tbuckley/cabot-search huggingface dataset:
Null Model Selection, Compositional Bias, Character State Bias, and the Limits of Phylogenetic Information
Authors: J. Lyons-Weiler, G. A. Hoelzer
Journal: Molecular Biology and Evolution (1999)

Evolutionary trends and processes can distort phylogenetic information in sequences such that they do not reliably reflect the evolutionary processes that generate them. This fact of molecular evolution has a ubiquitous influence on the ability of researchers to adequately reconstruct genealogical relationships and histories of the processes of molecular evolution. This feature of phylogenetic inference can limit the capacity of researchers to adequately specify a relevant null hypothesis for testing hypothesis of relationships, data informativeness, and processes of molecular evolution. We show how this feature of historical inference also influences the exactness of the relative apparent synapomorphy analysis (RASA) test for phylogenetic signal and demonstrate how a permutation modification of the null hypothesis can improve the robustness of the underlying distributional assumption of the test. The RASA test (using either null model) was found not only to appropriately reject the combinability of independent lines of evidence for the relationships among the Physalaemus pustulosusfrog species group, but also to be more appropriately sensitive to individual uninformative data sets than commonly used tree-based measures of signal, including the consistency index, the retention index, and the permutation tail probability test statistic.
A prospective study of the effects of weekly oral methotrexate on liver biopsy.
Authors: A.P. WARIN, J.W. LANDELLS, G.M. LEVENE, H. BAKER
Journal: British Journal of Dermatology (1975)

Journal Article A prospective study of the effects of weekly oral methotrexate on liver biopsy: FINDINGS IN SEVERE PSORIASIS Get access A.P. WARIN, A.P. WARIN Departments of Dermatology and Pathology, The London Hospital Search for other works by this author on: Oxford Academic Google Scholar J.W. LANDELLS, J.W. LANDELLS Departments of Dermatology and Pathology, The London Hospital Search for other works by this author on: Oxford Academic Google Scholar G.M. LEVENE, G.M. LEVENE St John's Hospital for Diseases of the Skin, London Search for other works by this author on: Oxford Academic Google Scholar H. BAKER H. BAKER Departments of Dermatology and Pathology, The London Hospital Reprint requests to: Dr H. Baker, The London Hospital, London, E.I. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 93, Issue 3, 1 September 1975, Pages 321–327, https://doi.org/10.1111/j.1365-2133.1975.tb06498.x Published: 01 September 1975
Effect of cilomilast (Ariflo) on TNF- , IL-8, and GM-CSF release by airway cells of patients with COPD
Authors: M Profita
Journal: Thorax (2003)

Inflammation in chronic obstructive pulmonary disease (COPD) is characterised by increased neutrophilic infiltration of the airways. Cilomilast, a novel selective phosphodiesterase 4 inhibitor in clinical development for COPD treatment, exerts anti-inflammatory effects. The ability of cilomilast to inhibit the release of neutrophil chemoattractants such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-8, and granulocyte-macrophage colony stimulating factor (GM-CSF) by bronchial epithelial cells and sputum cells isolated from 10 patients with COPD, 14 normal controls, and 10 smokers was investigated.Bronchial epithelial cells obtained by bronchial brushing and sputum cells isolated from induced sputum samples were cultured for 24 hours in the presence or absence of cilomilast (1 micro M). After incubation the supernatants were harvested and the levels of mediators measured by ELISA. Chemotactic activity in supernatants was also measured using a Boyden chamber.TNF-alpha and IL-8 release by bronchial epithelial cells and sputum cells was higher in patients with COPD than in controls (p<0.0001) and smokers (p<0.0001). GM-CSF was only detectable in sputum cell supernatants and its level was higher in patients with COPD than in controls and smokers (p<0.0001, respectively). Cilomilast significantly reduced TNF-alpha release by bronchial epithelial cells and sputum cells (p=0.005) and GM-CSF release by sputum cells (p=0.003), whereas IL-8 release was not statistically inhibited. Supernatants of sputum cells and bronchial epithelial cells treated with cilomilast significantly decreased neutrophil chemotaxis (p<0.006 and p<0.008, respectively).Cilomilast inhibits the production of some neutrophil chemoattractants by airway cells. This drug may play a role in the resolution of neutrophilic inflammation associated with COPD and cigarette smoke.
Pulmonary Function in Obese Persons12
Authors: George N. Bedell, William R. Wilson, Paul M. Seebohm
Journal: Journal of Clinical Investigation (1958)

The purpose of this paper is to report a study of lung function in extremely obese persons.In 1936, Kerr and Lagen (2) called attention to the fact that some obese persons develop dyspnea, cya- nosis, polycythemia, and cardiac failure.They thought that these signs and symptoms developed because of mechanical interference with ventilation, especially movement of the diaphragm.Sieker, Estes, Kelser and McIntosh (3) reported studies in four obese patients and postulated a cardiorespiratory syndrome peculiar to obese per- sons and characterized by somnolence, Cheyne-Stokes respirations, intermittent cyanosis, and polycythemia.At the same time that Sieker and his associates were working on this problem, Auchincloss, Cook and Renzetti (4) and Weil and Prasad (5) observed a peculiar type of polycy- themia associated with obesity.Most of the in- vestigators previously mentioned have reported additional patients characterized by obesity, hypoxemia, polycythemia and alveolar hypoventilation (6-9), and they have been joined by others (10-18).Burwell, Robin, Whaley and Bickel- mann (12) have given the picturesque name "Pickwickian Syndrome" to this combination of signs and symptoms.There is agreement that the cardinal character- istics of these patients are obesity, alveolar hypoventilation, and polycythemia.The basic physio- logic defect is alveolar hypoventilation.This leads to arterial hypoxemia and hypercapnia.Ar- terial hypoxemia provokes polycythemia.There- fore, the polycythemia of these patients is no longer of a mysterious type but is secondary to hypoxemia.No agreement exists on what initiates alveolar hypoventilation.Several theories have been ad-
Comparison of Weight-Loss Diets with Different Compositions of Fat, Protein, and Carbohydrates
Authors: Frank M. Sacks, George A. Bray, Vincent J. Carey, Steven R. Smith, Donna H. Ryan, Stephen D. Anton, Katherine McManus, Catherine M. Champagne, Louise M. Bishop, Nancy Laranjo, Meryl S. Leboff, Jennifer C. Rood, Lilian de Jonge, Frank L. Greenway, Catherine M. Loria, Eva Obarzanek, Donald A. Williamson
Journal: New England Journal of Medicine (2009)

The possible advantage for weight loss of a diet that emphasizes protein, fat, or carbohydrates has not been established, and there are few studies that extend beyond 1 year.We randomly assigned 811 overweight adults to one of four diets; the targeted percentages of energy derived from fat, protein, and carbohydrates in the four diets were 20, 15, and 65%; 20, 25, and 55%; 40, 15, and 45%; and 40, 25, and 35%. The diets consisted of similar foods and met guidelines for cardiovascular health. The participants were offered group and individual instructional sessions for 2 years. The primary outcome was the change in body weight after 2 years in two-by-two factorial comparisons of low fat versus high fat and average protein versus high protein and in the comparison of highest and lowest carbohydrate content.At 6 months, participants assigned to each diet had lost an average of 6 kg, which represented 7% of their initial weight; they began to regain weight after 12 months. By 2 years, weight loss remained similar in those who were assigned to a diet with 15% protein and those assigned to a diet with 25% protein (3.0 and 3.6 kg, respectively); in those assigned to a diet with 20% fat and those assigned to a diet with 40% fat (3.3 kg for both groups); and in those assigned to a diet with 65% carbohydrates and those assigned to a diet with 35% carbohydrates (2.9 and 3.4 kg, respectively) (P>0.20 for all comparisons). Among the 80% of participants who completed the trial, the average weight loss was 4 kg; 14 to 15% of the participants had a reduction of at least 10% of their initial body weight. Satiety, hunger, satisfaction with the diet, and attendance at group sessions were similar for all diets; attendance was strongly associated with weight loss (0.2 kg per session attended). The diets improved lipid-related risk factors and fasting insulin levels.Reduced-calorie diets result in clinically meaningful weight loss regardless of which macronutrients they emphasize. (ClinicalTrials.gov number, NCT00072995.)
Impact of two biological treatments in the functional capacity of a cohort of patients with rheumatoid arthritis
Authors: R. Martinez-Perez, S. Rodriguez-Montero, A. Munoz, M. Leon, F. Gallo, M. Velloso, J. Marenco
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Introduction</h3> Rheumatoid arthritis is a chronic inflammatory disease that can lead to disability in most patients. There are several ways to estimate the functional capacity, currently the most widespread methods are specific questionnaires for rheumatic diseases as HAQ (Health Assessment Questionnaire). This questionnaire is based on the patient9s own opinion about their disease and it9s a standardised instrument with proven reliability and validity, among which include disabilities, especially in relation with physical function and pain. The authors9 aim is to demonstrate that rituximab and infliximab improve functional capacity of our patients and to assess which treatment group gets the best response. <h3>Material and methods</h3> Observational, descriptive and retrospective study. The authors analysed 42 patients with rheumatoid arthritis. Twenty-three patients received infliximab, versus 19 rituximab. The authors excluded those patients who had started treatment for less than 6 months. They used several variables: visual analogue scale (VAS), patient global assessment (VGP) and HAQ, analysing before starting treatment, at 6 and 12 months. <h3>Results</h3> Forty-two patients, 12 men (28.6%) and 30 women (71.4%). Only 4.8% of infliximab9s group received previous biological treatment, compared to 100% in rituximab9s group. Results in table 1 <h3>Conclusions</h3> Infliximab and rituximab succeeded in improving the functional capacity of our patients, as well as gain a better perception of their clinical condition in the first 6 months of treatment. Infliximab got further reduction in VAS and VGP and before than rituximab. This may be because patients treated with rituximab had a more aggressive form, with previous failure to another biological in 100%. Also note that the baseline HAQ of patients with rituximab was lower than infliximab9s group. It is probably because, despite the need for change in treatment for persistent activity, other patients had an improvement in functional capacity after the first biological treatment.
Efficacy of modified-release versus standard prednisone to reduce duration of morning stiffness of the joints in rheumatoid arthritis (CAPRA-1): a double-blind, randomised controlled trial
Authors: Frank Buttgereit, Gisela Doering, Achim Schaeffler, Stephan Witte, Stanislaw Sierakowski, Erika Gromnica-Ihle, Slawomir Jeka, Klaus Krueger, Jacek Szechinski, Rieke Alten
Journal: The Lancet (2008)
Less Is More in Mammalian Phylogenomics: AT-Rich Genes Minimize Tree Conflicts and Unravel the Root of Placental Mammals
Authors: Jonathan Romiguier, Vincent Ranwez, Frédéric Delsuc, Nicolas Galtier, Emmanuel J.P. Douzery
Journal: Molecular Biology and Evolution (2013)

Despite the rapid increase of size in phylogenomic data sets, a number of important nodes on animal phylogeny are still unresolved. Among these, the rooting of the placental mammal tree is still a controversial issue. One difficulty lies in the pervasive phylogenetic conflicts among genes, with each one telling its own story, which may be reliable or not. Here, we identified a simple criterion, that is, the GC content, which substantially helps in determining which gene trees best reflect the species tree. We assessed the ability of 13,111 coding sequence alignments to correctly reconstruct the placental phylogeny. We found that GC-rich genes induced a higher amount of conflict among gene trees and performed worse than AT-rich genes in retrieving well-supported, consensual nodes on the placental tree. We interpret this GC effect mainly as a consequence of genome-wide variations in recombination rate. Indeed, recombination is known to drive GC-content evolution through GC-biased gene conversion and might be problematic for phylogenetic reconstruction, for instance, in an incomplete lineage sorting context. When we focused on the AT-richest fraction of the data set, the resolution level of the placental phylogeny was greatly increased, and a strong support was obtained in favor of an Afrotheria rooting, that is, Afrotheria as the sister group of all other placentals. We show that in mammals most conflicts among gene trees, which have so far hampered the resolution of the placental tree, are concentrated in the GC-rich regions of the genome. We argue that the GC content-because it is a reliable indicator of the long-term recombination rate-is an informative criterion that could help in identifying the most reliable molecular markers for species tree inference.
RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF DITIOCARB SODIUM ('IMUTHIOL') IN HUMAN IMMUNODEFICIENCY VIRUS INFECTION
Authors: Jean-Marie Lang, Christian Trepo, Myriam Kirstetter, Laurence Herviou, Geneviève Retornaz, Gérard Renoux, Mircea Musset, Jean-Louis Touraine, Patrick Choutet, Annie Falkenrodt, Jean-Michel Livrozet, Françoise Touraine, Micheline Renoux, Jean Caraux
Journal: The Lancet (1988)
Marked disruption and aberrant regulation of elastic fibres in early striae gravidarum
Authors: F. Wang, K. Calderone, N.R. Smith, T.T. Do, Y.R. Helfrich, T.R.B. Johnson, S. Kang, J.J. Voorhees, G.J. Fisher
Journal: British Journal of Dermatology (2015)

Striae gravidarum (SG), or 'stretch marks' of pregnancy, begin as erythematous streaks, and mature over months to years to become permanent scar-like bands that may be hypopigmented, atrophic and lax.To investigate early molecular alterations that may promote laxity of mature SG, we investigated the dermal elastic fibre network, which provides human skin with elastic properties.We obtained skin samples of newly developed, erythematous abdominal SG in healthy pregnant women. The elastic fibre network was examined by Verhoeff elastic staining and immunofluorescence staining of skin sections. Gene expression was measured by real-time polymerase chain reaction.The normal elastic fibre network appeared markedly disrupted in SG, compared with perilesional abdominal skin or control (normal-appearing hip skin). This disruption was accompanied by the emergence of short, disorganized, thin, thread-like 'fibrils', which were observed prominently in the mid-to-deep dermis. These fibrils were rich in tropoelastin (the main component of normal elastic fibres), and persisted into the postpartum period without forming normal-appearing elastic fibres. The emergence of these fibrils was accompanied by increased gene expression of tropoelastin and fibrillin-1, but not other elastic fibre components, including fibrillin-2 and fibulin-1, -2 or -5.In early SG, the elastic fibre network appears markedly disrupted, and newly synthesized tropoelastin-rich fibrils emerge, likely as a result of uncoordinated synthesis of elastic fibre components. Because they are thin and disorganized, tropoelastin-rich fibrils likely do not function as normal elastic fibres do. These observations provide the foundations for elucidating pathogenic mechanisms by which laxity may develop in SG.
Diversion colitis: a trigger for ulcerative colitis in the in-stream colon?
Authors: A G Lim, F L Langmead, R M Feakins, D S Rampton
Journal: Gut (1999)

The aetiology of ulcerative colitis is unknown. Two patients without pre-existing inflammatory bowel disease in whom end colostomy for faecal incontinence was complicated by diversion colitis in the defunctioned rectosigmoid colon, are described. In both instances, colitis with the clinical, colonoscopic, and microscopic features of ulcerative colitis developed about a year later in the previously normal in-stream colon proximal to the colostomy. These cases suggest that diversion colitis may be a risk factor for ulcerative colitis in predisposed individuals and that ulcerative colitis can be triggered by anatomically discontinuous inflammation elsewhere in the large intestine.
The physiological regulation of pacing strategy during exercise: a critical review
Authors: R Tucker, T D Noakes
Journal: British Journal of Sports Medicine (2009)

The regulation of the pacing strategy remains poorly understood, because much of classic physiology has focused on the factors that ultimately limit, rather than regulate, exercise performance. When exercise is self-paced and work rate is free to vary in response to external and internal physiological cues, then a complex system is proposed to be responsible for alterations in exercise intensity, possibly through altered activation of skeletal muscle motor units. The present review evaluates the evidence for such a complex system by investigating studies in which interventions such as elevated temperature, altered oxygen content of the air, reduced fuel availability and misinformation about distance covered have resulted in alterations to the pacing strategy. The review further investigates how such a pacing strategy might be regulated for optimal performance, while ensuring that irreversible physiological damage is not incurred.
Disturbed gastric emptying in the short bowel syndrome. Evidence for a 'colonic brake'.
Authors: J M Nightingale, M A Kamm, J R van der Sijp, G P Morris, E R Walker, S J Mather, K E Britton, J E Lennard-Jones
Journal: Gut (1993)

Gastric emptying of liquid (orange juice containing technetium-99m (99mTc) labelled antimony sulphide colloid) and solid (570 kcal pancake containing 0.5 mm resin microspheres labelled with Indium-111 (111-In)) was measured in seven patients with jejunum and no colon (jejunal lengths 30-160 cm), six patients with jejunum in continuity with the colon (jejunal length 25-75 cm), and in 12 normal subjects. In patients with no colon early emptying of liquid was rapid (median 25% emptying: 7 v 25 min, no colon v normal, p &lt; 0.05); early gastric emptying of solid was rapid in two (each with less than 100 cm jejunum) and normal in the other five. Gastric emptying of liquid and solid for patients with jejunum in continuity with the colon was normal for the first three hours. There was increased liquid and solid retained in the stomach at six hours in both groups of patients (p &lt; 0.01). Small bowel transit time was faster than in normal subjects for liquid in both groups of patients (p &lt; 0.05) and for solid in those with no colon (p &lt; 0.05). Rapid gastric emptying of liquid may contribute to the large stomal output in patients with a high jejunostomy. Preservation of the colon after a major small intestinal resection exerts a braking effect on the rate of early gastric emptying of liquid.
Exposure to Fumonisins and the Occurrence of Neural Tube Defects along the Texas–Mexico Border
Authors: Stacey A. Missmer, Lucina Suarez, Marilyn Felkner, Elaine Wang, Alfred H. Merrill, Kenneth J. Rothman, Katherine A. Hendricks
Journal: Environmental Health Perspectives (2005)

Along the Texas–Mexico border, the prevalence of neural tube defects (NTDs) among Mexican-American women doubled during 1990–1991. The human outbreak began during the same crop year as epizootics attributed to exposure to fumonisin, a mycotoxin that often contaminates corn. Because Mexican Americans in Texas consume large quantities of corn, primarily in the form of tortillas, they may be exposed to high levels of fumonisins. We examined whether or not maternal exposure to fumonisins increases the risk of NTDs in offspring using a population-based case–control study. We estimated fumonisin exposure from a postpartum sphinganine:sphingosine (sa:so) ratio, a biomarker for fumonisin exposure measured in maternal serum, and from maternal recall of periconceptional corn tortilla intake. After adjusting for confounders, moderate (301–400) compared with low (≤ 100) consumption of tortillas during the first trimester was associated with increased odds ratios (ORs) of having an NTD-affected pregnancy (OR = 2.4; 95% confidence interval, 1.1–5.3). No increased risks were observed at intakes higher than 400 tortillas (OR = 0.8 for 401–800, OR = 1.0 for > 800). Based on the postpartum sa:so ratio, increasing levels of fumonisin exposure were associated with increasing ORs for NTD occurrences, except for the highest exposure category (sa:so > 0.35). Our findings suggest that fumonisin exposure increases the risk of NTD, proportionate to dose, up to a threshold level, at which point fetal death may be more likely to occur. These results also call for population studies that can more directly measure individual fumonisin intakes and assess effects on the developing embryo.
Multiple gonococcal opacity proteins are expressed during experimental urethral infection in the male.
Authors: A E Jerse, M S Cohen, P M Drown, L G Whicker, S F Isbey, H S Seifert, J G Cannon
Journal: The Journal of Experimental Medicine (1994)

The opacity (Opa) proteins of Neisseria gonorrhoeae are a family of outer membrane proteins demonstrating phase and antigenic variation. N. gonorrhoeae strain FA0190 has 11 opa loci that encode at least 8 antigenically distinct Opa proteins. To determine if expression of one Opa protein or a subset of them is favored during gonococcal infection, we inoculated Opa-negative variants of strain FA1090 intraurethrally into male volunteers. The Opa phenotype of gonococci isolated from urine and urethral swab cultures from nine infected subjects was determined. Opa proteins were expressed in a large proportion of the reisolates from the infected subjects. Gonococci cultured from urine or urethral swab samples from six of the subjects were uniformly Opa positive, with the predominant Opa variants differing among subjects. Three different Opa proteins were represented as the predominant type in at least one subject each. In three subjects, there was more heterogeneity in Opa phenotype of the reisolates, including the presence of Opa-negative variants. An increase in the proportion of isolates expressing multiple Opa proteins occurred over time in most subjects. Passage of the inoculum in vitro did not result in similar changes in Opa expression. There was no detectable difference in infectivity of an Opa-negative variant and one expressing an Opa protein (OpaF) that was highly represented in reisolates from the original nine subjects. Reisolates from three infected volunteers inoculated with the OpaF variant showed continued expression of OpaF alone or in conjunction with other Opa proteins. These results demonstrate that there is strong selection for expression of one or more Opa proteins by strain FA1090 in vivo, but that no single protein is preferentially expressed during early infection in the male urethra.