tbuckley/cabot-search huggingface dataset:
Multiple Cross-Species Transmission Events of Human Adenoviruses (HAdV) during Hominine Evolution
Authors: Eileen Hoppe, Maude Pauly, Thomas R. Gillespie, Chantal Akoua-Koffi, Gottfried Hohmann, Barbara Fruth, Stomy Karhemere, Nadège F. Madinda, Lawrence Mugisha, Jean-Jacques Muyembe, Angelique Todd, Klara J. Petrzelkova, Maryke Gray, Martha Robbins, Richard A. Bergl, Roman M. Wittig, Klaus Zuberbühler, Christophe Boesch, Grit Schubert, Fabian H. Leendertz, Bernhard Ehlers, Sébastien Calvignac-Spencer
Journal: Molecular Biology and Evolution (2015)

Human adenoviruses (HAdV; species HAdV-A to -G) are highly prevalent in the human population, and represent an important cause of morbidity and, to a lesser extent, mortality. Recent studies have identified close relatives of these viruses in African great apes, suggesting that some HAdV may be of zoonotic origin. We analyzed more than 800 fecal samples from wild African great apes and humans to further investigate the evolutionary history and zoonotic potential of hominine HAdV. HAdV-B and -E were frequently detected in wild gorillas (55%) and chimpanzees (25%), respectively. Bayesian ancestral host reconstruction under discrete diffusion models supported a gorilla and chimpanzee origin for these viral species. Host switches were relatively rare along HAdV evolution, with about ten events recorded in 4.5 My. Despite presumably rare direct contact between sympatric populations of the two species, transmission events from gorillas to chimpanzees were observed, suggesting that habitat and dietary overlap may lead to fecal-oral cross-hominine transmission of HAdV. Finally, we determined that two independent HAdV-B transmission events to humans occurred more than 100,000 years ago. We conclude that HAdV-B circulating in humans are of zoonotic origin and have probably affected global human health for most of our species lifetime.
Methods for Analysis of Skewed Data Distributions in Psychiatric Clinical Studies: Working With Many Zero Values
Authors: Kevin L. Delucchi, Alan Bostrom
Journal: American Journal of Psychiatry (2004)

Psychiatric clinical studies, including those in drug abuse research, often provide data that are challenging to analyze and use for hypothesis testing because they are heavily skewed and marked by an abundance of zero values. The authors consider methods of analyzing data with those characteristics.The possible meaning of zero values and the statistical methods that are appropriate for analyzing data with many zero values in both cross-sectional and longitudinal designs are reviewed. The authors illustrate the application of these alternative methods using sample data collected with the Addiction Severity Index.Data that include many zeros, if the zero value is considered the lowest value on a scale that measures severity, may be analyzed with several methods other than standard parametric tests. If zero values are considered an indication of a case without a problem, for which a measure of severity is not meaningful, analyses should include separate statistical models for the zero values and for the nonzero values. Tests linking the separate models are available.Standard methods, such as t tests and analyses of variance, may be poor choices for data that have unique features. The use of proper statistical methods leads to more meaningful study results and conclusions.
Antiviral Effect of N-Phenylacetoaminomethylene-dl-p-nitrophenylalanine (A-101) on Murine Leukemia Viruses2
Authors: Haruhisa Fujita, Toshiharu Sakurai, Shigeshi Toyoshima
Journal: JNCI Journal of the National Cancer Institute (1979)

N-Phenylacetoaminomethylene-DL-p-nitrophenylalanine (A-101), when administered ip to male DDY mice infected with Friend leukemia virus, significantly inhibited virus-induced splenomegaly, reduced viable virus titers in spleen and plasma, and significantly prolonged survival time. A-101 also inhibited multiplication of the Friend and Moloney viruses in tissue culture systems.
Effects of continuous positive airway pressure on coagulability in obstructive sleep apnoea: a randomised, placebo-controlled crossover study
Authors: Craig L Phillips, Bradley J McEwen, Marie-Christine Morel-Kopp, Brendon J Yee, David R Sullivan, Christopher M Ward, Geoffrey H Tofler, Ronald R Grunstein
Journal: Thorax (2012)

<h3>Introduction</h3> Obstructive sleep apnoea (OSA) is associated with increased cardiovascular risk, however the mechanisms are not well established. <h3>Objectives</h3> This study aimed to determine whether treatment of OSA with nasal continuous positive airway pressure (CPAP) would favourably alter coagulability across the sleep–wake cycle. <h3>Methods</h3> In a randomised crossover trial, 28 patients received therapeutic or placebo CPAP, each for 2 months with a 1 month washout between treatments. After each treatment period, a 24 h coagulation study was conducted in the laboratory. Plasminogen activator inhibitor-1 (PAI-1), D-dimer, fibrinogen, von Willebrand Factor (vWF), factor VIII (FVIII), factor VII (FVII) and factor V (FV) were determined at seven time points over the day and night. <h3>Results</h3> At baseline, patients had severe OSA (Apnoea Hypopnoea Index 37.9±23.9 events/h). Treatment of OSA with CPAP compared with placebo resulted in lower 24 h levels of vWF (−3.9%, p=0.013), FVIII (−6.2%, p=0.007) and FV (−4.2%, p&lt;0.001). The greatest difference occurred during the nocturnal and early morning periods. In contrast, fibrinogen, D-dimer, FVII and PAI-1 did not differ between treatments, however all markers displayed diurnal variability independent of treatment. <h3>Conclusions</h3> In this randomised, placebo-controlled crossover trial, treatment of OSA with CPAP reduced the early morning level of vWF, and nocturnal levels of FVIII and FV. These findings suggest that CPAP may reduce cardiovascular risk in OSA, in part through reducing risk of thrombosis.
Impact of chronic airflow obstruction in a working population
Authors: N. Roche, F. Dalmay, T. Perez, C. Kuntz, A. Vergnenegre, F. Neukirch, J-P. Giordanella, G. Huchon
Journal: European Respiratory Journal (2008)

Data on the individual and collective impact of chronic airflow obstruction at a population level are scarce. In a nationwide survey, dyspnoea, quality of life and missed working days were compared between subjects with and without spirometrically diagnosed chronic airflow obstruction. Subjects aged ≥45 yrs were recruited in French health prevention centres (n = 5,008). Results of pre-bronchodilator spirometry and questionnaires (European Community Respiratory Health Survey-derived questionnaire and European quality of life five-dimension questionnaire) were collected. Adequate datasets were available for 4,764 subjects aged 60±10 yrs (only 2% were aged ≥80 yrs). The prevalence of airflow obstruction (forced expiratory volume in one second/forced vital capacity of &lt;0.70) was 7.5%. The vast majority (93.9%) of cases had not been diagnosed previously. Health status was significantly influenced by dyspnoea. Both were associated with the number of missed working days. Despite mild-to-moderate severity, subjects with chronic airflow obstruction exhibited more dyspnoea, poorer quality of life and higher numbers of missed working days (mean 6.71 <i>versus</i> 1.45 days·patient<sup>−1</sup>·yr<sup>−1</sup> in patients without airflow obstruction, for the population with no known heart or lung disease). In conclusion, even mild-to-moderate airflow obstruction is associated with an impaired health status, which represents an additional argument in favour of early detection in chronic obstructive pulmonary disease.
Dupilumab Treatment in Adults with Moderate-to-Severe Atopic Dermatitis
Authors: Lisa A. Beck, Diamant Thaçi, Jennifer D. Hamilton, Neil M. Graham, Thomas Bieber, Ross Rocklin, Jeffrey E. Ming, Haobo Ren, Richard Kao, Eric Simpson, Marius Ardeleanu, Steven P. Weinstein, Gianluca Pirozzi, Emma Guttman-Yassky, Mayte Suárez-Fariñas, Melissa D. Hager, Neil Stahl, George D. Yancopoulos, Allen R. Radin
Journal: New England Journal of Medicine (2014)

Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, has shown efficacy in patients with asthma and elevated eosinophil levels. The blockade by dupilumab of these key drivers of type 2 helper T-cell (Th2)-mediated inflammation could help in the treatment of related diseases, including atopic dermatitis.We performed randomized, double-blind, placebo-controlled trials involving adults who had moderate-to-severe atopic dermatitis despite treatment with topical glucocorticoids and calcineurin inhibitors. Dupilumab was evaluated as monotherapy in two 4-week trials and in one 12-week trial and in combination with topical glucocorticoids in another 4-week study. End points included the Eczema Area and Severity Index (EASI) score, the investigator's global assessment score, pruritus, safety assessments, serum biomarker levels, and disease transcriptome.In the 4-week monotherapy studies, dupilumab resulted in rapid and dose-dependent improvements in clinical indexes, biomarker levels, and the transcriptome. The results of the 12-week study of dupilumab monotherapy reproduced and extended the 4-week findings: 85% of patients in the dupilumab group, as compared with 35% of those in the placebo group, had a 50% reduction in the EASI score (EASI-50, with higher scores in the EASI indicating greater severity of eczema) (P<0.001); 40% of patients in the dupilumab group, as compared with 7% in the placebo group, had a score of 0 to 1 (indicating clearing or near-clearing of skin lesions) on the investigator's global assessment (P<0.001); and pruritus scores decreased (indicating a reduction in itch) by 55.7% in the dupilumab group versus 15.1% in the placebo group (P<0.001). In the combination study, 100% of the patients in the dupilumab group, as compared with 50% of those who received topical glucocorticoids with placebo injection, met the criterion for EASI-50 (P=0.002), despite the fact that patients who received dupilumab plus glucocorticoids used less than half the amount of topical glucocorticoids used by those who received placebo plus the topical medication (P=0.16). Adverse events, such as skin infection, occurred more frequently with placebo; nasopharyngitis and headache were the most frequent adverse events with dupilumab.Patients treated with dupilumab had marked and rapid improvement in all the evaluated measures of atopic dermatitis disease activity. Side-effect profiles were not dose-limiting. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov numbers, NCT01259323, NCT01385657, NCT01639040, and NCT01548404.).
Comparison of a New Multiplexed Multigene Approach with Pyrosequencing in Diagnostic Molecular Biology of Colorectal Cancer (CRC)
Authors: De Maglio Giovanna, Cernic Sara, Pagani Lucia, Ongaro Elena, Ferrari Laura, Aprile Giuseppe, Fasola Gianpiero, Pizzolitto Stefano
Journal: Annals of Oncology (2014)
Predicting distant recurrence in receptor-positive breast cancer patients with limited clinicopathological risk: using the PAM50 Risk of Recurrence score in 1478 postmenopausal patients of the ABCSG-8 trial treated with adjuvant endocrine therapy alone
Authors: M. Gnant, M. Filipits, R. Greil, H. Stoeger, M. Rudas, Z. Bago-Horvath, B. Mlineritsch, W. Kwasny, M. Knauer, C. Singer, R. Jakesz, P. Dubsky, F. Fitzal, R. Bartsch, G. Steger, M. Balic, S. Ressler, J.W. Cowens, J. Storhoff, S. Ferree, C. Schaper, S. Liu, C. Fesl, T.O. Nielsen
Journal: Annals of Oncology (2013)
Depletion of Mitogen-Activated Protein Kinase Using an Antisense Oligodeoxynucleotide Approach Downregulates the Phenylephrine-Induced Hypertrophic Response in Rat Cardiac Myocytes
Authors: Peter E. Glennon, Samer Kaddoura, Elizabeth M. Sale, Graham J. Sale, Stephen J. Fuller, Peter H. Sugden
Journal: Circulation Research (1996)

Abstract An antisense oligodeoxynucleotide (ODN) approach was used to investigate whether mitogen-activated protein kinase (MAPK) is necessary for the hypertrophic response in cardiac myocytes. A phosphorothioate-protected 17-mer directed against the initiation of translation sites of the p42 and p44 MAPK isoform mRNAs was introduced into cultured cardiac myocytes by liposomal transfection. At an antisense ODN concentration of 0.2 μmol/L, p42 MAPK protein was reduced by 82% (immunoblot) after 48 hours, and p42 and p44 MAPK activities were reduced by 44% and 60%, respectively. The same concentration of anti-MAPK ODN inhibited development of the morphological features of hypertrophy (sarcomerogenesis, increased cell size) in myocytes exposed to phenylephrine. Phenylephrine-induced activation of the atrial natriuretic factor (ANF) promoter (measured by the activity of a transfected ANF promoter/luciferase reporter gene) and induction of ANF mRNA (measured by RNase protection assay) were also attenuated. We conclude that MAPK is important for the development of the hypertrophic phenotype in this model of hypertrophy.
Receptors of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) in fetal and adult human kidney
Authors: M Simon, W Röckl, C Hornig, E F Gröne, H Theis, H A Weich, E Fuchs, A Yayon, H J Gröne
Journal: Journal of the American Society of Nephrology (1998)

Vascular endothelial growth factor (VEGF) has an important function in renal vascular ontogenesis and is constitutively expressed in podocytes of the adult kidney. The ability of VEGF to be chemotactic for monocytes and to increase the activity of collagenase and plasminogen activator may have implications for renal development and renal disease. In humans, the cellular actions of VEGF depend on binding to two specific receptors: Flt-1 and KDR. The aims of this study were: (1) to localize VEGF receptor proteins in human renal ontogenesis; (2) to quantify VEGF binding in human fetal and adult kidney; and (3) to dissect the binding into its two known components: the KDR and Flt-1 receptors. The latter aim was achieved by competitive binding of VEGF and placenta growth factor-2, which only binds to Flt-1. Quantification of 125I-VEGF binding sites was performed by autoradiography and computerized densitometry. By double-label immunohistochemistry, VEGF receptor proteins were localized solely to endothelial cells of preglomerular vessels, glomeruli, and postglomerular vessels. In developing glomeruli, VEGF receptor protein appeared as soon as endothelial cells were positive for von Willebrand factor. Specific 125I-VEGF binding could be localized to renal arteries and veins, glomeruli, and the tubulointerstitial capillary network in different developmental stages. Affinity (Kd) of adult (aK) and fetal (fK) kidneys was: Kd: glomeruli 38.6 +/- 11.2 (aK, n = 5), 36.3 +/- 7.1 (fK, n = 5); cortical tubulointerstitium 19.4 +/- 2.6 (aK, n = 5), 11.6 +/- 7.0 (fK, n = 5) pmol. Placenta growth factor-2 displaced VEGF binding in all renal structures by approximately 60%. VEGF receptor proteins thus were found only in renal endothelial cells. A coexpression of both VEGF binding sites could be shown, with Flt-1 demonstrating the most abundant VEGF receptor binding sites in the kidney. These studies support the hypothesis of a function for VEGF in adult kidney that is independent of angiogenesis.
External symbols are a better bet than perceptual symbols
Authors: A. J. Wells
Journal: Behavioral and Brain Sciences (1999)

Barsalou's theory rightly emphasizes the perceptual basis of cognition. However, the perceptual symbols that he proposes seem ill suited to carry the representational burden entailed by the architecture in which they function, given that Barsalou accepts the requirement for productivity. A more radical proposal is needed in which symbols are largely external to the cognizer and linked to internal states via perception.
Are We Getting Closer to Molecular Population Screening for Colorectal Cancer?
Authors: G. Rennert
Journal: JNCI Journal of the National Cancer Institute (2009)

The best methods to bring about a reduction in the incidence and mortality of colorectal cancer in the world have been the subject of much debate in recent years. Colorectal cancer is highly preventable through behavioral changes in diet and physical activity; still, much effort has been invested in developing efficient screening technologies for secondary prevention. Public health theory stresses a number of requirements that must be met before screening for a disease can be initiated ( 1 ). This line of thought differs from the usual clinical situation in which symptomatic patients present themselves to the health system in search of medical help. The screening setting refers to very large populations that are usually symptom free and at a very low probability of having the disease of interest at any given round of screening. The disease of concern needs to be clinically signifi cant in terms of incidence, prevalence, mortality, or suffering and have a natural history that can be infl uenced by a timely intervention. Screening technologies need to have proven and substantial effi cacy. Specifi city takes priority over sensitivity, contrary to the case when diagnosing symptomatic patients. Effi cacy is best proven through randomized controlled trials that show disease-specifi c mortality reduction. Studies that are designed in a nonrandomized manner are prone to major biases, such as length bias, lead-time bias, and selection bias ( 1 ), all of which can seriously diminish the validity of the results in terms of the direction and the magnitude of the effect. The screening technology needs to be as simple as possible, easy to perform, cheap, and, most importantly, acceptable to the population, that is, noninvasive and with an overall balance of more benefi t than harm. Clinical practice, however, often strays from these rules, which leads to unjustifi ed, unnecessary, and sometimes risky screening recommendations and behavior.
Fetal cells in maternal tissue following pregnancy: what are the consequences?
Authors: K. L. Johnson
Journal: Human Reproduction Update (2004)

The presence and persistence of fetal cells in murine maternal tissue was first reported over 20 years ago, although it is only more recently that the occurrence and potential consequences of fetomaternal cell trafficking in humans have been fully appreciated. Fetal cell microchimerism is a growing field of investigation, although the data are contradictory relative to the health consequences of persistent fetal cells in maternal tissues. Understanding of the types of cells being transferred from fetus to mother, the location of these fetal cells within the various maternal tissue types, and the functionality of these cells may ultimately lead to measures to minimize or eliminate the deleterious effects of the cells, or to efforts to take advantage of the presence of these cells for therapeutic purposes. This review focuses on the origins of fetal cell microchimerism research and the different hypotheses regarding the consequences of persistent fetal cells in the mother, the various diseases that have been evaluated with respect to fetomaternal cell trafficking, the potential variables associated with the frequency, persistence and tissue distribution of fetal cells in maternal tissue, and an assessment of future direction in this innovative field of inquiry.
Impaired gastric relaxation in patients with achalasia.
Authors: F Mearin, M Papo, J R Malagelada
Journal: Gut (1995)

Achalasia is considered a primary motility disorder confined to the oesophagus. The lower oesophageal sphincter (LOS) in achalasia is frequently hypertonic and manifests absent or incomplete relaxation in response to deglution. On the other hand, the LOS and the proximal stomach act physiologically as a functional unit whereby relaxation of the LOS during deglution is associated with receptive relaxation of the proximal stomach. Thus, this study investigated the hypothesis that impaired LOS relaxation in patients with achalasia might be associated with impaired relaxation of the proximal stomach. The study consisted of 20 patients with achalasia and 10 healthy controls. Gastric tone variations were quantified using an electronic barostat. Firstly, the study established the basal gastric tone (intragastric volume at the minimal distending pressure+1 mm Hg) and gastric compliance (volume/pressure relation) during isobaric distension (increasing stepwise the intragastric pressure from 0 to 20 mm Hg up to 600 ml). Secondly, the gastric tone response to cold stress (hand immersion into ice water for five minutes) or to control stimuli (water at 37 degrees) was determined. Basal gastric tone mean (SEM) was similar in achalasia and in healthy controls (125 (9) ml v 138 (9) ml, respectively). Compliance was linear and similar in both groups, which also showed similar gastric extension ratios (58 (7) ml/mm Hg v 57 (6) ml/mm Hg). Cold stress induced a gastric relaxatory response that, as a group, was significantly lower in achalasia than in healthy controls (volume: 43 (20) ml v 141 (42) ml; p < 0.05). The responses in each group were not uniform, five of the 20 patients with achalasia showed definite (volume > 100 ml) relaxatory responses whereas four of the 10 healthy controls did not. In conclusion, reflex gastric relaxation is impaired in most patients with achalasia showing that the proximal stomach, and not exclusively the oesophagus, may be effected by the disease.
Ultrastructural changes suggestive of immune reactions in the jejunal mucosa of coeliac children following gluten challenge
Authors: M. Shiner
Journal: Gut (1973)

The jejunal mucosa of eight coeliac children on a gluten-free diet and two non-coeliac children was studied by light and electron microscopy two to 98 hours after a single challenge dose of gluten. In all coeliac patients the early cytopathological reactions were principally confined to the structures within the subepithelial connective tissue. Changes were observed in the connective tissue fibrils, the basement membranes of epithelial and endothelial cells, the endothelium of small blood vessels, and the type and degree of inflammatory cell infiltration. The timing of these reactions was compatible with the concept that gluten acts as an antigen and combines with antibody in the form of immune complexes in the connective tissue close to the epithelium and to small blood vessels. These changes appeared to precede epithelial cell damage. No subepithelial tissue changes were seen in the non-coeliac patients after gluten challenge.
Interleukin-33 and Thymic Stromal Lymphopoietin Are Preferentially Elevated In The Sera Of Infants With Eosinophilic Gastroenteritis
Authors: Ichiro Nomura, Akio Matsuda, Tetsuo Shoda, Hideaki Morita, Katsuhiro Arai, Hirotaka Shimizu, Yoshiyuki Yamada, Yukihiro Ohya, Hirohisa Saito, Kenji Matsumoto
Journal: Journal of Allergy and Clinical Immunology (2014)