tbuckley/cabot-search huggingface dataset:
Insight into Evolution of Bordetella pertussis from Comparative Genomic Analysis: Evidence of Vaccine-Driven Selection
Authors: Sophie Octavia, Ram P. Maharjan, Vitali Sintchenko, Gordon Stevenson, Peter R. Reeves, Gwendolyn L. Gilbert, Ruiting Lan
Journal: Molecular Biology and Evolution (2010)

Despite high vaccine coverage, pertussis incidence has increased substantially in recent years in many countries. A significant factor that may be contributing to this increase is adaptation to the vaccine by Bordetella pertussis, the causative agent of pertussis. In this study, we first assessed the genetic diversity of B. pertussis by microarray-based comparative genome sequencing of 10 isolates representing diverse genotypes and different years of isolation. We discovered 171 single nucleotide polymorphisms (SNPs) in a total of 1.4 Mb genome analyzed. The frequency of base changes was estimated as one per 32 kb per isolate, confirming that B. pertussis is one of the least variable bacterial pathogens. We then analyzed an international collection of 316 B. pertussis isolates using a subset of 65 of the SNPs and identified 42 distinct SNP profiles (SPs). Phylogenetic analysis grouped the SPs into six clusters. The majority of recent isolates belonged to clusters I-IV and were descendants of a single prevaccine lineage. Cluster I appeared to be a major clone with a worldwide distribution. Typing of genes encoding acellular vaccine (ACV) antigens, ptxA, prn, fhaB, fim2, and fim3 revealed the emergence and increasing incidence of non-ACV alleles occurring in clusters I and IV, which may have been driven by ACV immune selection. Our findings suggest that B. pertussis, despite its high population homogeneity, is evolving in response to vaccination pressure with recent expansion of clones carrying variants of genes encoding ACV antigens.
Evaluation of a card collection-based faecal immunochemical test in screening for colorectal cancer using a two-tier reflex approach
Authors: C. G Fraser, C. M Mathew, N A. G Mowat, J. A Wilson, F. A Carey, R. J C Steele
Journal: Gut (2007)

The guaiac faecal occult blood test (gFOBT) has been proved as a screening investigation for colorectal cancer, but has disadvantages. Newer faecal immunochemical tests (FITs) have many advantages, but yield higher positivity rates and are expensive. A two-tier reflex follow-up of gFOBT-positive individuals with a FIT before colonoscopy has been advocated as an efficient and effective approach.A new simple and stable card collection FIT was evaluated.1124 individuals who were gFOBT positive were asked to provide samples. 558 individuals participated, 320 refused and 246 did not return samples. No evidence of sampling bias was found. 302 individuals tested FIT negative and 256 tested positive. In the 302 FIT-negative individuals, 2 (0.7%) had cancer and 12 (4.0%) had large or multiple (high-risk) adenomatous polyps. In contrast, of 254 positive individuals, 47 (18.5%) had cancer and 54 (21.3%) had high-risk polyps. 93 (30.8%) of the FIT-negative individuals had a normal colonoscopy, but only 34 (13.4%) of the FIT-positive individuals had no pathology. Sensitivity, specificity, and positive and negative likelihood ratios (and 95% CIs) for cancer were 95.9% (84.8 to 99.3), 59.2% (54.7 to 63.5), 2.35 (2.08 to 2.65) and 0.07 (0.02 to 0.27), and for cancer and high-risk polyps were 87.8% (80.1 to 92.9), 65.3% (60.6 to 69.7), 2.53 (2.19 to 2.93) and 0.19 (0.11 to 0.31), respectively.A two-tier reflex screening algorithm, in which gFOBT-positive participants are tested with a FIT, is effective in identifying individuals at high risk of significant colorectal neoplasia. This strategy is transferable across different FIT formats. This approach has been adopted for the Scottish Bowel Screening Programme.
Phosphoinositide 3-Kinase–Dependent Membrane Recruitment of P62dok Is Essential for Its Negative Effect on Mitogen-Activated Protein (Map) Kinase Activation
Authors: Mingming Zhao, Arndt A.P. Schmitz, Yi Qin, Antonio Di Cristofano, Pier Paolo Pandolfi, Linda Van Aelst
Journal: The Journal of Experimental Medicine (2001)

A major pathway by which growth factors, such as platelet-derived growth factor (PDGF), regulate cell proliferation is via the receptor tyrosine kinase/Ras/mitogen-activated protein kinase (MAPK) signaling cascade. The output of this pathway is subjected to tight regulation of both positive and negative regulators. One such regulator is p62(dok), the prototype of a newly identified family of adaptor proteins. We recently provided evidence, through the use of p62(dok)-deficient cells, that p62(dok) acts as a negative regulator of growth factor-induced cell proliferation and the Ras/MAPK pathway. We show here that reintroduction of p62(dok) into p62(dok)-(/)- cells can suppress the increased cell proliferation and prolonged MAPK activity seen in these cells, and that plasma membrane recruitment of p62(dok) is essential for its function. We also show that the PDGF-triggered plasma membrane translocation of p62(dok) requires activation of phosphoinositide 3-kinase (PI3-kinase) and binding of its pleckstrin homology (PH) domain to 3'-phosphorylated phosphoinositides. Furthermore, we demonstrate that p62(dok) can exert its negative effect on the PDGFR/MAPK pathway independently of its ability to associate with RasGAP and Nck. We conclude that p62(dok) functions as a negative regulator of the PDGFR/Ras/MAPK signaling pathway through a mechanism involving PI3-kinase-dependent recruitment of p62(dok) to the plasma membrane.
Variation in Medication Adherence in Heart Failure
Authors: Yuting Zhang, Shang-Hua Wu, A. Mark Fendrick, Katherine Baicker
Journal: JAMA Internal Medicine (2013)

Although recent studies have demonstrated geographic variation in pharmaceutical use and spending,1–4 regional variation in medication adherence in Medicare has not been explored.5 Medication adherence is a critical quality measure, and is especially important for Medicare beneficiaries with heart failure (HF), a common condition where medications can save lives and reduce downstream costs.6 We used 2007–2009 national Part D data for a 5% random sample of Medicare beneficiaries to study regional variation in HF medication adherence.
SUBSTRATES OF HAGEMAN FACTOR
Authors: Louis W. Heck, Allen P. Kaplan
Journal: The Journal of Experimental Medicine (1974)

Unactivated partial thromboplastin antecedent (PTA) has been purified by sequential chromatography of plasma on quaternary aminoethyl Sephadex, sulphoprophyl Sephadex, Sephadex G-150, and passage over an anti-IgG immunoadsorbant. The preparation gave a single band after alkaline disc gel electrophoresis, sodium dodecyl sulfate (SDS) gel electrophoresis and isoelectric focusing in acrylamide gels and was found to have a mol wt of 175,000 by gel filtration, 163,000 by SDS gel electrophoresis, and an isoelectric point of 8.8-9.4 (peak 9.0-9.1). Pre-PTA was activated directly by activated Hageman factor or by Hageman factor prealbumin fragments. Its coagulant activity was inhibited by DFP, soybean trypsin inhibitor and trasylol but not by lima bean trypsin inhibitor or ovomucoid trypsin inhibitor indicating that activated PTA possesses the same inhibition profile utilizing these reagents as does plasma kallikrein. A major plasma inhibitor of activated PTA was found to be a 65,000 mol wt alpha-globulin which was isolated free of alpha(1)-chymotrypsin inhibitor, inter alpha-trypsin inhibitor, alpha(2)-macroglobulin, and the other known inhibitors of activated PTA, the activated first component of complement (C1 INH), and antithrombin III. Its physicochemical properties were identical to alpha(1)-antitrypsin, and it was absent in alpha(1)-antitrypsin-deficient plasma thereby identifying this PTA inhibitor as alpha(1)-antitrypsin.
Lack of clinically relevant differences between combination therapy and monotherapy in COPD
Authors: Eric Bateman
Journal: European Respiratory Journal (2014)

Lack of clinically relevant differences between combination therapy and monotherapy in COPDTo the Editor: BATEMAN et al. [1] reported significantly greater mean improvements with indacaterol/glycopyrronium combination therapy, Ultibro Breezhaler (QVA149) compared to monotherapy with either indacaterol (0.07 L), glycopyrronium (0.09 L) or tiotropium (0.08 L) for the primary outcome of trough forced expiratory volume in 1 s (FEV1) at week 26 in patients with chronic obstructive pulmonary disease (COPD).However, such improvements were all less than the 0.1-0.14L range that represents the minimal clinically important difference (MCID) for FEV1 [2].Pointedly, the mean differences between combination therapy and monotherapy for the secondary outcomes of dyspnoea (transition dyspnoea index score) and health status (St.George's Respiratory Questionnaire score) were also less than the respective MCID values, with a significant difference between Ultibro Breezhaler (QVA149) and tiotropium at week 26.Analysis of individual responders revealed a significantly higher proportion of patients exceeding the MCID for transition dyspnoea index (o1 unit) and St. George's Respiratory Questionnaire (o4 units) with QVA149 versus tiotropium but not indacaterol or glycopyrronium.These data do not therefore support the conclusion that QVA149 demonstrated clinically relevant superiority versus their respective monotherapy components in COPD.Clinically relevant differences not found between combination and monotherapy http://ow.ly/thbE4
BENZOL THERAPY IN LEUKAEMIA AND LYMPHO-SARCOMA
Authors: T. G. Moorhead
Journal: BMJ (1915)

410 MV1DIC.I JOURNALI B BYNZOL '1TITER1APY IN LEUIKAEMIA AN-D LY-MAPHO-SAICOMA.[LARlcI I (-I5 _~~~~~~~~~~~~~~~~~~~~~~11 thle red c p,l)uscies numiberci 2,070,000 pet cubic miiillimuetre, the liaemogJo;iii w as 45 pei cent., anid the colour index 11.He lhad four injections of neo-salvarsan s June le4th, 0.4 gram;July 2ind.0.6 graia-Jly-16th, 0.6 gramn August 1st, 0.6 gram).Marked improyeintent in tle general condition resulled, but the blood showed little ch&ange'.-'n Xignust 4th, 1913, the -red corpuscles niiumbered 2,300,000 )er cubic miIIirnetre, the haemo- globin was 40 )er cenit.. anliI tire colour indlex 0.9, OIn Atgtust 12thj, 1913, lie was discliaifgied from' hospital feeling greatly nI proved.After getting liome hie continule(d to improve.On February 19tlh, 1914, his wife wrote me: '" The change for the better in my bhusband is most remarkable; lhe lias beelback.tobusiness since Christmas, and iii his spare time plays golf.All my friends say he looks better tlhani he has donle for y-ears."On D)ecember 30thl, 1914, lhe was well.D)uratio,b. up to dlate sinice the salvarsani treatment was com- menilcecl, niineteen miionths.-Reuttarl;s.-Theinmiprovement, whichl-at first was.very'slOW, lhas been very strikiing
Advancement of global health: key messages from the Disease Control Priorities Project
Authors: Ramanan Laxminarayan, Anne J Mills, Joel G Breman, Anthony R Measham, George Alleyne, Mariam Claeson, Prabhat Jha, Philip Musgrove, Jeffrey Chow, Sonbol Shahid-Salles, Dean T Jamison
Journal: The Lancet (2006)
Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia
Authors: Assam El-Osta, Daniella Brasacchio, Dachun Yao, Alessandro Pocai, Peter L. Jones, Robert G. Roeder, Mark E. Cooper, Michael Brownlee
Journal: The Journal of Experimental Medicine (2008)

The current goal of diabetes therapy is to reduce time-averaged mean levels of glycemia, measured as HbA1c, to prevent diabetic complications. However, HbA1c only explains &amp;lt;25% of the variation in risk of developing complications. Because HbA1c does not correlate with glycemic variability when adjusted for mean blood glucose, we hypothesized that transient spikes of hyperglycemia may be an HbA1c–independent risk factor for diabetic complications. We show that transient hyperglycemia induces long-lasting activating epigenetic changes in the promoter of the nuclear factor κB (NF-κB) subunit p65 in aortic endothelial cells both in vitro and in nondiabetic mice, which cause increased p65 gene expression. Both the epigenetic changes and the gene expression changes persist for at least 6 d of subsequent normal glycemia, as do NF-κB–induced increases in monocyte chemoattractant protein 1 and vascular cell adhesion molecule 1 expression. Hyperglycemia-induced epigenetic changes and increased p65 expression are prevented by reducing mitochondrial superoxide production or superoxide-induced α-oxoaldehydes. These results highlight the dramatic and long-lasting effects that short-term hyperglycemic spikes can have on vascular cells and suggest that transient spikes of hyperglycemia may be an HbA1c–independent risk factor for diabetic complications.
How important is specificity?
Authors: John Pickering
Journal: Behavioral and Brain Sciences (2001)

There is good neuropsychological evidence for an amodal, relational basis for perception and action. Using this idea, it may be possible to define more accurately what is meant by specificity, in the Gibsonian sense of the term. However, for complex organisms, and most especially for creative, open-ended perceivers and actors such as human beings, specification may not be relevant.
Place Cells, Grid Cells, and the Brain's Spatial Representation System
Authors: Edvard I. Moser, Emilio Kropff, May-Britt Moser
Journal: Annual Review of Neuroscience (2008)

More than three decades of research have demonstrated a role for hippocampal place cells in representation of the spatial environment in the brain. New studies have shown that place cells are part of a broader circuit for dynamic representation of self-location. A key component of this network is the entorhinal grid cells, which, by virtue of their tessellating firing fields, may provide the elements of a path integration-based neural map. Here we review how place cells and grid cells may form the basis for quantitative spatiotemporal representation of places, routes, and associated experiences during behavior and in memory. Because these cell types have some of the most conspicuous behavioral correlates among neurons in nonsensory cortical systems, and because their spatial firing structure reflects computations internally in the system, studies of entorhinal-hippocampal representations may offer considerable insight into general principles of cortical network dynamics.
Vasopressin-stimulated prostaglandin E biosynthesis in the toad urinary bladder. Effect of water flow.
Authors: R M Zusman, H R Keiser, J S Handler
Journal: Journal of Clinical Investigation (1977)

Prostaglandin E biosynthesis and its effect on water permeability were investigated in the toad urinary bladder. Arginine vasopressin (1 mU/ml) increased prostaglandin E (PGE) biosynthesis from 0.5+/-0.1 to 5.0+/-0.4 pmol/min per hemibladder (mean +/-SEM, n= 8, P less than 0.001). Maximal vasopressin-stimulated PGE biosynthesis, 6.4+/-0.2 pmol/min per hemibladder, occurred at vasopressin concentrations in excess of 3 mU/ml. Half-maximal stimulation of PGE biosynthesis occurred at a vasopressin concentration of approximately 0.7 mU/ml, whereas half-maximal stimulation of water flow occurred at a vasopressin concentration of approximately 5 mU/ml. Vasopressin-stimulated PGE biosynthesis did not depend on water flow along an osmotic gradient or upon sodium transport. Thin-layer chromatographic analysis of the lipids released from hemibladders labeled with tritium-arachidonic acid revealed that vasopressin stimulates the release of arachidonic acid from intracellular lipid stores without affecting the percentage of free arachidonic acid converted to PGE. Neither cyclic AMP nor theophylline stimulated PGE biosynthesis although they mimic arginine vasopressin (AVP) in stimulating water permeability. Biosynthesis of PGE was inhibited by mepacrine, a phospholipase inhibitor, and by agents that inhibit arachidonic acid oxygenase. The inhibition of PGE biosynthesis resulted in augmented vasopressin- and theophylline-stimulated water flow, but had no effect on cyclic AMP-stimulated water flow. We interpret these results to mean that endogenous PGE inhibits basal and vasopressin-stimulated adenylate cyclase activity. In contrast to the effects of AVP on permeability and transport, AVP stimulates PGE biosynthesis by a mechanism that does not depend on an increase in cellular cyclic AMP levels. The water permeability response of the toad urinary bladder to vasopressin is inhibited by PGE synthesized by the bladder in response to vasopressin.
Activation of Src kinase Lyn by the Kaposi sarcoma–associated herpesvirus K1 protein: implications for lymphomagenesis
Authors: Om Prakash, O. Rama Swamy, Xiochang Peng, Zhen-Ya Tang, Li Li, Janet E. Larson, J. Craig Cohen, Javed Gill, Gist Farr, Suizhao Wang, Felipe Samaniego
Journal: Blood (2005)
Prescribing by general practitioners after an osteoporotic fracture
Authors: D. J Torgerson, P. Dolan
Journal: Annals of the Rheumatic Diseases (1998)

Osteoporosis is a major cause of morbidity and cost. Patients sustaining one osteoporotic fracture are at increased risk of having another fracture. The objective of this study was to examine the use of "bone drugs" for the prevention of further osteoporotic fractures among patients who have had a "typical" osteoporotic fracture.This study took a random sample of 300 women aged 50 and over who had sustained either a vertebral, hip or Colles fracture in 1995 from the General Practice Research Database (GPRD) and compared their use of bone drugs with 300 age and practice matched controls.Compared with age and practice matched control patients only vertebral fracture patients showed a statistically significant increase in the use of bone drugs in the year after fracture (39% and 2% for cases and controls respectively; 95% CI of difference 27% to 47%). Etidronate was the most commonly used compound.The majority of patients sustaining an osteoporotic fracture are not prescribed any pharmaceutical agents for the secondary prevention of fracture one year after a primary fracture.
Polyunsaturated lecithin prevents acetaldehyde-mediated hepatic collagen accumulation by stimulating collagenase activity in cultured lipocytes
Authors: Jianjun Li, Cho-Il Kim, Maria A. Leo, Ki M. Mak, Marcos Rojkind, Charles S. Lieber
Journal: Hepatology (1992)

We recently found that polyunsaturated lecithin prevents ethanol from causing cirrhosis in the baboon. Because transformation of lipocytes to transitional cells plays a key role in hepatic fibrogenesis in vivo, and because this process in alcohol-fed baboons was found to be attenuated by polyunsaturated lecithin, we focused on lipocytes to study the mechanism of the protective effect. Rat lipocytes cultured on plastic undergo spontaneous activation, accompanied by expression of α-smooth muscle actin isoform and production of substantial amounts of type I collagen. The latter was further increased on incubation with acetaldehyde. This in vitro model was used here to study how acetaldehyde-mediated collagen production and accumulation can be turned off. Addition of polyunsaturated lecithin (10 μmol/L) was found to prevent the acetaldehyde-induced increase in collagen accumulation by 83% (p < 0.001). By contrast, a saturated phospholipid (10 μmol/L dilauroyl phosphatidylcholine), a monounsaturated one (10 μmol/L linoleoylpalmitoyl phosphatidylcholine) or linoleic acid (20 μmol/L bound to albumin) had no such effect. Incorporation of [3H]proline into collagen and the expression of ä-1 (I) procollagen mRNA were increased by acetaldehyde; the latter was not significantly affected by polyunsaturated lecithin. Polyunsaturated lecithin increased lipocyte collagenase activity by 100% (p < 0.001), whereas dilauroyl phosphatidylcholine, linoleoyl-palmitoyl phosphatidylcholine and linoleic acid had no such action. We concluded that (a) polyunsaturated lecithin selectively prevents the acetaldehyde-induced increase in collagen accumulation in lipocyte cultures, whereas other phospholipids or linoleate have no such effect; and (b) polyunsaturated lecithin does not modify the acetaldehydemediated increase in ä-1 (I) procollagen mRNA, but it increases collagenase activity, suggesting that the protective effect exerted by polyunsaturated lecithin against alcohol induced fibrosis in vivo is due at least in part to stimulation of collagenase activity, which may prevent excess collagen accumulation by offsetting increased collagen production. (Hepatology 1992;15:373–381).
International Myeloma Working Group guidelines for the management of multiple myeloma patients ineligible for standard high-dose chemotherapy with autologous stem cell transplantation
Authors: Antonio Palumbo, O. Sezer, Robert Kyle, Jesús Fernando San Miguel, Robert Orlowski, P. Moreau, R. Niesvizky, Gareth Morgan, R.L. Comenzo, Pieter Sonneveld, Shaji Kumar, Roman Hajek, S. Giralt, Sara Bringhen, Kenneth Anderson, Paul Gerard Richardson, Michele Cavo, Faith Davies, Joan Bladé, Hermann Einsele, Meletios Dimopoulos, Andrew Spencer, Angela Dispenzieri, T. Reiman, K. Shimizu, J.H. Lee, Michel Attal, Mario Boccadoro, M.V. Mateos, Wei Chen, Heinz Ludwig, D. Joshua, J. Chim, V. Hungria, I. Turesson, Brian Durie, Sagar Lonial
Journal: Leukemia (2009)
Is Alcohol Consumption Related to Breast Cancer? Results From the Framingham Heart Study
Authors: A. Schatzkin, C. L. Carter, S. B. Green, B. E. Kreger, G. L. Splansky, K. M. Anderson, s. Helsel, W. B. Kannel
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Is Alcohol Consumption Related to Breast Cancer? Results From the Framingham Heart Study Get access Arthur Schatzkin, Arthur Schatzkin Cancer Prevention Studies Branch, Division of Cancer Prevention and Control, National Cancer InstituteBethesda, MD Correspondence to: Dr. Arthur Schatzkin, Executive Plaza North, Rm. 211J, National Institutes of Health, Bethesda, MD 20892. Search for other works by this author on: Oxford Academic PubMed Google Scholar Christine L. Carter, Christine L. Carter Cancer Prevention Studies Branch, Division of Cancer Prevention and Control, National Cancer InstituteBethesda, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar Sylvan B. Green, Sylvan B. Green Biometry Branch, Division of Cancer Prevention and Control, National Cancer InstituteBethesda, MD Search for other works by this author on: Oxford Academic PubMed Google Scholar Bernard E. Kreger, Bernard E. Kreger Boston University School of MedicineBoston, MA. Search for other works by this author on: Oxford Academic PubMed Google Scholar Greta L. Splansky, Greta L. Splansky Boston University School of MedicineBoston, MA. Search for other works by this author on: Oxford Academic PubMed Google Scholar Keaven M. Anderson, Keaven M. Anderson Field Studies Branch, Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood InstituteBethesda, MD. Search for other works by this author on: Oxford Academic PubMed Google Scholar surname Helsel, surname Helsel Information Management ServicesSilver Spring, MD. Search for other works by this author on: Oxford Academic PubMed Google Scholar William B. Kannel William B. Kannel Boston University School of MedicineBoston, MA. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 1, January 1989, Pages 31–35, https://doi.org/10.1093/jnci/81.1.31 Published: 01 January 1989 Article history Received: 03 August 1988 Revision received: 04 October 1988 Accepted: 11 October 1988 Published: 01 January 1989