tbuckley/cabot-search huggingface dataset:
Genomic epidemiology of a protracted hospital outbreak caused by multidrug-resistant Acinetobacter baumanniiin Birmingham, England
Authors: Mihail R Halachev, Jacqueline Z-M Chan, Chrystala I Constantinidou, Nicola Cumley, Craig Bradley, Matthew Smith-Banks, Beryl Oppenheim, Mark J Pallen
Journal: Genome Medicine (2014)

Multidrug-resistant Acinetobacter baumannii commonly causes hospital outbreaks. However, within an outbreak, it can be difficult to identify the routes of cross-infection rapidly and accurately enough to inform infection control. Here, we describe a protracted hospital outbreak of multidrug-resistant A. baumannii, in which whole-genome sequencing (WGS) was used to obtain a high-resolution view of the relationships between isolates.To delineate and investigate the outbreak, we attempted to genome-sequence 114 isolates that had been assigned to the A. baumannii complex by the Vitek2 system and obtained informative draft genome sequences from 102 of them. Genomes were mapped against an outbreak reference sequence to identify single nucleotide variants (SNVs).We found that the pulsotype 27 outbreak strain was distinct from all other genome-sequenced strains. Seventy-four isolates from 49 patients could be assigned to the pulsotype 27 outbreak on the basis of genomic similarity, while WGS allowed 18 isolates to be ruled out of the outbreak. Among the pulsotype 27 outbreak isolates, we identified 31 SNVs and seven major genotypic clusters. In two patients, we documented within-host diversity, including mixtures of unrelated strains and within-strain clouds of SNV diversity. By combining WGS and epidemiological data, we reconstructed potential transmission events that linked all but 10 of the patients and confirmed links between clinical and environmental isolates. Identification of a contaminated bed and a burns theatre as sources of transmission led to enhanced environmental decontamination procedures.WGS is now poised to make an impact on hospital infection prevention and control, delivering cost-effective identification of routes of infection within a clinically relevant timeframe and allowing infection control teams to track, and even prevent, the spread of drug-resistant hospital pathogens.
Next-generation community genetics for low- and middle-income countries
Authors: Stephen F Kingsmore, John D Lantos, Darrell L Dinwiddie, Neil A Miller, Sarah E Soden, Emily G Farrow, Carol J Saunders
Journal: Genome Medicine (2012)

A recent report by the World Health Organization calls for implementation of community genetics programs in low- and middle-income countries (LMICs). Their focus is prevention of congenital disorders and genetic diseases at the population level, in addition to providing genetics services, including diagnosis and counseling. The proposed strategies include both newborn screening and population screening for carrier detection, in addition to lowering the incidence of congenital disorders and genetic diseases through the removal of environmental factors. In this article, we consider the potential impact of such testing on global health and highlight the near-term relevance of next-generation sequencing (NGS) and bioinformatic approaches to their implementation. Key attributes of NGS for community genetics programs are homogeneous approach, high multiplexing of diseases and samples, as well as rapidly falling costs of new technologies. In the near future, we estimate that appropriate use of population-specific test panels could cost as little as $10 for 10 Mendelian disorders and could have a major impact on diseases that currently affect 2% of children worldwide. However, the successful deployment of this technological innovation in LMICs will require high value for human life, thoughtful implementation, and autonomy of individual decisions, supported by appropriate genetic counseling and community education.
iASPP preferentially binds p53 proline-rich region and modulates apoptotic function of codon 72–polymorphic p53
Authors: Daniele Bergamaschi, Yardena Samuels, Alexandra Sullivan, Marketa Zvelebil, Hilde Breyssens, Andrea Bisso, Giannino Del Sal, Nelofer Syed, Paul Smith, Milena Gasco, Tim Crook, Xin Lu
Journal: Nature Genetics (2006)
Evaluation of screening-detected lung nodules: minimising the risk of unnecessary biopsy and surgery
Authors: M. K. Gould
Journal: Thorax (2011)

Screening for lung cancer has a long and controversial history. Successful screening is predicated on two fundamental principles.1 First, the screening test should be able to detect disease in an early preclinical phase before symptoms develop. Second, treatment should be available and more effective when provided during the preclinical phase. On the surface it would appear that screening for lung cancer passes both of these tests, given our experience with treating ‘early’ versus ‘late’ stage lung cancer that is clinically detected. However, if we acknowledge that at least some cases of clinically detected stage I and II lung cancer might represent disease that is relatively indolent biologically as opposed to ‘early’, then the possibility exists that early detection will not alter the natural history of lung cancer and result in more frequent cure. Fortunately, the hypothesis that lung cancer screening with CT scanning reduces mortality is currently being evaluated in several large randomised controlled trials in both the USA and Europe.2–6

Another set of prerequisites for any screening programme is that both the screening test and any downstream testing should be convenient for patients, relatively inexpensive and without a high risk of complications. Recent attention has focused on previously discounted risks from the radiation exposure that are associated with undergoing CT screening and follow-up.7 Smith-Bindman et al estimated that the median effective radiation dose associated with a single non-contrast CT examination of the chest (8 mSV) was approximately equal to that of 117 chest x-rays and that, in 40-year-old women, one radiation-induced cancer would ultimately develop for every 720 who underwent CT.8 In a population-based analysis, Berrington de Gonzalez et al calculated that the approximately 72 million CT scans performed in the USA in 2007 would ultimately be responsible for 29 000 future radiation-induced cancers including 4100 related …
Lack of correlation between bronchoconstrictor response and bronchodilator response in a population-based study
Authors: WR Douma, A de Gooijer, B Rijcken, JP Schouten, GH Koeter, ST Weiss, DS Postma
Journal: European Respiratory Journal (1997)

Bronchodilator and bronchoconstrictor responsiveness have been considered physiological opposites in patients with obstructive airways disease. Provocation challenges have been replaced by bronchodilator tests in the assessment of cases of severe airways obstruction. The aim of this study was to examine the relationship between bronchoconstrictor and bronchodilator responsiveness, and their supposed interchangeability, in a general population. From the Vlagtwedde-Vlaardingen follow-up study, 101 adults were recruited (mean (SD) age 55 (11) yrs, 67 males and 34 females, and 31 were smokers). All completed a questionnaire on airways symptoms. Bronchoconstrictor and bronchodilator responsiveness were assessed with cumulative dose-response curves, using histamine and terbutaline, respectively. Thus, it was possible to relate histamine sensitivity of the airways (the concentration of histamine, at which forced expiratory volume in one second (FEV1) falls by 10% (PC10)) to the maximal bronchodilator response (delta FEV1) and the sensitivity to the bronchodilator (cumulative dose of inhaled terbutaline at which FEV1 increases by 10% (RD10)). Subjects with a bronchoconstrictor response (PC10 &lt; or = 16 mg x mL(-1); n=38) had more respiratory symptoms than those without (n=63) (40 versus 21%) and also lower baseline FEV1 values (90 versus 96% predicted), but had comparable bronchodilator responsiveness. Subjects with a bronchodilator response (delta FEV1 &gt; or = 9% of the predicted value; n=13) did not differ from those without (n=88) for all parameters, including symptoms, allergy and pulmonary function. In those with a bronchoconstrictor response, there was a weak but significant correlation between the PC10 and RD10 (rho=-0.32), but not between PC10 and delta FEV1. This study suggests that bronchoconstrictor and bronchodilator responsiveness are not highly correlated, even in subjects with airways obstruction. Symptoms were associated with the presence of a bronchoconstrictor, but not a bronchodilator, response. We conclude that bronchoconstrictor and bronchodilator responsiveness are two different phenotypic markers that are not interchangeable in epidemiological studies.
640 EPIDERMAL GROWTH FACTOR GENETIC POLYMORPHISM PREDICTS RISK OF HEPATOCELLULAR CARCINOMA IN EGYPTIAN PATIENTS WITH HCV (GENOTYPE 4)-RELATED CIRRHOSIS
Authors: M. El-Bendary, M. Neamatallah, M. Abd El-Maksoud, A. El-Gendy, A. El-Wehedy, M. Amin
Journal: Journal of Hepatology (2013)
Estimating the Risk of Developing Type 2 Diabetes: A Comparison of Several Risk Scores
Authors: Rémy Schmid, Peter Vollenweider, Gérard Waeber, Pedro Marques-Vidal
Journal: Diabetes Care (2011)

To compare in the Swiss population the results of several scores estimating the risk of developing type 2 diabetes.This was a single-center, cross-sectional study conducted between 2003 and 2006 in Lausanne, Switzerland. Overall, 3,251 women and 2,937 men, aged 35-75 years, were assessed, of which 5,760 (93%) were free from diabetes and included in the current study. The risk of developing type 2 diabetes was assessed using seven different risk scores, including clinical data with or without biological data. Participants were considered to be eligible for primary prevention according to the thresholds provided for each score. The results were then extrapolated to the Swiss population of the same sex and age.The risk of developing type 2 diabetes increased with age in all scores. The prevalence of participants at high risk ranged between 1.6 and 24.9% in men and between 1.1 and 15.7% in women. Extrapolated to the Swiss population of similar age, the overall number of participants at risk, and thus susceptible to intervention, ranged between 46,708 and 636,841. In addition, scores that included the same clinical variables led to a significantly different prevalence of participants at risk (4.2% [95% CI 3.4-5.0] vs. 12.8% [11.5-14.1] in men and 2.9% [2.4-3.6] vs. 6.0% [5.2-6.9] in women). CONCLUSIONS; The prevalence of participants at risk for developing type 2 diabetes varies considerably according to the scoring system used. To adequately prevent type 2 diabetes, risk-scoring systems must be validated for each population considered.
Functional and morphological organization of the rabbit sinus node.
Authors: W K Bleeker, A J Mackaay, M Masson-Pévet, L N Bouman, A E Becker
Journal: Circulation Research (1980)

In isolated right atria of the rabbit heart, we studied the activation pattern within the sinus node, using the microelectrode technique. After the electrophysiological experiments, the preparations were subjected to a correlative morphological investigation, using light or electron microscopy. Different criteria for defining the dominant pacemaker were compared. A group of at least 5000 cells, located within the central part of the node where the most characteristic tissue architecture was found, was considered to be responsible for generation of the impulse. At the ultrastructural level, this leading cell group appeared to be part of a larger uniform cell group. The number of gap junctions observed suggests that all nodal cells are coupled by these structures. Toward the periphery, the excitation wave was propagated preferentially in an oblique cranial direction toward the crista terminalis. Neither morphologically nor electrophysiologically specific pathways were found for the conduction, but the preferential direction could be explained by the tissue architecture.
Everolimus-Eluting Stents or Bypass Surgery for Multivessel Coronary Disease
Authors: Sripal Bangalore, Yu Guo, Zaza Samadashvili, Saul Blecker, Jinfeng Xu, Edward L. Hannan
Journal: New England Journal of Medicine (2015)

Results of trials and registry studies have shown lower long-term mortality after coronary-artery bypass grafting (CABG) than after percutaneous coronary intervention (PCI) among patients with multivessel disease. These previous analyses did not evaluate PCI with second-generation drug-eluting stents.
STUDIES RELATING TO THE SERUM RESISTANCE OF CERTAIN GRAM-NEGATIVE BACTERIA
Authors: Etsuko Osawa, Louis H. Muschel
Journal: The Journal of Experimental Medicine (1964)

Paracolobactrum ballerup, an organism considered completely insusceptible to the bactericidal action of the antibody-complement system, became extremely sensitive to immune serum and even to normal serum, in conjunction with complement, when cultivated at temperatures above 37 degrees C. This conversion to serum sensitivity was associated with the loss of the organism's Vi antigen and its tendency to assume a rough state. It did not result in a genetic change in the organism, however, since reincubation of serum-sensitive P. ballerup at 37 degrees C resulted in a restoration of its resistance. The loss of serum resistance as a result of cultivation temperatures above 37 degrees C may be of significance as an example of the enhancement of host defense mechanisms induced by fever. Special conditions of testing indicated that P. ballerup cultured at 37 degrees C and S. paratyphosa C, organisms considered insusceptible to serum bactericidal action, were not entirely refractory to serum. These conditions included simply a relatively low ratio of the number of test organisms to serum volume and an extended incubation period of the organisms with serum bactericidal substances, or even without these substances, prior to the initiation of bactericidal action. It is likely, therefore, that an absolute distinction between serum-sensitive and serum-resistant Gram-negative organisms does not exist, but rather that there is a very broad distribution of serum sensitivity among these organisms.
Allergic contact dermatitis from latex rubber
Authors: S.M. WILKINSON, M.H. BECK
Journal: British Journal of Dermatology (1996)

Journal Article Allergic contact dermatitis from latex rubber Get access S.M. WILKINSON, S.M. WILKINSON The Skin Hospital, Chapel Street, Salford M60 9EP, U.K. Dr S.M.Wilkinson, Department of Dermatology, the General Infirmary at Leeds, Leeds LS1 3EX, U.K. Search for other works by this author on: Oxford Academic Google Scholar M.H. BECK M.H. BECK The Skin Hospital, Chapel Street, Salford M60 9EP, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 134, Issue 5, 1 May 1996, Pages 910–914, https://doi.org/10.1046/j.1365-2133.1996.126861.x Published: 01 May 1996 Article history Accepted: 07 September 1995 Published: 01 May 1996
Proteinuria in passive Heymann nephritis is associated with lipid peroxidation and formation of adducts on type IV collagen.
Authors: T J Neale, P P Ojha, M Exner, H Poczewski, B Rüger, J L Witztum, P Davis, D Kerjaschki
Journal: Journal of Clinical Investigation (1994)

Passive Heymann nephritis (PHN) is a model of human membranous nephropathy that is characterized by formation of granular subepithelial immune deposits in the glomerular capillary wall which results in complement activation. This is causally related to damage of the filtration barrier and subsequent proteinuria. The local accumulation of injurious reactive oxygen species (ROS) is a major effector mechanism in PHN. ROS may induce tissue damage by initiating lipid peroxidation (LPO). In turn, this leads to adduct formation between breakdown products of LPO with structural proteins, such as formation of malondialdehyde (MDA) or 4-hydroxynonenal-lysine adducts. To examine the role of LPO in the development of proteinuria we have localized MDA and 4-hydroxynonenal-lysine adducts in glomeruli of PHN rats by immunofluorescence microscopy, using specific monoclonal antibodies. By immunogold electron microscopy, MDA adducts were localized to cytoplasmic vesicles and cell membranes of glomerular epithelial cells, to the glomerular basement membrane (GBM), and also to immune deposits. Type IV collagen was specifically identified as being modified by MDA adducts, using a variety of techniques. Collagenase pretreatment of GBM extracts indicated that the NC-1 domain of type IV collagen was a site of adduct formation. When LPO was inhibited by pretreatment of PHN rats with the antioxidant probucol, proteinuria was reduced by approximately 85%, and glomerular immunostaining for dialdehyde adducts was markedly reduced, even though the formation of immune deposits was not affected. By contrast, lowering of the serum cholesterol levels had no influence on the development of proteinuria. These findings are consistent with the premise that ROS-induced glomerular injury in PHN involves LPO and that this results not only in damage of cell membranes but in modification of type IV collagen in the GBM as well. The close temporal correlation of the occurrence of LPO with proteinuria and the ability of probucol to inhibit proteinuria support a causal role for LPO in the the alteration of the glomerular permselectivity which results in proteinuria.
Regulation of the hepatic transferrin receptor in hereditary hemochromatosis
Authors: Martin Lombard, Adrian Bomford, Miriam Hynes, Nikolai V. Naoumov, Stephanie Roberts, John Crowe, Roger Williams
Journal: Hepatology (1989)

The liver is the main site of iron accumulation and pathologic sequelae in hereditary hemochromatosis. Whether this is a result solely of inappropriately increased absorption of iron by the gastrointestinal tract or a more generalized regulatory failure of iron balance is unknown. Using immunohistochemical techniques, we have examined the effects of therapeutic changes in liver iron stores on the expression of the hepatic trans-ferrin receptor in hereditary hemochromatosis. Ten patients with untreated hereditary hemochromatosis had no detectable staining for transferrin receptor in their liver biopsies. All had increased hepatic ferritin (mean = 19.9 μg per mg protein, range = 1 to 31.7 μg per mg protein) and hepatic iron levels (mean = 36.2 μg per mg protein, range = 3.6 to 69.9 μg per mg protein). In contrast, hepatocyte transferrin receptor was detected in seven patients in whom hepatic iron stores were markedly depleted by venesection (hepatic ferritin mean = 0.32 μg per mg protein, range = 0.16 to 0.53 μg per mg protein; hepatic iron mean = 0.98 μg per mg protein, range = 0.3 to 2.1 μg per mg protein). Sequential data from one patient confirmed the reexpression of receptor in response to therapeutic iron depletion, whereas data from another patient studied during treatment illustrated a reciprocal relationship between liver tissue distribution of iron and expression of transferrin receptor. The finding that appropriate physiologic regulation of the hepatic transferrin receptor operates in hereditary hemochromatosis does not support the concept of a generalized defect in receptor-mediated uptake of trans-ferrin-bound iron.
Lung Clearance Index and High-Resolution Computed Tomography Scores in Primary Ciliary Dyskinesia
Authors: Samantha J. Irving, Andrew Ives, Gwyneth Davies, Jackie Donovan, Anthony J. Edey, Simon S. Gill, Arjun Nair, Clare Saunders, Nevin T. Wijesekera, Eric W. F. W. Alton, David Hansell, Claire Hogg, Jane C. Davies, Andrew Bush
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: Lung clearance index (LCI) is a more sensitive measure of lung function than spirometry in cystic fibrosis (CF) and correlates well with abnormalities in high-resolution computed tomography (HRCT) scanning. We hypothesized LCI would be equally sensitive to lung disease in primary ciliary dyskinesia (PCD).Objectives: To test the relationships between LCI, spirometry, and HRCT in PCD and to compare them to the established relationships in CF.Methods: Cross-sectional study of 127 patients with CF and 33 patients with PCD, all of whom had spirometry and LCI, of which a subset of 21 of each had HRCT performed. HRCT was scored for individual features and these features compared with physiological parameters.Measurements and Main Results: Unlike in CF, and contrary to our hypothesis, there was no correlation between spirometry and LCI in PCD and no correlation between HRCT features and LCI or spirometry in PCD.Conclusions: We show for the first time that HRCT, spirometry, and LCI have different relationships in different airway diseases and that LCI does not appear to be a sensitive test of airway disease in advanced PCD. We hypothesize that this results from dissimilarities between the components of large and small airway disease in CF and PCD. These differences may in part lead to the different prognosis in these two neutrophilic airway diseases.
Long-term reversal of chronic anemia using a hypoxia-regulated erythropoietin gene therapy
Authors: Katie Binley, Zoe Askham, Sharifah Iqball, Hayley Spearman, Leigh Martin, Mahesh de Alwis, Adrian J. Thrasher, Robin R. Ali, Patrick H. Maxwell, Susan Kingsman, Stuart Naylor
Journal: Blood (2002)
Studies on Surface Antigen Variants. Isolation of Two Complementary Variants for Thy 1.22
Authors: Robert Hyman
Journal: JNCI Journal of the National Cancer Institute (1973)

Two variants for the antigen Thy 1.2 were characterized. These variants had <0.001 the amount of Thy 1.2 antigen present on parental cells. Cell fusion studies indicated that absence of Thy 1.2 antigen was recessive in these variants and that the Thy 1.2 antigen was expressed when the 2 variants were fused to each other. Possible explanations for the variants were discussed in terms of these results.