tbuckley/cabot-search huggingface dataset:
Testing for Covarion-like Evolution in Protein Sequences
Authors: Huai-Chun Wang, Matthew Spencer, Edward Susko, Andrew J. Roger
Journal: Molecular Biology and Evolution (2006)

The covarion hypothesis of molecular evolution proposes that selective pressures on an amino acid or nucleotide site change through time, thus causing changes of evolutionary rate along the edges of a phylogenetic tree. Several kinds of Markov models for the covarion process have been proposed. One model, proposed by Huelsenbeck (2002), has 2 substitution rate classes: the substitution process at a site can switch between a single variable rate, drawn from a discrete gamma distribution, and a zero invariable rate. A second model, suggested by Galtier (2001), assumes rate switches among an arbitrary number of rate classes but switching to and from the invariable rate class is not allowed. The latter model allows for some sites that do not participate in the rate-switching process. Here we propose a general covarion model that combines features of both models, allowing evolutionary rates not only to switch between variable and invariable classes but also to switch among different rates when they are in a variable state. We have implemented all 3 covarion models in a maximum likelihood framework for amino acid sequences and tested them on 23 protein data sets. We found significant likelihood increases for all data sets for the 3 models, compared with a model that does not allow site-specific rate switches along the tree. Furthermore, we found that the general model fit the data better than the simpler covarion models in the majority of the cases, highlighting the complexity in modeling the covarion process. The general covarion model can be used for comparing tree topologies, molecular dating studies, and the investigation of protein adaptation.
Radioactive Stents Delay but Do Not Prevent In-Stent Neointimal Hyperplasia
Authors: I. Patrick Kay, Alexander J. Wardeh, Ken Kozuma, David P. Foley, A. H. Marco Knook, Attila Thury, George Sianos, Willem J. van der Giessen, Peter C. Levendag, Patrick W. Serruys
Journal: Circulation (2001)

Background —Restenosis after conventional stenting is almost exclusively caused by neointimal hyperplasia. β-Particle–emitting radioactive stents decrease in-stent neointimal hyperplasia at 6-month follow-up. The purpose of this study was to evaluate the 1-year outcome of 32 P radioactive stents with an initial activity of 6 to 12 μCi using serial quantitative coronary angiography and volumetric ECG-gated 3D intravascular ultrasound (IVUS). Methods and Results —Of 40 patients undergoing initial stent implantation, 26 were event-free after the 6-month follow-up period and 22 underwent repeat catheterization and IVUS at 1 year; they comprised half of the study population. Significant luminal deterioration was observed within the stents between 6 months and 1 year, as evidenced by a decrease in the angiographic minimum lumen diameter (−0.43±0.56 mm; P =0.028) and in the mean lumen diameter in the stent (−0.55±0.63 mm; P =0.001); a significant increase in in-stent neointimal hyperplasia by IVUS (18.16±12.59 mm 3 at 6 months to 27.75±11.99 mm 3 at 1 year; P =0.001) was also observed. Target vessel revascularization was performed in 5 patients (23%). No patient experienced late occlusion, myocardial infarction, or death. By 1 year, 21 of the initial 40 patients (65%) remained event-free. Conclusions —Neointimal proliferation is delayed rather than prevented by radioactive stent implantation. Clinical outcome 1 year after the implantation of stents with an initial activity of 6 to 12 μCi is not favorable when compared with conventional stenting.
Systematic Review and Meta-Analysis of Multiple-Session Early Interventions Following Traumatic Events
Authors: Neil P. Roberts, Neil J. Kitchiner, Justin Kenardy, Jonathan I. Bisson
Journal: American Journal of Psychiatry (2009)

The authors sought to determine the efficacy of multiple-session psychological interventions to prevent and treat traumatic stress symptoms beginning within 3 months of a traumatic event.Nine computerized databases were searched, and manual searches were conducted of reference lists of selected articles as well as two journals. In addition, key researchers in the field were contacted to determine whether they were aware of other relevant studies. The reviewers identified randomized controlled trials of multiple-session psychological treatments aimed at preventing or reducing traumatic stress symptoms in individuals within 3 months of exposure to a traumatic event. Details of the studies were independently extracted by two reviewers, and outcome data were entered into the Review Manager software package. Quality assessment was also conducted by two researchers independently.Twenty-five studies examining a range of interventions were identified. For treatment of individuals exposed to a trauma irrespective of their symptoms, there was no significant difference between any intervention and usual care. For treatment of traumatic stress symptoms irrespective of diagnosis, trauma-focused cognitive-behavioral therapy (CBT) was more effective than waiting list or supportive counseling conditions. The difference was greatest for treatment of acute stress disorder and acute posttraumatic stress disorder.Trauma-focused CBT within 3 months of a traumatic event appears to be effective for individuals with traumatic stress symptoms, especially those who meet the threshold for a clinical diagnosis.
A Biologic Definition of Burkitt's Lymphoma from Transcriptional and Genomic Profiling
Authors: Michael Hummel, Stefan Bentink, Hilmar Berger, Wolfram Klapper, Swen Wessendorf, Thomas F.E. Barth, Heinz-Wolfram Bernd, Sergio B. Cogliatti, Judith Dierlamm, Alfred C. Feller, Martin-Leo Hansmann, Eugenia Haralambieva, Lana Harder, Dirk Hasenclever, Michael Kühn, Dido Lenze, Peter Lichter, Jose Ignacio Martin-Subero, Peter Möller, Hans-Konrad Müller-Hermelink, German Ott, Reza M. Parwaresch, Christiane Pott, Andreas Rosenwald, Maciej Rosolowski, Carsten Schwaenen, Benjamin Stürzenhofecker, Monika Szczepanowski, Heiko Trautmann, Hans-Heinrich Wacker, Rainer Spang, Markus Loeffler, Lorenz Trümper, Harald Stein, Reiner Siebert
Journal: New England Journal of Medicine (2006)

The distinction between Burkitt's lymphoma and diffuse large-B-cell lymphoma is unclear. We used transcriptional and genomic profiling to define Burkitt's lymphoma more precisely and to distinguish subgroups in other types of mature aggressive B-cell lymphomas.We performed gene-expression profiling using Affymetrix U133A GeneChips with RNA from 220 mature aggressive B-cell lymphomas, including a core group of 8 Burkitt's lymphomas that met all World Health Organization (WHO) criteria. A molecular signature for Burkitt's lymphoma was generated, and chromosomal abnormalities were detected with interphase fluorescence in situ hybridization and array-based comparative genomic hybridization.We used the molecular signature for Burkitt's lymphoma to identify 44 cases: 11 had the morphologic features of diffuse large-B-cell lymphomas, 4 were unclassifiable mature aggressive B-cell lymphomas, and 29 had a classic or atypical Burkitt's morphologic appearance. Also, five did not have a detectable IG-myc Burkitt's translocation, whereas the others contained an IG-myc fusion, mostly in simple karyotypes. Of the 176 lymphomas without the molecular signature for Burkitt's lymphoma, 155 were diffuse large-B-cell lymphomas. Of these 155 cases, 21 percent had a chromosomal breakpoint at the myc locus associated with complex chromosomal changes and an unfavorable clinical course.Our molecular definition of Burkitt's lymphoma clarifies and extends the spectrum of the WHO criteria for Burkitt's lymphoma. In mature aggressive B-cell lymphomas without a gene signature for Burkitt's lymphoma, chromosomal breakpoints at the myc locus were associated with an adverse clinical outcome.
Effects of Varying Carbohydrate Content of Diet in Patients With Non—Insulin-Dependent Diabetes Mellitus
Authors: Abhimanyu Garg
Journal: JAMA (1994)

<h3>Objective.</h3> —To study effects of variation in carbohydrate content of diet on glycemia and plasma lipoproteins in patients with non—insulin-dependent diabetes mellitus (NIDDM). <h3>Design.</h3> —A four-center randomized crossover trial. <h3>Setting.</h3> —Outpatient and inpatient evaluation in metabolic units. <h3>Patients.</h3> —Forty-two NIDDM patients receiving glipizide therapy. <h3>Interventions.</h3> —A high-carbohydrate diet containing 55% of the total energy as carbohydrates and 30% as fats was compared with a high—monounsaturated-fat diet containing 40% carbohydrates and 45% fats. The amounts of saturated fats, polyunsaturated fats, cholesterol, sucrose, and protein were similar. The study diets, prepared in metabolic kitchens, were provided as the sole nutrients to subjects for 6 weeks each. To assess longer-term effects, a subgroup of 21 patients continued the diet they received second for an additional 8 weeks. <h3>Main Outcome Measures.</h3> —Fasting plasma glucose, insulin, lipoproteins, and glycosylated hemoglobin concentrations. Twenty-four-hour profiles of glucose, insulin, and triglyceride levels. <h3>Results.</h3> —The site of study as well as the diet order did not affect the results. Compared with the high—monounsaturated-fat diet, the high-carbohydrate diet increased fasting plasma triglyceride levels and very low-density lipoprotein cholesterol levels by 24% (<i>P</i>&lt;.0001) and 23% (<i>P</i>=.0001), respectively, and increased daylong plasma triglyceride, glucose, and insulin values by 10% (<i>P</i>=.03), 12% (<i>P</i>&lt;.0001), and 9% (<i>P</i>=.02), respectively. Plasma total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels remained unchanged. The effects of both diets on plasma glucose, insulin, and triglyceride levels persisted for 14 weeks. <h3>Conclusions.</h3> —In NIDDM patients, high-carbohydrate diets compared with high—monounsaturated-fat diets caused persistent deterioration of glycemic control and accentuation of hyperinsulinemia, as well as increased plasma triglyceride and very-low-density lipoprotein cholesterol levels, which may not be desirable. (<i>JAMA</i>. 1994;271:1421-1428)
Treatment of patients with acute nonlymphocytic leukemia in relapse: A leukemia intergroup study
Authors: J. Goldberg, H. Grunwald, W. R. Vogler, E. Winton, G. Browman, I. Walker, A. Benger, K. B. Miller, K. Rai, A. J. Gottlieb, J. K. Brennan, J. M. Bennett, P. Chervenick, R. Joyce, N. Azarnia, R. L. Priore, H. D. Preisler
Journal: American Journal of Hematology (1985)

Abstract Forty patients with acute nonlymphocytic leukemia (ANLL) in first relapse were treated at eight member institutions of the Leukemia Intergroup with a 10‐day continuous intravenous infusion of cytosine arabinoside and an anthracycline antibiotic administered on days 1, 2, and 3. Twenty of the 40 patients achieved a complete response. Seven of the patients who did not enter remission were drug‐resistant failures, while 13 patients failed to enter remission for reasons other than persistent leukemia. Pretreatment parameters such as age, presence of infection, platelet count, and liver function tests were important predictors of survival. The percent bone marrow cellularity, the percent circulating abnormal (leukemic) cells, and the height of the white blood cell count prior to treatment were helpful in distinguishing patients who would enter remission from those who would not enter remission because of persistent leukemia.
Clinical ethics committees
Authors: Anne-Marie Slowther, Tony Hope
Journal: BMJ (2000)

Research ethics committees, both local and for multicentre research, are now well established in the United Kingdom. Clinical ethics committees, which deal with issues that arise in clinical practice, are a more recent phenomenon. Earlier this year people from 14 clinical ethics committees within the United Kingdom met to compare their experiences—at a time when the pressure for such committees, or other mechanisms for dealing with the ethics of everyday practice, is growing.

The first clinical ethics committees in the United Kingdom developed for a variety of local reasons. Some were an institutional response to one or two problem cases. Others developed because a few clinicians were particularly concerned with, and interested in, the ethical aspects of clinical practice. Now that medical ethics is part of the core of medical education,1 and with the high profile of medical ethics in the media, clinicians are increasingly aware of the ethical …
Bedside measurement of systolic and diastolic time intervals using the stethometer
Authors: D. ABELSON, E. A. KAMENS
Journal: Cardiovascular Research (1977)

Using a modified electronic stethoscope, a simple visual method has been developed for bedside estimation of systolic and diastolic intervals. This has been applied to the measurement of S1-S2, LVET, and 2-OS as well as the intervals produced by prosthetic valve sounds.
Socioeconomic deprivation and asthma prevalence and severity in young adolescents
Authors: M.A. Poyser, H. Nelson, R.I. Ehrlich, E.D. Bateman, S. Parnell, A. Puterman, E. Weinberg
Journal: European Respiratory Journal (2002)

This study used the international study of asthma and allergies in childhood (ISAAC) to investigate the association between asthma and socioeconomic deprivation among young adolescents in Cape Town, South Africa. The completed ISAAC written and video questionnaires of 4,706 13–14-yr-old school pupils were used. The prevalence of asthma symptoms was analysed by a local index of socioeconomic deprivation, based on residential location and defined on a 10-category scale from least to most deprived. Linear trends were examined visually and the prevalence odds ratio was used to summarize overall trends. In general, the least socioeconomically deprived pupils reported higher prevalences of asthma symptoms “ever” and “in the last 12 months”. In contrast, the most socioeconomically deprived pupils reported higher asthma-symptom occurrence monthly or more frequently in the previous 12 months. A subgroup of pupils from low-income areas commuting to better-off schools showed the highest symptom prevalences. The findings are consistent with a model in which an increase in the incidence of asthma is driven by factors associated with improved social circumstances, whereas severity is determined by factors associated with poverty. The impact of social mobility on asthma, including reporting of symptoms, deserves closer study.
Successful treatment of malignant pheochromocytoma with combination chemotherapy containing anthracycline
Authors: M. Nakane, S. Takahashi, I. Sekine, I. Fukui, M. Koizumi, K. Kage, Y. Ito, K. Aiba, N. Horikoshi, K. Hatake, Y. Ishikawa, E. Ogata
Journal: Annals of Oncology (2003)
Good Care of the Dying Patient
Authors: Ronald M. Davis, Myron Genel, John P. Howe, Mitchell S. Karlan, William R. Kennedy, Patricia A. Numann, Joseph A. Riggs, W. Douglas Skelton, Priscilla J. Slanetz, Monique A. Spillman, Michael A. Williams, Donald C. Young, James R. Allen, Robert C. Rinaldi, Joanne G. Schwartzberg, Joanne Lynn, Joan Teno
Journal: JAMA (1996)

SUFFERING patients are now requesting physician assistance to end their lives. Physicians who serve the sick are now called on to discern whether that service should include helping to speed the death of the sufferer. The discourse has centered on cases, arguing whether there is or should be a right to stop particular examples of severe suffering, and often relying on reflections about American culture and history. The debate must include review of how the health care system actually serves persons who are dying. What is known about these matters is the subject of this review, which is the third in a series of reports on physician-assisted suicide requested by the American Medical Association (AMA) Board of Trustees in response to Resolution 3 at the 1993 House of Delegates Annual Meeting. The first two reports were presented at the 1993 Interim Meeting: Council on Ethical and Judicial Affairs Report 8,
Aspirin protects human coronary artery endothelial cells against atherogenic electronegative LDL via an epigenetic mechanism: a novel cytoprotective role of aspirin in acute myocardial infarction
Authors: Po-Yuan Chang, Yi-Jie Chen, Fu-Hsiung Chang, Jonathan Lu, Wen-Huei Huang, Tzu-Ching Yang, Yuan-Teh Lee, Shwu-Fen Chang, Shao-Chun Lu, Chu-Huang Chen
Journal: Cardiovascular Research (2013)

L5 is the most negatively charged subfraction of human low-density lipoprotein (LDL) and is the only subfraction of LDL capable of inducing apoptosis in cultured vascular endothelial cells (ECs) by inhibiting fibroblast growth factor-2 (FGF2) transcription. We examined whether plasma L5 levels are elevated in patients with ST-segment elevation myocardial infarction (STEMI) and whether aspirin provides epigenetic protection of human coronary artery ECs (HCAECs) exposed to L5.Plasma L5 levels were compared between patients with STEMI (n = 10) and control subjects with chest pain syndrome but a normal coronary arteriogram (n = 5). L5 was isolated from the plasma of STEMI patients and control subjects, and apoptosis, FGF2 expression, and FGF2 promoter methylation were examined in HCAECs treated with L5 and aspirin. Plasma L5 levels were significantly higher in STEMI patients than in control subjects (P < 0.001). Treatment of HCAECs with L5 resulted in reduced survival and FGF2 expression and increased CpG methylation of the FGF2 promoter. Co-treatment of HCAECs with L5 and a physiologically relevant, low concentration of aspirin (0.2 mM) attenuated the adverse effects of L5 on HCAEC survival, FGF2 expression, and FGF2 promoter methylation. In contrast, high concentrations of aspirin (≥1.0 mM) accentuated the effects of L5.Our results show that L5 levels are significantly increased in STEMI patients. Furthermore, L5 impairs HCAEC function through CpG methylation of the FGF2 promoter, which is suppressed in the presence of low-concentration aspirin. Our results provide evidence of a novel mechanism of aspirin in the prevention of MI.
His Electrogram Alternans Reveal Dual-Wavefront Inputs Into and Longitudinal Dissociation Within the Bundle of His
Authors: Youhua Zhang, Saroja Bharati, Kent A. Mowrey, Shaowei Zhuang, Patrick J. Tchou, Todor N. Mazgalev
Journal: Circulation (2001)

Background His electrogram (HE) amplitude and morphology changes were observed in our previous studies during transition from “fast” to “slow” atrioventricular nodal (AVN) conduction. This phenomenon and its significance for the dual-AVN electrophysiology are not well recognized and have not been studied. Methods and Results Experiments were performed on 17 healthy rabbit atrial-AVN preparations during standard programmed electrical pacing. HEs were mapped along the His bundle with roving surface electrodes, along with recording of cellular action potentials (APs). HEs recorded from the superior margin of the His bundle were of greater amplitude during basic beats and decreased substantially, by 42±19% ( P &lt;0.01), when premature A 1 A 2 shortened to 178±20 ms. In contrast, the HEs from the inferior margin increased dramatically, 2.9±1.7 times ( P &lt;0.01), during short A 1 A 2 and remained high until AVN block occurred. In addition, during long A 1 A 2 , the superior HEs consistently preceded the inferior by 1.9±0.7 ms. In contrast, at short A 1 A 2 , the superior HEs occurred 2.7±0.8 ms after the inferior. Cellular AP recordings demonstrated clearly the presence of and the transition between early (fast) and late (slow) excitation wavefronts that accompanied HE alternans. Conclusions The morphological-electrophysiological evidence from the AV junction suggests that fast and slow wavefronts reach the His bundle differently, producing functional longitudinal dissociation into 2 domains. The characteristic HE alternans recorded from these domains are a new sensitive tool to determine the presence of distinctly different wavefronts and their participation in the conduction during reentrant or other arrhythmias. These findings provide further understanding of the mechanisms of dual-AVN electrophysiology.
Substance P accelerates hypercellularity and angiogenesis in tendon tissue and enhances paratendinitis in response to Achilles tendon overuse in a tendinopathy model
Authors: Gustav Andersson, Ludvig J Backman, Alexander Scott, Ronny Lorentzon, Sture Forsgren, Patrik Danielson
Journal: British Journal of Sports Medicine (2011)

Tenocytes produce substance P (SP), and its receptor (neurokinin-1 receptor (NK-1R)) is expressed throughout the tendon tissue, especially in patients with tendinopathy and tissue changes (tendinosis) including hypercellularity and vascular proliferation. Considering the known effects of SP, one might ask whether SP contributes to these changes.To test whether development of tendinosis-like changes (hypercellularity and angiogenesis) is accelerated during a 1-week course of exercise with local administration of SP in an established Achilles tendinopathy model.Rabbits were subjected to a protocol of Achilles tendon overuse for 1 week, in conjunction with SP injections in the paratenon. Exercised control animals received NaCl injections or no injections, and unexercised, uninjected controls were also used. Tenocyte number and vascular density, as well as paratendinous inflammation, were evaluated. Immunohistochemistry and in situ hybridisation to detect NK-1R were conducted. Results There was a significant increase in tenocyte number in the SP-injected and NaCl-injected groups compared with both unexercised and exercised, uninjected controls. Tendon blood vessels increased in number in the SP-injected group compared with unexercised controls, a finding not seen in NaCl-injected controls or in uninjected, exercised animals. Paratendinous inflammation was more pronounced in the SP-injected group than in the NaCl controls. NK-1R was detected in blood vessel walls, nerves, inflammatory cells and tenocytes.SP accelerated the development of tendinosis-like changes in the rabbit Achilles tendon, which supports theories of a potential role of SP in tendinosis development; a fact of clinical interest since SP effects can be effectively blocked. The angiogenic response to SP injections seems related to paratendinitis.
L-Arginine Supplementation Improves Function and Reduces Inflammation in Renal Allografts
Authors: INGRID H. C. VOS, TON J. RABELINK, BERT DORLAND, REMKO LOOS, BEN VAN MIDDELAAR, HERMANN-JOSEF GRO[Combining Diaeresis]NE, JAAP A. JOLES
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Recovery from ischemia/reperfusion and immune-mediated injury in the renal transplant is associated with reduced renal hemodynamics and increased leukocyte infiltration. In diverse models of renal failure, L-arginine supplementation improved hemodynamics and reduced inflammation. However in a proinflammatory environment, L-arginine can worsen renal injury. This study investigated the therapeutic potential of L-arginine supplementation in allogeneic renal transplantation: Brown Norway rat kidneys were transplanted into Lewis rat recipients, with one native kidney remaining. Recipients received low-dose cyclosporin A (2.5 mg/kg per d subcutaneously) to obtain moderate vascular and interstitial rejection, with or without 1% L-arginine in drinking water for 7 d posttransplantation. Transplantation increased renal vasoconstriction (from 16.9 ± 1.33 to 35.1 ± 8.6 units; P &lt; 0.01), thereby reducing GFR (from 0.96 ± 0.09 to 0.48 ± 0.10 ml/min; P &lt; 0.05). Treatment with L-arginine restored renal graft function to levels found in normal donors (renal vascular resistance, 15.7 ± 1.69 units; GFR, 0.80 ± 0.06 ml/min). L-arginine significantly reduced vascular occlusion because of less inflammation, endothelial disruption, and thrombosis. L-arginine also decreased tubulitis, interstitial injury, and macrophage infiltration. These protective effects suggest that L-arginine might be useful as additive therapy to conventional immune suppression.