tbuckley/cabot-search huggingface dataset:
Antibiotics in Addition to Systemic Corticosteroids for Acute Exacerbations of Chronic Obstructive Pulmonary Disease
Authors: Johannes M. A. Daniels, Dominic Snijders, Casper S. de Graaff, Fer Vlaspolder, Henk M. Jansen, Wim G. Boersma
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

The role of antibiotics in acute exacerbations is controversial and their efficacy when added to systemic corticosteroids is unknown.We conducted a randomized, placebo-controlled trial to determine the effects of doxycycline in addition to corticosteroids on clinical outcome, microbiological outcome, lung function, and systemic inflammation in patients hospitalized with an acute exacerbation of chronic obstructive pulmonary disease.Of 223 patients, we enrolled 265 exacerbations defined on the basis of increased dyspnea and increased sputum volume with or without increased sputum purulence. Patients received 200 mg of oral doxycycline or matching placebo for 7 days in addition to systemic corticosteroids. Clinical and microbiological response, time to treatment failure, lung function, symptom scores, and serum C-reactive protein were assessed.On Day 30, clinical success was similar in intention-to-treat patients (odds ratio, 1.3; 95% confidence interval, 0.8 to 2.0) and per-protocol patients. Doxycycline showed superiority over placebo in terms of clinical success on Day 10 in intention-to-treat patients (odds ratio, 1.9; 95% confidence interval, 1.1 to 3.2), but not in per-protocol patients. Doxycycline was also superior in terms of clinical cure on Day 10, microbiological outcome, use of open label antibiotics, and symptoms. There was no interaction between the treatment effect and any of the subgroup variables (lung function, type of exacerbation, serum C-reactive protein, and bacterial presence).Although equivalent to placebo in terms of clinical success on Day 30, doxycycline showed superiority in terms of clinical success and clinical cure on Day 10, microbiological success, the use of open label antibiotics, and symptoms. Clinical trial registered with www.clinicaltrials.gov (NCT00170222).
A study of the science of taste: On the origins and influence of the core ideas
Authors: Robert P. Erickson
Journal: Behavioral and Brain Sciences (2008)

Abstract Our understanding of the sense of taste is largely based on research designed and interpreted in terms of the traditional four “basic” tastes: sweet, sour, salty, and bitter, and now a few more. This concept of basic tastes has no rational definition to test, and thus it has not been tested. As a demonstration, a preliminary attempt to test one common but arbitrary psychophysical definition of basic tastes is included in this article; that the basic tastes are unique in being able to account for other tastes. This definition was falsified in that other stimuli do about as well as the basic words and stimuli. To the extent that this finding might show analogies with other studies of receptor, neural, and psychophysical phenomena, the validity of the century-long literature of the science of taste based on a few “basics” is called into question. The possible origins, meaning, and influence of this concept are discussed. Tests of the model with control studies are suggested in all areas of taste related to basic tastes. As a stronger alternative to the basic tradition, the advantages of the across-fiber pattern model are discussed; it is based on a rational data-based hypothesis, and has survived attempts at falsification. Such “population coding” has found broad acceptance in many neural systems.
NOTE ON THE TREATMENT OF THE SYMPTOMS ARISING FROM INHALATION OF IRRITANT GASES AND VAPOURS
Authors: W. L. Symes
Journal: BMJ (1915)

of the bulb.The two points thus found are joined respec- tively to X1 and X2, and tlle intersection of these last lines is vertically over tlhe-point of the foreign body whicli casts the shladows XI and X2.The ladder can be affixed immediately to a plate facing in aniy clirection, and can be used with any type of apparatus.The procedure is quick and simple, and could be used at the bedside in case of need.The distance from plate to alnticatlhode and the distance the bulb is moved are not required; the shadow displacement has not to be measured, but merely set off with compasses and matched, a simpler and more accurate proceeding.The estimation of depth cani be easily imiade to a millimetre without any measure- ment whatever, and the one plate carries the complete data of localization of all foreign bodlies whiose shadows fall upon it.The instrument is made by Messrs. Newton and Wriglht, 72, Wigmore Street, W.
ACQUIRED IMMUNODEFICIENCY SYNDROME IN A HETEROSEXUAL POPULATION IN ZAIRE
Authors: Peter Piot, Henri Taelman, Kapita Bila Minlangu, N. Mbendi, K. Ndangi, Kayembe Kalambayi, Chris Bridts, ThomasC. Quinn, FredM. Feinsod, Odio Wobin, P. Mazebo, Wim Stevens, Sheila Mitchell, JosephB. Mccormick
Journal: The Lancet (1984)
Plexiform and Dermal Neurofibromas and Pigmentation Are Caused by Nf1 Loss in Desert Hedgehog-Expressing Cells
Authors: Jianqiang Wu, Jon P. Williams, Tilat A. Rizvi, Jennifer J. Kordich, David Witte, Dies Meijer, Anat O. Stemmer-Rachamimov, Jose A. Cancelas, Nancy Ratner
Journal: Cancer Cell (2008)
Antiphospholipid syndrome dilemmas still to be solved: 2008 status: Table 1
Authors: Yehuda Shoenfeld, Pier Luigi Meroni, Ricard Cervera
Journal: Annals of the Rheumatic Diseases (2008)

Extensive investigation of antiphospholipid syndrome (APS) has improved our knowledge of the disease, but raised new questions. Although the pathogenic role of antiphospholipid antibodies (aPL) is widely accepted, the fact that aPL induces thrombotic events only occasionally suggests the need for a “second hit” to display the thrombogenic effect. Infectious agents are thought to trigger autoantibody production through a molecular mimicry mechanism, but may also induce an inflammatory process that eventually favours clotting. The involvement of complement and cytokines in the pathogenesis further supports the role of inflammation in APS as well as the possibility for new therapeutic approaches. The question of whether other environmental triggers or a genetic individual susceptibility can behave as a second hit is still open. The clinical involvement of different organs and systems poses the question of whether the syndrome should be considered a true systemic autoimmune disease, rather than an acquired autoimmune coagulopathy. A positivity for more than one laboratory test displays a higher predictive value for clinical events, but it is still not known which other parameters are useful in clinical practice to identify all the aPL positive subjects at risk for manifestation. In particular, there is no clear evidence when a more aggressive treatment must be used in primary prophylaxis. The standard anticoagulant therapy has dramatically changed the prognosis of APS; however, the vascular and/or obstetrical recurrences in spite of the treatment pose the question whether additional therapeutic strategies (ie, immunosuppression) should be used, or whether alternative therapies (ie, inhibitory/tolerogenic peptides) should be sought.

Antiphospholipid syndrome (APS) was first described in 1983.1 Extensive investigations and several congresses have addressed the basic and the clinical aspects of APS.2–8 Consequntly, 25 years later a large knowledge base has been built up on the aetiology, the pathogenesis and the therapy of …
Interrelations of the renal kallikrein-kinin system and renal prostaglandins in the conscious rat. Influence of mineralocorticoids.
Authors: A Nasjletti, J C McGiff, J Colina-Chourio
Journal: Circulation Research (1978)

To investigate possible relationships between mineralocorticoids, the renal kallikreinkinin system, and renal prostaglandins, we studied the effects of aldosterone and deoxycorticosterone acetate (DOCA) and of an inhibitor of kallikrein, aprotinin, on the urinary excretion of kallikrein and prostaglandin E-like substance (PGE) by the conscious rat. Aldosterone (0.25 mg/day, sc), injected into six rats for 14 consecutive days, increased PGE and kallikrein excretion from 52.3 +/- 8.7 (mean +/- SE) ng/day and 29.8 +/- 3.0 U/day to 141.5 +/- 30.7 ng/day (P less than 0.02) and 105.6 +/- 28.1 U/day (P less than 0.05), respectively. Similarly, injections of DOCA (5 mg/day) into 14 rats increased the excretion of PGE and kallikrein, measured before and after 10 days of treatment, from 41.6 +/- 3.9 ng/day and 39.4 +/-4.9 U/day to 194.3 +/- 20.7 ng/day (P less than 0.001) and 90.6 +/- 14.7 U/day (P less than 0.001), respectively. Injections of aprotinin for 4 days (50,000 KIU twice daily, sc) in conjunction with DOCA into eight rats pretreated with the steroid for 10 days decreased the urinary excretion of kallikrein and PGE, measured on the 4th day of aprotinin administration, by 61% (P less than 0.01) and 80% (P less than 0.001), respectively. Urinary potassium excretion decreased throughout the course of aprotinin treatment, whereas sodium excretion and urine volume decreased during the first 2 days but subsequently returned toward control values. This study demonstrates that mineralocorticoids enhance the urinary excretion of PGE, and this effect appears to be a consequence of activation of the renal kallikrein-kinin system by the steroids. Thus, changes in the intrarenal activity of the kallikrein-kinin system may modulate renal prostaglandin release.
Physical activity and public health. A recommendation from the Centers for Disease Control and Prevention and the American College of Sports Medicine
Authors: R. R. Pate
Journal: JAMA (1995)

To encourage increased participation in physical activity among Americans of all ages by issuing a public health recommendation on the types and amounts of physical activity needed for health promotion and disease prevention.A planning committee of five scientists was established by the Centers for Disease Control and Prevention and the American College of Sports Medicine to organize a workshop. This committee selected 15 other workshop discussants on the basis of their research expertise in issues related to the health implications of physical activity. Several relevant professional or scientific organizations and federal agencies also were represented.The panel of experts reviewed the pertinent physiological, epidemiologic, and clinical evidence, including primary research articles and recent review articles.Major issues related to physical activity and health were outlined, and selected members of the expert panel drafted sections of the paper from this outline. A draft manuscript was prepared by the planning committee and circulated to the full panel in advance of the 2-day workshop. During the workshop, each section of the manuscript was reviewed by the expert panel. Primary attention was given to achieving group consensus concerning the recommended types and amounts of physical activity. A concise "public health message" was developed to express the recommendations of the panel. During the ensuing months, the consensus statement was further reviewed and revised and was formally endorsed by both the Centers for Disease Control and Prevention and the American College of Sports Medicine.Every US adult should accumulate 30 minutes or more of moderate-intensity physical activity on most, preferably all, days of the week.
O52 APOLIPOPROTEIN E MEDIATES HCV ESCAPE FROM HOST NEUTRALIZING ANTIBODIES
Authors: D.J. Felmlee, C. Fauvelle, M. Le Févre, L. Heydmann, M.-S. Hiet, R. Bartenschlager, I. Fofana, F. Habersetzer, R. Milne, A. Patel, K. Vercauteren, P. Meuleman, M.B. Zeisel, C. Schuster, S. Fafl-Kremer, T.F. Baumert
Journal: Journal of Hepatology (2014)
Global Epidemiology of Influenza: Past and Present
Authors: N. J. Cox, K. Subbarao
Journal: Annual Review of Medicine (2000)

Pandemics are the most dramatic presentation of influenza. Three have occurred in the twentieth century: the 1918 H1N1 pandemic, the 1957 H2N2 pandemic, and the 1968 H3N2 pandemic. The tools of molecular epidemiology have been applied in an attempt to determine the origin of pandemic viruses and to understand what made them such successful pathogens. An excellent example of this avenue of research is the recent phylogenetic analysis of genes of the virus that caused the devastating 1918 pandemic. This analysis has been used to identify evolutionarily related influenza virus genes as a clue to the source of the pandemic of 1918. Molecular methods have been used to investigate the avian H5N1 and H9N2 influenza viruses that recently infected humans in Hong Kong. Antigenic, genetic, and epidemiologic analyses have also furthered our understanding of interpandemic influenza. Although many questions remain, advances of the past two decades have demonstrated that several widely held concepts concerning the global epidemiology of influenza were false.
Circulating CD4+ T Cells That Produce IL4 or IL17 When Stimulated by Melan-A but Not by NY-ESO-1 Have Negative Impacts on Survival of Patients with Stage IV Melanoma
Authors: Henning Zelba, Benjamin Weide, Alexander Martens, Evelyna Derhovanessian, Jithendra Kini Bailur, Christina Kyzirakos, Annette Pflugfelder, Thomas K. Eigentler, Anna Maria Di Giacomo, Michele Maio, Erik H.J.G. Aarntzen, Jolanda de Vries, Antje Sucker, Dirk Schadendorf, Petra Büttner, Claus Garbe, Graham Pawelec
Journal: Clinical Cancer Research (2014)

We initially observed that the presence of circulating NY-ESO-1- and/or Melan-A-specific T cells in patients with stage IV melanoma was significantly associated with prolonged survival. Here, we report the ways in which the phenotypes and functions of these T cells differentially affect survival in patients preselected for NY-ESO-1 and/or Melan-A reactivity.We assayed functional antigen-reactive T cells recognizing NY-ESO-1 and/or Melan-A after in vitro stimulation using overlapping peptide pools. After restimulation, we assayed six cytokines simultaneously by intracellular cytokine staining. This allowed us to analyze the functional antigen response of both CD4(+) and CD8(+) T cells at the single-cell level.We observed that NY-ESO-1 stimulated mainly CD4(+) T cells, whereas Melan-A more often stimulated CD8(+) T cells. NY-ESO-1 reactivity was not associated with an additional impact on survival, whether CD4(+) T cells, CD8(+) T cells, or both types of T cells were responding. In contrast, recognition of Melan-A by CD4(+) T cells was associated with reduced survival in our cohort of patients preselected for NY-ESO-1 and/or Melan-A reactivity (that is, in patients with exceptionally long survival). We further observed a negative effect on survival in patients with CD4(+) T cells producing IL4 and IL17 upon Melan-A stimulation. Their prognosis was comparable to patients without any Melan-A reactivity.The nature and prognostic impact of specific T-cell responses is different according to targeted antigen. Independent from phenotype and functional aspects, NY-ESO-1 reactivity is associated with good prognosis. In terms of Melan-A, antigen-specific CD8(+) but not CD4(+) responses are associated with prolonged survival. Clin Cancer Res; 20(16); 4390-9. ©2014 AACR.
Natural history of hepatic haemangiomas: clinical and ultrasound study.
Authors: L Gandolfi, P Leo, L Solmi, E Vitelli, G Verros, A Colecchia
Journal: Gut (1991)

Hepatic haemangiomas are the most common benign tumours of the liver and commonly present as incidental findings on sonographic examination of the abdomen. Since little is known of the natural course of these tumours, we performed a clinical and sonographic follow up of 123 haemangioma patients. Our prospective study investigated clinical and sonographic findings in 158 haemangiomas for periods of 12 to 60 months. Ninety nine haemangiomas measured less than 2 cm and had an echogenic pattern; 40 were between 2 cm and 5 cm with a mainly echogenic structure; 19 measured greater than 5 cm and showed a mixed echo pattern. At the first examination only eight patients, all with giant haemangiomas, presented symptoms which could be attributed to the tumour. During follow up only one haemangioma changed in shape and size. One patient who was symptom free at the first examination experienced right upper abdominal quadrant pain during follow up. No deterioration occurred in any of the patients with symptoms at the first examination, and all had a satisfactory quality of life. No complications arose during the follow up period. This study shows that in adults haemangiomas remain stable in size and echo patterns rarely change. Only haemangiomas greater than 5 cm may cause symptoms. Prolonged clinical and sonographic follow up of small and medium sized haemangiomas is not warranted.
Do adjunct tuberculosis tests, when combined with Xpert MTB/RIF, improve accuracy and the cost of diagnosis in a resource-poor setting?
Authors: Grant Theron, Anil Pooran, Jonny Peter, Richard van Zyl-Smit, Hridesh Kumar Mishra, Richard Meldau, Greg Calligaro, Brian Allwood, Surendra Kumar Sharma, Rod Dawson, Keertan Dheda
Journal: European Respiratory Journal (2011)

Information regarding the utility of adjunct diagnostic tests in combination with Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) is limited. We hypothesised adjunct tests could enhance accuracy and/or reduce the cost of tuberculosis (TB) diagnosis prior to MTB/RIF testing, and rule-in or rule-out TB in MTB/RIF-negative individuals. We assessed the accuracy and/or laboratory-associated cost of diagnosis of smear microscopy, chest radiography (CXR) and interferon-γ release assays (IGRAs; T-SPOT-TB (Oxford Immunotec, Oxford, UK) and QuantiFERON-TB Gold In-Tube (Cellestis, Chadstone, Australia)) combined with MTB/RIF for TB in 480 patients in South Africa. When conducted prior to MTB/RIF: 1) smear microscopy followed by MTB/RIF (if smear negative) had the lowest cost of diagnosis of any strategy investigated; 2) a combination of smear microscopy, CXR (if smear negative) and MTB/RIF (if imaging compatible with active TB) did not further reduce the cost per TB case diagnosed; and 3) a normal CXR ruled out TB in 18% of patients (57 out of 324; negative predictive value (NPV) 100%). When downstream adjunct tests were applied to MTB/RIF-negative individuals, radiology ruled out TB in 24% (56 out of 234; NPV 100%), smear microscopy ruled in TB in 21% (seven out of 24) of culture-positive individuals and IGRAs were not useful in either context. In resource-poor settings, smear microscopy combined with MTB/RIF had the highest accuracy and lowest cost of diagnosis compared to either technique alone. In MTB/RIF-negative individuals, CXR has poor rule-in value but can reliably rule out TB in approximately one in four cases. These data inform upon the programmatic utility of MTB/RIF in high-burden settings.
Characterisation of endogenous IL-33 using a model of Alternaria-induced pulmonary inflammation
Authors: Suzanne Cohen, Jayesh Majithiya, Nicola Davis, Ian Scott, Laura Robinson, Arthur Lewis, Andrew Prior, Marlon Rebelatto, Dominic Corkill, Matthew Sleeman, Richard May
Journal: European Respiratory Journal (2012)

Background   IL-33 is a potential mediator of chronic inflammatory diseases including asthma. However, endogenous forms of IL-33 are poorly understood. Here we have used a model of  Alternaria alternata  (ALT) challenge to investigate  in vivo  mechanisms of IL-33 processing and release.   Methods   Cytokines were quantified in bronchoalveolar lavage (BAL) from BALB/c mice by MSD assay. Mast cells were differentiated from bone marrow over 5 weeks and stimulated with BAL or recombinant IL-33 for 24 hours.   Results   Intranasal challenge with 50µg ALT, but not 25µg house dust mite, extract in 50µL to anaesthetised BALB\c mice caused a spike (∼2000pg at 15-30min) of IL-33 in BAL followed by rapid clearance (below detection limit of 2pg within 4-5 hrs). Key downstream effects were an increase in 5 and 24 hours BAL IL-5 (∼400pg and ∼600pg, respectively) and eosinophilia at 24 hours. Dependence on the IL-33-ST2 axis was confirmed in ST2 and IL-33 KO mice which showed no IL-5 or eosinophilia after challenge. IL-33 is considered an alarmin, released on cell damage, yet histological analysis of ALT challenged lungs showed no overt damage to the airway epithelium. The presence of active IL-33 in WT but not IL-33KO BAL was confirmed  ex vivo  by stimulation of mouse mast cells. Western blot analysis of BAL demonstrated the presence of full length IL-33 (∼31kDa) and a ∼20kDa processed form in WT, but not IL-33KO, ALT-treated mice.   Conclusion   IL-33 is released rapidly and in large quantities following ALT exposure. This occurs in the absence of overt epithelial injury and results in generation of a ∼20kDa processed form of IL-33  in vivo . These data support the current view of IL-33 as an alarmin-type molecule.
Unnecessary x-rays?
Authors: H A Constable
Journal: BMJ (1970)

Classification).There were 27 spontaneous deliveries, 8 forceps deliveries, and 9 caes- arean sections.In brief, there was a sharp fall in C.V.P. on delivery of the child in every case.During the third stage of labour the C.V.P. ranged from -2 to + 9 cm.H20 (zero level was the sternal angle).Each pa- tient received ergometrine 0-25 mg. or 0-5 mg.intravenously, sometimes before and sometimes after placental separation.Placental separation and the injection of ergometrine produced small and transient rises in C.V.P. (never more than 3 cm.H20 and never lasting for more than 4 minutes).Blood loss was measured at these deliveries and was of the anticipated magnitude.1 2 It is believed that the direct effects of ergo- metrine on the veins were to a variable extent cancelled out by the effects of haemorrhage.
Interpretation, Stratification and Evidence for Sequence Variants Affecting mRNA Splicing in Complete Human Genome Sequences
Authors: Ben C. Shirley, Eliseos J. Mucaki, Tyson Whitehead, Paul I. Costea, Pelin Akan, Peter K. Rogan
Journal: Genomics Proteomics & Bioinformatics (2013)

Abstract Information theory-based methods have been shown to be sensitive and specific for predicting and quantifying the effects of non-coding mutations in Mendelian diseases. We present the Shannon pipeline software for genome-scale mutation analysis and provide evidence that the software predicts variants affecting mRNA splicing. Individual information contents (in bits) of reference and variant splice sites are compared and significant differences are annotated and prioritized. The software has been implemented for CLC-Bio Genomics platform. Annotation indicates the context of novel mutations as well as common and rare SNPs with splicing effects. Potential natural and cryptic mRNA splicing variants are identified, and null mutations are distinguished from leaky mutations. Mutations and rare SNPs were predicted in genomes of three cancer cell lines (U2OS, U251 and A431), which were supported by expression analyses. After filtering, tractable numbers of potentially deleterious variants are predicted by the software, suitable for further laboratory investigation. In these cell lines, novel functional variants comprised 6–17 inactivating mutations, 1–5 leaky mutations and 6–13 cryptic splicing mutations. Predicted effects were validated by RNA-seq analysis of the three aforementioned cancer cell lines, and expression microarray analysis of SNPs in HapMap cell lines.