Wei Shen 
Published: August 2012

Asthmatics hospitalised because of influenza A infection are less likely to require intensive care or die compared with nonasthmatics. The reasons for this are unknown.We performed a retrospective analysis of data on 1520 patients admitted to 75 UK hospitals with confirmed influenza A/H1N1 2009 infection. A multivariable model was used to investigate reasons for the association between asthma and severe outcomes (intensive care unit support or death).Asthmatics were less likely than nonasthmatics to have severe outcome (11.2%versus19.8%, unadjusted OR 0.51, 95% CI 0.36–0.72) despite a greater proportion requiring oxygen on admission (36.4%versus26%, unadjusted OR 1.63) and similar rates of pneumonia (17.1%versus16.6%, unadjusted OR 1.04). The results of multivariable logistic regression suggest the association of asthma with outcome (adjusted OR 0.62, 95% CI 0.36–1.05; p=0.075) are explained by pre-admission inhaled corticosteroid use (adjusted OR 0.34, 95% CI 0.18–0.66) and earlier admission (≤4 days from symptom onset) (adjusted OR 0.60, 95% CI 0.38–0.94). In asthmatics, systemic corticosteroids were associated with a decreased likelihood of severe outcomes (adjusted OR 0.36, 95% CI 0.18–0.72).Corticosteroid use and earlier hospital admission explained the association of asthma with less severe outcomes in hospitalised patients.
Sleep in children with asthma: results of the PIAMA study
Authors: van Maanen Annette , Wijga Alet H. , Gehring Ulrike , Postma Dirkje S. , Smit Henriëtte A. , Oort Frans J. , Rodenburg Roos , Meijer Anne Marie 
Published: August 2012

Children with asthma are thought to have impaired sleep quality and quantity. In this study, we investigated which of the many sleep aspects are associated with asthma.Our sample consisted of 2529 children (aged 11 years) who participated in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study. Parents reported about asthma symptoms (wheezing, dyspnoea, prescription of inhaled corticosteroids and asthma diagnosis) and children reported about different aspects of sleep (bedtime, rise time, sleep quality and daytime sleepiness/tiredness). Results were analysed with (logistic) regression analysis.Children with frequent asthma symptoms significantly more often reported that they felt sleepy or tired during the day (34.4% experienced daytime sleepiness/tiredness at least once a week) than children without asthma symptoms (22.2%) and children with infrequent asthma symptoms (21.9%). This association was not confounded by sex, age of the child, parental educational level or smoking inside the house; the effect was also not modified by sex. There were no associations between asthma and bedtime, time spent in bed or sleep quality.Children with frequent asthma symptoms experienced daytime sleepiness/tiredness more often than children with infrequent or no asthma symptoms. Otherwise, children with asthma did not differ much from children without asthma with regard to sleep.
Rapid diagnosis of primary ciliary dyskinesia: cell culture and soft computing analysis
Authors: Pifferi Massimo , Bush Andrew , Montemurro Francesca , Pioggia Giovanni , Piras Martina , Tartarisco Gennaro , Di Cicco Maria , Chinellato Iolanda , Cangiotti Angela M. , Boner Attilio L. 
Published: August 2012

Diagnosis of primary ciliary dyskinesia (PCD) sometimes requires repeated nasal brushing to exclude secondary ciliary alterations. Our aim was to evaluate whether the use of a new method of nasal epithelial cell culture can speed PCD diagnosis in doubtful cases and to identify which are the most informative parameters by means of a multilayer artificial neural network (ANN).A cross-sectional study was performed in patients with suspected PCD. All patients underwent nasal brushing for ciliary motion analysis, ultrastructural assessment and evaluation of ciliary function after ciliogenesis in culture by ANN.151 subjects were studied. A diagnostic suspension cell culture was obtained in 117 nasal brushings. A diagnosis of PCD was made in 36 subjects (29 of whom were children). In nine out of the 36 patients the diagnosis was made only after a second brushing, because of equivocal results of both tests at first examination. In each of these subjects diagnosis of PCD was confirmed by cell culture results.Cell culture in suspension evaluated by means of ANN allows the separation of PCD from secondary ciliary dyskinesia patients after only 5 days of culture and allows diagnosis to be reached in doubtful cases, thus avoiding the necessity of a second sample.
Vascular and right ventricular remodelling in chronic thromboembolic pulmonary hypertension
Authors: Delcroix Marion , Vonk Noordegraaf Anton , Fadel Elie , Lang Irene , Simonneau Gérald , Naeije Robert 
Published: August 2012

In chronic thromboembolic pulmonary hypertension (CTEPH) increased pulmonary vascular resistance is caused by fibrotic organisation of unresolved thromboemboli. CTEPH mainly differs from pulmonary arterial hypertension (PAH) by the proximal location of pulmonary artery obliteration, although distal arteriopathy can be observed as a consequence of non-occluded area over-perfusion. Accordingly, there is proportionally more wave reflection in CTEPH, impacting on pressure and flow wave morphology. However, the time constant,i.e.resistance×compliance, is not different in CTEPH and PAH, indicating only trivial effects of proximal wave reflection on hydraulic right ventricular load. More discriminative is the analysis of the pressure decay after pulmonary arterial occlusion, which is more rapid in the absence of significant distal arteriopathy.Structure and function of the right ventricle show a similar pattern to right ventricular hypertrophy, namely dilatation and wall thickening, as well as loss of function in CTEPH and PAH. This is probably related to similar loading conditions. Hyperventilation with hypocapnia is characteristic of both PAH and CTEPH. Ventilatory equivalents for carbon dioxide, as a function of arterial carbon dioxide tension, conform to the alveolar ventilation equation in both conditions, indicating a predominant role of increased chemosensitivity. However, a slight increase in the arterial to end-tidal carbon dioxide tension gradient in CTEPH shows a contribution of increased dead space ventilation.
Second-line anti-tuberculosis drug concentrations for susceptibility testing in the MODS assay
Authors: Fitzwater Sean Patrick , Sechler G. Andrew , Jave Oswaldo , Coronel Jorge , Mendoza Alberto , Gilman Robert H. , Friedland Jon S. , Moore David A.J. 
Published: August 2012

Multidrug-resistant tuberculosis (TB) threatens TB control worldwide. The microscopic observation drug susceptibility (MODS) assay is a low-cost, high-performance TB diagnostic tool for rapid liquid culture and direct isoniazid and rifampicin drug susceptibility testing (DST). The objective of this study was to explore the potential for extending the MODS assay to rapid second-line DST and to identify critical concentrations of candidate drugs for prospective testing.Sputum samples from 94 TB culture-positive patients receiving second-line TB agents were cultured following standardised MODS protocols, with a range of titrations of antimicrobial drugs added. Critical concentrations were determined using a modified Kaplan–Meier survival curve analysis.Candidate critical concentrations were determined for capreomycin (10 μg·mL−1), ciprofloxacin (1.25 μg·mL−1), cycloserine (40 μg·mL−1), ethambutol (10 μg·mL−1), ethionamide (5 μg·mL−1), kanamycin (5 μg·mL−1), para-aminosalicylic acid (10 μg·mL−1) and streptomycin (10 μg·mL−1). No cut-off point was identified for the other second-line drugs or for pyrazinamide.At particular concentrations of some second-line TB drugs this novel Kaplan–Meier analysis clearly differentiated populations that were susceptible or resistant. These candidate critical concentrations should now be tested in a range of epidemiological settings to define the performance of direct, second-line TB DST with MODS, offering potential low-cost second-line TB DST capacity.
Prediction of in-hospital death from community-acquired pneumonia by varying CRB-age groups
Authors: Ewig Santiago , Bauer Torsten , Richter Klaus , Szenscenyi Joachim , Heller Günther , Strauss Richard , Welte Tobias 
Published: August 2012

C(U)RB-65 (confusion, (urea >7 mol·L−1,) respiratory frequency ≥30 breaths·min−1, systolic blood pressure <90 mmHg or diastolic blood pressure ≤60 mmHg and age ≥65 years) is now the generally accepted severity score for patients with community-acquired pneumonia (CAP) in Europe.In an observational study based on the large database from the German nationwide performance measurement programme in healthcare quality, including data from all hospitalised patients with CAP during 2008–2010, different CRB-age groups (≥50 and ≥60 years) across the total CAP population and three entities of CAP (younger population aged <65 years, patients aged ≥65 years not residing in nursing homes and those with nursing home-acquired pneumonia (NHAP)) were validated for their potential to predict in-hospital death.660 594 patients were investigated. Mortality was n=93 958 (14.0%). In the total population, CRB-80 had the optimal area under the curve (0.690, 95% CI 0.688–0.691). However, in the younger cohort, CRB-50 performed best (0.730, 95% CI 0.724–0.736), with good identification of low-risk patients (CRB-50 risk class 1: 1.28% deaths, negative predictive value 98.7%). In the elderly, CRB-80 as the optimal age group performed worse (0.663, 95% CI 0.660–0.655 in patients not residing in nursing homes; 0.608, 95% CI 0.605–0.611 in those with NHAP). In the latter group, all CRB-age groups failed to identify low-risk patients (CRB-80 risk class 1: 22.75% deaths, negative predictive value 81.8%).Patients with hospitalised CAP aged <65 years may be assessed by the CRB-50 score. In those aged ≥65 years (not NHAP) assessed by the CRB-65 score, low-risk patients are already are at an increased risk of death. In NHAP patients, even the use of CRB-80 does not identify low-risk patients and should be accompanied by the evaluation of functional status and comorbidity.
The significance of early recurrent wheeze for asthma outcomes in late childhood
Authors: Hovland Vegard , Riiser Amund , Mowinckel Petter , Carlsen Kai-Håkon , Lødrup Carlsen Karin C. 
Published: August 2012

Recurrent early life wheeze is not always asthma, and up to 50% of children are reported to remit. With reports of adult asthma symptom relapse, we assessed the prognosis of recurrent bronchial obstruction (rBO) through adolescence in the Environment and Childhood Asthma (ECA) prospective birth cohort study.The present study is based on data from investigations at ages 2, 10 and 16 years of 550 young people (52% males) attending at 16 years of age. Based on the presence of rBO from 0–2 years, defined as recurrent (at least two episodes) doctor-diagnosed wheeze, and asthma from 2–10 years and 10–16 years, defined as at least two episodes of doctor-diagnosed asthma, symptoms and medication use, prognosis of rBO was assessed. Bronchial hyperresponsiveness (BHR) was diagnosed by a metacholine provocation dose ≤8 μmol that caused 20% reduction in the forced expiratory volume in 1 s.At 10–16 years, 34% of the 143 rBO children had asthma. All children with rBO had reduced lung function compared with the never asthmatics. Of the rBO children in remission, 48.4% had asthma symptoms, medication use and/or BHR compared with 26.7% with never asthma (p<0.001).Only 34.3% of rBO children were without asthma symptoms, medication use or BHR by 16 years, possibly indicating future asthma risk.
Cardiovascular biomarkers predict susceptibility to lung injury in World Trade Center dust-exposed firefighters
Authors: Weiden Michael D. , Naveed Bushra , Kwon Sophia , Cho Soo Jung , Comfort Ashley L. , Prezant David J. , Rom William N. , Nolan Anna 
Published: August 2012

Pulmonary vascular loss is an early feature of chronic obstructive pulmonary disease. Biomarkers of inflammation and of metabolic syndrome predict loss of lung function in World Trade Center (WTC) lung injury (LI). We investigated if other cardiovascular disease (CVD) biomarkers also predicted WTC-LI.This nested case–cohort study used 801 never-smoker, WTC-exposed firefighters with normal pre-9/11 lung function presenting for subspecialty pulmonary evaluation (SPE) before March 2008. A representative subcohort of 124 out of 801 subjects with serum drawn within 6 months of 9/11 defined CVD biomarker distribution. Post-9/11 forced expiratory volume in 1 s (FEV1) at defined cases were as follows: susceptible WTC-LI cases with FEV1≤77% predicted (66 out of 801) and resistant WTC-LI cases with FEV1≥107% predicted (68 out of 801). All models were adjusted for WTC exposure intensity, body mass index at SPE, age on 9/11 and pre-9/11 FEV1.Susceptible WTC-LI cases had higher levels of apolipoprotein-AII, C-reactive protein and macrophage inflammatory protein-4 with significant relative risks (RRs) of 3.85, 3.93 and 0.26, respectively, with an area under the curve (AUC) of 0.858. Resistant WTC-LI cases had significantly higher soluble vascular cell adhesion molecule and lower myeloperoxidase, with RRs of 2.24 and 2.89, respectively (AUC 0.830).Biomarkers of CVD in serum 6 months post-9/11 predicted either susceptibility or resistance to WTC-LI. These biomarkers may define pathways either producing or protecting subjects from pulmonary vascular disease and associated loss of lung function after an irritant exposure.
Haemodynamic responses to exercise in patients with COPD
Authors: Hilde Janne Mykland , Skjørten Ingunn , Hansteen Viggo , Melsom Morten Nissen , Hisdal Jonny , Humerfelt Sjur , Steine Kjetil 
Published: August 2012

The present study aimed to explore the prevalence of pre-capillary pulmonary hypertension (PH) and characterise haemodynamic vascular responses to physical exercise in chronic obstructive pulmonary disease (COPD) outpatients, where left ventricular dysfunction and comorbidities were excluded.98 patients with COPD underwent right heart catheterisation at rest and during supine exercise. Mean pulmonary artery pressure (Ppa), pulmonary capillary wedge pressure (Ppcw) and cardiac output (CO) were measured at rest and during exercise. Exercise-induced increase in meanPpawas interpreted relative to increase in blood flow, meanPpa/CO, workload (W) and meanPpa/W. Pulmonary vascular resistance (PVR) and pulmonary artery compliance (PAC) were calculated. PH at rest was defined as meanPpaat rest ≥25 mmHg andPpcwat rest <15 mmHg.Prevalence of PH was 5%, 27% and 53% in Global Initiative for Chronic Obstructive Lung Disease stages II, III and IV, respectively. The absolute exercise-induced rise in meanPpadid not differ between subjects with and without PH. Patients without PH showed similar abnormal haemodynamic responses to exercise as the PH group, with increased PVR, reduced PAC and steeper slopes for meanPpa/CO and meanPpa/W.Exercise revealed abnormal physiological haemodynamic responses in the majority of the COPD patients. The future definition of PH on exercise in COPD should rely on the slope of meanPparelated to cardiac output and workload rather than the absolute values of meanPpa.
Short cigarette smoke exposure facilitates sensitisation and asthma development in mice
Authors: Lanckacker Ellen A. , Tournoy Kurt G. , Hammad Hamida , Holtappels Gabriele , Lambrecht Bart N. , Joos Guy F. , Maes Tania 
Published: August 2012

Epidemiological studies indicate that cigarette smoke exposure is a risk factor for increased sensitisation and asthma development. The aim of this study was to examine the impact of cigarette smoke on sensitisation and allergic airway inflammation in response to a low dose of house dust mite (HDM), and to obtain potential mechanistic insights.Mice were exposed to low doses of HDM extract combined with air or cigarette smoke exposure, either during allergen sensitisation or during the development of allergic airway disease.Mice concomitantly exposed to low-dose HDM, combined with cigarette smoke for 3 weeks, demonstrated an asthmatic phenotype with significantly increased airway eosinophilia, goblet cell metaplasia, airway hyperresponsiveness and a rise in HDM-specific serum immunoglobulin G1, compared to sole HDM or cigarette smoke exposure. In addition, short cigarette smoke inhalation, during the initial contact with HDM allergens, was sufficient to facilitate sensitisation and development of a complete asthmatic phenotype after rechallenge with HDM. Mechanistically, short cigarette smoke exposure amplified dendritic cell-mediated transport of fluorescein isothiocyanate-labelled HDM allergens to the intrathoracic lymph nodes and generated a local T-helper cell type 2 response.Short cigarette smoke exposure is sufficient to facilitate allergic sensitisation and the development of low-dose HDM-induced allergic asthma, possibly by affecting dendritic cell function.