tbuckley/cabot-search huggingface dataset:
Quinolone-3-Diarylethers: A New Class of Antimalarial Drug
Authors: Aaron Nilsen, Alexis N. LaCrue, Karen L. White, Isaac P. Forquer, R. Matthew Cross, Jutta Marfurt, Michael W. Mather, Michael J. Delves, David M. Shackleford, Fabian E. Saenz, Joanne M. Morrisey, Jessica Steuten, Tina Mutka, Yuexin Li, Grennady Wirjanata, Eileen Ryan, Sandra Duffy, Jane Xu Kelly, Boni F. Sebayang, Anne-Marie Zeeman, Rintis Noviyanti, Robert E. Sinden, Clemens H. M. Kocken, Ric N. Price, Vicky M. Avery, Iñigo Angulo-Barturen, María Belén Jiménez-Díaz, Santiago Ferrer, Esperanza Herreros, Laura M. Sanz, Francisco-Javier Gamo, Ian Bathurst, Jeremy N. Burrows, Peter Siegl, R. Kiplin Guy, Rolf W. Winter, Akhil B. Vaidya, Susan A. Charman, Dennis E. Kyle, Roman Manetsch, Michael K. Riscoe
Journal: Science Translational Medicine (2013)

ELQ-300, an investigational drug for treating and preventing malaria, shows potent transmission-blocking activity in rodent models of malaria.
Multiple Biomarkers for the Prediction of First Major Cardiovascular Events and Death
Authors: Thomas J. Wang, Philimon Gona, Martin G. Larson, Geoffrey H. Tofler, Daniel Levy, Christopher Newton-Cheh, Paul F. Jacques, Nader Rifai, Jacob Selhub, Sander J. Robins, Emelia J. Benjamin, Ralph B. D'Agostino, Ramachandran S. Vasan
Journal: New England Journal of Medicine (2006)

Few investigations have evaluated the incremental usefulness of multiple biomarkers from distinct biologic pathways for predicting the risk of cardiovascular events.We measured 10 biomarkers in 3209 participants attending a routine examination cycle of the Framingham Heart Study: the levels of C-reactive protein, B-type natriuretic peptide, N-terminal pro-atrial natriuretic peptide, aldosterone, renin, fibrinogen, D-dimer, plasminogen-activator inhibitor type 1, and homocysteine; and the urinary albumin-to-creatinine ratio.During follow-up (median, 7.4 years), 207 participants died and 169 had a first major cardiovascular event. In Cox proportional-hazards models adjusting for conventional risk factors, the following biomarkers most strongly predicted the risk of death (each biomarker is followed by the adjusted hazard ratio per 1 SD increment in the log values): B-type natriuretic peptide level (1.40), C-reactive protein level (1.39), the urinary albumin-to-creatinine ratio (1.22), homocysteine level (1.20), and renin level (1.17). The biomarkers that most strongly predicted major cardiovascular events were B-type natriuretic peptide level (adjusted hazard ratio, 1.25 per 1 SD increment in the log values) and the urinary albumin-to-creatinine ratio (1.20). Persons with "multimarker" scores (based on regression coefficients of significant biomarkers) in the highest quintile as compared with those with scores in the lowest two quintiles had elevated risks of death (adjusted hazard ratio, 4.08; P<0.001) and major cardiovascular events (adjusted hazard ratio, 1.84; P=0.02). However, the addition of multimarker scores to conventional risk factors resulted in only small increases in the ability to classify risk, as measured by the C statistic.For assessing risk in individual persons, the use of the 10 contemporary biomarkers that we studied adds only moderately to standard risk factors.
Apixaban versus Enoxaparin for Thromboprophylaxis after Hip Replacement
Authors: Michael Rud Lassen, Alexander Gallus, Gary E. Raskob, Graham Pineo, Dalei Chen, Luz Margarita Ramirez
Journal: New England Journal of Medicine (2010)

There are various regimens for thromboprophylaxis after hip replacement. Low-molecular-weight heparins such as enoxaparin predominantly inhibit factor Xa but also inhibit thrombin to some degree. Orally active, specific factor Xa inhibitors such as apixaban may provide effective thromboprophylaxis with a lower risk of bleeding and improved ease of use.In this double-blind, double-dummy study, we randomly assigned 5407 patients undergoing total hip replacement to receive apixaban at a dose of 2.5 mg orally twice daily or enoxaparin at a dose of 40 mg subcutaneously every 24 hours. Apixaban therapy was initiated 12 to 24 hours after closure of the surgical wound; enoxaparin therapy was initiated 12 hours before surgery. Prophylaxis was continued for 35 days after surgery, followed by bilateral venographic studies. The primary efficacy outcome was the composite of asymptomatic or symptomatic deep-vein thrombosis, nonfatal pulmonary embolism, or death from any cause during the treatment period. Patients were followed for an additional 60 days after the last intended dose of study medication.A total of 1949 patients in the apixaban group (72.0%) and 1917 patients in the enoxaparin group (71.0%) could be evaluated for the primary efficacy analysis. The primary efficacy outcome occurred in 27 patients in the apixaban group (1.4%) and in 74 patients in the enoxaparin group (3.9%) (relative risk with apixaban, 0.36; 95% confidence interval [CI], 0.22 to 0.54; P<0.001 for both noninferiority and superiority; absolute risk reduction, 2.5 percentage points; 95% CI, 1.5 to 3.5). The composite outcome of major and clinically relevant nonmajor bleeding occurred in 129 of 2673 patients assigned to apixaban (4.8%) and 134 of 2659 assigned to enoxaparin (5.0%) (absolute difference in risk, -0.2 percentage points; 95% CI, -1.4 to 1.0).Among patients undergoing hip replacement, thromboprophylaxis with apixaban, as compared with enoxaparin, was associated with lower rates of venous thromboembolism, without increased bleeding. (Funded by Bristol-Myers Squibb and Pfizer; ClinicalTrials.gov number, NCT00423319.).
Adhesion Mechanisms in Platelet Function
Authors: Zaverio M. Ruggeri, G. Loredana Mendolicchio
Journal: Circulation Research (2007)

Platelet adhesion is an essential function in response to vascular injury and is generally viewed as the first step during which single platelets bind through specific membrane receptors to cellular and extracellular matrix constituents of the vessel wall and tissues. This response initiates thrombus formation that arrests hemorrhage and permits wound healing. Pathological conditions that cause vascular alterations and blood flow disturbances may turn this beneficial process into a disease mechanism that results in arterial occlusion, most frequently in atherosclerotic vessels of the heart and brain. Besides their relevant role in hemostasis and thrombosis, platelet adhesive properties are central to a variety of pathophysiological processes that extend from inflammation to immune-mediated host defense and pathogenic mechanisms as well as cancer metastasis. All of these activities depend on the ability of platelets to circulate in blood as sentinels of vascular integrity, adhere where alterations are detected, and signal the abnormality to other platelets and blood cells. In this respect, therefore, platelet adhesion to vascular wall structures, to one another (aggregation), or to other blood cells, represent different aspects of the same fundamental biological process. Detailed studies by many investigators over the past several years have been aimed to dissect the complexity of these functions, and the results obtained now permit an attempt to integrate all the available information into a picture that highlights the balanced diversity and synergy of distinct platelet adhesive interactions.
Characterization of Drosophila Telomeric Retroelement TAHRE: Transcription, Transpositions, and RNAi-based Regulation of Expression
Authors: S. Shpiz, D. Kwon, A. Uneva, M. Kim, M. Klenov, Y. Rozovsky, P. Georgiev, M. Savitsky, A. Kalmykova
Journal: Molecular Biology and Evolution (2007)

Telomeres in Drosophila are maintained by transpositions of specialized telomeric retroelements HeT-A and TART rather than by the telomerase activity adding short DNA repeats to chromosome ends in other eukaryotes. A novel element TAHRE was previously found in the telomeric regions of the genome of Drosophila melanogaster stock sequenced by the Genome Project. Comparative genomic analysis confirmed by Southern analysis and in situ hybridization of polytene chromosomes reveals conserved TAHRE elements in the genomes of melanogaster subgroup species. Spontaneous attachment of TAHRE retroelement to the broken end of terminally deleted chromosome allows us to consider TAHRE as the third retrotransposon family involved in telomere maintenance in Drosophila. The abundance of TAHRE transcripts in ovaries is strongly upregulated owing to mutations in the RNA interference genes spn-E, aub, piwi, and vasa locus. spn-E mutations eliminate TAHRE-specific short RNAs in the ovaries. These data suggest that TAHRE is a conservative element involved along with HeT-A and TART in telomere maintenance and a target of the RNAi-based system in the Drosophila germ line. This study reveals similar distribution of TAHRE and HeT-A transcripts, which accumulate in the oocyte, whereas TART transcripts localize in nurse cells. Taking into account a common pattern of HeT-A and TAHRE expression, one may consider TAHRE as a source of reverse transcriptase enzymatic activity for HeT-A transpositions in ovaries.
Trends in Pathogens Among Patients Hospitalized for Pneumonia From 1993 to 2011
Authors: Sean B. Smith, Gregory W. Ruhnke, Curtis H. Weiss, Grant W. Waterer, Richard G. Wunderink
Journal: JAMA Internal Medicine (2014)

The Nationwide Inpatient Sample aggregated data from approximately 20% of US hospital admissions from 1993 to 2011. Prior literature found that pneumonia admissions decreased following the introduction of the pneumococcal vaccine in 2000.1 The International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), codes provide information regarding pneumonia pathogens, but no studies, to our knowledge, have used these codes to analyze longitudinal trends in the pathogens documented during hospitalizations for pneumonia.
[3H]-8-cyclopentyl-1,3-dipropylxanthine binding to A1 adenosine receptors of intact rat ventricular myocytes.
Authors: D Martens, M J Lohse, U Schwabe
Journal: Circulation Research (1988)

The purpose of the present study was the identification of A1 adenosine receptors in intact rat ventricular myocytes, which are thought to mediate the negative inotropic effects of adenosine. The adenosine receptor antagonist [3H]-8-cyclopentyl-1,3-dipropylxanthine was used as radioligand. Binding of the radioligand to intact myocytes was rapid, reversible, and saturable with a binding capacity of 40,000 binding sites per cell. The dissociation constant of the radioligand was 0.48 nM. The adenosine receptor antagonists 8-cyclopentyl-1,3-dipropylxanthine, "xanthine amine congener," and theophylline were competitive inhibitors with affinities in agreement with results obtained for A1 receptors in other tissues. Competition experiments using the adenosine receptor agonists R-N(6)-phenylisopropyladenosine, 5'-N-ethylcarboxamidoadenosine, and S-N(6)-phenylisopropyladenosine gave monophasic displacement curves with Ki values of 50 nM, 440 nM, and 4,300 nM, which agreed well with the GTP-inducible low affinity state in cardiac membranes. The low affinity for agonists was not due to agonist-induced desensitization, and correlated well with the corresponding IC50 values for the inhibition of cyclic AMP accumulation by isoprenaline. It is suggested that only a low affinity state of A1 receptors can be detected in intact rat myocytes due to the presence of high concentrations of guanine nucleotides in intact cells.
Enhanced Plating Efficiency of Herpesvirus DNA on Herpes Simplex Virus Type 1 DNA-Transformed Cells&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: F Colbère-Garapin, F Horodniceanu
Journal: JNCI Journal of the National Cancer Institute (1979)

Partial resistance of hamster cells transformed by sheared herpes simplex virus (HSV) DNA to superinfection by intact HSV could be overcome by transfection with viral DNA's. HSV DNA plated more efficiently on HSV type 1 DNA-transformed hamster cells than on spontaneously transformed hamster or rabbit cells or on hamster cells transformed by other DNA viruses.
Chest wall kinematics and respiratory muscle action in ankylosing spondylitis patients
Authors: I. Romagnoli
Journal: European Respiratory Journal (2004)

No direct measurements of the pressures produced by the ribcage muscles, the diaphragm and the abdominal muscles during hyperventilation have been reported in patients with ankylosing spondylitis. Based on recent evidence indicating that abdominal muscles are important contributors to stimulation of ventilation, it was hypothesised that, in ankylosing spondylitis patients with limited ribcage expansion, a respiratory centre strategy to help the diaphragm function may involve coordinated action of this muscle with abdominal muscles. In order to validate this hypothesis, the chest wall response to a hypercapnic/hyperoxic rebreathing test was assessed in six ankylosing spondylitis patients and seven controls by combined analysis of: 1) chest wall kinematics, using optoelectronic plethysmography, this system is accurate in partitioning chest wall expansion into the contributions of the ribcage and the abdomen; and 2) respiratory muscle pressures, oesophageal, gastric and transdiaphragmatic (Pdi); the pressure/volume relaxation characteristics of both the ribcage and the abdomen allowed assessment of the peak pressure of both inspiratory and expiratory ribcage muscles, and of the abdominal muscles. During rebreathing, chest wall expansion increased to a similar extent in patients to that in controls; however, the abdominal component increased more and the ribcage component less in patients. Peak inspiratory ribcage, but not abdominal, muscle pressure was significantly lower in patients than in controls. End-inspiratory Pdi increased similarly in both groups, whereas inspiratory swings in Pdi increased significantly only in patients. No pressure or volume signals correlated with disease severity. The diaphragm and abdominal muscles help to expand the chest wall in ankylosing spondylitis patients, regardless of the severity of their disease. This finding supports the starting hypothesis that a coordinated response of respiratory muscle activity optimises the efficiency of the thoracoabdominal compartment in conditions of limited ribcage expansion.
CTLA-4-mediated regulatory phenotype of T-cells in tolerant lung recipients
Authors: K. Botturi, Y. Lacoeuille, P. Thomas, S. Boniface, M. Reynaud-Gaubert, A. Magnan
Journal: European Respiratory Journal (2008)

Obliterative bronchiolitis (OB) is the major cause of long-term lung allograft loss resulting from an unclear immune process occurring in the absence of the donor's immune cells. The present authors hypothesised that interactions of autologous dendritic cells (DCs) with T-cells could differ in OB patients compared with healthy lung transplant recipients (LTRs). Monocyte-derived DCs from 14 OB and 35 non-OB LTRs were cultured with autologous T-cells. T-regulatory (T reg ) cells, co-receptors, cytokine production, DC phenotype and indoleamine 2,3-dioxygenase (IDO) expression were assessed by flow cytometry. Experiments were repeated in the presence of Pseudomonas aeruginosa or anti-co-receptor antibodies. DCs from non-OB LTR upregulated T reg cells, cytotoxic T-lymphocyte antigen (CTLA)-4 and interleukin (IL)-10. By contrast CD28 and inducible T-cell co-stimulator were downregulated concomitantly to IL-13 and IL-4. Compared to OB, non-OB DCs displayed an immature phenotype with lower CD80 and CD83 and higher IDO levels of expression. Stimulation by P. aeruginosa did not abolish the tolerogenic effects of DCs on non-OB T-cells. Finally, decreased T reg cells and IL-10 production were detected when adding anti-CTLA-4 antibodies in non-OB LTR. The present study demonstrates that dendritic cells from nonobliterative bronchiolitis lung transplant recipients induce a tolerant T-cell phenotype which is dependent on cytotoxic T-lymphocyte antigen-4 engagement.
Epidemic of Diabetic and Nondiabetic Renal Disease among the Zuni Indians
Authors: Vallabh O. Shah, Marina Scavini, Christine A. Stidley, Francesca Tentori, Thomas K. Welty, Jean W. MacCluer, Andrew S. Narva, Arlene Bobelu, Carleton P. Albert, David S. Kessler, Antonia M. Harford, Craig S. Wong, Alexis A. Harris, Susan Paine, Philip G. Zager
Journal: Journal of the American Society of Nephrology (2003)

There is an epidemic of renal disease among the Zuni Indians. The prevalence of end-stage renal disease among the Zuni Indians is 18.4-fold and 7.4-fold higher than among European Americans and American Indians/Alaskan Natives, respectively. In contrast to other American Indian tribes, nondiabetic renal disease accounts for a significant percent of the renal disease burden among the Zuni Indians. To explore this hypothesis, a community epidemiologic study of the Zuni Pueblo was conducted. A questionnaire was administered, blood and urine samples were collected, and BP, height, and weight were measured. Neighborhood household clusters were used as the sampling frame to maximize ascertainment and minimize bias. Age and gender distributions in the sample (n = 1483) were similar to those of the eligible Zuni population (n = 9228). The prevalence, age-adjusted and gender-adjusted to the Zuni population, of incipient (0.03 < or = UACR < 0.3) albuminuria (IA) (15.0% [95% confidence interval, 13.1 to 16.9%]), and overt (UACR > or = 0.3) albuminuria (OA) (4.7% [3.6 to 5.8%]) was high. The prevalence estimates for IA and OA were higher among diabetic participants (IA: 33.6% [27.6 to 39.7%]; OA: 18.7% [13.7 to 23.7%]) than nondiabetic participants (IA: 10.8% [9.0 to 12.6%]; OA: 1.8% [1.0 to 2.5%]). However, there were more nondiabetic participants; therefore, they comprised 58.0% [51.4 to 64.6%] and 30.9% [20.0 to 41.7%] of participants with IA and OA, respectively. In contrast to most other American Indian tribes, nondiabetic renal disease contributes significantly to the overall burden of renal disease among the Zuni Indians.
Plasmacytoid DCs help lymph node DCs to induce anti-HSV CTLs
Authors: Hiroyuki Yoneyama, Kenjiro Matsuno, Etsuko Toda, Tetsu Nishiwaki, Naoki Matsuo, Akiko Nakano, Shosaku Narumi, Bao Lu, Craig Gerard, Sho Ishikawa, Kouji Matsushima
Journal: The Journal of Experimental Medicine (2005)

Antiviral cell–mediated immunity is initiated by the dendritic cell (DC) network in lymph nodes (LNs). Plasmacytoid DCs (pDCs) are known to migrate to inflamed LNs and produce interferon (IFN)-α, but their other roles in antiviral T cell immunity are unclear. We report that LN-recruited pDCs are activated to create local immune fields that generate antiviral cytotoxic T lymphocytes (CTLs) in association with LNDCs, in a model of cutaneous herpes simplex virus (HSV) infection. Although pDCs alone failed to induce CTLs, in vivo depletion of pDCs impaired CTL-mediated virus eradication. LNDCs from pDC-depleted mice showed impaired cluster formation with T cells and antigen presentation to prime CTLs. Transferring circulating pDC precursors from wild-type, but not CXCR3-deficient, mice to pDC-depleted mice restored CTL induction by impaired LNDCs. In vitro co-culture experiments revealed that pDCs provided help signals that recovered impaired LNDCs in a CD2- and CD40L-dependent manner. pDC-derived IFN-α further stimulated the recovered LNDCs to induce CTLs. Therefore, the help provided by pDCs for LNDCs in primary immune responses seems to be pivotal to optimally inducing anti-HSV CTLs.
Rheumatoid Arthritis
Authors: Franklin H. Epstein, Edward D. Harris
Journal: New England Journal of Medicine (1990)

IN 1947, a technician who had rheumatoid arthritis and who worked in the laboratory of Dr. Harry Rose at Columbia University discovered that her own serum agglutinated excessively. Dr. Rose suggested that this serologic reaction might have been caused by the arthritis. Charles Ragan, a rheumatologist, pursued this suggestion and developed the sheep-cell agglutination test,1 , 2 which we know as a test for rheumatoid factor. For the first time, physicians had a key to the black box that was rheumatoid arthritis and could begin to study the immunologic abnormalities in patients with the disease. The classification of patients could also begin; . . .
PentaLyte Decreases Lung Injury after Aortic Occlusion–Reperfusion
Authors: ROBERT N. AXON, MANUEL S. BAIRD, JOHN D. LANG, AMY E. BRIX, VANCE G. NIELSEN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Lung injury often occurs after hepatoenteric ischemia, with xanthine oxidase (XO, an oxidant-generating enzyme), released from reperfusing liver and intestines, mediating a significant component of this injury. Since pentastarch administration decreases intestinal reperfusion injury, we determined whether resuscitation with PentaLyte (a pentastarch-containing solution) would decrease hepatoenteric reperfusion injury, xanthine oxidase release, and concomitant lung injury after aortic occlusion– reperfusion. Aortic occlusion was established in rabbits for 40 min, and was followed by 3 h of reperfusion, during which either PentaLyte or lactated Ringer's solution-based resuscitation was administered. Sham-operated animals served as controls. Hepatoenteric reperfusion injury, as manifested by release of the enzyme aspartate aminotransferase and decreased gastric intramucosal pH, was significantly (p < 0.0167) attenuated by PentaLyte administration after aortic occlusion–reperfusion, as compared with its occurrence in animals given lactated Ringer's solution. The release of XO after aortic occlusion–reperfusion was 4-fold smaller after PentaLyte administration than after resuscitation with lactated Ringer's solution (p < 0.05). Pulmonary injury, as defined by an increase in bronchoalveolar lavage fluid (BALF) protein content and lactate dehydrogenase (LDH) activity, was 4-fold less after PentaLyte administration following aortic occlusion–reperfusion than after administration of lactated Ringer's solution (p < 0.05). We conclude that remote pulmonary injury is significantly decreased by concomitant PentaLyte-mediated reduction of hepatoenteric reperfusion injury and XO release.
Surgical vs Nonoperative Treatment for Lumbar Disk Herniation
Authors: James N. Weinstein, Jon D. Lurie, Tor D. Tosteson, Jonathan S. Skinner, Brett Hanscom, Anna N. A. Tosteson, Harry Herkowitz, Jeffrey Fischgrund, Frank P. Cammisa, Todd Albert, Richard A. Deyo
Journal: JAMA (2006)

COMPARED2][3] Results for the Spine Patient Outcomes Research Trial (SPORT) randomized trial for intervertebral disk herniation are reported in a companion article.In that study, both surgical and nonoperative patients experienced significant improvement over time and intent-to-treat analyses showed no significant differences between the randomized groups for the primary outcome measures.Randomized trials of surgery face a number of challenges 4 and their gen-See also pp 2441, 2483, and 2485.