bluuebunny/crossref_metadata_2025_split huggingface dataset:
Next-generation sequencing of the TET2 gene in 355 MDS and CMML patients reveals low-abundance mutant clones with early origins, but indicates no definite prognostic value
Authors: Smith Alexander E. , Mohamedali Azim M. , Kulasekararaj Austin , Lim ZiYi , Gäken Joop , Lea Nicholas C. , Przychodzen Bartlomiej , Mian Syed A. , Nasser Erick E. , Shooter Claire , Westwood Nigel B. , Strupp Corinna , Gattermann Norbert , Maciejewski Jaroslaw P. , Germing Ulrich , Mufti Ghulam J. 
Published: August 2010

Abstract
Mutations in the TET2 gene are frequent in myeloid disease, although their biologic and prognostic significance remains unclear. We analyzed 355 patients with myelodysplastic syndromes using “next-generation” sequencing for TET2 aberrations, 91 of whom were also subjected to single-nucleotide polymorphism 6.0 array karyotyping. Seventy-one TET2 mutations, with a relative mutation abundance (RMA) ≥ 10%, were identified in 39 of 320 (12%) myelodysplastic syndrome and 16 of 35 (46%) chroni myelomonocytic leukemia patients (P < .001). Interestingly, 4 patients had multiple mutations likely to exist as independent clones or on alternate alleles, suggestive of clonal evolution. “Deeper” sequencing of 96 patient samples identified 4 additional mutations (RMA, 3%-6.3%). Importantly, TET2 mutant clones were also found in T cells, in addition to CD34+ and total bone marrow cells (23.5%, 38.5%, and 43% RMA, respectively). Only 20% of the TET2-mutated patients showed loss of heterozygosity at the TET2 locus. There was no difference in the frequency of genome-wide aberrations, TET2 expression, or the JAK2V617F 46/1 haplotype between TET2-mutated and nonmutated patients. There was no significant prognostic association between TET2 mutations and World Health Organization subtypes, International Prognostic Scoring System score, cytogenetic status, or transformation to acute myeloid leukemia. On multivariate analysis, age (> 50 years) was associated with a higher incidence of TET2 mutation (P = .02).
Inhibition of p38 MAPK-dependent bronchial contraction after ozone by corticosteroids
Authors: Li F. , Zhang M. , Hussain F. , Triantaphyllopoulos K. , Clark A.R. , Bhavsar P.K. , Zhou X. , Chung K.F. 
Published: August 2010

We determined the role of p38 mitogen-activated protein kinase (MAPK) in the increased airway smooth muscle (ASM) contractile responses following ozone and modulation by corticosteroids.Mice were exposed to air or ozone (3 ppm for 3 h) and isometric contractile responses of bronchial rings to acetylcholine (ACh) were measured using a myograph in the presence of p38 MAPK inhibitor, SB239063 (10−6M) or dexamethasone (10−6M). Because MAPK phosphatase (MKP)-1 is a negative regulator of p38 MAPK, we also studied these effects in MKP-1-/-mice.Bronchial rings from ozone-exposed wild-type and MKP-1-/-mice showed increased contractile responses, with a leftward shift of the dose–response curve in MKP-1-/-mice. SB239063 inhibited bronchial contraction equally in air- and ozone-exposed C57/BL6 and MKP-1-/-mice. Dexamethasone inhibited ACh-induced bronchial contraction in both air- and ozone-exposed C57/BL6 mice, but not in air- or ozone-exposed MKP-1-/-mice. ACh-stimulated p38 MAPK and heat shock protein (HSP)27 phosphorylation, as measured by Western blotting, and this effect was suppressed by SB239063 in C57/BL6 and MKP-1-/-mice, but not by dexamethasone in either air- or ozone-exposed MKP-1-/-mice.p38 MAPK plays a role in maximal ACh-induced isometric contractile responses and increased contractility induced by ozone. Dexamethasone inhibits ACh-induced ASM contraction through phosphorylation of p38 MAPK and HSP27.
Dexamethasone reverses monocrotaline-induced pulmonary arterial hypertension in rats
Authors: Price L.C. , Montani D. , Tcherakian C. , Dorfmüller P. , Souza R. , Gambaryan N. , Chaumais M-C. , Shao D.M. , Simonneau G. , Howard L.S. , Adcock I.M. , Wort S.J. , Humbert M. , Perros F. 
Published: August 2010

Pulmonary arterial hypertension (PAH) is associated with dysregulated bone morphogenetic protein receptor (BMPR)-II signaling and pulmonary vascular inflammation. We evaluated the effects of dexamethasone on monocrotaline (MCT)-induced PAH in rats for potential reversal of PAH at late time-points.Saline-treated control, MCT-exposed, MCT-exposed and dexamethasone-treated rats (5 mg·kg−1·day−1, 1.25 mg·kg−1and 2.5 mg·kg−1·48 h−1) were evaluated at day 28 and day 35 following MCT for haemodynamic parameters, right ventricular hypertrophy, morphometry, immunohistochemistry, andIL6andBMPR2expression.Dexamethasone improved haemodynamics and pulmonary vascular remodelling, preventing PAH development at early (day 1–14 and 1–28) and reversing PAH at late (day 14–28 and 21–35) time-points following MCT, as well as improving survival in MCT-exposed rats compared with controls. Both MCT-induced pulmonaryIL6overexpression and interleukin (IL)-6-expressing adventitial inflammatory cell infiltration were reduced with dexamethasone. This was associated with pulmonaryBMPR2downregulation following MCT, which was increased with dexamethasone, in whole lung and control pulmonary artery smooth muscle cells. Dexamethasone also reduced proliferation of rat pulmonary artery smooth muscle cellsin vitro.Experimental PAH can be prevented and reversed by dexamethasone, and survival is improved. In this model, mechanisms may involve reduction of IL-6-expressing inflammatory cells, restoration of pulmonaryBMPR2expression and reduced proliferation of vascular smooth muscle cells.
Once-daily indacaterolversustwice-daily salmeterol for COPD: a placebo-controlled comparison
Authors: Kornmann O. , Dahl R. , Centanni S. , Dogra A. , Owen R. , Lassen C. , Kramer B. 
Published: August 2010

Indacaterol is a novel, inhaled, once-daily, ultra-long-acting β2-agonist bronchodilator recently approved in Europe for the treatment of chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the efficacy and safety of indacaterol compared with placebo and the twice-daily β2-agonist, salmeterol, as an active control.Patients with moderate-to-severe COPD were randomised to 6 months double-blind treatment with indacaterol (150 μg once daily), salmeterol (50 μg twice daily) or placebo. The primary efficacy end-point was trough (24 h post-dose) forced expiratory volume in 1 s (FEV1) after 12 weeks.1,002 patients were randomised and 838 (84%) completed the study. Indacaterol increased trough FEV1at week 12 by 170 mL over placebo (p<0.001) and by 60 mL over salmeterol (p<0.001). Both active treatments improved health status (St George's Respiratory Questionnaire) and dyspnoea (transition dyspnoea index) compared with placebo, with differences between them favouring indacaterol. Safety profiles were similar across the treatment groups, and both indacaterol and salmeterol were well tolerated.Once-daily treatment with 150 μg indacaterol had a significant and clinically relevant bronchodilator effect over 24 h post-dose and improved health status and dyspnoea to a greater extent than twice-daily 50 μg salmeterol. Indacaterol should prove a useful additional treatment for patients with COPD.
The minimal important difference of exercise tests in severe COPD
Authors: Puhan M.A. , Chandra D. , Mosenifar Z. , Ries A. , Make B. , Hansel N.N. , Wise R.A. , Sciurba F. 
Published: August 2010

Our aim was to determine the minimal important difference (MID) for 6-min walk distance (6MWD) and maximal cycle exercise capacity (MCEC) in patients with severe chronic obstructive pulmonary disease (COPD).1,218 patients enrolled in the National Emphysema Treatment Trial completed exercise tests before and after 4–6 weeks of pre-trial rehabilitation, and 6 months after randomisation to surgery or medical care. The St George's Respiratory Questionnaire (domain and total scores) and University of California San Diego Shortness of Breath Questionnaire (total score) served as anchors for anchor-based MID estimates. In order to calculate distribution-based estimates, we used the standard error of measurement, Cohen's effect size and the empirical rule effect size.Anchor-based estimates for the 6MWD were 18.9 m (95% CI 18.1–20.1 m), 24.2 m (95% CI 23.4–25.4 m), 24.6 m (95% CI 23.4–25.7 m) and 26.4 m (95% CI 25.4–27.4 m), which were similar to distribution-based MID estimates of 25.7, 26.8 and 30.6 m. For MCEC, anchor-based estimates for the MID were 2.2 W (95% CI 2.0–2.4 W), 3.2 W (95% CI 3.0–3.4 W), 3.2 W (95% CI 3.0–3.4 W) and 3.3 W (95% CI 3.0–3.5 W), while distribution-based estimates were 5.3 and 5.5 W.We suggest a MID of 26±2 m for 6MWD and 4±1 W for MCEC for patients with severe COPD.
Interstitial pressure and lung oedema in chronic hypoxia
Authors: Rivolta I. , Lucchini V. , Rocchetti M. , Kolar F. , Palazzo F. , Zaza A. , Miserocchi G. 
Published: August 2010

We evaluated how the increase in lung interstitial pressure correlates with the pulmonary vascular response to chronic hypoxia.In control and hypoxic (30 days; 10% O2) Wistar male rats, we measured: pulmonary interstitial pressure (Pip), cardiac and haemodynamic parameters by echocardiography, and performed lung morphometry on tissue specimens fixedin situ.In control animals, mean±sdPip, air/tissue volume ratio and capillary vascularity index in the air–blood barrier were -12±2.03 cmH2O, 3.9 and 0.43, respectively. After hypoxia exposure, the corresponding values of these indices in apparently normal lung regions were 2.6±1.7 cmH2O, 3.6, and 0.5, respectively. In oedematous regions, the corresponding values were 12±4 cmH2O, 0.4 and 0.3, respectively. Furthermore, in normal regions, the density of pre-capillary vessels (diameter ∼50–200 μm) increased and their thickness/internal diameter ratio decreased, while opposite results were found in oedematous regions. Pulmonary artery pressure increased in chronic hypoxia relative to the control (39.8±5.9versus26.2±2.2 mmHg).Heterogeneity in local lung vascular response contributes to developing pulmonary hypertension in chronic hypoxia. In oedematous regions, the decrease in capillary vascularity correlated with the remarkable increase in interstitial pressure and morphometry of the pre-capillary vessels suggested an increase in vascular resistance; the opposite was true in apparently normal regions.
Radial probe endobronchial ultrasound for the diagnosis of peripheral lung cancer: systematic review and meta-analysis
Authors: Steinfort D.P. , Khor Y.H. , Manser R.L. , Irving L.B. 
Published: August 2010

Improved diagnostic sensitivity of bronchsocopy for the investigation of peripheral pulmonary lesions (PPLs) with the use of radial probe endobroncial ultrasound (EBUS) has been reported, although diagnostic performance varies considerably.A systematic review of published literature evaluating radial probe EBUS accuracy was performed to determine point sensitivity and specificity, and to construct a summary receiver-operating characteristic curve. Sub-group analysis and linear regression was used to identify possible sources of study heterogeneity.16 studies with 1,420 patients fulfilled inclusion criteria. Significant inter-study variation in EBUS method was noted. EBUS had point specificity of 1.00 (95% CI 0.99–1.00) and point sensitivity of 0.73 (95% CI 0.70–0.76) for the detection of lung cancer, with a positive likelihood ratio of 26.84 (12.60–57.20) and a negative likelihood ratio of 0.28 (0.23–0.36). Significant inter-study heterogeneity for sensitivity was observed, with prevalence of malignancy, lesion size and reference standard used being possible sources.EBUS is a safe and relatively accurate tool in the investigation of PPLs. Diagnostic sensitivity of EBUS may be influenced by the prevalence of malignancy in the patient cohort being examined and lesion size. Further methodologically rigorous studies on well-defined patient populations are required to evaluate the generalisability of our results.
Hypersensitivity pneumonitis and metalworking fluids contaminated by mycobacteria
Authors: Tillie-Leblond I. , Grenouillet F. , Reboux G. , Roussel S. , Chouraki B. , Lorthois C. , Dalphin J-C. , Wallaert B. , Millon L. 
Published: August 2010

Metalworking fluids (MWF) are responsible for hypersensitivity pneumonitis (HP). The aim of the present study was to identify the antigen (Ag) responsible for MWF-associated HP, and to optimise serological diagnosis by definition of a threshold allowing discrimination between HP patients and asymptomatic exposed workers.13 patients, who were workers at a car engine manufacturing plant, were suspected of MWF-associated HP. Microbial analysis of 83 used MWFs was carried out. Sera from 13 MWF-associated HP patients, 12 asymptomatic exposed workers and 18 healthy unexposed controls were tested to determine their immunological responses to three Ags, includingMycobacterium immunogenum.M. immunogenumwas identified in 40% of used fluids by culture and confirmed by DNA sequencing. The threshold for differentiating MWF-associated HP patients from asymptomatic exposed workers was five arcs of precipitation (sensitivity 77% and specificity 92%), as determined by electrosyneresis (ES). Using ELISA methods with protein extract fromM. immunogenum, a threshold leading to 92% sensitivity and 100% specificity was established.The detection of specific antibodies againstM. immunogenumAg at high levels in case sera suggests thatM. immunogenum-contaminated MWF is responsible for MWF-associated HP. To discriminate MWF-associated HP patients from asymptomatic exposed workers, we suggest a five-arc threshold for ES and a 1.6-AU threshold for ELISA methods.
Distributed probing of chromatin structure in vivo reveals pervasive chromatin accessibility for expressed and non-expressed genes during tissue differentiation in C. elegans
Authors: Sha Ky , Gu Sam G , Pantalena-Filho Luiz C , Goh Amy , Fleenor Jamie , Blanchard Daniel , Krishna Chaya , Fire Andrew 
Published: August 2010

Abstract

Background
Tissue differentiation is accompanied by genome-wide changes in the underlying chromatin structure and dynamics, or epigenome. By controlling when, where, and what regulatory factors have access to the underlying genomic DNA, the epigenome influences the cell's transcriptome and ultimately its function. Existing genomic methods for analyzing cell-type-specific changes in chromatin generally involve two elements: (i) a source for purified cells (or nuclei) of distinct types, and (ii) a specific treatment that partitions or degrades chromatin by activity or structural features. For many cell types of great interest, such assays are limited by our inability to isolate the relevant cell populations in an organism or complex tissue containing an intertwined mixture of other cells. This limitation has confined available knowledge of chromatin dynamics to a narrow range of biological systems (cell types that can be sorted/separated/dissected in large numbers and tissue culture models) or to amalgamations of diverse cell types (tissue chunks, whole organisms).

Results
Transgene-driven expression of DNA/chromatin modifying enzymes provides one opportunity to query chromatin structures in expression-defined cell subsets. In this work we combine in vivo expression of a bacterial DNA adenine methyltransferase (DAM) with high throughput sequencing to sample tissue-specific chromatin accessibility on a genome-wide scale. We have applied the method (DALEC: Direct Asymmetric Ligation End Capture) towards mapping a cell-type-specific view of genome accessibility as a function of differentiated state. Taking advantage of C. elegans strains expressing the DAM enzyme in diverse tissues (body wall muscle, gut, and hypodermis), our efforts yield a genome-wide dataset measuring chromatin accessibility at each of 538,000 DAM target sites in the C. elegans (diploid) genome.

Conclusions
Validating the DALEC mapping results, we observe a strong association between observed coverage by nucleosomes and low DAM accessibility. Strikingly, we observed no extended regions of inaccessible chromatin for any of the tissues examined. These results are consistent with "local choreography" models in which differential gene expression is driven by intricate local rearrangements of chromatin structure rather than gross impenetrability of large chromosomal regions.
Differences in prevalence of self-reported musculoskeletal symptoms among computer and non-computer users in a Nigerian population: a cross-sectional study
Authors: Ayanniyi O , Ukpai BOO , Adeniyi AF 
Published: August 2010

Abstract

Background
Literature abounds on the prevalent nature of Self Reported Musculoskeletal Symptoms (SRMS) among computer users, but studies that actually compared this with non computer users are meagre thereby reducing the strength of the evidence. This study compared the prevalence of SRMS between computer and non computer users and assessed the risk factors associated with SRMS.

Methods
A total of 472 participants comprising equal numbers of age and sex matched computer and non computer users were assessed for the presence of SRMS. Information concerning musculoskeletal symptoms and discomforts from the neck, shoulders, upper back, elbows, wrists/hands, low back, hips/thighs, knees and ankles/feet were obtained using the Standardized Nordic questionnaire.

Results
The prevalence of SRMS was significantly higher in the computer users than the non computer users both over the past 7 days (χ2 = 39.11, p = 0.001) and during the past 12 month durations (χ2 = 53.56, p = 0.001). The odds of reporting musculoskeletal symptoms was least for participants above the age of 40 years (OR = 0.42, 95% CI = 0.31-0.64 over the past 7 days and OR = 0.61; 95% CI = 0.47-0.77 during the past 12 months) and also reduced in female participants. Increasing daily hours and accumulated years of computer use and tasks of data processing and designs/graphics significantly (p < 0.05) increased the risk of reporting musculoskeletal symptoms. Over the past 7 day duration, the neck (33.9%) and low back (11.4%) had highest prevalence of SRMS for the computer and non computer users respectively.

Conclusion
The prevalence of SRMS was significantly higher in the computer users than the non computer users and younger age, being male, working longer hours daily, increasing years of computer use, data entry tasks and computer designs/graphics were the significant risk factors for reporting musculoskeletal symptoms among the computer users. Computer use may explain the increase in prevalence of SRMS among the computer users.
In vitroevaluation of marine-microorganism extracts for anti-viral activity
Authors: Yasuhara-Bell Jarred , Yang Yongbo , Barlow Russell , Trapido-Rosenthal Hank , Lu Yuanan 
Published: August 2010

Abstract
Viral-induced infectious diseases represent a major health threat and their control remains an unachieved goal, due in part to the limited availability of effective anti-viral drugs and measures. The use of natural products in drug manufacturing is an ancient and well-established practice. Marine organisms are known producers of pharmacological and anti-viral agents. In this study, a total of 20 extracts from marine microorganisms were evaluated for their antiviral activity. These extracts were tested against two mammalian viruses, herpes simplex virus (HSV-1) and vesicular stomatitis virus (VSV), using Vero cells as the cell culture system, and two marine virus counterparts, channel catfish virus (CCV) and snakehead rhabdovirus (SHRV), in their respective cell cultures (CCO and EPC). Evaluation of these extracts demonstrated that some possess antiviral potential. In sum, extracts 162M(4), 258M(1), 298M(4), 313(2), 331M(2), 367M(1) and 397(1) appear to be effective broad-spectrum antivirals with potential uses as prophylactic agents to prevent infection, as evident by their highly inhibitive effects against both virus types. Extract 313(2) shows the most potential in that it showed significantly high inhibition across all tested viruses. The samples tested in this study were crude extracts; therefore the development of antiviral application of the few potential extracts is dependent on future studies focused on the isolation of the active elements contained in these extracts.
Epidural cement leakage through pedicle violation after balloon kyphoplasty causing paraparesis in osteoporotic vertebral compression fractures - a report of two cases
Authors: Park Si-Young , Modi Hitesh N , Suh Seung-Woo , Hong Jae-Young , Noh Won , Yang Jae-Hyuk 
Published: August 2010

Abstract
Kyphoplasty is advantageous over vertebroplasty in terms of better kyphosis correction and diminished risk of cement extravasations. Literature described cement leakage causing neurological injury mainly after vertebroplasty procedure; only a few case reports show cement leakage with kyphoplasty without neurological injury or proper cause of leakage. We present a report two cases of osteoporotic vertebral compression fracture treated with kyphoplasty and developed cement leakage causing significant neurological injury. In both cases CT scan was the diagnostic tool to identify cause of cement leakage. CT scan exhibited violation of medial pedicle wall causing cement leakage in the spinal canal. Both patients displayed clinical improvement after decompression surgery with or without instrumentation. Retrospectively looking at stored fluoroscopic images, we found that improper position of trocar in AP and lateral view simultaneously while taking entry caused pedicle wall violation. We suggest not to cross medial pedicle wall in AP image throughout the entire procedure and keeping the trocar in the center of pedicle in lateral image would be the most important precaution to prevent such complication. Our case reports adds the neurological complications with kyphoplasty procedure and suggested that along with other precautions described in the literature, entry with trocar along the entire procedure keeping the oval shape of pedicle in mind (under C-arm) will probably help to prevent such complications.
Apolipoprotein E genotype and mortality in Southern European and Anglo-Celt patients with type 2 diabetes: the Fremantle Diabetes Study
Authors: Davis Wendy A , Chin Eunice , Jee Adelle , Martins Jen , Bruce David G , Beilby John , Davis Timothy M E 
Published: August 2010

ObjectiveTo determine whether cardiac and all-cause mortality are lower in Southern European (SE) patients than in Anglo-Celt (AC) patients with type 2 diabetes in an urban Australian setting, and, if so, whether ethnicity-specific differences in apolipoprotein E (APOE) genotypes are contributory.DesignLongitudinal observational cohort study.MethodsWe analysed detailed data from 1057 patients from the community-based Fremantle Diabetes Study, 238 were of an SE migrant background and 819 of AC ethnicity. Cox proportional hazards modelling was used to identify independent predictors of cardiac and all-cause mortality.ResultsDuring 9.8±3.5 years of follow-up, 411 (38.9%) participants died, 161 (39.2%) from cardiac causes. Significant positive baseline independent predictors of cardiac death were age, male gender, coronary heart disease, cerebrovascular disease, peripheral arterial disease, retinopathy and peripheral neuropathy (P≤0.004), while maternal history of diabetes was protective (P=0.014). After adjusting for these variables,APOE4carriage was predictive (hazard ratio (95% confidence interval) 1.61 (1.01–2.58);P=0.048). SE ethnicity did not add significantly to the model either as a single variable or as an interaction term withAPOE4carriage (P≥0.86). Significant independent predictors of all-cause mortality were age, male gender, smoking, coronary heart disease, cerebrovascular disease, peripheral arterial disease, retinopathy, peripheral neuropathy and microalbuminuria (P≤0.047), while overweight/obesity, lipid-lowering therapy and recent exercise were protective (P≤0.008).APOE4carriage, SE ethnicity and their interaction did not add to the model (P≥0.32).ConclusionsSE ethnicity does not confer an independent survival advantage in community-based Australian type 2 diabetic patients, butAPOE4carriers are at higher risk of cardiac death.