tbuckley/cabot-search huggingface dataset:
The Comparative Method Rules! Codon Volatility Cannot Detect Positive Darwinian Selection Using a Single Genome Sequence
Authors: Tal Dagan, Dan Graur
Journal: Molecular Biology and Evolution (2004)

All established methods for detecting positive selection at the molecular level rely on comparisons between nucleotide sequences. An exceptional method that purports to detect selection on the basis of a single genomic sequence has recently been proposed. This method uses a measure called “codon volatility,” defined for each codon as the ratio between the number of nonsynonymous codons that differ from the codon under study at a single nucleotide position and the number of sense codons that differ from the codon under study at a single nucleotide position. Here, we examine various properties of codon volatility and its derivatives and use simulation of evolutionary processes to determine whether they can be used to detect selective pressures. Codons for only four amino acids (glycine, leucine, arginine, and serine) show any variation in codon volatility. Thus, codon volatility is mainly a proxy for amino acid usage, rather than for codon usage, with 65% of all synonymous changes and 27% of all nonsynonymous changes being undetectable by this measure. Genes identified by the volatility method as being subject to positive selection tend to have idiosyncratic amino acid compositions (e.g., they are glycine rich or arginine poor). An additional property of codon volatility is the near zero variance of its mean expectation, which translates into overestimated statistical significance estimates, especially in the absence of corrections for multiple comparisons. A comparison with measures of selection inferred through comparative methodology reveals no relationship between the results of the two methods. Finally, we show that codon volatility can increase in the absence of positive Darwinian selection; that is, increased codon volatility is not indicative of positive selection.
An inventory of yeast proteins associated with nucleolar and ribosomal components.
Authors: Eike Staub, Sebastian Mackowiak, Martin Vingron
Journal: Genome biology (2006)

Abstract Background Although baker's yeast is a primary model organism for research on eukaryotic ribosome assembly and nucleoli, the list of its proteins that are functionally associated with nucleoli or ribosomes is still incomplete. We trained a naïve Bayesian classifier to predict novel proteins that are associated with yeast nucleoli or ribosomes based on parts lists of nucleoli in model organisms and large-scale protein interaction data sets. Phylogenetic profiling and gene expression analysis were carried out to shed light on evolutionary and regulatory aspects of nucleoli and ribosome assembly. Results We predict that, in addition to 439 known proteins, a further 62 yeast proteins are associated with components of the nucleolus or the ribosome. The complete set comprises a large core of archaeal-type proteins, several bacterial-type proteins, but mostly eukaryote-specific inventions. Expression of nucleolar and ribosomal genes tends to be strongly co-regulated compared to other yeast genes. Conclusion The number of proteins associated with nucleolar or ribosomal components in yeast is at least 14% higher than known before. The nucleolus probably evolved from an archaeal-type ribosome maturation machinery by recruitment of several bacterial-type and mostly eukaryote-specific factors. Not only expression of ribosomal protein genes, but also expression of genes encoding the 90S processosome, are strongly co-regulated and both regulatory programs are distinct from each other.
Geographic and Socioeconomic Variation in the Treatment of Prostate Cancer
Authors: Tracey L. Krupski, Lorna Kwan, Abdelmonem A. Afifi, Mark S. Litwin
Journal: Journal of Clinical Oncology (2005)

Within a framework of quality assessment, primary treatment choice constitutes an indicator of quality of care. This study examines geographic and socioeconomic variation in the primary treatment of men with prostate cancer during the era of prostate-specific antigen testing.Using the National Cancer Institute's Surveillance, Epidemiology, and End Results public use data files, we identified men with localized/regional prostate cancer who underwent surgery, radiation therapy, or watchful waiting. We used the year 2000 US Census information to ascribe education and income levels to these men based on their county of residence and ethnicity.Among the 96,769 men with localized/regional prostate cancer (during 1995 to 1999) who had sufficient information for analysis, we observed significant geographic variation nationwide in surgical, radiation, and watchful waiting treatment rates (P <.0015). Patterns noted 10 years ago, such as higher surgical rates in western regions, persisted. Ethnicity, income, and grade were all independently associated with primary treatment, or lack thereof. Blacks and low-income patients had the lowest rates of surgery and radiation. Grade was the best predictor of aggressive treatment.Nonclinical factors, such as ethnicity and income, were associated with the use of watchful waiting rather than surgery or radiation in men with early-stage prostate cancer. These findings have implications for quality of care.
Diphenylhydantoin in the Treatment of Alcohol Withdrawal
Authors: H. Patrick Adams
Journal: JAMA (1971)

<h3>To the Editor.—</h3> In full support of Finer's letter (<b>217</b>:211,1971) advocating diphenylhydantoin in alcohol withdrawal, I would like to call attention to the statement in<i>AMA Drug Evaluations</i>(Chicago, American Medical Assoc, 1971) that the hydantoins are usually of little value in treating the major motor seizures in the withdrawal syndrome from alcohol and other drugs. Several other articles beside that of Gessner (<b>216</b>:887, 1971) have also negated its use in this area by commission or direct discredit. Though Finer states that it is "well established and recorded in standard textbooks of pharmacology" and its use advised for suspected convulsions in a standard psychiatry text, I find the use of diphenylhydantoin totally absent from two standard textbooks of medicine in sections on alcoholism treatment. Having had contact with too many patients with a history of convulsions and delirium tremens due often to misinformed or injudicious attempts to "shake
Atrial natriuretic factor in normal subjects and heart failure patients. Plasma levels and renal, hormonal, and hemodynamic responses to peptide infusion.
Authors: R J Cody, S A Atlas, J H Laragh, S H Kubo, A B Covit, K S Ryman, A Shaknovich, K Pondolfino, M Clark, M J Camargo
Journal: Journal of Clinical Investigation (1986)

We investigated atrial natriuretic factor (ANF) in humans, measuring plasma immunoreactive (ir) ANF (in femtomoles per milliliter), and renal, hormonal, and hemodynamic responses to ANF infusion, in normal subjects (NL) and congestive heart failure patients (CHF). Plasma irANF was 11 +/- 0.9 fmol/ml in NL and 71 +/- 9.9 in CHF (P less than 0.01); the latter with twofold right ventricular increment (P less than 0.05). In NL, ANF infusion of 0.10 microgram/kg per min (40 pmol/kg per min) induced increases (P less than 0.05) of absolute (from 160 +/- 23 to 725 +/- 198 mueq/min) and fractional (1-4%) sodium excretion, urine flow rate (from 10 +/- 1.6 to 20 +/- 2.6 ml/min), osmolar (from 3.2 +/- 0.6 to 6.8 +/- 1.2 ml/min) and free water (from 6.8 +/- 1.6 to 13.6 +/- 1.6 ml/min) clearances, and filtration fraction (from 20 +/- 1 to 26 +/- 2%). Plasma renin and aldosterone decreased 33% and 40%, respectively (P less than 0.01). Systolic blood pressure fell (from 112 +/- 3 to 104 +/- 5 mmHg, P less than 0.05) in seated NL; but in supine NL, the only hemodynamic response was decreased pulmonary wedge pressure (from 11 +/- 1 to 7 +/- 1 mmHg, P less than 0.05). In CHF, ANF induced changes in aldosterone and pulmonary wedge pressure, cardiac index, and systemic vascular resistance (all P less than 0.05); however, responses of renin and renal excretion were attenuated. ANF infusion increased hematocrit and serum protein concentration by 5-7% in NL (P less than 0.05) but not in CHF.
Angiotensin II Antagonist Prevents Electrical Remodeling in Atrial Fibrillation
Authors: Hideko Nakashima, Koichiro Kumagai, Hidenori Urata, Naoki Gondo, Munehito Ideishi, Kikuo Arakawa
Journal: Circulation (2000)

The blockade of angiotensin II (Ang II) formation has protective effects on cardiovascular tissue; however, the role of Ang II in atrial electrical remodeling is unknown. The purpose of this study was to investigate the effects of candesartan and captopril on atrial electrical remodeling.In 24 dogs, the atrial effective refractory period (AERP) was measured before, during, and after rapid atrial pacing. Rapid atrial pacing at 800 bpm was maintained for 180 minutes. The infusion of saline (n=8), candesartan (n=5), captopril (n=6), or Ang II (n=5) was initiated 30 minutes before rapid pacing and continued throughout the study. In the saline group, AERP was significantly shortened during rapid atrial pacing (from 149+/-11 to 132+/-16 ms, P<0.01). There was no significant difference in AERP shortening between the saline group and the Ang II group. However, in the candesartan and captopril groups, shortening of the AERP after rapid pacing was completely inhibited (from 142+/-9 to 147+/-12 ms with candesartan, from 153+/-15 to 153+/-14 ms with captopril, P=NS). Although rate adaptation of the AERP was lost in the saline group, this phenomenon was preserved in the candesartan and captopril groups.The inhibition of endogenous Ang II prevented AERP shortening during rapid atrial pacing. These results indicate for the first time that Ang II may be involved in the mechanism of atrial electrical remodeling and that the blockade of Ang II may lead to the better therapeutic management of human atrial fibrillation.
Cardiac Mortality Is Higher Around Christmas and New Year’s Than at Any Other Time
Authors: David P. Phillips, Jason R. Jarvinen, Ian S. Abramson, Rosalie R. Phillips
Journal: Circulation (2004)

Background— Research published in Circulation has shown that cardiac mortality is highest during December and January. We investigated whether some of this spike could be ascribed to the Christmas/New Year’s holidays rather than to climatic factors. Methods and Results— We fitted a locally weighted polynomial regression line to daily mortality to estimate the number of deaths expected during the holiday period, using the null hypothesis that natural-cause mortality is unaffected by the Christmas/New Year’s holidays. We then compared the number of deaths expected during the holiday period, given the null hypothesis, with the number of deaths observed. For cardiac and noncardiac diseases, a spike in daily mortality occurs during the Christmas/New Year’s holiday period. This spike persists after adjusting for trends and seasons and is particularly large for individuals who are dead on arrival at a hospital, die in the emergency department, or die as outpatients. For this group during the holiday period, 4.65% (±0.30%; 95% CI, 4.06% to 5.24%) more cardiac and 4.99% (±0.42%; 95% CI, 4.17% to 5.81%) more noncardiac deaths occur than would be expected if the holidays did not affect mortality. Cardiac mortality for individuals who are dead on arrival, die in the emergency department, or die as outpatients peaks at Christmas and again at New Year’s. These twin holiday spikes also are conspicuous for noncardiac mortality. The excess in holiday mortality is growing proportionately larger over time, both for cardiac and noncardiac mortality. Conclusions— Our findings suggest that the Christmas/New Year’s holidays are a risk factor for cardiac and noncardiac mortality. There are multiple explanations for this association, including the possibility that holiday-induced delays in seeking treatment play a role in producing the twin holiday spikes.
New DNA Methylation Markers for Pancreatic Cancer: Discovery, Tissue Validation, and Pilot Testing in Pancreatic Juice
Authors: John B. Kisiel, Massimo Raimondo, William R. Taylor, Tracy C. Yab, Douglas W. Mahoney, Zhifu Sun, Sumit Middha, Saurabh Baheti, Hongzhi Zou, Thomas C. Smyrk, Lisa A. Boardman, Gloria M. Petersen, David A. Ahlquist
Journal: Clinical Cancer Research (2015)

Discriminant markers for pancreatic cancer detection are needed. We sought to identify and validate methylated DNA markers for pancreatic cancer using next-generation sequencing unbiased by known targets.
Polymorphisms in Toll-Like Receptor 4 Are Not Associated with Asthma or Atopy-related Phenotypes
Authors: Benjamin A. Raby, Walter T. Klimecki, Catherine Laprise, Yannick Renaud, Janet Faith, Mathieu Lemire, Celia Greenwood, Katherine M. Weiland, Christoph Lange, Lyle J. Palmer, Ross Lazarus, Donata Vercelli, David J. Kwiatkowski, Edwin K. Silverman, Fernando D. Martinez, Thomas J. Hudson, Scott T. Weiss
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Toll-like receptor 4 (TLR4) is the principal receptor for bacterial endotoxin recognition, and functional variants in the gene confer endotoxin-hyporesponsiveness in humans. Furthermore, there is evidence that endotoxin exposure during early life is protective against the development of atopy and asthma, although this relationship remains poorly understood. It is therefore possible that genetic variation in the TLR4 locus contributes to asthma susceptibility. In this study we characterize the genetic diversity in the TLR4 locus and test for association between the common genetic variants and asthma-related phenotypes. In a cohort of 90 ethnically diverse subjects, we resequenced the TLR4 locus and identified a total of 29 single nucleotide polymorphisms. We assessed five common polymorphisms for evidence of association with asthma in two large family-based cohorts: a heterogeneous North American cohort (589 families), and a more homogenous population from northeastern Quebec, Canada (167 families). Using the transmission-disequilibrium test, we found no evidence of association for any of the polymorphisms tested, including two functional variants. Furthermore, we found no evidence for association between the TLR4 variants and four quantitative intermediate asthma- and atopy-related phenotypes. Based on these results, we found no evidence that genetic variation in TLR4 contributes to asthma susceptibility.
Exercise-Induced Asthma
Authors: E.R. McFadden, Ileen A. Gilbert
Journal: New England Journal of Medicine (1994)

Exercise-induced asthma is a condition in which vigorous physical activity triggers acute airway narrowing in people with heightened airway reactivity. A more accurate description would be exercise-induced bronchospasm. Long usage, however, has left the former term firmly fixed in the lexicon. To emphasize the underlying pathogenesis, the term "thermally induced asthma" has been proposed1.Exercise-induced asthma is not an isolated disorder or a specific disease. Exercise is but one of many stimuli that result in a limitation of airflow. It is not uncommon for physical exertion to be the first precipitant of asthma. With time, however, others may emerge. . . .
(7) Coexistent incontinentia pigmnti and tuberous sclerosis
Authors: M.J. Tidman, B.G.R. Neville, R.S. Wells
Journal: British Journal of Dermatology (1985)

Journal Article (7) Coexistent incontinentia pigmnti and tuberous sclerosis Get access M.J. Tidman, M.J. Tidman Guy's Hospital, London SE1 Search for other works by this author on: Oxford Academic Google Scholar B.G.R. Neville, B.G.R. Neville Guy's Hospital, London SE1 Search for other works by this author on: Oxford Academic Google Scholar R.S. Wells R.S. Wells Guy's Hospital, London SE1 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 113, Issue s29, 1 July 1985, Page 52, https://doi.org/10.1111/j.1365-2133.1985.tb13022.x Published: 01 July 1985
Relationship between hip strength and frontal plane posture of the knee during a forward lunge
Authors: Youri Thijs, Damien Van Tiggelen, Tine Willems, Dirk De Clercq, Erik Witvrouw
Journal: British Journal of Sports Medicine (2007)

Excessive frontal plane knee movement during forward lunge movements might be associated with the occurrence of knee injuries in tennis. Here, we attempt to determine whether hip muscle strength is related to the frontal plane motion of the knee during a functional lunge movement.A correlational study.A total of 84 healthy subjects (76 men, 8 women), with no history of knee or lower leg complaints.Muscle strength of six hip muscle groups was measured using a handheld dynamometer. Subjects were videotaped during a forward lunge and peak knee valgus or varus angles were determined using a digital video analysis software program.A correlation was examined between hip muscle strength and the amount of frontal plane movement of the knee during a forward lunge.There were no significant differences in hip muscle strength between the valgus group and the varus group during the forward lunge movement. No significant correlation was found between the strength of the assessed hip muscles and the amount of movement into valgus/varus. In the varus group a moderate positive correlation was found between the External Rotation/Internal Rotation force ratio and the amount of knee varus during the forward lunge movement (r = 0.31, p = 0.03).The findings suggest that in healthy subjects hip muscle strength is not correlated to the amount of valgus/varus movement of the knee during a forward lunge. This suggests that other factors (eg, proprioception, core hip stability) might be more important in controlling knee movement during this tennis-specific movement.
Adverse drug reactions and outcomes of tuberculosis treatment using fixed-dose combination (FDC) regimen
Authors: Fernanda Silva, Marli Costa, Pedro Brasil, Simone Carvalho, Valeria Rolla, Liane DeCastro
Journal: European Respiratory Journal (2012)

Background  4-drugs Fixed-dose combinations (4FDCs) for treatment of tuberculosis (TB) have been encouraged to prevent the emergence of drug resistance; increase compliance and tolerance to treatment. However, there are limited data regarding adverse drug events (ADE) with this therapeutic regimen.  Objective:  To assess the ADE and outcomes of 4FDCs for the treatment of tuberculosis.  Methods: C linical and laboratories information were collected from medical records of 70 outpatients treated with 4FDCs including a tablet doses: rifampicin 150mg/isoniazida75mg/ pirazinamida 400mg/ ethambutol 275, as recommended by World Health Organization and adopted by Brazilian guidelines at 2010.  Results:  The results showed that 17% were human immunodeficiency virus (HIV) infected.The pulmonary form was predominant (76%). ADE occurred in 86%, including 29 different types of events. The most frequent were hiperuricemia (63%) followed by nausea and epigastralgia in 22% and pruridus in 11%.The majority of patients (66%), presented more than one event. Around the 15 th  day of treatment, laboratorial abnormalities (hepatotoxicity and hiperuricemia) related with drugs were detected in blood samples in 71% of patients. The change in therapeutic regimen due to serious ADE was required in just 2 patients (due to liver toxicity and hiperuricemia). Other outcomes were bacterial resistances (2) defaults (14) and cures (52).   Conclusions:  The ADE was frequent with The 4FDCs regimen TB treatment, but changes in therapeutic regimens were necessary in less than 3% of patients. These findings support, at least, the need of clinical surveillance as it may avoid unnecessary changes in therapeutic regimens.
Portal myofibroblasts promote vascular remodeling underlying cirrhosis formation through the release of microparticles
Authors: Sara Lemoinne, Axelle Cadoret, Pierre‐Emmanuel Rautou, Haquima El Mourabit, Vlad Ratziu, Christophe Corpechot, Colette Rey, Nelly Bosselut, Véronique Barbu, Dominique Wendum, Gérard Feldmann, Chantal Boulanger, Corneliu Henegar, Chantal Housset, Dominique Thabut
Journal: Hepatology (2014)

Liver fibrosis expanding from portal tracts and vascular remodeling are determinant factors in the progression of liver diseases to cirrhosis. In the present study, we examined the potential contribution of portal myofibroblasts (PMFs) to the vascular changes leading to cirrhosis. The analyses of liver cells based on the transcriptome of rat PMFs, compared to hepatic stellate cell HSC-derived myofibroblasts in culture, identified collagen, type XV, alpha 1 (COL15A1) as a marker of PMFs. Normal liver contained rare COL15A1-immunoreactive cells adjacent to the bile ducts and canals of Hering in the portal area. A marked increase in COL15A1 expression occurred together with that of the endothelial marker, von Willebrand factor, in human and rat liver tissue, at advanced stages of fibrosis caused by either biliary or hepatocellular injury. In cirrhotic liver, COL15A1-expressing PMFs adopted a perivascular distribution outlining vascular capillaries proximal to reactive ductules, within large fibrotic septa. The effect of PMFs on endothelial cells (ECs) was evaluated by in vitro and in vivo angiogenesis assays. PMF-conditioned medium increased the migration and tubulogenesis of liver ECs as well as human umbilical vein ECs and triggered angiogenesis within Matrigel plugs in mice. In coculture, PMFs developed intercellular junctions with ECs and enhanced the formation of vascular structures. PMFs released vascular endothelial growth factor (VEGF)A-containing microparticles, which activated VEGF receptor 2 in ECs and largely mediated their proangiogenic effect. Cholangiocytes potentiated the angiogenic properties of PMFs by increasing VEGFA expression and microparticle shedding in these cells.PMFs are key cells in hepatic vascular remodeling. They signal to ECs through VEGFA-laden microparticles and act as mural cells for newly formed vessels, driving scar progression from portal tracts into the parenchyma.
Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow
Authors: Sapna Devi, Yilin Wang, Weng Keong Chew, Ronald Lima, Noelia A-González, Citra N.Z. Mattar, Shu Zhen Chong, Andreas Schlitzer, Nadja Bakocevic, Samantha Chew, Jo L. Keeble, Chi Ching Goh, Jackson L.Y. Li, Maximilien Evrard, Benoit Malleret, Anis Larbi, Laurent Renia, Muzlifah Haniffa, Suet Mien Tan, Jerry K.Y. Chan, Karl Balabanian, Takashi Nagasawa, Françoise Bachelerie, Andrés Hidalgo, Florent Ginhoux, Paul Kubes, Lai Guan Ng
Journal: The Journal of Experimental Medicine (2013)

Blood neutrophil homeostasis is essential for successful host defense against invading pathogens. Circulating neutrophil counts are positively regulated by CXCR2 signaling and negatively regulated by the CXCR4–CXCL12 axis. In particular, G-CSF, a known CXCR2 signaler, and plerixafor, a CXCR4 antagonist, have both been shown to correct neutropenia in human patients. G-CSF directly induces neutrophil mobilization from the bone marrow (BM) into the blood, but the mechanisms underlying plerixafor-induced neutrophilia remain poorly defined. Using a combination of intravital multiphoton microscopy, genetically modified mice and novel in vivo homing assays, we demonstrate that G-CSF and plerixafor work through distinct mechanisms. In contrast to G-CSF, CXCR4 inhibition via plerixafor does not result in neutrophil mobilization from the BM. Instead, plerixafor augments the frequency of circulating neutrophils through their release from the marginated pool present in the lung, while simultaneously preventing neutrophil return to the BM. Our study demonstrates for the first time that drastic changes in blood neutrophils can originate from alternative reservoirs other than the BM, while implicating a role for CXCR4–CXCL12 interactions in regulating lung neutrophil margination. Collectively, our data provides valuable insights into the fundamental regulation of neutrophil homeostasis, which may lead to the development of improved treatment regimens for neutropenic patients.