tbuckley/cabot-search huggingface dataset:
Networks of Coevolving Sites in Structural and Functional Domains of Serpin Proteins
Authors: Michael J. Buck, William R. Atchley
Journal: Molecular Biology and Evolution (2005)

Amino acids do not occur randomly in proteins; rather, their occurrence at any given site is strongly influenced by the amino acid composition at other sites, the structural and functional aspects of the region of the protein in which they occur, and the evolutionary history of the protein. The goal of our research study is to identify networks of coevolving sites within the serpin proteins (serine protease inhibitors) and classify them as being caused by structural-functional constraints or by evolutionary history. To address this, a matrix of pairwise normalized mutual information (NMI) values was computed among amino acid sites for the serpin proteins. The NMI matrix was partitioned into orthogonal patterns of amino acid variability by factor analysis. Each common factor pattern was interpreted as having phylogenetic and/or structural-functional explanations. In addition, we used a bootstrap factor analysis technique to limit the effects of phylogenetic history on our factor patterns. Our results show an extensive network of correlations among amino acid sites in key functional regions (reactive center loop, shutter, and breach). Additionally, we have discovered long-range coevolution for packed amino acids within the serpin protein core. Lastly, we have discovered a group of serpin sites which coevolve in the hydrophobic core region (s5B and s4B) and appear to represent sites important for formation of the “native” instead of the “latent” serpin structure. This research provides a better understanding on how protein structure evolves; in particular, it elucidates the selective forces creating coevolution among protein sites.
Alterations in Cardiac Function Immediately Following Electrical Conversion of Atrial Fibrillation to Normal Sinus Rhythm
Authors: WILLIAM SHAPIRO, GARNER KLEIN
Journal: Circulation (1968)

An assessment was made of cardiac function by means of right heart catheterization before and immediately after conversion of atrial fibrillation to sinus rhythm in 11 studies on 10 human subjects. Comparable data during exercise were available in five studies. Medical management of patients in this study was identical to that employed routinely for this procedure. After conversion to normal sinus rhythm cardiac output response was significantly increased only during exercise. The relationship of mean right atrial and mean pulmonary wedge pressures to right and left ventricular stroke work was uniformly improved both because of decreases in these pressures and increases in work. Indirect evidence of mitral valvular regurgitation was diminished to absent after conversion. "A" waves and the pulse pressure of atrial contraction were very small in the right atrial tracings after conversion and these contours were usually inapparent on pulmonary wedge tracings. It is concluded that over-all cardiac performance was improved with re-establishment of sinus rhythm and that diminutions in atrial-venous pressure behind each ventricle may be important in explaining symptomatic improvement following electroconversion. Measures of both pressure and flow were required for complete description of the alterations induced by this intervention.
Heat, Heat Waves, and Hospital Admissions among the Elderly in the United States, 1992–2006
Authors: Carina J. Gronlund, Antonella Zanobetti, Joel D. Schwartz, Gregory A. Wellenius, Marie S. O’Neill
Journal: Environmental Health Perspectives (2014)

Heat-wave frequency, intensity, and duration are increasing with global climate change. The association between heat and mortality in the elderly is well documented, but less is known regarding associations with hospital admissions.Our goal was to determine associations between moderate and extreme heat, heat waves, and hospital admissions for nonaccidental causes among Medicare beneficiaries ≥ 65 years of age in 114 cities across five U.S. climate zones.We used Medicare inpatient billing records and city-specific data on temperature, humidity, and ozone from 1992 through 2006 in a time-stratified case-crossover design to estimate the association between hospitalization and moderate [90th percentile of apparent temperature (AT)] and extreme (99th percentile of AT) heat and heat waves (AT above the 95th percentile over 2-8 days). In sensitivity analyses, we additionally considered confounding by ozone and holidays, different temperature metrics, and alternate models of the exposure-response relationship.Associations between moderate heat and hospital admissions were minimal, but extreme heat was associated with a 3% (95% CI: 2%, 4%) increase in all-cause hospital admissions over the subsequent 8 days. In cause-specific analyses, extreme heat was associated with increased hospitalizations for renal (15%; 95% CI: 9%, 21%) and respiratory (4%; 95% CI: 2%, 7%) diseases, but not for cardiovascular diseases. An added heat-wave effect was observed for renal and respiratory admissions.Extreme heat is associated with increased hospital admissions, particularly for renal causes, among the elderly in the United States.
The Football Association Medical Research Programme: an audit of injuries in professional football—analysis of hamstring injuries
Authors: C Woods, R D Hawkins, S Maltby, M Hulse, A Thomas, A Hodson
Journal: British Journal of Sports Medicine (2004)

To conduct a detailed analysis of hamstring injuries sustained in English professional football over two competitive seasons.Club medical staff at 91 professional football clubs annotated player injuries over two seasons. A specific injury audit questionnaire was used together with a weekly form that documented each clubs' current injury status.Completed injury records for the two competitive seasons were obtained from 87% and 76% of the participating clubs respectively. Hamstring strains accounted for 12% of the total injuries over the two seasons with nearly half (53%) involving the biceps femoris. An average of five hamstring strains per club per season was observed. A total of 13 116 days and 2029 matches were missed because of hamstring strains, giving an average of 90 days and 15 matches missed per club per season. In 57% of cases, the injury occurred during running. Hamstring strains were most often observed during matches (62%) with an increase at the end of each half (p<0.01). Groups of players sustaining higher than expected rates of hamstring injury were Premiership (p<0.01) and outfield players (p<0.01), players of black ethnic origin (p<0.05), and players in the older age groups (p<0.01). Only 5% of hamstring strains underwent some form of diagnostic investigation. The reinjury rate for hamstring injury was 12%.Hamstring strains are common in football. In trying to reduce the number of initial and recurrent hamstring strains in football, prevention of initial injury is paramount. If injury does occur, the importance of differential diagnosis followed by the management of all causes of posterior thigh pain is emphasised. Clinical reasoning with treatment based on best available evidence is recommended.
The Oregon Experiment — Effects of Medicaid on Clinical Outcomes
Authors: Katherine Baicker, Sarah L. Taubman, Heidi L. Allen, Mira Bernstein, Jonathan H. Gruber, Joseph P. Newhouse, Eric C. Schneider, Bill J. Wright, Alan M. Zaslavsky, Amy N. Finkelstein
Journal: New England Journal of Medicine (2013)

Despite the imminent expansion of Medicaid coverage for low-income adults, the effects of expanding coverage are unclear. The 2008 Medicaid expansion in Oregon based on lottery drawings from a waiting list provided an opportunity to evaluate these effects.
A Cell-penetrating Helical Polymer For siRNA Delivery to Mammalian Cells
Authors: Nathan P Gabrielson, Hua Lu, Lichen Yin, Kyung Hoon Kim, Jianjun Cheng
Journal: Molecular Therapy (2012)

Cell-penetrating peptides (CPPs) are routinely used for intracellular delivery of a variety of cargo, including drugs, genes, and short interfering RNA (siRNA). Most CPPs are active only upon exposure to acidic environments inside of late endosomes, thereby facilitating the endosomal escape of internalized vectors. Here, we describe the generation of a synthetic polypeptide—PVBLGn-8—that is able to adopt a helical structure independent of pH. Like other CPPs, the helical structure of PVBLGn-8 allows the polypeptide to destabilize membranes. However, since the helix is stable at all physiologically relevant pH values between pH 2 and pH 7.4, the membrane permeation properties of PVBLGn-8 are irreversible. Given its pH-insensitive activity, our results suggest that PVBLGn-8 is able to facilitate efficient siRNA delivery by causing pore formation in the cell membranes through which either free or complexed siRNA is able to diffuse. This nonspecific form of entry into the cell cytosol may prove useful when trying to deliver siRNA to cells which have proven to be difficult to transfect. Cell-penetrating peptides (CPPs) are routinely used for intracellular delivery of a variety of cargo, including drugs, genes, and short interfering RNA (siRNA). Most CPPs are active only upon exposure to acidic environments inside of late endosomes, thereby facilitating the endosomal escape of internalized vectors. Here, we describe the generation of a synthetic polypeptide—PVBLGn-8—that is able to adopt a helical structure independent of pH. Like other CPPs, the helical structure of PVBLGn-8 allows the polypeptide to destabilize membranes. However, since the helix is stable at all physiologically relevant pH values between pH 2 and pH 7.4, the membrane permeation properties of PVBLGn-8 are irreversible. Given its pH-insensitive activity, our results suggest that PVBLGn-8 is able to facilitate efficient siRNA delivery by causing pore formation in the cell membranes through which either free or complexed siRNA is able to diffuse. This nonspecific form of entry into the cell cytosol may prove useful when trying to deliver siRNA to cells which have proven to be difficult to transfect.
Novel Locus for an Inherited Cardiomyopathy Maps to Chromosome 7
Authors: Lei Song, Steven R. DePalma, Maria Kharlap, Andrey G. Zenovich, Allison Cirino, Richard Mitchell, Barbara McDonough, Barry J. Maron, Christine E. Seidman, J.G. Seidman, Carolyn Y. Ho
Journal: Circulation (2006)

Genetic mutations are the most common cause of hypertrophic cardiomyopathy (HCM) and an increasingly recognized cause of dilated cardiomyopathy. Autosomal dominant HCM is caused by mutations in sarcomere proteins; such mutations are not universally present, however, and fail to account for &40% of cases of phenotypic HCM. To add further complexity, other genetic origins can mimic the gross clinical phenotype of HCM, and mutations in sarcomere genes have been demonstrated to cause dilated cardiomyopathy.To explore novel genetic causes of inherited cardiomyopathies, genome-wide linkage analysis was used to study one kindred (4 generations, 32 individuals) with predominant clinical features of left ventricular hypertrophy in addition to cardiac dilation, end-stage heart failure, and sudden death. Of note, histopathology from 2 family members did not demonstrate myocyte disarray and fibrosis, indicating that this phenotype is not typical sarcomere mutation HCM. Direct DNA sequencing was performed on sarcomere genes known to cause HCM and dilated cardiomyopathy, and no mutations were identified. Linkage was then established to a novel locus on chromosome 7 (7p12.1-7q21). A maximum 2-point logarithm of odds score of 4.11 was obtained. Recombination events refine the disease interval between D7S506 and D7S3314, corresponding to a distance of 27.2 megabases.The discovery of a novel genetic locus in this family provides more evidence that molecular pathways leading to inherited cardiac hypertrophy extend beyond the sarcomere. Identification of the causal gene mutation and additional genotype-phenotype correlation studies will provide fundamental insight into mechanisms of cardiac remodeling.
Evaluation of heliox or oxygen breathing on improved quadriceps muscle oxygen delivery during exercise in COPD
Authors: Vasilis Andrianopoulos, Zafeiris Louvaris, Eleni Kortianou, Helmut Habazettl, Spyros Zakynthinos, Peter D. Wagner, Ioannis Vogiatzis
Journal: European Respiratory Journal (2011)

Introduction:  It is known that both normoxic heliox and pure oxygen breathing significantly increase locomotor O 2  delivery during exercise in COPD. However, it remains unknown which of the two gases is the most beneficial in terms of enhancing exercise tolerance and locomotor muscle O 2  availability.   Methods:  12 COPD patients [FEV 1 =42±12%pred] performed 3 constant-load exercise tests at 75% of maximum work rate while breathing air, normoxic heliox or pure O 2 . We measured cardiac output (Fick method), haemodynamic responses, quadriceps muscle blood flow by near infrared spectroscopy with ICG dye and changes in quadriceps muscle deoxygenation ([HHb], an index of fractional O 2 extraction) at the transition from rest to exercise (on-kinetics).   Results:  Exercise endurance time was not significantly different between heliox and O 2  [ ( mean±SEM )  He: 637±46 vs  O 2  : 670±43 vs Air: 394±35 s] . Peak cardiac output was significantly greater on heliox  (He: 9.3±0.5 vs  O 2  : 8.2±0.6 vs air: 8.9 l/min)  but O 2  caused a significant greater elevation of arterial oxygen content  (He: 183±6 vs  O 2  : 213±7 vs air: 180±5 ml/min).  However, neither quadriceps muscle blood flow  (He: 32±5 vs  O 2  : 31±6 vs Air: 22±5 ml/min/100gr)  nor quadriceps O 2  delivery  (He: 5.8±0.9 vs  O 2  : 6.3±1.1 vs Air: 3.9±0.8 ml  O 2  /min/100gr)  were significantly different between heliox and O 2 . Mean response time of deoxygenated HHb on heliox  (MRT=18.1±1.7s)  and O 2  (MRT=17.4 ± 1.4s ) were not significantly different but were both greater compared to air  (MRT=13.8±1.3s) (P    Conclusion:  Supplementation of heliox or O 2  is equally beneficial in terms of enhancing exercise tolerance and locomotor muscle O 2  availability during exercise in COPD.
Enhancement of Claims Data to Improve Risk Adjustment of Hospital Mortality
Authors: Michael Pine, Harmon S. Jordan, Anne Elixhauser, Donald E. Fry, David C. Hoaglin, Barbara Jones, Roger Meimban, David Warner, Junius Gonzales
Journal: JAMA (2007)

ContextComparisons of risk-adjusted hospital performance often are important components of public reports, pay-for-performance programs, and quality improvement initiatives. Risk-adjustment equations used in these analyses must contain sufficient clinical detail to ensure accurate measurements of hospital quality.ObjectiveTo assess the effect on risk-adjusted hospital mortality rates of adding present on admission codes and numerical laboratory data to administrative claims data.Design, Setting, and PatientsComparison of risk-adjustment equations for inpatient mortality from July 2000 through June 2003 derived by sequentially adding increasingly difficult-to-obtain clinical data to an administrative database of 188 Pennsylvania hospitals. Patients were hospitalized for acute myocardial infarction, congestive heart failure, cerebrovascular accident, gastrointestinal tract hemorrhage, or pneumonia or underwent an abdominal aortic aneurysm repair, coronary artery bypass graft surgery, or craniotomy.Main Outcome MeasuresC statistics as a measure of the discriminatory power of alternative risk-adjustment models (administrative, present on admission, laboratory, and clinical for each of the 5 conditions and 3 procedures).ResultsThe mean (SD) c statistic for the administrative model was 0.79 (0.02). Adding present on admission codes and numerical laboratory data collected at the time of admission resulted in substantially improved risk-adjustment equations (mean [SD] c statistic of 0.84 [0.01] and 0.86 [0.01], respectively). Modest additional improvements were obtained by adding more complex and expensive to collect clinical data such as vital signs, blood culture results, key clinical findings, and composite scores abstracted from patients' medical records (mean [SD] c statistic of 0.88 [0.01]).ConclusionsThis study supports the value of adding present on admission codes and numerical laboratory values to administrative databases. Secondary abstraction of difficult-to-obtain key clinical findings adds little to the predictive power of risk-adjustment equations.
"DELIRIUM TREMENS" FOLLOWING WITHDRAWAL OF ETHCHLORVINOL
Authors: HOWARD P. WOOD, HARRISON F. FLIPPIN
Journal: American Journal of Psychiatry (1965)

A mental syndrome indistinguishable from delirium tremens developed after withdrawal in a case of chronic ethchlorvinol intoxication. Our findings are compared with the 3 other published cases, which appear quite similar. As Engel and Romano have noted, this type of abstinence state, with cerebral overactivity, may well have more in common with the effects of hallucinogens than with the cerebral hypofunction of the usual delirium. Convulsive seizures are a regular feature of this syndrome, and anticonvulsants should be administered routinely in addition to the standard phenothiazine drugs.
A Prospective Evaluation of Undiagnosed Joint Hypermobility Syndrome in Patients With Gastrointestinal Symptoms
Authors: Asma Fikree, Rodney Grahame, Rubina Aktar, Adam D. Farmer, Alan J. Hakim, Joan K. Morris, Charles H. Knowles, Qasim Aziz
Journal: Clinical Gastroenterology and Hepatology (2014)
Functional and electrophysiological effects of oxidant stress on isolated ventricular muscle: a role for oscillatory calcium release from sarcoplasmic reticulum in arrhythmogenesis?
Authors: M. J Shattock, H. Matsuura, D. J Hearse
Journal: Cardiovascular Research (1991)

Study objective — The aim was to investigate the cellular basis of oxidant stress induced arrhythmias by studying the influence of oxidant stress on the contractile and electrophysiological function of isolated cardiac muscle. Design — Oxidant stress was induced by the photoactivation of rose bengal added to the solution superfusing isolated ventricular muscles from a number of species. Measurements of contractile and electrophysiological function were made under control conditions, during exposure to oxidant stress, and under a number of experimental conditions. Experimental material — Isolated supervised papillary muscles or trabeculae from rat, rabbit, or frog hearts were used in all studies. Measurements and main results — The contractile response to oxidant stress was assessed by measuring isometric developed tension and resting tension throughout the experiment, and the electrophysiological response was assessed by recording action potentials using conventional 3 M KC1 filled intracellular electrodes. Oxidant stress induced a transient positive inotropy, after contractions, and eventually contracture. Associated with these contractile changes were prolongation of the action potential, early afterdepolarisations, oscillations in resting membrane potential, and automaticity. These effects were concentration and species dependent and the oscillations in both tension and membrane potential were abolished by inhibition of calcium release from the sarcoplasmic reticulum with caffeine. Conclusions — The contractile and electrophysiological effects of rose bengal induced oxidant stress are consistent with a cellular calcium overload. The observation that the oscillations in tension and membrane potential were abolished by caffeine and that these effects were species dependent (rat>rabbit>frog) suggests a role for oscillatory sarcoplasmic reticulum calcium release in these effects. The oscillations in membrane potential and the automaticity induced by rose bengal are likely to underlie the arrhythmias observed in isolated hearts exposed to oxidant stress that have previously been described.
Generation and Targeting of Human Tumor-Specific Tc1 and Th1 Cells Transduced with a Lentivirus Containing a Chimeric Immunoglobulin T-Cell Receptor
Authors: Hiroshi Gyobu, Takemasa Tsuji, Yoshinori Suzuki, Takayuki Ohkuri, Kenji Chamoto, Masahide Kuroki, Hiroyuki Miyoshi, You Kawarada, Hiroyuki Katoh, Tsuguhide Takeshima, Takashi Nishimura
Journal: Cancer Research (2004)

CD4+ Th cells, in particular IFN-gamma-producing Th1 cells, play a critical role in the activation and maintenance of Tc1 cells that are essential for tumor eradication. Here, we report the generation of artificial tumor-specific Th1 and Tc1 cells from nonspecifically activated T cells using a lentiviral transduction system. Anti-CD3-activated T cells from healthy human donors were transduced with a lentivirus containing a chimeric immunoglobulin T-cell receptor gene composed of single-chain variable fragments derived from an anticarcinoembryonic antigen (CEA)-specific monoclonal antibody fused to an intracellular signaling domain derived from the cytoplasmic portions of membrane-bound CD28 and CD3zeta. These artificial tumor-specific Tc1 and Th1 cells, termed Tc1- and Th1-T bodies, respectively, could be targeted to CEA+ tumor cells independently of MHC restriction. Specifically, Tc1-T bodies demonstrated high cytotoxicity and produced IFN-gamma in response to CEA+ tumor cell lines but not CEA- tumors. Although Th1-T bodies exhibited low cytotoxicity, they secreted high levels of IFN-gamma and interleukin-2 in response to CEA+ tumor cells. Such CEA+ tumor-specific activation was not observed in mock gene-transduced nonspecific Tc1 and Th1 cells. Moreover, Tc1- and Th1-T bodies exhibited strong antitumor activities against CEA+ human lung cancer cells implanted into RAG2(-/-) mice. Furthermore, combined therapy with Tc1- and Th1-T bodies resulted in enhanced antitumor activities in vivo. Taken together, our findings demonstrate that Tc1- and Th1-T bodies represent a promising alternative to current methods for the development of effective adoptive immunotherapies.
Understanding the Environmental Issues in Diabetes Self-Management Education Research: A Reexamination of 8 Studies in Community-Based Settings
Authors: Leonard Jack, Leandris Liburd, Tirzah Spencer, Collins O. Airhihenbuwa
Journal: Annals of Internal Medicine (2004)

Eight studies included in a recent systematic review of the efficacy of diabetes self-management education were qualitatively reexamined to determine the presence of theoretical frameworks, methods used to ensure cultural appropriateness, and the quality of the instrument. Theoretical frameworks that help to explain complex pathways that produce health outcomes were lacking; culture indices were not incorporated into diabetes self-management education; and the instruments used to measure outcomes were inadequate. We provide recommendations to improve research on diabetes self-management education in community settings through use of a contextual framework that encourages targeting multiple levels of influence—individual, family, organizational, community, and policy.
Hypoxia in Tumors: A Paradigm for the Approach to Biochemical and Physiologic Heterogeneity
Authors: C. N. Coleman
Journal: JNCI Journal of the National Cancer Institute (1988)

While the inherent radiosensitivity of tumor cells is likely to affect treatment outcome, the biochemical and physiologic state of the cell may have a major impact. Tumors are likely to be highly heterogeneous for these dynamic properties. Hypoxic cells are radioresistant, requiring two to three times the radiation dose to kill them compared to the same cells in a eu-oxic state. Hypoxia can be of two types: 1) chronic hypoxia, which is diffusion limited, and 2) acute hypoxia, which is perfusion limited. The mechanism of and approaches toward these are different and can serve as a model for other biochemical and physiologic processes that may affect treatment outcome.
Asymptomatic rectal carriage of blaKPC producing carbapenem-resistant Enterobacteriaceae: who is prone to become clinically infected?
Authors: V. Schechner, T. Kotlovsky, M. Kazma, H. Mishali, D. Schwartz, S. Navon-Venezia, M.J. Schwaber, Y. Carmeli
Journal: Clinical Microbiology and Infection (2012)