tbuckley/cabot-search huggingface dataset:
Fast Statistical Tests for Detecting Heterotachy in Protein Evolution
Authors: H.-C. Wang, E. Susko, A. J. Roger
Journal: Molecular Biology and Evolution (2011)

The w statistic introduced by Lockhart et al. (1998. A covariotide model explains apparent phylogenetic structure of oxygenic photosynthetic lineages. Mol Biol Evol. 15:1183-1188) is a simple and easily calculated statistic intended to detect heterotachy by comparing amino acid substitution patterns between two monophyletic groups of protein sequences. It is defined as the difference between the fraction of varied sites in both groups and the fraction of varied sites in each group. The w test has been used to distinguish a covarion process from equal rates and rates variation across sites processes. Using simulation we show that the w test is effective for small data sets and for data sets that have low substitution rates in the groups but can have difficulties when these conditions are not met. Using site entropy as a measure of variability of a sequence site, we modify the w statistic to a w' statistic by assigning as varied in one group those sites that are actually varied in both groups but have a large entropy difference. We show that the w' test has more power to detect two kinds of heterotachy processes (covarion and bivariate rate shifts) in large and variable data. We also show that a test of Pearson's correlation of the site entropies between two monophyletic groups can be used to detect heterotachy and has more power than the w' test. Furthermore, we demonstrate that there are settings where the correlation test as well as w and w' tests do not detect heterotachy signals in data simulated under a branch length mixture model. In such cases, it is sometimes possible to detect heterotachy through subselection of appropriate taxa. Finally, we discuss the abilities of the three statistical tests to detect a fourth mode of heterotachy: lineage-specific changes in proportion of variable sites.
Early transcriptional programming links progression to hepatitis C virus-induced severe liver disease in transplant patients
Authors: Angela L. Rasmussen, Nicolas Tchitchek, Nathan J. Susnow, Alexei L. Krasnoselsky, Deborah L. Diamond, Matthew M. Yeh, Sean C. Proll, Marcus J. Korth, Kathie-Anne Walters, Sharon Lederer, Anne M. Larson, Robert L. Carithers, Arndt Benecke, Michael G. Katze
Journal: Hepatology (2012)

Liver failure resulting from chronic hepatitis C virus (HCV) infection is a major cause for liver transplantation worldwide. Recurrent infection of the graft is universal in HCV patients after transplant and results in a rapid progression to severe fibrosis and end-stage liver disease in one third of all patients. No single clinical variable, or combination thereof, has, so far, proven accurate in identifying patients at risk of hepatic decompensation in the transplant setting. A combination of longitudinal, dimensionality reduction and categorical analysis of the transcriptome from 111 liver biopsy specimens taken from 57 HCV-infected patients over time identified a molecular signature of gene expression of patients at risk of developing severe fibrosis. Significantly, alterations in gene expression occur before histologic evidence of liver disease progression, suggesting that events that occur during the acute phase of infection influence patient outcome. Additionally, a common precursor state for different severe clinical outcomes was identified. Conclusion : Based on this patient cohort, incidence of severe liver disease is a process initiated early during HCV infection of the donor organ. The probable cellular network at the basis of the initial transition to severe liver disease was identified and characterized. (HEPATOLOGY 2012;56:17–27)
The Past, Present, and Future of HIV Prevention: Integrating Behavioral, Biomedical, and Structural Intervention Strategies for the Next Generation of HIV Prevention
Authors: Mary Jane Rotheram-Borus, Dallas Swendeman, Gary Chovnick
Journal: Annual Review of Clinical Psychology (2009)

In the past 25 years, the field of HIV prevention research has been transformed repeatedly. Today, effective HIV prevention requires a combination of behavioral, biomedical, and structural intervention strategies. Risk of transmitting or acquiring HIV is reduced by consistent male- and female-condom use, reductions in concurrent and/or sequential sexual and needle-sharing partners, male circumcision, and treatment with antiretroviral medications. At least 144 behavioral prevention programs have been found effective in reducing HIV transmission acts; however, scale up of these programs has not occurred outside of the United States. A series of recent failures of HIV-prevention efficacy trials for biomedical innovations such as HIV vaccines, treating herpes simplex 2 and other sexually transmitted infections, and diaphragm and microbicide barriers highlights the need for behavioral strategies to accompany biomedical strategies. This challenges prevention researchers to reconceptualize how cost-effective, useful, realistic, and sustainable prevention programs will be designed, delivered, tested, and diffused. The next generation of HIV prevention science must draw from the successes of existing evidence-based interventions and the expertise of the market sector to integrate preventive innovations and behaviors into everyday routines.
NOVEL TELECOMMUNICATIONS SOFTWARE FOR TWO-WAY INTERACTION DURING STEMI MANAGEMENT IMPROVES DOOR-TO-BALLOON TIMES
Authors: Gabriel Sardi, Ana Laynez Carnicero, Rebecca Torguson, Salem Badr, Israel Barbash, Danny Dvir, Zhenyi Xue, William Suddath, Kenneth Kent, Augusto Pichard, Lowell Satler, Ron Waksman
Journal: Journal of the American College of Cardiology (2012)
Response to Letter Regarding Article, “Implantable Cardioverter-Defibrillators in Tetralogy of Fallot”
Authors: Paul Khairy, Louise Harris, Amanda Barlow, Luc Beauchesne, Judith Therrien, Elaine Gordon, Isabelle Vonder Muhll, Philippe Chetaille, Michael A. Gatzoulis, Michael J. Landzberg, Susan M. Fernandes, Frank Cecchin
Journal: Circulation (2008)
Adverse Effects of Newly Marketed Drugs
Authors: Robert J. Temple, Judith K. Jones, J. Richard Crout
Journal: New England Journal of Medicine (1979)

In this issue of the Journal, Van Thiel et al. describe effects of cimetidine that have not been reported previously in man. Their paper also provides an opportunity to consider the general problem of identifying previously unrecognized adverse effects of newly marketed drugs.New drugs are always marketed on the basis of comparatively limited information. In the United States, about 500 to 2000 patients usually receive a new drug during clinical trials, and at most only a few hundred of them are treated more than three to six months.A major objective of pre-market clinical research is the assessment . . .
Diaphragm mechanics in dogs with unilateral emphysema.
Authors: R D Hubmayr, G A Farkas, H Y Tao, G C Sieck, S S Margulies
Journal: Journal of Clinical Investigation (1993)

We studied dogs with unilateral papain-induced emphysema to answer two questions: (1) Do emphysema lung-apposed hemidiaphragm (DiE) and normal lung-apposed hemidiaphragm (DiN) have equal capacities for lowering lung surface pressure? and (2) Are side-to-side differences in intrathoracic pressure the result of unequal force outputs by DiE and DiN or are they caused by differences in their mechanical efficiency as pressure generators? After the airways of the emphysematous and normal lungs were intubated with a dual lumen endotracheal tube, both phrenic nerves were maximally stimulated at rates between 1 and 50 Hz and the changes in airway occlusion pressure (delta PaoE,N) and diaphragm length (sonomicrometry) were recorded. In all animals, delta PaoN exceeded delta PaoE. Differences in pressure ranged from 1.2 +/- 0.6 cm H2O during a twitch to 6.0 +/- 2.9 cm H2O during a 50-Hz tetanus. Midcostal bundles of DiE shortened less than corresponding bundles of DiN, but both reached the same active length relative to their optimal lengths, which were measured in vitro. There was no significant difference in fiber type distribution, fiber cross-sectional area, or maximal isometric tetanic tensions among midcostal regions of DiE and DiN. We conclude that unilateral hyperinflation impairs the mechanical efficiency of the apposing hemidiaphragm as a pressure generator.
Long-term Results of Aortopulmonary Anastomosis for Tetralogy of Fallot
Authors: ROGER B. COLE, ALEXANDER J. MUSTER, DAVID E. FIXLER, MILTON H. PAUL
Journal: Circulation (1971)

A review of 340 patients with tetralogy of Fallot undergoing aortopulmonary anastomosis of the Potts-Smith type (descending aorta to pulmonary artery) has been made for assessment of the complications and long-term results (1946-1969) of this procedure. There were 30 operative deaths (9%) and 52 late medical deaths (20%) The symptomatic improvement has remained impressive in the survivors even up to 20 years after shunt surgery, with 85% of the patients having a functional classification of I or II. The major late complications have been related to anastomotic channels which were made or eventually became too large, resulting in congestive heart failure (20 late medical deaths) or in pulmonary hypertension with pulmonary vascular obstructive disease. These complications are not unique to the Potts operation, and may be anticipated in patients with excessively large ascending aorta to right pulmonary artery anastomoses. Careful patient follow-up is indicated and, in the event of congestive heart failure or evidence for pulmonary hypertension, an aggressive approach with either shunt take down and intracardiac repair or shunt revision should be considered.
Regulation of colony-stimulating factor 1 during pregnancy.
Authors: A Bartocci, J W Pollard, E R Stanley
Journal: The Journal of Experimental Medicine (1986)

Pregnancy results in an elevation in serum and tissue concentrations of the mononuclear phagocytic growth factor, CSF-1 (colony-stimulating factor 1). These increases are associated with an increase in the number of monocytes in the circulation, and with increases in the number of splenic macrophage precursors. In contrast to the approximately 2-fold elevation of the CSF-1 concentrations in serum and most tissues, pregnancy results in a 1,000-fold increase in the concentration of uterine CSF-1. The roughly fivefold elevation in uterine CSF-1 concentration observed at day 5 of pregnancy could be mimicked by administration of chorionic gonadotrophin in intact but not ovariectomized mice. These dramatic changes in uterine CSF-1 concentrations may indicate a role for CSF-1 in the regulation of nonmononuclear phagocytic cell types.
Should the indications for prenatal chromosome analysis be changed?
Authors: J Philip, J Bang, M Madsen
Journal: BMJ (1977)

Amniocentesis for chromosome analysis was performed in 1086 pergnant women, 739 of whom had an increased risk of giving birth to a child with chromosome abnormalities. Such abnormalities were found in almost identical proportions among the fetuses with an increased risk (1.2%) and among those with no increased risk (1.4%). Findings in several other studies seem to confirm that there is no significant difference between the risk groups in the proportion of abnormalities found. This suggests that our current risk groups may not be the right ones, but a much larger study is needed to confirm this.
Trends in auto emissions and gasoline composition.
Authors: R F Sawyer
Journal: Environmental Health Perspectives (1993)

The invention of the spark-ignited internal combustion engine provided a market for a petroleum middle distillate, gasoline, about 100 years ago. The internal combustion engine and gasoline have co-evolved until motor vehicles now annually consume about 110 billion gallons of gasoline in the United States. Continuing air pollution problems and resulting regulatory pressures are driving the need for further automotive emissions reductions. Engine and emissions control technology provided most earlier reductions. Changing the composition of gasoline will play a major role in the next round of reductions. The engineering and regulatory definition of a reformulated gasoline is proceeding rapidly, largely as the result of an auto and oil industry cooperative data generation program. It is likely that this new, reformulated gasoline will be introduced in high-ozone regions of the United States in the mid-1990s. Alternative clean fuels, primarily methane, methanol, and liquid petroleum gas, will become more widely used during this same period, probably first in fleet operations.
Retreatment of rheumatoid arthritis patients with 1x1000 mg rituximab results in sustained clinical response in clinical responders initially treated with 2x1000 mg rituximab
Authors: M. J. H. Boumans, A. J. K. Roelse, M. Geerdink, D. M. Gerlag, P. P. Tak
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> Treatment with rituximab may reduce disease activity in patients with rheumatoid arthritis (RA). The current dosing schedule of rituximab 2×1000 mg has been shown to induce and maintain a clinical response in initial responders, and is also protective against progression of joint destruction. Recently, the treatment schedules of 2×1000 and 2×500 mg rituximab were compared side-by-side in early active RA patients.1 It was shown that only initial treatment with 2×1000 mg rituximab resulted in statistically significant protection against progression of structural damage, whereas 2×500 mg and 2×1000 mg resulted in comparable clinical efficacy. Exploratory analysis suggested that retreatment with 2×500 mg rituximab after 6 months might be protective in terms of inhibition of structural damage. Induction therapy with 2×1000 mg rituximab followed by retreatment with 2×500 mg or 1×1000 mg after 6 months could be a very cost effective approach. <h3>Objective</h3> To investigate if clinical response induced by treatment of RA patients with 2×1000 mg rituximab can be sustained following retreatment after 24 weeks with 1×1000 mg rituximab. <h3>Methods</h3> 11 patients with RA, who were previous tumour necrosis factor inadequate responders with a good or moderate response to initial treatment with 2×1000 mg rituximab according to the European League Against Rheumatism response criteria, were retreated after at least 24 weeks with 1×1000 mg rituximab when their Disease Activity Score of 28 joints (DAS28) was ≤2.6. Patients were followed-up for 48 weeks with monthly assessment of the DAS28. At baseline and at week 48, radiographs of hand and feet were taken and the change in Total Van der Heijde Modified Sharp Score (TvdHS) was determined. <h3>Results</h3> Nine out of 11 patients completed the 48 weeks of follow-up, 2 patients were lost to follow-up after 24 weeks. The mean DAS28 did not reach the baseline level at any visit, meaning that the clinical response was sustained (figure 1A,B). The mean change in TvdHS after 1 year was −0.60 (±2.9), indicating there was no progression of structural damage after retreatment with 1×1000 mg rituximab on the group level. 3 out of 11 patients did show progression of structural damage: two patients showed an increase in TvdHS of two points in 1 year and one patient an increase of three points in 6 months. <h3>Conclusion</h3> The clinical response and the inhibition of structural damage induced by 2×1000 mg rituximab can be sustained in most RA patients by retreatment with 1×1000 mg rituximab.
Psychosomatic Assessment of Hirsute Women
Authors: Giovanni A. Fava, Silvana Grandi, Gianni Savron, Giovanna Bartolucci, Giuseppe Santarsiero, Giancarlo Trombini, Camillo Orlandi
Journal: Psychotherapy and Psychosomatics (1989)

Psychiatric illness, psychological distress and illness behavior were investigated in 30 hirsute women and 30 nonhirsute healthy control subjects matched for sociodemographic variables. The majority of patients showed a good psychological adaptation to illness: they did not report significantly more anxiety, depression, and abnormal illness behavior than controls. One-sixth of the patients, however, suffered from a clinically meaningful affective disorder. Further, hirsute patients displayed significantly more hostility and irritable mood than controls (p less than 0.01).
Effects of a Single Bout of Ultraendurance Exercise on Lipid Levels and Susceptibility of Lipids to Peroxidation in Triathletes
Authors: Geoffrey S. Ginsburg
Journal: JAMA (1996)

<h3>Objective.</h3> —To determine the effects of a single bout of ultraendurance exercise, as a model for physiologic stress, on lipid and lipoprotein levels, and oxidative susceptibility of lipids in highly trained athletes. <h3>Design.</h3> —Observational trial. <h3>Population and Setting.</h3> —Thirty-nine volunteer subjects (26 men, 13 women; mean age, 38±10 years) who competed in and completed the 1994 Hawaii lronman World Championship Triathlon consisting of a consecutive 3.9-km (2.4-mi) swim, 180.2-km (112-mi) bike ride, and a 42.2-km (26.2-mi) run. Subjects answered questionnaires and had blood samples obtained 2 days prior to and within 15 minutes of completion of the triathlon. <h3>Main Outcome Measures.</h3> —Prerace vs postrace changes in lipid and lipoprotein levels, and susceptibility of lipids to peroxidation. <h3>Results.</h3> —The mean duration of exercise was 753± 128 minutes. With exercise, plasma volume—corrected levels of triglycerides decreased 39% from 1.58±0.83 to 0.97±0.68 mmol/L (139.6±73.6 to 85.8±60.5 mg/dL) (<i>P</i>&lt;.001). Levels of total cholesterol decreased 9% from 4.94±0.88 to 4.50±0.79 mmol/L (190.8±33.8 to 173.8±30.6 mg/dL) (<i>P</i>&lt;.001), low-density lipoprotein cholesterol decreased 11% from 2.59±0.77 to 2.30±0.86 mmol/L (100.1±29.9 to 88.7±33.3 mg/dL) (<i>P</i>=.02), and apolipoprotein B decreased 10% from 0.91± 0.20 to 0.82±0.18 g/L (90.7±20.0 to 82.0± 17.9 mg/dL) (<i>P</i>&lt;.001). High-density lipoprotein cholesterol and apolipoprotein A-l increased with exercise but not significantly. The susceptibility of lipids to peroxidation decreased significantly (4.51±1.91 μmol/L, preexercise, vs 2.42±2.27 μmol/L, postexercise,<i>P</i>&lt;.001), an effect that was not related to antioxidant use or levels of vitamins A, C, or E. Serum iron, a potential pro-oxidant, also decreased by 45% with exercise from 15.75±5.55 to 8.59±4.30 μmol/L (88±31 to 48±24 μg/dL) (<i>P</i>&lt;.001), an effect that was weakly correlated with changes in lipid peroxidation (<i>P</i>=.05). <h3>Conclusions.</h3> —These data suggest that a single bout of prolonged exercise can reduce lipid and lipoprotein risk factors for developing cardiovascular disease. Moreover, susceptibility of lipids to peroxidation is reduced by exercise, thereby adding to the benefits of physical activity. This effect appears to be independent of antioxidant supplement use and may be mediated by induction of endogenous antioxidants. These observations may explain in part the reduced risk of developing vascular and other diseases in individuals who are physically active.
Unilateral Tremor of the Lower Extremity
Authors: Charles J. Sutro
Journal: New England Journal of Medicine (1946)

ON orthopedic examination of 500 soldiers with recent or long-standing post-traumatic lesions of the knee, the existence of a bizarre type of intentional tremor involving the ipsilateral lower extremity was noted in 8. Most of these 500 soldiers had experienced pain in their knees in civilian life. Each of the 8 soldiers in question complained of recurrent swelling and pain of a single knee and weakness of the ipsilateral leg. Three of the 8 were not able actively to extend the affected leg to 180°, and this was first noted from three to ten years prior to entrance into the . . .
Urinary Gonadotrophins in Post-menopausal Women with Breast Cancer
Authors: F. I. R. Martin
Journal: BMJ (1964)

Age of Menopause-Frommer BRlAL 351since both factors are known to be associated with increased and earlier development.The same factors may therefore be responsible for the accompanying delay in the menopause.Tanner (1962) suggests that the pituitary gland may be involved in both the change in age of menarche and of menopause, and this is made more plausible by the fact that adolescence is not only reached earlier than previously but that boys and girls are also bigger than before.Since an earlier age of menarche accompanies an earlier and increased development at adolescence it seems possible that a later age of menopause may accompany a delayed or decreased rate of "physiological degeneration "-that is, decreased rate of ageing.The answer to this problem, however, requires further research."., 48 U.
Stringent constraints on use of patients' data are harming research
Authors: Clare Dyer
Journal: BMJ (2007)

The drug industry is "burying its head in the sand" when dealing with health in developing countries and denying poorer people access to life saving drugs, a report claims this week.A critical report by the international agency Oxfam says that the drug industry is refusing to change the way it does business in poor countries, despite promising that it would, and is undermining its own future.Oxfam's report looks at the world's top 12 drug companies, including their drug pricing policies, their record in developing drugs that are relevant to health care in poor countries, and their stance on protecting intellectual property rights.The report says that the industry shows various shortcomings, including:• Failure to implement a systematic and transparent tiered pricing policy that is based on people's ability to pay • Continuing to neglect research and development concerning diseases that affect developing countries, and • Inflexibility in protecting intellectual property, which includes challenging poor countries in court to stop them using legal safeguards to protect public health.Oxfam interviewed 12 companies in preparing the report: Abbott, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Eli Lilly, Johnson & Johnson, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, and Wyeth
Adolescent idiopathic scoliosis
Authors: F. Altaf, A. Gibson, Z. Dannawi, H. Noordeen
Journal: BMJ (2013)

#### Summary points

Scoliosis is a three dimensional deformity of the spine defined as a lateral curvature of the spine in the coronal plane of more than 10°.1 It can be categorised into three major types—congenital, syndromic, and idiopathic. Congenital scoliosis refers to spinal deformity caused by abnormally formed vertebrae. Syndromic scoliosis is associated with a disorder of the neuromuscular, skeletal, or connective tissue systems; neurofibromatosis; or other important medical condition. Idiopathic scoliosis has no known cause and can be subdivided based on the age of onset—infantile idiopathic scoliosis includes patients aged 0-3 years, juvenile idiopathic scoliosis includes patients aged 4-10 years, and adolescent idiopathic scoliosis affects people aged >10 years.

Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity seen by primary care physicians, paediatricians, and spinal surgeons.2 This review is focused on AIS and reviews the diagnosis, management, and controversies surrounding this condition based on the available literature.

#### Sources and selection criteria

We searched Medline and the Cochrane Library using MeSH terms “adolescent idiopathic scoliosis”, and “scoliosis bracing”. We included systematic reviews, randomised controlled trials, and good quality prospective observational studies mainly from the past 15 years but did not …