tbuckley/cabot-search huggingface dataset:
Sustained Ventricular Arrhythmias Among Patients With Acute Coronary Syndromes With No ST-Segment Elevation
Authors: Sana M. Al-Khatib, Christopher B. Granger, Yao Huang, Kerry L. Lee, Robert M. Califf, Maarten L. Simoons, Paul W. Armstrong, Frans Van de Werf, Harvey D. White, R. John Simes, David J. Moliterno, Eric J. Topol, Robert A. Harrington
Journal: Circulation (2002)

The prognosis of ventricular arrhythmias among patients with non-ST-elevation acute coronary syndromes is unknown. We studied the incidence, predictors, and outcomes of sustained ventricular arrhythmias in 4 large randomized trials of such patients.We pooled the datasets of the Global Use of Streptokinase and tPA for Occluded Arteries (GUSTO)-IIb, Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT), Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network (PARAGON)-A, and PARAGON-B trials (n=26 416). We identified independent predictors of ventricular fibrillation (VF) and ventricular tachycardia (VT) and compared the 30-day and 6-month mortality rates of patients who did (n=552) and did not (n=25 864) develop these arrhythmias during the index hospitalization. Independent predictors of in-hospital VF included prior hypertension, chronic obstructive pulmonary disease, prior myocardial infarction, and ST-segment changes at presentation. Except for hypertension, these variables also independently predicted in-hospital VT. In Cox proportional-hazards modeling, in-hospital VF and VT were independently associated with 30-day mortality (hazard ratio [HR], 23.2 [95% CI, 18.1 to 29.8] for VF and HR, 7.6 [95% CI, 5.5 to 10.4] for VT) and 6-month mortality (HR, 14.8 [95% CI, 12.1 to 18.3] for VF and HR, 5.0 [95% CI, 3.8 to 6.5] for VT). These differences remained significant after excluding patients with heart failure or cardiogenic shock and those who died <24 hours after enrollment.Despite the use of effective therapies for non-ST-elevation acute coronary syndromes, ventricular arrhythmias in this setting are associated with increased 30-day and 6-month mortality. More effective therapies are needed to improve the survival of patients with these arrhythmias.
Vascular endothelial growth factors and vascular permeability
Authors: D. O. Bates
Journal: Cardiovascular Research (2010)

Vascular endothelial growth factors (VEGFs) are key regulators of permeability. The principal evidence behind how they increase vascular permeability in vivo and in vitro and the consequences of that increase are addressed here. Detailed analysis of the published literature has shown that in vivo and in vitro VEGF-mediated permeability differs in its time course, but has common involvement of many specific signalling pathways, in particular VEGF receptor-2 activation, calcium influx through transient receptor potential channels, activation of phospholipase C gamma and downstream activation of nitric oxide synthase. Pathways downstream of endothelial nitric oxide synthase appear to involve the guanylyl cyclase-mediated activation of the Rho–Rac pathway and subsequent involvement of junctional signalling proteins such as vascular endothelial cadherin and the tight junctional proteins zona occludens and occludin linked to the actin cytoskeleton. The signalling appears to be co-ordinated through spatial organization of the cascade into a signalplex, and arguments for why this may be important are considered. Many proteins have been identified to be involved in the regulation of vascular permeability by VEGF, but still the mechanisms through which these are thought to interact to control permeability are dependent on the experimental system, and a synthesis of existing data reveals that in intact vessels the co-ordination of the pathways is still not understood.
NITRIC OXIDE SYNTHASE: Role in the Genesis of Vascular Disease
Authors: John P. Cooke, MD, Victor J. Dzau, MD
Journal: Annual Review of Medicine (1997)

▪ Abstract The product of nitric oxide (NO) synthase is the most potent endogenous vasodilator known. NO not only is a potent vasodilator, it also inhibits platelet adherence and aggregation, reduces adherence of leukocytes to the endothelium, and suppresses proliferation of vascular smooth muscle cells. A number of disorders are associated with reduced synthesis and/or increased degradation of vascular NO. These include hypercholesterolemia, diabetes mellitus, hypertension, and tobacco use. The endothelial dysfunction caused by these disorders contributes to the alterations in vascular function and structure observed in these conditions. A reduction in the activity of vascular NO likely plays a significant role in the development of atherosclerosis. Insights into the mechanisms by which NO production or activity is altered in these states will lead to new therapeutic strategies in the treatment of a number of vascular disorders, including hypertension, atherosclerosis, restenosis, and thrombosis.
Remission in early rheumatoid arthritis defined by 28 joint counts: limited consequences of residual disease activity in the forefeet on outcome
Authors: Lilian H D van Tuyl, Karin Britsemmer, George A Wells, Josef S Smolen, Bin Zhang, Julia Funovits, Dirkjan van Schaardenburg, David Felson, Maarten Boers
Journal: Annals of the Rheumatic Diseases (2011)

Introduction The new American College for Rheumatology (ACR)/European League Against Rheumatism (EULAR) remission criteria are based on the assessment of 28 joints. A study was undertaken to study the consequences of remission misclassification due to residual disease activity in the feet on physical function and joint damage in the subsequent year in an observational early disease cohort.All patients with rheumatoid arthritis at inclusion or at 1-year follow-up in the early arthritis cohort of the Jan van Breemen Institute, The Netherlands were included. ACR/EULAR remission definitions for trials and clinical practice were calculated twice, once using a 28-joint count and once using a 38-joint count that included the 10 metatarsophalangeal joints. Disease stability was defined as stable x-ray scores over 1 year (change ≤ 0 in Sharp/van der Heijde scores) and stable and low scores on the Health Assessment Questionnaire (HAQ change ≤ 0 and HAQ score consistently ≤ 0.5), all during the second year after inclusion. Analyses comprised residual disease activity (swollen or tender joints >0) in the feet of patients who fulfilled the candidate remission criteria using a 28-joint count and likelihood ratios of remission definitions to predict disease stability.Of 421 patients, 9-15% reached remission at 1 year using a 28-joint count. Of these, 26-40% showed activity in the feet. Misclassification due to reduced joint counts was observed in 2-3%. A state of remission increased the likelihood of stability of both x-ray and HAQ, with similar likelihood ratios for definitions using 38-joint counts and those using 28-joint counts.The ability of remission definitions with 28-joint counts versus 38-joint counts to predict long-term good radiological and functional outcome is similar. This confirms that inclusion of ankles and forefeet in the assessment of remission is not required, although inclusion of these joints in the examination is recommended.
Expression of a marker for colonic crypt base cells is correlated with poor prognosis in human colorectal cancer
Authors: A A M van der Wurff, J ten Kate, P T J Marx, E P M van der Linden, C C L Beek, F-J Bovelander, J Dekker, W N M Dinjens, M F von Meyenfeldt, J-W Arends, F T Bosman
Journal: Gut (1998)

Background —There is a need for markers in colorectal cancer which will allow subclassification of stage groups into subgroups with high versus low risk of recurrent disease. Aims —To develop monoclonal antibodies that recognise antigens on immature crypt base cells, on the assumption that in a neoplasm undifferentiated but not the terminally differentiated cells will be responsible for tumour progression. Methods —Colon crypt cells which were isolated from human colonic mucosa by EDTA/EGTA incubation were studied. By stepwise harvesting, crypt base cell enriched fractions were obtained, and after incubation with antibodies against dominant antigens, used as immunogens. Results —Of one crypt base cell specific antibody (5E9), the reactive epitope appeared to be a non-terminal carbohydrate in the mucin O-glycans of the colon. The epitope did not seem to be colon specific, but was expressed in a variety of other tissues. In colorectal carcinomas, 5E9 immunoreactivity identified a subgroup of patients with a tendency for worse prognosis. Conclusion —A mucin associated maturation epitope was identified in colonic crypt base cells, the expression of which in Dukes’ stage B3 colorectal carcinoma may be associated with poor prognosis.
Production of the Novel Mesangial Autocrine Growth Factors GDNF and IL-10 Is Regulated by the Immunomodulator AS101
Authors: Yona Kalechman, Benjamin Sredni, Talia Weinstein, Ilya Freidkin, Ana Tobar, Michael Albeck, Uzi Gafter
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Mesangial cell (MC) proliferation is essential for the pathogenesis and progression of various glomerular diseases. This study shows that glial cell line-derived neurotrophic factor (GDNF) and IL-10 are mesangial autocrine growth factors that play a pivotal role in rat MC proliferation in vitro. Downstream targets of GDNF signaling and their role in MC hyperplasia are identified. The phosphatidylinositol 3-kinase (PI3K) pathway and its downstream target NF-κB were found to mediate GDNF-induced MC mitogenesis. This pathway also mediates GDNF-induced decrease in the cyclin-dependent kinase inhibitor p27kip1 expression, resulting in the increased formation of cyclin D1/cdk4 and cyclin E/cdk2 complexes, followed by hyperphosphorylation of retinoblastoma, a key event for G1 to S phase progression. IL-10 appears to be a more potent MC growth factor that negatively regulates GDNF expression. Indeed, its inhibition by the nontoxic tellurium anti-IL-10 compound, ammonium trichloro(dioxoethylene-o,o') tellurate (AS101), extensively decreased MC clonogenicity despite GDNF upregulation. Identification of the mesangial GDNF and IL-10 pathways as critical mediators of mesangial cell proliferation may provide another target for therapeutic intervention in certain glomerular diseases. In vivo animal studies using AS101, currently undergoing phase II clinical trials on cancer patients, are warranted to determine its potential in the management of glomerular diseases associated with mesangial cell proliferation. E-mail: [email protected]
Does the chimpanzee have a theory of mind?
Authors: David Premack, Guy Woodruff
Journal: Behavioral and Brain Sciences (1978)

Abstract An individual has a theory of mind if he imputes mental states to himself and others. A system of inferences of this kind is properly viewed as a theory because such states are not directly observable, and the system can be used to make predictions about the behavior of others. As to the mental states the chimpanzee may infer, consider those inferred by our own species, for example, purpose or intention , as well as knowledge, belief, thinking, doubt, guessing, pretending, liking , and so forth. To determine whether or not the chimpanzee infers states of this kind, we showed an adult chimpanzee a series of videotaped scenes of a human actor struggling with a variety of problems. Some problems were simple, involving inaccessible food – bananas vertically or horizontally out of reach, behind a box, and so forth – as in the original Kohler problems; others were more complex, involving an actor unable to extricate himself from a locked cage, shivering because of a malfunctioning heater, or unable to play a phonograph because it was unplugged. With each videotape the chimpanzee was given several photographs, one a solution to the problem, such as a stick for the inaccessible bananas, a key for the locked up actor, a lit wick for the malfunctioning heater. The chimpanzee's consistent choice of the correct photographs can be understood by assuming that the animal recognized the videotape as representing a problem, understood the actor's purpose, and chose alternatives compatible with that purpose.
A Note on the Treatment of Locomotor Ataxia by Precise Nerve-Vibration
Authors: J. M. Granville
Journal: BMJ (1882)

TREATMENT OF LOCOMOTOR two cases, in my experience, have been alike, although as a rule they h'ave surface-features of typical resemblance.For example, there is ATAXYV BY PRECISE NERVE-VIBRATION, nearly always somethingr wrong with one of the ulnar nerves, not as an By J.
Pulmonary Apoplexy and Emphysema as a Post-Mortem Appearance in Cases of Death from Epilepsy
Authors: J. W. Burman
Journal: BMJ (1879)

For the sake of those who may wish to see the data on which the figures given in the preceding tables are based, I append others, show- ing the population and number of deaths from phthisis for the whole colony, and for Melbourne separately, in i86i and I871.
The Role of MicroRNAs and Human Epidermal Growth Factor Receptor 2 in Proliferative Lupus Nephritis
Authors: Patrícia Costa‐Reis, Pierre A. Russo, Zhe Zhang, Lucrezia Colonna, Kelly Maurer, Stefania Gallucci, Steffan W. Schulz, Adnan N. Kiani, Michelle Petri, Kathleen E. Sullivan
Journal: Arthritis & Rheumatology (2015)

To understand the roles of microRNAs (miRNAs) in proliferative lupus nephritis (LN).A high-throughput analysis of the miRNA pattern of the kidneys of LN patients and controls was performed by molecular digital detection. Urinary miRNAs were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Target gene expression in human mesangial cells was evaluated by arrays and qRT-PCR. Human epidermal growth factor receptor 2 (HER-2) was analyzed by immunohistochemistry in kidney samples from LN patients and in a murine model of lupus. Urinary levels of HER-2, monocyte chemotactic protein 1 (MCP-1), and vascular cell adhesion molecule 1 (VCAM-1) were measured by enzyme-linked immunosorbent assay.Levels of the miRNAs miR-26a and miR-30b were decreased in the kidneys and urine of LN patients. In vitro these miRNAs controlled mesangial cell proliferation, and their expression was regulated by HER-2. HER-2 was overexpressed in lupus-prone NZM2410 mice and in the kidneys of patients with LN, but not in other mesangioproliferative glomerulonephritides. HER-2 was found to be up-regulated by interferon-α and interferon regulatory factor 1. Urinary HER-2 was increased in LN and reflected disease activity, and its levels correlated with those of 2 other recognized LN biomarkers, MCP-1 and VCAM-1.The kidney miRNA pattern is broadly altered in LN, which contributes to uncontrolled cell proliferation. Levels of the miRNAs miR-26a and miR-30b are decreased in the kidneys and urine of LN patients, and they directly regulate the cell cycle in mesangial cells. The levels of these miRNAs are controlled by HER-2, which is overexpressed in NZM2410 mice and in the kidneys and urine of LN patients. HER-2, miR-26a, and miR-30b are thus potential LN biomarkers, and blocking HER-2 may be a promising new strategy to decrease cell proliferation and damage in this disease.
Accelerated Reendothelialization With Suppressed Thrombogenic Property and Neointimal Hyperplasia of Rabbit Jugular Vein Grafts by Adenovirus-Mediated Gene Transfer of C-Type Natriuretic Peptide
Authors: N. Ohno, H. Itoh, T. Ikeda, K. Ueyama, K. Yamahara, K. Doi, J. Yamashita, M. Inoue, K. Masatsugu, N. Sawada, Y. Fukunaga, S. Sakaguchi, M. Sone, T. Yurugi, H. Kook, M. Komeda, K. Nakao
Journal: Circulation (2002)

Vein graft disease limits the late results of coronary revascularization. C-type natriuretic peptide (CNP) inhibits the growth of vascular smooth muscle cells. Given the effects of CNP on cGMP cascade, we hypothesized that transfected CNP genes modulate endothelial repair and thrombogenicity in the vein graft.Autologous rabbit jugular vein grafts were incubated ex vivo in a solution of adenovirus vectors containing CNP gene (Ad.CNP) or Escherichia coli lac Z gene (Ad.LacZ) and then interposed in the carotid artery. Reendothelialization, mural thrombi formation, and intima/media ratio were evaluated on the 14th and 28th postoperative days. More reendothelialization was seen in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts both at 14 days (0.81+/-0.05 versus 0.30+/-0.14, P<0.01) and at 28 days (0.96+/-0.01 versus 0.45+/-0.08, P<0.001). The mural thrombus area was smaller in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts. Neointimal thickening was significantly suppressed in the Ad.CNP group. The in vitro wound assay with human coronary artery endothelial cells revealed significant potentiation of the wound repair process by CNP and atrial natriuretic peptide administration.Infected Ad.CNP accelerated reendothelialization and suppressed thrombosis and neointimal hyperplasia. The method may potentially prevent vein graft disease in patients undergoing coronary artery revascularization.
Use of Allogeneic Hematopoietic Stem-Cell Transplantation Based on Minimal Residual Disease Response Improves Outcomes for Children With Relapsed Acute Lymphoblastic Leukemia in the Intermediate-Risk Group
Authors: Cornelia Eckert, Günter Henze, Karlheinz Seeger, Nikola Hagedorn, Georg Mann, Renate Panzer-Grümayer, Christina Peters, Thomas Klingebiel, Arndt Borkhardt, Martin Schrappe, André Schrauder, Gabriele Escherich, Lucie Sramkova, Felix Niggli, Johann Hitzler, Arend von Stackelberg
Journal: Journal of Clinical Oncology (2013)

In children with intermediate risk of relapse of acute lymphoblastic leukemia (ALL), it is essential to identify patients in need of treatment intensification. We hypothesized that the prognosis of patients with unsatisfactory reduction of minimal residual disease (MRD) can be improved by allogeneic hematopoietic stem-cell transplantation (HSCT).In the Acute Lymphoblastic Leukemia-Relapse Study of the Berlin-Frankfurt-Münster Group (ALL-REZ BFM) 2002, patients with an MRD level of ≥ 10(-3) (n = 99) at the end of induction therapy were allocated to HSCT, whereas those with an MRD level less than 10(-3) (n = 109) continued to receive chemotherapy. MRD was quantified by real-time polymerase chain reaction for clone-specific T-cell receptor/immunoglobulin gene rearrangements.The probability of event-free survival for patients with MRD ≥ 10(-3) was 64% ± 5% in ALL-REZ BFM 2002 compared with 18% ± 7% in the predecessor study ALL-REZ BFM P95/96 (P < .001). This was mainly achieved by reducing the cumulative incidence of subsequent relapse (CIR) at 8 years from 59% ± 9% to 27% ± 5% (P < .001). The favorable prognosis of patients with MRD less than 10(-3) could be confirmed in those with a late combined or isolated bone marrow B-cell precursor (BCP) -ALL relapse (CIR, 20% ± 5%), whereas patients with an early combined BCP-ALL relapse had an unfavorable outcome (CIR, 63% ± 13%; P < .001).Allogeneic HSCT markedly improved the prognosis of patients with intermediate risk of relapse of ALL and unsatisfactory MRD response. As a result, outcomes in this group approximated those of patients with favorable MRD response. Patients with early combined relapse require treatment intensification even in case of favorable MRD response, demonstrating the prognostic impact of time to relapse.
Medical management of brain tumors and the sequelae of treatment
Authors: D. Schiff, E. Q. Lee, L. Nayak, A. D. Norden, D. A. Reardon, P. Y. Wen
Journal: Neuro-Oncology (2014)

Patients with malignant brain tumors are prone to complications that negatively impact their quality of life and sometimes their overall survival as well. Tumors may directly provoke seizures, hypercoagulable states with resultant venous thromboembolism, and mood and cognitive disorders. Antitumor treatments and supportive therapies also produce side effects. In this review, we discuss major aspects of supportive care for patients with malignant brain tumors, with particular attention to management of seizures, venous thromboembolism, corticosteroids and their complications, chemotherapy including bevacizumab, and fatigue, mood, and cognitive dysfunction.
Are rules and entries enough? Historical reflections on a longstanding controversy
Authors: Brigitte Nerlich, David D. Clarke
Journal: Behavioral and Brain Sciences (1999)

For language to function we clearly need two formal ordering principles: lexical entries and rules. Clahsen's target article provides multiple empirical evidence for this distinction, but this may be simply to overconfirm the undeniable and to overlook the hidden motor of language use and language development, namely, function. Since at least 1859, linguists have argued for the primacy of function, and these arguments are worth rediscovering today.
Fibulin-3 as a blood and effusion biomarker for pleural mesothelioma
Authors: James Murray
Journal: Thorax (2013)

Fibulin-3 as a blood and effusion biomarker for pleural mesotheliomaThis study investigated whether plasma and pleural effusion levels of fibulin-3 (an extracellular glycoprotein found to be expressed by mesothelioma cells) could be used to differentiate pleural mesothelioma from other pleural effects of asbestos exposure; benign pleural effusions, pleural effusions from other malignancy and healthy controls.Previously identified biomarkers have shown unacceptable sensitivity and specificity.In two cohorts plasma fibulin-3 levels were significantly higher in mesothelioma patients than in the other groups.An overall comparison of patients (with and without mesothelioma) showed that the receiver-operating-characteristic curve had a sensitivity of 96.7% and specificity of 95.5%.Importantly, levels did not vary according to age, sex, duration of asbestos exposure or radiographic change.Fibulin-3 levels in mesothelioma related pleural effusions were also shown to be significantly higher than those effusions from other causes (including other malignancies).Samples from both cohorts were identified prospectively and it is not clear why only some patients had plasma fibulin-3 levels measured.Blinded validation was performed with plasma specimens from a separate cohort.Compared with previous attempts to identify biomarkers these results show promise.However, numbers in this study are small and there appears to have been selection bias in the samples analysed.If larger international studies can validate these findings then it has important implications for the role of early surgical or medical intervention in mesothelioma, and also for the financial compensation available to patients.