bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac Risks Associated With Marathon Running
Authors: Day Sharlene M. , Thompson Paul D. 
Published: June 2010

Context: A recent cluster of sudden cardiac deaths in marathon runners has attracted considerable media attention and evoked concern over the safety of long-distance running and competition. This review discusses the acute and potential long-term risks associated with marathon running and puts these into perspective with the many health benefits afforded by habitual vigorous exercise. Evidence Acquisition: Data sources included peer-reviewed publications from 1979 to January 2010 as identified via PubMed and popular media. Results: Marathon running is associated with a transient and low risk of sudden cardiac death. This risk appears to be even lower in women and is independent of marathon experience or the presence of previously reported symptoms. Most deaths are due to underlying coronary artery disease. The value of preparticipation screening is limited by its insensitivity and impracticality of widespread implementation. Appropriate preparation and deployment of trained medical personnel and availability of automatic external defibrillators are expected to have a major impact on survival from cardiac arrests during marathons. Cardiac biochemical and functional abnormalities are commonly observed transiently following completion of a marathon, although their clinical significance is unknown. Conclusions: Sudden cardiac deaths associated with marathon running are exceedingly rare events. Prevention should focus on recognition and investigation of prodromal symptoms, if present, and access to rapid defibrillation and trained medical personnel. The robust association of endurance running with improved quality of life and longevity underscores the importance of putting risks into perspective with other well-established health benefits of regular vigorous exercise.
Exercise-Induced Bronchospasm
Authors: Molis Marc A. , Molis Whitney E. 
Published: June 2010

Context: Exercise-induced bronchospasm (EIB) is a phenomenon of airway narrowing that occurs during or after exercise or physical exertion. This condition has been reported in a range of sporting activities but is most common in participants of cold-weather sports (eg, Nordic skiing) and indoor sports (eg, ice-skating and swimming). Traditionally, the terms exercise induced-asthma ( EIA) and EIB have been used interchangeably; however, more recent evidence suggests that these entities are separate and should be described as such, given that their treatments differ. Evidence Acquisition: Literature from 2000 to 2010 was obtained through searches of PubMed, Medline, and Google, with the keywords exercise-induced asthma, exercise-induced bronchospasm, asthma and athlete, and asthma and sport and with an emphasis on the current literature (last 3 to 4 years). Results: Although the current literature suggests a differentiation between EIA and EIB, this differentiation is not always clear, and the terms are still often used interchangeably. This lack of distinction makes it difficult to draw conclusions on optimal diagnosis and treatment of EIB. Conclusion: EIB is prevalent in elite-level athletes, with certain groups being at increased risk. Diagnostic testing should be used when possible, given that recent studies suggest poor correlation between symptoms and testing. The mainstay of treatment remains the use of short-acting β-adrenergic agonists.
Serum response factor is an essential transcription factor in megakaryocytic maturation
Authors: Halene Stephanie , Gao Yuan , Hahn Katherine , Massaro Stephanie , Italiano Joseph E. , Schulz Vincent , Lin Sharon , Kupfer Gary M. , Krause Diane S. 
Published: June 2010

AbstractSerum response factor (Srf) is a MADS–box transcription factor that is critical for muscle differentiation. Its function in hematopoiesis has not yet been revealed. Mkl1, a cofactor of Srf, is part of the t(1;22) translocation in acute megakaryoblastic leukemia, and plays a critical role in megakaryopoiesis. To test the role of Srf in megakaryocyte development, we crossed Pf4-Cre mice, which express Cre recombinase in cells committed to the megakaryocytic lineage, to SrfF/F mice in which functional Srf is no longer expressed after Cre-mediated excision. Pf4-Cre/SrfF/F knockout (KO) mice are born with normal Mendelian frequency, but have significant macrothrombocytopenia with approximately 50% reduction in platelet count. In contrast, the BM has increased number and percentage of CD41+ megakaryocytes (WT: 0.41% ± 0.06%; KO: 1.92% ± 0.12%) with significantly reduced ploidy. KO mice show significantly increased megakaryocyte progenitors in the BM by FACS analysis and CFU-Mk. Megakaryocytes lacking Srf have abnormal stress fiber and demarcation membrane formation, and platelets lacking Srf have abnormal actin distribution. In vitro and in vivo assays reveal platelet function defects in KO mice. Critical actin cytoskeletal genes are down-regulated in KO megakaryocytes. Thus, Srf is required for normal megakaryocyte maturation and platelet production partly because of regulation of cytoskeletal genes.
Dissolution of arterial platelet thrombi in vivo with a bifunctional platelet GPIIIa49-66 ligand which specifically targets the platelet thrombus
Authors: Zhang Wei , Li Yong-Sheng , Nardi Michael A. , Dang Suying , Yang Jing , Ji Yong , Li Zongdong , Karpatkin Simon , Wisniewski Thomas 
Published: June 2010

Abstract
Patients with HIV-1 immune-related thrombocytopenia have a unique antibody (Ab) against integrin GPIIIa49-66 capable of inducing oxidative platelet fragmentation via Ab activation of platelet nicotinamide adenine dinucleotide phosphate oxidase and 12-lipoxygenase releasing reactive oxygen species. Using a phage display single-chain antibody (scFv) library, we developed a novel human monoclonal scFv Ab against GPIIIa49-66 (named A11) capable of inducing fragmentation of activated platelets. In this study, we investigated the in vivo use of A11. We show that A11 does not induce significant thrombocytopenia or inhibit platelet function. A11 can prevent the cessation of carotid artery flow produced by induced artery injury and dissolve the induced thrombus 2 hours after cessation of blood flow. In addition, A11 can prevent, as well as ameliorate, murine middle cerebral artery stroke, without thrombocytopenia or brain hemorrhage. To further optimize the antithrombotic activity of A11, we produced a bifunctional A11-plasminogen first kringle agent (SLK), which homes to newly deposited fibrin strands within and surrounding the platelet thrombus, reducing effects on nonactivated circulating platelets. Indeed, SLK is able to completely reopen occluded carotid vessels 4 hours after cessation of blood flow, whereas A11 had no effect at 4 hours. Thus, a new antithrombotic agent was developed for platelet thrombus clearance.
MLN4924, a NEDD8-activating enzyme inhibitor, is active in diffuse large B-cell lymphoma models: rationale for treatment of NF-κB–dependent lymphoma
Authors: Milhollen Michael A. , Traore Tary , Adams-Duffy Jennifer , Thomas Michael P. , Berger Allison J. , Dang Lenny , Dick Lawrence R. , Garnsey James J. , Koenig Erik , Langston Steven P. , Manfredi Mark , Narayanan Usha , Rolfe Mark , Staudt Louis M. , Soucy Teresa A. , Yu Jie , Zhang Julie , Bolen Joseph B. , Smith Peter G. 
Published: June 2010

AbstractMLN4924 is a potent and selective small molecule NEDD8-activating enzyme (NAE) inhibitor. In most cancer cells tested, inhibition of NAE leads to induction of DNA rereplication, resulting in DNA damage and cell death. However, in preclinical models of activated B cell–like (ABC) diffuse large B-cell lymphoma (DLBCL), we show that MLN4924 induces an alternative mechanism of action. Treatment of ABC DLBCL cells with MLN4924 resulted in rapid accumulation of pIκBα, decrease in nuclear p65 content, reduction of nuclear factor-κB (NF-κB) transcriptional activity, and G1 arrest, ultimately resulting in apoptosis induction, events consistent with potent NF-κB pathway inhibition. Treatment of germinal-center B cell–like (GCB) DLBCL cells resulted in an increase in cellular Cdt-1 and accumulation of cells in S-phase, consistent with cells undergoing DNA rereplication. In vivo administration of MLN4924 to mice bearing human xenograft tumors of ABC- and GCB-DLBCL blocked NAE pathway biomarkers and resulted in complete tumor growth inhibition. In primary human tumor models of ABC-DLBCL, MLN4924 treatment resulted in NF-κB pathway inhibition accompanied by tumor regressions. This work describes a novel mechanism of targeted NF-κB pathway modulation in DLBCL and provides strong rationale for clinical development of MLN4924 against NF-κB–dependent lymphomas.
Multicenter survey on the outcome of transplantation of hematopoietic cells in patients with the complete form of DiGeorge anomaly
Authors: Janda Ales , Sedlacek Petr , Hönig Manfred , Friedrich Wilhelm , Champagne Martin , Matsumoto Tadashi , Fischer Alain , Neven Benedicte , Contet Audrey , Bensoussan Danielle , Bordigoni Pierre , Loeb David , Savage William , Jabado Nada , Bonilla Francisco A. , Slatter Mary A. , Davies E. Graham , Gennery Andrew R. 
Published: June 2010

Abstract
Seventeen patients transplanted with hematopoietic cells to correct severe T lymphocyte immunodeficiency resulting from complete DiGeorge anomaly were identified worldwide, and retrospective data were obtained using a questionnaire-based survey. Patients were treated at a median age of 5 months (range, 2-53 months) between 1995 and 2006. Bone marrow was used in 11 procedures in 9 cases: 6 from matched unrelated donors, 4 from human leukocyte antigen (HLA)-identical siblings, and one haploidentical parent with T-cell depletion. Unmobilized peripheral blood was used in 8 cases: 5 from HLA-identical siblings, one from a matched unrelated donor, one from an HLA-identical parent, and one unrelated matched cord blood. Conditioning was used in 5 patients and graft-versus-host disease prophylaxis in 11 patients. Significant graft-versus-host disease occurred in 9 patients, becoming chronic in 3. Median length of follow-up was 13 months, with transplantation from HLA-matched sibling showing the best results. Median survival among deceased patients (10 patients) was 7 months after transplantation (range, 2-18 months). The overall survival rate was 41%, with a median follow-up of 5.8 years (range, 4-11.5 years). Among survivors, median CD3 and CD4 counts were 806 (range, 644-1224) and 348 (range, 225-782) cells/mm3, respectively, CD4+/CD45RA+ cells remained very low, whereas mitogen responses were normalized.
Factors influencing age at diagnosis of primary ciliary dyskinesia in European children
Authors: Kuehni C.E. , Frischer T. , Strippoli M-P.F. , Maurer E. , Bush A. , Nielsen K.G. , Escribano A. , Lucas J.S.A. , Yiallouros P. , Omran H. , Eber E. , O'Callaghan C. , Snijders D. , Barbato A. 
Published: June 2010

Primary ciliary dyskinesia (PCD) is a hereditary disorder of mucociliary clearance causing chronic upper and lower airways disease. We determined the number of patients with diagnosed PCD across Europe, described age at diagnosis and determined risk factors for late diagnosis.Centres treating children with PCD in Europe answered questionnaires and provided anonymous patient lists.In total, 223 centres from 26 countries reported 1,009 patients aged <20 yrs. Reported cases per million children (for 5–14 yr olds) were highest in Cyprus (111), Switzerland (47) and Denmark (46). Overall, 57% were males and 48% hadsitus inversus. Median age at diagnosis was 5.3 yrs, lower in children withsitus inversus(3.5versus5.8 yrs; p<0.001) and in children treated in large centres (4.1versus4.8 yrs; p = 0.002). Adjusted age at diagnosis was 5.0 yrs in Western Europe, 4.8 yrs in the British Isles, 5.5 yrs in Northern Europe, 6.8 yrs in Eastern Europe and 6.5 yrs in Southern Europe (p<0.001). This strongly correlated with general government expenditures on health (p<0.001).This European survey suggests that PCD in children is under-diagnosed and diagnosed late, particularly in countries with low health expenditures. Prospective studies should assess the impact this delay might have on patient prognosis and on health economic costs across Europe.
Rhinovirus induces MUC5AC in a human infection model andin vitroviaNF-κB and EGFR pathways
Authors: Hewson C.A. , Haas J.J. , Bartlett N.W. , Message S.D. , Laza-Stanca V. , Kebadze T. , Caramori G. , Zhu J. , Edbrooke M.R. , Stanciu L.A. , Kon O.M. , Papi A. , Jeffery P.K. , Edwards M.R. , Johnston S.L. 
Published: June 2010

Rhinovirus (RV) infections are the major cause of asthma exacerbations, the major cause of morbidity and mortality in asthma. MUC5AC is the major mucin produced by bronchial epithelial cells. Whether RV infection upregulates MUC5ACin vivois unknown and the molecular mechanisms involved are incompletely understood.We investigated RV induction of MUC5ACin vivoandin vitroto identify targets for development of new therapies for asthma exacerbations.RV infection increased MUC5AC release in normal and asthmatic volunteers experimentally infected with RV-16, and in asthmatic, but not normal, subjects, this was related to virus load. Bronchial epithelial cells were confirmed a source of MUC5ACin vivo. RV induction of MUC5AC in bronchial epithelial cellsin vitrooccurredvianuclear factor-κB-dependent induction of matrix metalloproteinase-mediated transforming growth factor-α release, thereby activating an epidermal growth factor receptor-dependent cascade culminating,viamitogen-activated protein kinase activation, in specificity protein-1 transactivation of the MUC5AC promoter.RV induction of MUC5AC may be an important mechanism in RV-induced asthma exacerbationsin vivo. Revealing the complex serial signalling cascade involved identifies targets for development of pharmacologic intervention to treat mucus hypersecretion in RV-induced illness.
Choice of nasal nitric oxide technique as first-line test for primary ciliary dyskinesia
Authors: Marthin J.K. , Nielsen K.G. 
Published: June 2010

Nasal nitric oxide (nNO) has a well-known potential as an indirect discriminative marker between patients with primary ciliary dyskinesia (PCD) and healthy subjects, but real-life experience and usefulness in young children is sparsely reported. Three nNO sampling methods were examined and compared as first-line tests for PCD.Healthy subjects, confirmed PCDs, consecutive referrals with PCD-like symptoms and patients with cystic fibrosis (CF) had nNO sampled during breath hold (BH-nNO), oral exhalation against resistance (OE-R-nNO) and tidal breathing (TB-nNO) aiming to expand age range into infancy.282 subjects, 117 consecutive referrals, 59 PCDs, 49 CF patients and 57 healthy subjects, were included. All methods separated significantly between PCD and non-PCD, including CF with reliability, in ranking order BH-nNO>OE-R-nNO>TB-nNO. Acceptability in children ranked in reverse order. A problematic high fraction (39%) of false positive TB-nNO was found in young children. An unexpected large fraction (6.8%) of PCDs had nNO values above cut-off.nNO is a helpful first-line tool in real-life PCD work-up in all age groups if the sampling method is chosen according to age. nNO can be misleading in a few patients with true PCD. Further studies are strongly needed in young children.
Smoke exposure as a determinant of autoantibody titre in α1-antitrypsin deficiency and COPD
Authors: Wood A.M. , de Pablo P. , Buckley C.D. , Ahmad A. , Stockley R.A. 
Published: June 2010

Liberation of elastin peptides from damaged lung may be a mechanism of autoimmune lung disease. Citrullination, and anti-citrullinated protein antibody formation occurs in smokers, but the role of smoking in autoantibody generation relevant to pulmonary disease is unclear.Anti-elastin, anti-cyclic citrullinated peptide (anti-CCP) and anti-mutated citrullinated vimentin (anti-MCV) antibodies were measured in 257 subjects with α1-antitrypsin deficiency (AATD), 113 subjects with usual chronic obstructive pulmonary disease (COPD) and 22 healthy nonsmokers. Levels were compared between groups, against phenotypic features and against smoke exposure.Anti-elastin antibodies were higher in controls relative to AATD (p = 0.008) and usual COPD (p<0.00001), and in AATD relative to usual COPD (p<0.00001). Anti-elastin levels showed a threshold at 10 pack-yrs, being higher in those who had smoked less (p = 0.004). No relationships between antibody levels and clinical phenotype were seen after adjustment for smoke exposure. Anti-CCP antibodies were higher in usual COPD than AATD (p = 0.002) but the relationship to smoke exposure was less clear.Smoke exposure is the main determinant of anti-elastin antibody levels, which fall after 10 pack-yrs. Local antibody complexes may be a better measure of elastin directed autoimmunity than circulating levels.
Streptococcus pneumoniaeinfection suppresses allergic airways disease by inducing regulatory T-cells
Authors: Preston J.A. , Thorburn A.N. , Starkey M.R. , Beckett E.L. , Horvat J.C. , Wade M.A. , O'Sullivan B.J. , Thomas R. , Beagley K.W. , Gibson P.G. , Foster P.S. , Hansbro P.M. 
Published: June 2010

An inverse association exists between some bacterial infections and the prevalence of asthma. We investigated whetherStreptococcus pneumoniaeinfection protects against asthma using mouse models of ovalbumin (OVA)-induced allergic airway disease (AAD).Mice were intratracheally infected or treated with killedS. pneumoniaebefore, during or after OVA sensitisation and subsequent challenge. The effects ofS. pneumoniaeon AAD were assessed.Infection or treatment with killedS. pneumoniaesuppressed hallmark features of AAD, including antigen-specific T-helper cell (Th) type 2 cytokine and antibody responses, peripheral and pulmonary eosinophil accumulation, goblet cell hyperplasia, and airway hyperresponsiveness. The effect of infection on the development of specific features of AAD depended on the timing of infection relative to allergic sensitisation and challenge. Infection induced significant increases in regulatory T-cell (Treg) numbers in lymph nodes, which correlated with the degree of suppression of AAD. Tregs reduced T-cell proliferation and Th2 cytokine release. The suppressive effects of infection were reversed by anti-CD25 treatment.Respiratory infection or treatment withS. pneumoniaeattenuates allergic immune responses and suppresses AAD. These effects may be mediated byS. pneumoniae-induced Tregs. This identifies the potential for the development of therapeutic agents for asthma fromS. pneumoniae.
Combined airway and oesophageal stenting in malignant airway–oesophageal fistulas: a prospective study
Authors: Herth F.J.F. , Peter S. , Baty F. , Eberhardt R. , Leuppi J.D. , Chhajed P.N. 
Published: June 2010

Malignant airway–oesophageal fistulas (AEF) are a serious complication of advance oesophageal or lung cancer.The aim of this study was to assess the quality of life before and after stent insertion, and to examine the role of treatment and location of AEF as factors influencing survival in AEF patients managed with airway and/or oesophageal stent insertion.112 patients with AEF were included prospectively. 83 (74%) patients had advanced lung cancer and 29 (26%) patients had oesophageal cancers.Airway stents were inserted in 65 (58%) patients, oesophageal stents in 37 (33%) patients, and both airway and oesophageal stents in 10 (9%) patients. Seven (6%) patients developed respiratory failure and required transient ventilator support in the intensive care unit (four patients with airway stenting, two patients with double stents and one patient in the oesophageal stenting group). None of the patients developed stent migration or needed stent repositioning. Overall, mean survival was 236.6 days (airway stent 219.1 days, oesophageal stent 262.8 days and combined airway–oesophageal stent 252.9 days). Backward, stepwise regression revealed the site of stent placement (airway and/or oesophagus; p<0.028), exact location of the fistula in airway (p = 0.011) and additional treatment with chemotherapy and/or radiation (p<0.001) as independent risk factors predicting increased survival. The mean quality of life score (QoL) was 81 prior to stent insertion and 72 post-stent insertion (p<0.001).Airway and/or oesophageal stent insertion provides an effective approach to improve the QoL in patients with malignant AEF.
Lean mass predicts asthma better than fat mass among females
Authors: Sood A. , Qualls C. , Li R. , Schuyler M. , Beckett W.S. , Smith L.J. , Thyagarajan B. , Lewis C.E. , Jacobs D.R. 
Published: June 2010

The obesity phenotype associated with asthma is not known. Our objective was to define the relative contribution of various distributions of fat and lean mass to asthma prevalence.Data were obtained from 2,525 participants (including 1,422 females) who underwent dual-energy X-ray absorptiometry (DEXA) at the year 20 examination in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. Total, truncal, arm and leg distributions of fat and lean mass were adjusted to the person's height. Self-reported asthma was the outcome.Asthma among females was associated with greater total fat mass, arm fat mass, total lean mass, truncal lean mass and arm lean mass. Among males, none of these mass measures were significantly associated with asthma. Among females, the association with asthma was stronger for total lean mass than for total fat mass. Further, among various regional distributions of lean and fat mass in females, truncal lean mass was the strongest predictor.Total lean mass is more strongly associated with asthma than total fat mass among females. These findings are contrary to the popular perception that excess physiological fat drives the obesity–asthma association. Rather, we hypothesise that ectopic fat within the “lean” tissues drives this association among females.
The 6-min walk distance in healthy subjects: reference standards from seven countries
Authors: Casanova C. , Celli B.R. , Barria P. , Casas A. , Cote C. , de Torres J.P. , Jardim J. , Lopez M.V. , Marin J.M. , Montes de Oca M. , Pinto-Plata V. , Aguirre-Jaime A. 
Published: June 2010

The 6-min walk distance (6MWD) predicted values have been derived from small cohorts mostly from single countries. The aim of the present study was to investigate differences between countries and identify new reference values to improve 6MWD interpretation.We studied 444 subjects (238 males) from seven countries (10 centres) ranging 40–80 yrs of age. We measured 6MWD, height, weight, spirometry, heart rate (HR), maximum HR (HRmax) during the 6-min walk test/the predicted maximum HR (HRmax% pred), Borg dyspnoea score and oxygen saturation.The mean±sd6MWD was 571±90 m (range 380–782 m). Males walked 30 m more than females (p<0.001). A multiple regression model for the 6MWD included age, sex, height, weight and HRmax% pred (adjusted r2= 0.38; p<0.001), but there was variability across centres (adjusted r2= 0.09–0.73) and its routine use is not recommended. Age had a great impact in 6MWD independent of the centres, declining significantly in the older population (p<0.001). Age-specific reference standards of 6MWD were constructed for male and female adults.In healthy subjects, there were geographic variations in 6MWD and caution must be taken when using existing predictive equations. The present study provides new 6MWD standard curves that could be useful in the care of adult patients with chronic diseases.