tbuckley/cabot-search huggingface dataset:
Atrial Fibrillation After Isolated Coronary Surgery Affects Late Survival
Authors: Giovanni Mariscalco, Catherine Klersy, Marco Zanobini, Maciej Banach, Sandro Ferrarese, Paolo Borsani, Cristiano Cantore, Paolo Biglioli, Andrea Sala
Journal: Circulation (2008)

Atrial fibrillation (AF) after coronary artery bypass graft surgery is a difficult problem and a continuing source of morbidity and mortality. However, the prognostic implications of postoperative AF are still in dispute. Our aim was to ascertain the impact of AF after coronary artery bypass graft on postoperative survival and to assess its prognostic role in cause-specific mortality.We conducted a prospective observational study of 1832 patients undergoing isolated coronary artery bypass graft between January 2000 and December 2005 at 2 cardiac surgery centers in northern Italy. Patients affected by postoperative AF were identified and followed up until death or study end (April 30, 2007). A total of 570 patients (31%) developed AF after coronary surgery. Patients affected by postoperative AF experienced a longer hospital stay (7 days [25th to 75th percentile, 7 to 10 days] versus 7 days [25th to 75th percentile, 6 to 8 days]; P<0.001). Hospital mortality also was higher in AF patients (3.3% versus 0.5%; P<0.001). On discharge, 1806 patients were alive; 143 were lost to follow-up. The remaining 1663 were followed up for a median of 51 months (25th to 75th percentile, 41 to 63 months); 126 of them died after a median of 14 months (25th to 75th percentile, 5 to 32 months). Long-term mortality rates were significantly higher for patients with postoperative AF (2.99 per 100 person-years; 95% confidence interval, 2.33 to 3.84; 61 deaths) compared with those without the arrhythmia (1.34 per 100 person-years; 95% confidence interval, 1.05 to 1.71; 65 deaths), with an adjusted hazard ratio of 2.13 (P<0.001) and 2.56 (P=0.001) when also accounting for the prescription of warfarin at discharge. With Cox regression, patients with AF were shown to be at higher risk of dying from embolism (adjusted hazard ratio, 4.33; 95% confidence interval, 1.78 to 10.52) but not from other causes.Postoperative AF affects early and late mortality after isolated coronary artery bypass graft surgery. Patients affected by AF are at higher risk of fatal embolic events. Careful postoperative surveillance with a specific antiarrhythmic and antithrombotic prophylaxis, aimed at reducing AF and its complications, is recommended.
Pilot Study of Vaccination with Recombinant CEA-MUC-1-TRICOM Poxviral-Based Vaccines in Patients with Metastatic Carcinoma
Authors: James L. Gulley, Philip M. Arlen, Kwong-Yok Tsang, Junko Yokokawa, Claudia Palena, Diane J. Poole, Cinzia Remondo, Vittore Cereda, Jacquin L. Jones, Mary P. Pazdur, Jack P. Higgins, James W. Hodge, Seth M. Steinberg, Herbert Kotz, William L. Dahut, Jeffrey Schlom
Journal: Clinical Cancer Research (2008)

Poxviral vectors have a proven safety record and can be used to incorporate multiple transgenes. Prior clinical trials with poxviral vaccines have shown that immunologic tolerance to self-antigens can be broken. Carcinoembryonic antigen (CEA) and MUC-1 are overexpressed in a substantial proportion of common solid carcinomas. The primary end point of this study was vaccine safety, with immunologic and clinical responses as secondary end points.We report here a pilot study of 25 patients treated with a poxviral vaccine regimen consisting of the genes for CEA and MUC-1, along with a triad of costimulatory molecules (TRICOM; composed of B7.1, intercellular adhesion molecule 1, and lymphocyte function-associated antigen 3) engineered into vaccinia (PANVAC-V) as a prime vaccination and into fowlpox (PANVAC-F) as a booster vaccination.The vaccine was well tolerated. Apart from injection-site reaction, no grade > or =2 toxicity was seen in more than 2% of the cycles. Immune responses to MUC-1 and/or CEA were seen following vaccination in 9 of 16 patients tested. A patient with clear cell ovarian cancer and symptomatic ascites had a durable (18-month) clinical response radiographically and biochemically, and one breast cancer patient had a confirmed decrease of >20% in the size of large liver metastasis.This vaccine strategy seems to be safe, is associated with both CD8 and CD4 immune responses, and has shown evidence of clinical activity. Further trials with this agent, either alone or in combination with immunopotentiating and other therapeutic agents, are warranted.
Comparative assessment of metalaxyl enhanced protection of pearl millet varieties in the control of downy mildew
Authors: B. Aliyu, S. S. Hati, G. A. Dimari, P. O. Donli
Journal: Journal of Clinical Oncology (2011)

A comparative assessment was carried out to determine the enhanced protection by metalaxyl in the control of downy mildew on three varieties of pearl millet (SOSAT-C-88, Ex-Borno and GB 8735). Field trials were carried out in 2007 and 2008 growing seasons. The split-plot design was used with the chemical treatments (metalaxyl, and control) in the main plots while the varieties were assessed in the sub-plots. The treatments were replicated three times. The result of this study showed varying enhanced protections of the pearl millet varieties against downy mildew incidence on the vegetative shoots. SOSAT-C-88 showed the most significantly enhanced (p  Ex-Borno > GB 8735 of enhanced protection was recorded. This trend was consistent for the year 2007 and 2008 under study. Gene effects have been attributed to the resistance potentials of pear millet varieties against downy mildew incidence as indicated also from the results of this study. However, with enhanced protection by suitable fungicides such as metalaxyl, a significant protection against downy mildew incidences can be achieved and yield increased.

	 

	Key words: Metalaxyl, pearl millet, downy mildew, enhanced protection.
Microbiota-Targeted Therapies: An Ecological Perspective
Authors: Katherine P. Lemon, Gary C. Armitage, David A. Relman, Michael A. Fischbach
Journal: Science Translational Medicine (2012)

The connection between disease and the disruption of homeostatic interactions between the host and its microbiota is now well established. Drug developers and clinicians are starting to rely more heavily on therapies that directly target the microbiota and on the ecology of the microbiota to understand the outcomes of these treatments. The effects of those microbiota-targeted therapies that alter community composition range in scale from eliminating individual strains of a single species (for example, with antibacterial conjugate vaccines) to replacing the entire community with a new intact microbiota (for example, by fecal transplantation). Secondary infections linked to antibiotic use provide a cautionary tale of the unintended consequences of perturbing a microbial species network and highlight the need for new narrow-spectrum antibiotics with rapid companion diagnostics. Insights into microbial ecology will also benefit the development of probiotics, whose therapeutic prospects will depend on rigorous clinical testing. Future probiotics may take the form of a consortium of long-term community residents: "a fecal transplant in a capsule." The efficacy of microbiota-targeted therapies will need to be assessed using new diagnostic tools that measure community function rather than composition, including the temporal response of a microbial community to a defined perturbation such as an antibiotic or probiotic.
Cardiac Electrophysiological Actions of the Histamine H <sub>1</sub> -Receptor Antagonists Astemizole and Terfenadine Compared With Chlorpheniramine and Pyrilamine
Authors: Joseph J. Salata, Nancy K. Jurkiewicz, Audrey A. Wallace, Raymond F. Stupienski, Peter J. Guinosso, Joseph J. Lynch
Journal: Circulation Research (1995)

Abstract We compared the cardiac electrophysiological actions of two types of H 1 -receptor antagonists—the piperidines, astemizole and terfenadine, and the nonpiperidines, chlorpheniramine and pyrilamine—in vitro in guinea pig ventricular myocytes and in vivo in chloralose-anesthetized dogs. Astemizole and terfenadine significantly increased action potential duration of guinea pig myocytes. This concentration-dependent prolongation of action potential duration was reverse frequency dependent and led to development of early afterdepolarizations, which occurred more frequently at higher concentrations and slower pacing frequencies. Astemizole and terfenadine potently blocked the rapidly activating component of the delayed rectifier, I Kr , with IC 50 values of 1.5 and 50 nmol/L, respectively. At 10 μmol/L, terfenadine but not astemizole blocked the slowly activating component of the delayed rectifier, I Ks (58.4±3.1%), and the inward rectifier, I K1 (20.5±3.4%). Chlorpheniramine and pyrilamine blocked I Kr relatively weakly (IC 50 =1.6 and 1.1 μmol/L, respectively) and I Ks and I K1 less than 20% at 10 μmol/L. Astemizole and terfenadine (1.0 to 3.0 mg/kg IV) significantly prolonged the QTc interval and ventricular effective refractory period in vivo. Chlorpheniramine and pyrilamine (≤3.0 mg/kg) did not significantly affect these parameters. Block of repolarizing K + currents, particularly I Kr , by astemizole and terfenadine produces reverse rate–dependent prolongation of action potential duration and development of early afterdepolarizations, delays ventricular repolarization, and may underlie the development of torsade de pointes ventricular arrhythmias observed with the use and abuse of these agents.
Fludarabine in paediatric steroid-refractory inflammatory lung injury after stem cell transplantation
Authors: Martine F. Raphael, Bart L. Rottier, Jaap Jan Boelens
Journal: European Respiratory Journal (2013)

studies, the performances of endobronchial elastography will have to be assessed against the results of mediastinoscopy as the gold standard approach.From this experience, we conclude that transbronchial biomechanical analysis can be performed during bronchial endoscopic ultrasound.Tracheobronchial cartilage does not appear to interfere with collection of this type of information.The preliminary results suggest that elastography could possibly improve the diagnostic yield of bronchial endoscopic ultrasound, as has already been demonstrated in gastrointestinal endoscopy.This is all the more important as endobronchial ultrasonography has a low negative predictive value regarding the neoplastic involvement of mediastinal lymph nodes (see [11] for an example).We propose that our preliminary results justify the setting-up of large-scale studies to precisely describe the operating characteristics of bronchial endoscopic ultrasound elastography.It would also be interesting to determine whether elastography could improve guidance of TBNA in heterogeneous lymph node masses or limit the number of TBNAs performed, by primarily targeting the lymph nodes most likely to be malignant.
High prevalence of jumper’s knee and sonographic changes in Swedish elite junior volleyball players compared to matched controls
Authors: K Gisslèn, C Gyulai, K Söderman, H Alfredson
Journal: British Journal of Sports Medicine (2005)

Background: Jumper’s knee is a common and troublesome condition among senior volleyball players, but its prevalence among elite junior players compared to matched non-sports active controls is not known. Objective: To clinically, and by sonography, examine the patellar tendons in elite junior volleyball players (15–19 years) at the Swedish National Centre for volleyball and in matched controls. Methods: The patellar tendons in the 57 students at the Swedish National Centre for high school volleyball and in 55 age, height, and weight matched not regularly sports active controls were evaluated clinically and by grey scale ultrasonography (US) and power Doppler (PD) sonography. Results: There were no significant differences in mean age, height, and weight between the volleyball players and the controls. In the volleyball group, jumper’s knee was diagnosed clinically and by US in 12 patellar tendons (10 male and two female). In 12/12 tendons, PD sonography demonstrated a neovascularisation in the area with structural tendon changes. In another 10 pain free tendons, there were structural tendon changes and neovessels. In the control group, no individual had a clinical diagnosis of jumper’s knee. US demonstrated structural tendon changes in 11 tendons, but there was no neovascularisation on PD sonography. Conclusions: A clinical diagnosis of jumper’s knee, together with structural tendon changes and neovascularisation visualised with sonography, was seen among Swedish elite junior volleyball players but not in matched not regularly sports active controls. Structural tendon change alone was seen in 10% of the control tendons.
Inferences Drawn from a Risk Assessment Compared Directly with a RandomizedTrial of a Home Drinking Water Intervention
Authors: Joseph N.S. Eisenberg, Alan Hubbard, Timothy J. Wade, Matthew D. Sylvester, Mark W. LeChevallier, Deborah A. Levy, John M. Colford
Journal: Environmental Health Perspectives (2006)

Risk assessments and intervention trials have been used by the U.S. Environmental Protection Agency to estimate drinking water health risks. Seldom are both methods used concurrently. Between 2001 and 2003, illness data from a trial were collected simultaneously with exposure data, providing a unique opportunity to compare direct risk estimates of waterborne disease from the intervention trial with indirect estimates from a risk assessment. Comparing the group with water treatment (active) with that without water treatment (sham), the estimated annual attributable disease rate (cases per 10,000 persons per year) from the trial provided no evidence of a significantly elevated drinking water risk [attributable risk=-365 cases/year, sham minus active; 95% confidence interval (CI) , -2,555 to 1,825]. The predicted mean rate of disease per 10,000 persons per person-year from the risk assessment was 13.9 (2.5, 97.5 percentiles: 1.6, 37.7) assuming 4 log removal due to viral disinfection and 5.5 (2.5, 97.5 percentiles: 1.4, 19.2) assuming 6 log removal. Risk assessments are important under conditions of low risk when estimates are difficult to attain from trials. In particular, this assessment pointed toward the importance of attaining site-specific treatment data and the clear need for a better understanding of viral removal by disinfection. Trials provide direct risk estimates, and the upper confidence limit estimates, even if not statistically significant, are informative about possible upper estimates of likely risk. These differences suggest that conclusions about waterborne disease risk may be strengthened by the joint use of these two approaches. Key words: drinking water, gastrointestinal, intervention trial, microbial risk assessment, waterborne pathogens.
Sustained, neuron-specific IKK/NF-κB activation generates a selective neuroinflammatory response promoting local neurodegeneration with aging
Authors: Ayesha Maqbool, Michael Lattke, Thomas Wirth, Bernd Baumann
Journal: Molecular Neurodegeneration (2013)

Abstract Background Increasing evidence indicates that neuroinflammation is a critical factor contributing to the progression of various neurodegenerative diseases. The IKK/NF-κB signalling system is a central regulator of inflammation, but it also affects neuronal survival and differentiation. A complex interplay between different CNS resident cells and infiltrating immune cells, which produce and respond to various inflammatory mediators, determines whether neuroinflammation is beneficial or detrimental. The IKK/NF-κB system is involved in both production of and responses to these mediators, although the precise contribution depends on the cell type as well as the cellular context, and is only partially understood. Here we investigated the specific contribution of neuronal IKK/NF-κB signalling on the regulation of neuroinflammatory processes and its consequences. To address this issue, we established and analysed a conditional gain-of-function mouse model that expresses a constitutively active allele of IKK2 in principal forebrain neurons (IKK2 nCA ). Proinflammatory gene and growth factor expression, histopathology, microgliosis, astrogliosis, immune cell infiltration and spatial learning were assessed at different timepoints after persistent canonical IKK2/NF-κB activation. Results In contrast to other cell types and organ systems, chronic IKK2/NF-κB signalling in forebrain neurons of adult IKK2 nCA animals did not cause a full-blown inflammatory response including infiltration of immune cells. Instead, we found a selective inflammatory response in the dentate gyrus characterized by astrogliosis, microgliosis and Tnf-α upregulation. Furthermore, downregulation of the neurotrophic factor Bdnf correlated with a selective and progressive atrophy of the dentate gyrus and a decline in hippocampus-dependent spatial learning. Neuronal degeneration was associated with increased Fluoro-jade staining, but lacked activation of apoptosis. Remarkably, neuronal loss could be partially reversed when chronic IKK2/NF-κB signalling was turned off and Bdnf expression was restored. Conclusion Our results demonstrate that persistent IKK2/NF-κB signalling in forebrain neurons does not induce overall neuroinflammation, but elicits a selective inflammatory response in the dentate gyrus accompanied by decreased neuronal survival and impaired learning and memory. Our findings further suggest that chronic activation of neuronal IKK2/NF-κB signalling, possibly as a consequence of neuroinflammatory conditions, is able to induce apoptosis-independent neurodegeneration via paracrine suppression of Bdnf synthesis.
Comment on Brethauer et al. Bariatric Surgery Improves the Metabolic Profile of Morbidly Obese Patients With Type 1 Diabetes. Diabetes Care 2014;37:e51–e52
Authors: Alice Tang, Kerry-Lee Milner, Katherine Tonks, Lesley V. Campbell, Jerry R. Greenfield
Journal: Diabetes Care (2014)

Recently, Brethauer et al. (1) reported that bariatric surgery improved HbA1c in obese patients with type 1 diabetes. However, our data and existing literature demonstrate that improvement in glycemic control is not universal.

We reviewed case files of six obese female patients with type 1 diabetes who had bariatric surgery. Mean age was 36 ± 7.8 years, median duration of diabetes was 18 years (range 2–31), and median follow-up from surgery was 16 months (range 7–119). Baseline weight was 124.7 ± 15.7 kg and BMI was 46.4 ± 8.4 kg/m2. Weight loss was 24.3 ± 1.9% of baseline and BMI reduction was 11.4 ± 2.7 kg/m2.

There was no overall reduction in HbA1c following surgery (8.1 ± 1.3% [65 ± 14 mmol/mol] at baseline vs. 8.2 ± 1.6% [66 …
SNPTransformer: A Lightweight Toolkit for Genome-Wide Association Studies
Authors: Changzheng Dong
Journal: Genomics Proteomics & Bioinformatics (2010)

Abstract High-throughput genotyping chips have produced huge datasets for genome-wide association studies (GWAS) that have contributed greatly to discovering susceptibility genes for complex diseases. There are two strategies for performing data analysis for GWAS. One strategy is to use open-source or commercial packages that are designed for GWAS. The other is to take advantage of classic genetic programs with specific functions, such as linkage disequilibrium mapping, haplotype inference and transmission disequilibrium tests. However, most classic programs that are available are not suitable for analyzing chip data directly and require custom-made input, which results in the inconvenience of converting raw genotyping files into various data formats. We developed a powerful, user-friendly, lightweight program named SNPTransformer for GWAS that includes five major modules (Transformer, Operator, Previewer, Coder and Simulator). The toolkit not only works for transforming the genotyping files into ten input formats for use with classic genetics packages, but also carries out useful functions such as relational operations on IDs, previewing data files, recoding data formats and simulating marker files, among other functions. It bridges upstream raw genotyping data with downstream genetic programs, and can act as an in-hand toolkit for human geneticists, especially for non-programmers. SNPTransformer is freely available at http://snptransformer.sourceforge.net.
Multidrug-resistant tuberculosis: eight years of surveillance in France
Authors: J. Robert, D. Trystram, C. Truffot-Pernot, V. Jarlier
Journal: European Respiratory Journal (2003)

The aim of this study was to evaluate the annual prevalence of multidrug-resistant tuberculosis (MDRTB) and to describe the characteristics of the patients with MDRTB in France. Annual questionnaire surveys from 1992-1999 were mailed to all French microbiological laboratories performing mycobacterial cultures. A total of 264 distinct patients were reported to the National Reference Centre for Resistance of Mycobacteria to Antituberculosis Drugs during the 8-yr surveillance period resulting in a mean annual prevalence of MDRTB of 0.6%. A mean of 16% of the MDRTB patients were reported over several subsequent years. The majority of patients were male (69.7%), foreign-born (55.7%), with a previous history of treatment (65.9%), and pulmonary involvement (92.8%) with smear-positive results (59.1%). Human immunodeficiency virus (HIV) coinfection was present in 20.8% of the patients. Strains were resistant only to isoniazid and rifampin in 37.9% of the cases, and additional resistance to both streptomycin and ethambutol was present in 25.8%. HIV coinfection and female status were statistically associated with primary resistance, whereas smear-positive results were associated with secondary resistance. Foreign-birth and smear-positive results were associated with a chronic status. The prevalence of multidrug-resistant tuberculosis is low in France (<1%). However, a substantial proportion of patients remain positive for several years, suggesting nonoptimal management. Therefore, as recommended by the World Health Organization, a few reference teams, working in collaboration with national associations of physicians and microbiologists, should be established to improve the outcome of multidrug-resistant tuberculosis.