tbuckley/cabot-search huggingface dataset:
IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC–activated Th2 memory cells
Authors: Yui-Hsi Wang, Pornpimon Angkasekwinai, Ning Lu, Kui Shin Voo, Kazuhiko Arima, Shino Hanabuchi, Andreas Hippe, Chris J. Corrigan, Chen Dong, Bernhard Homey, Zhengbin Yao, Sun Ying, David P. Huston, Yong-Jun Liu
Journal: The Journal of Experimental Medicine (2007)

Interleukin (IL) 25 (IL-17E), a distinct member of the IL-17 cytokine family, plays important roles in evoking T helper type 2 (Th2) cell–mediated inflammation that features the infiltrations of eosinophils and Th2 memory cells. However, the cellular sources, target cells, and underlying mechanisms remain elusive in humans. We demonstrate that human Th2 memory cells expressing distinctive levels of IL-25 receptor (R) are one of the responding cell types. IL-25 promotes cell expansion and Th2 cytokine production when Th2 central memory cells are stimulated with thymic stromal lymphopoietin (TSLP)–activated dendritic cells (DCs), homeostatic cytokines, or T cell receptor for antigen triggering. The enhanced functions of Th2 memory cells induced by IL-25 are associated with sustained expression of GATA-3, c-MAF, and JunB in an IL-4–independent manner. Although keratinocytes, mast cells, eosinophils, and basophils express IL-25 transcripts, activated eosinophils and basophils from normal and atopic subjects were found to secrete bioactive IL-25 protein, which augments the functions of Th2 memory cells. Elevated expression of IL-25 and IL-25R transcripts was observed in asthmatic lung tissues and atopic dermatitis skin lesions, linking their possible roles with exacerbated allergic disorders. Our results provide a plausible explanation that IL-25 produced by innate effector eosinophils and basophils may augment the allergic inflammation by enhancing the maintenance and functions of adaptive Th2 memory cells.
Effects of Recombinant Erythropoietin in Palliative Treatment of Unselected Cancer Patients
Authors: Elisabet Lindholm, Peter Daneryd, Ulla Körner, Anders Hyltander, Marita Fouladiun, Kent Lundholm
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose is to evaluate relationships between objectively assessed exercise capacity and subjectively assessed scoring of physical functioning and well-being after erythropoietin treatment in cancer patients on palliative care. Experimental Design: Unselected cancer patients (n = 108) who experienced progressive cachexia were randomized to receive either anti-inflammatory treatment alone (indomethacin) or recombinant erythropoietin plus indomethacin to prevent the appearance of disease-induced anemia and thereby protect patients’ exercise capacity. Follow-up investigations of nutritional status, exercise capacity, and health-related quality of life assessed by SF-36 and the European Organization for Research and Treatment of Cancer QLQ-C30 were compared. Results: Effective treatment by erythropoietin on top of basal whole body anti-inflammatory treatment was confirmed and indicated by time course changes of biochemical, physiologic, and nutritional objectives, whereas individual self-reported scoring of physical functioning and general health did not indicate a clear-cut effectiveness, particularly at moderately subnormal hemoglobin levels. Conclusions: Discrepancies between objective and subjective self-reported measures may be either fundamental or indicate scoring limitations for evaluation of therapeutic results. Present results demonstrate a clinical benefit of erythropoietin treatment in cancer patients with subnormal to normal hemoglobin levels, whereas the patients’ own subjective scoring was insufficient to sense such improvements. The discrepancy may be either fundamental or methodological but emphasizes the importance to document therapeutic outcome in both subjective and objective perspectives in palliative care of cancer patients.
The effect of chronotype on sleepiness, fatigue, and psychomotor vigilance of ICU nurses during the night shift
Authors: Laurens Reinke, Yusuf Özbay, Willem Dieperink, Jaap E. Tulleken
Journal: Intensive Care Medicine (2015)

In general, sleeping and activity patterns vary between individuals. This attribute, known as chronotype, may affect night shift performance. In the intensive care unit (ICR), night shift performance may impact patient safety. We have investigated the effect of chronotype and social demographics on sleepiness, fatigue, and night shift on the performance of nurses. This was a prospective observational cohort study which assessed the performance of 96 ICU night shift nurses during the day and night shifts in a mixed medical–surgical ICU in the Netherlands. We determined chronotype and assessed sleeping behaviour for each nurse prior to starting shift work and before free days. The level of sleepiness and fatigue of nurses during the day and night shifts was determined, as was the effect of these conditions on psychomotor vigilance and mathematical problem-solving. The majority of ICU nurses had a preference for early activity (morning chronotype). Compared to their counterparts (i.e. evening chronotypes), they were more likely to nap before commencing night shifts and more likely to have young children living at home. Despite increased sleepiness and fatigue during night shifts, no effect on psychomotor vigilance was observed during night shifts. Problem-solving accuracy remained high during night shifts, at the cost of productivity. Most of the ICU night shift nurses assessed here appeared to have adapted well to night shift work, despite the high percentage of morning chronotypes, possibly due to their 8-h shift duration. Parental responsibilities may, however, influence shift work tolerance.
CellProfiler: image analysis software for identifying and quantifying cell phenotypes.
Authors: Anne E Carpenter, Thouis R Jones, Michael R Lamprecht, Colin Clarke, In Han Kang, Ola Friman, David A Guertin, Joo Han Chang, Robert A Lindquist, Jason Moffat, Polina Golland, David M Sabatini
Journal: Genome biology (2006)

Abstract Biologists can now prepare and image thousands of samples per day using automation, enabling chemical screens and functional genomics (for example, using RNA interference). Here we describe the first free, open-source system designed for flexible, high-throughput cell image analysis, CellProfiler. CellProfiler can address a variety of biological questions quantitatively, including standard assays (for example, cell count, size, per-cell protein levels) and complex morphological assays (for example, cell/organelle shape or subcellular patterns of DNA or protein staining).
Mechanics of the Human Common Carotid Artery in Vivo
Authors: JOSEPH C. GREENFIELD, GEORGE T. TINDALL, MARCUS L. DILLON, M. S. MAHALEY
Journal: Circulation Research (1964)

The relationships between lateral intravascular pressure, vessel radius, and vessel length were evaluated in the common carotid artery in vivo in thirteen patients during treatment by surgery. Strain was measured in the wall of the carotid artery by means of an electrical caliper sutured to the vessel wall. Lateral intravascular pressure was measured directly with either an 18-gauge needle or a short polyethylene catheter connected to a Statham, P23Db, strain gauge. The results indicate that circumferential and longitudinal strains in the common carotid artery were both small. The mean systolic change in cross-sectional area was 2.10% (±SD 1.08) of the end diastolic area. In three patients a negative circumferential strain was produced by making the cross section of the vessel elliptical. During systole, longitudinal strain increased in four patients and decreased in six patients. The average change in vessel segment length during systole was approximately 1.0% of the end diastolic length.
Growth of Triple-Negative Breast Cancer Cells Relies upon Coordinate Autocrine Expression of the Proinflammatory Cytokines IL-6 and IL-8
Authors: Zachary C. Hartman, Graham M. Poage, Petra den Hollander, Anna Tsimelzon, Jamal Hill, Nattapon Panupinthu, Yun Zhang, Abhijit Mazumdar, Susan G. Hilsenbeck, Gordon B. Mills, Powel H. Brown
Journal: Cancer Research (2013)

Abstract Triple-negative breast cancers (TNBC) are aggressive with no effective targeted therapies. A combined database analysis identified 32 inflammation-related genes differentially expressed in TNBCs and 10 proved critical for anchorage-independent growth. In TNBC cells, an LPA-LPAR2-EZH2 NF-κB signaling cascade was essential for expression of interleukin (IL)-6, IL-8, and CXCL1. Concurrent inhibition of IL-6 and IL-8 expression dramatically inhibited colony formation and cell survival in vitro and stanched tumor engraftment and growth in vivo. A Cox multivariable analysis of patient specimens revealed that IL-6 and IL-8 expression predicted patient survival times. Together these findings offer a rationale for dual inhibition of IL-6/IL-8 signaling as a therapeutic strategy to improve outcomes for patients with TNBCs. Cancer Res; 73(11); 3470–80. ©2013 AACR.
Association of severe asthma attacks with weather, pollen, and air pollutants.
Authors: O V Rossi, V L Kinnula, J Tienari, E Huhti
Journal: Thorax (1993)

BACKGROUND: The association between exacerbations of asthma and weather or air pollution is not well understood. The relationships between visits to the emergency room for asthma attacks and the meteorological, aerobiological, and chemical characteristics of the outdoor air have been evaluated. METHODS: The number of daily attendances for asthma attacks at the emergency room of Oulu University Central Hospital was recorded over one year together with daily meteorological readings (temperature, humidity, barometric pressure, rainfall), levels of air pollutants (nitrogen dioxide (NO2), sulphur dioxide (SO2), hydrogen sulphide (H2S), total suspended particles (TSP)), and pollen counts (birch, alder, pine, willow, total pollen). The relationship between the number of attendances and the measured variables was then analysed by multiple regression and stepwise discriminant analysis. RESULTS: The total number of attendances during the year was 232, with lower figures in summer and higher in winter. No association was found between visits for asthma attacks and airborne pollen levels or meteorological factors except for temperature, which had a low inverse correlation with attendance. The most significant correlations were found between asthma visits and the levels of NO2; those for SO2, TSP, and H2S were also significant. Intercorrelations between SO2 and temperature or NO2 and between temperature and TSP or NO2 were also found, but only NO2 correlated significantly with attendances after standardisation for temperature. CONCLUSIONS: Increased levels of pollutants, especially NO2, were associated with attacks of asthma, but the explanation for this is unclear. Air pollen levels were not associated with asthma attacks and only temperature among the meteorological factors had a small association with asthma.
Exercise Protects Against Myocardial Ischemia–Reperfusion Injury via Stimulation of β <sub>3</sub> -Adrenergic Receptors and Increased Nitric Oxide Signaling: Role of Nitrite and Nitrosothiols
Authors: John W. Calvert, Marah E. Condit, Juan Pablo Aragón, Chad K. Nicholson, Bridgette F. Moody, Rebecca L. Hood, Amy L. Sindler, Susheel Gundewar, Douglas R. Seals, Lili A. Barouch, David J. Lefer
Journal: Circulation Research (2011)

Exercise training confers sustainable protection against ischemia-reperfusion injury in animal models and has been associated with improved survival following a heart attack in humans. It is still unclear how exercise protects the heart, but it is apparent that endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) play a role.To determine the role of β(3)-adrenergic receptors (β(3)-ARs), eNOS activation, and NO metabolites (nitrite and nitrosothiols) in the sustained cardioprotective effects of exercise.Here we show that voluntary exercise reduces myocardial injury in mice following a 4-week training period and that these protective effects can be sustained for at least 1 week following the cessation of the training. The sustained cardioprotective effects of exercise are mediated by alterations in the phosphorylation status of eNOS (increase in serine 1177 and decrease in threonine 495), leading to an increase in NO generation and storage of NO metabolites (nitrite and nitrosothiols) in the heart. Further evidence revealed that the alterations in eNOS phosphorylation status and NO generation were mediated by β(3)-AR stimulation and that in response to exercise a deficiency of β(3)-ARs leads to an exacerbation of myocardial infarction following ischemia-reperfusion injury.Our findings clearly demonstrate that exercise protects the heart against myocardial ischemia-reperfusion injury by stimulation of β(3)-ARs and increased cardiac storage of nitric oxide metabolites (ie, nitrite and nitrosothiols).
Satisfaction and Regret after Open Retropubic or Robot-Assisted Laparoscopic Radical Prostatectomy
Authors: Florian R. Schroeck, Tracey L. Krupski, Leon Sun, David M. Albala, Marva M. Price, Thomas J. Polascik, Cary N. Robertson, Alok K. Tewari, Judd W. Moul
Journal: European Urology (2008)
Converting venous acid–base and oxygen status to arterial in patients with lung disease
Authors: S. E. Rees, A. Hansen, M. Toftegaard, J. Pedersen, S. R. Kristiensen, H. Harving
Journal: European Respiratory Journal (2009)

The aim of the present study was to evaluate a method for calculating arterial values of pH, carbon dioxide tension (P(CO(2))) and oxygen tension (P(O(2))) from peripheral venous values. In total, 40 patients were studied. Arterial and peripheral venous blood were sampled at a department of respiratory diseases. Arterial values were calculated from venous, and measured and calculated values of arterial pH, P(CO(2)) and P(O(2)) were compared. Measured and calculated values of pH and P(CO(2)) correlated well, with the difference between them having a very small bias and standard deviation (pH -0.001+/-0.013, P(CO(2)) -0.09+/-0.28 kPa) within those considered acceptable for laboratory equipment and clinical practice. All but four patients had peripheral oxygen saturation (S(p,O(2))) <or=96%, and for these measured and calculated P(O(2)) correlated well, with a difference such that the bias and standard deviation suggested that calculated P(O(2)) may be clinically useful (P(O(2)) 0.11+/-0.53 kPa). The present study evaluates a method for calculating arterial pH, carbon dioxide tension and oxygen tension from venous blood. It has been shown that arterial pH and carbon dioxide tension can be calculated precisely, and that oxygen tension can be calculated with reasonable precision in the vast majority of patients. This method might be useful in reducing the need for painful arterial punctures.
Potential therapeutic role for statins in respiratory disease
Authors: E Hothersall, C McSharry, N C Thomson
Journal: Thorax (2006)

Statins reduce cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and have an established role in the treatment of atherosclerotic disease. Recent research has identified anti-inflammatory properties of statins. Statins appear to reduce the stability of lipid raft formation with subsequent effects on immune activation and regulation, and also prevent the prenylation of signalling molecules with subsequent downregulation of gene expression. Both these effects result in reduced cytokine, chemokine, and adhesion molecule expression, with effects on cell apoptosis or proliferation. This review considers the evidence for the anti-inflammatory properties of statins in the lung, and how these effects are being applied to research into the role of statins as a novel treatment of respiratory diseases.
Increasing PEEP while preventing hyperinflation reduces hypoxaemia but not mortality
Authors: James Walters
Journal: Thorax (2008)

It has previously been shown that lung protection with low tidal volume ventilation improves mortality in patients with acute lung injury (ALI) and adult respiratory distress syndrome (ARDS). Two randomised controlled multicentre studies have looked at different ways of using increased positive end expiratory pressure (PEEP) to aid alveolar recruitment while limiting hyperinflation to see if this further reduces mortality.

The first study, involving 767 patients, compared groups which were randomly assigned to either a minimal distension strategy (PEEP 5–9 cm H2O) or increased recruitment strategy …
Open access fibresigmoidoscopy: a comparative audit of efficacy
Authors: L Kalra, W R Price, B J M Jones, A N Hamlyn
Journal: BMJ (1988)

A total of 541 open access referrals for fibresigmoidoscopy over five years were compared with 495 hospital initiated procedures during the same period. The number of open access fibresigmoidoscopies doubled during the five years but diagnostic yield remained unchanged at about 40% and was similar to that of the hospital initiated procedures. Colorectal carcinoma was seen in 64 open access patients compared with 47 hospital referred patients, the proportion of Dukes9s type A lesions being similar (34%) in both groups. Polyps, colitis, and diverticular disease were equally common in open access and hospital referred patients. Fibresigmoidoscopy failed to detect disease in only 12 patients (1·2%) and the procedure was unsatisfactory in only 54. Referral was considered justified in 475 (88%) open access patients, and only 54 (17%) patients with normal appearances at endoscopy required further investigations. Diagnostic yields were low (19%; 30/156 cases) in open access patients under 40 and in patients with abdominal pain, constipation, or abdominal pain with constipation (0-17%). Most of these young patients presumably suffer from the irritable bowel syndrome and do not justify fibresigmoidoscopy. In contrast, there was a high diagnostic yield (90-100%) in patients of all ages referred for diarrhoea and rectal bleeding, altered blood from the rectum, and rectal bleeding associated with abdominal pain. Open access fibresigmoidoscopy is an effective service that should be freely available to general practitioners.
Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2
Authors: Tadashi Yokosuka, Masako Takamatsu, Wakana Kobayashi-Imanishi, Akiko Hashimoto-Tane, Miyuki Azuma, Takashi Saito
Journal: The Journal of Experimental Medicine (2012)

Programmed cell death 1 (PD-1) is a negative costimulatory receptor critical for the suppression of T cell activation in vitro and in vivo. Single cell imaging elucidated a molecular mechanism of PD-1–mediated suppression. PD-1 becomes clustered with T cell receptors (TCRs) upon binding to its ligand PD-L1 and is transiently associated with the phosphatase SHP2 (Src homology 2 domain–containing tyrosine phosphatase 2). These negative costimulatory microclusters induce the dephosphorylation of the proximal TCR signaling molecules. This results in the suppression of T cell activation and blockade of the TCR-induced stop signal. In addition to PD-1 clustering, PD-1–TCR colocalization within microclusters is required for efficient PD-1–mediated suppression. This inhibitory mechanism also functions in PD-1hi T cells generated in vivo and can be overridden by a neutralizing anti–PD-L1 antibody. Therefore, PD-1 microcluster formation is important for regulation of T cell activation.
Induced Pluripotent Stem Cells in Cardiovascular Drug Discovery
Authors: Mark Mercola, Alexandre Colas, Erik Willems
Journal: Circulation Research (2013)

The unexpected discovery that somatic cells can be reprogrammed to a pluripotent state yielding induced pluripotent stem cells has made it possible to produce cardiovascular cells exhibiting inherited traits and disorders. Use of these cells in high throughput analyses should broaden our insight into fundamental disease mechanisms and provide many benefits for patients, including new therapeutics and individually tailored therapies. Here we review recent progress in generating induced pluripotent stem cell-based models of cardiovascular disease and their multiple applications in drug development.
Role of the Polycomb Repressive Complex 2 in Acute Promyelocytic Leukemia
Authors: Raffaella Villa, Diego Pasini, Arantxa Gutierrez, Lluis Morey, Manuela Occhionorelli, Emmanuelle Viré, Josep F. Nomdedeu, Thomas Jenuwein, Pier Giuseppe Pelicci, Saverio Minucci, Francois Fuks, Kristian Helin, Luciano Di Croce
Journal: Cancer Cell (2007)
An Evaluation of Three Wound Measurement Techniques in Diabetic Foot Wounds
Authors: Julia Shaw, Ciara M. Hughes, Katie M. Lagan, Patrick M. Bell, Michael R. Stevenson
Journal: Diabetes Care (2007)

Approximately 80% of diabetes-related amputations are preceded by a diabetic foot ulcer (1,2). Wound measurement is an important component of successful wound management (3–6). Accurate identification of the wound margin and the calculation of wound area are crucial (7–9). Although more complex methods of wound measurement exist (planimetry, digitizing techniques, and stereophotogrammetry) (4,10–14), current practice focuses on wound measurement using simple ruler-based methods or by wound tracing. Ruler-based schemes tended to be less reliable in wounds >5 cm2 (11). Various mathematical formulae (including the calculation of area based on the formula for an ellipse) have been proposed to improve accuracy in wound surface area calculation in wounds <40 cm2 in size (10,11,15–17). The aim of this study was to evaluate and compare three wound measurement techniques: the Visitrak system (Smith and Nephew Healthcare, Hull, U.K.), a digital photography and image processing system (Analyze, version 6.0; AnalyzeDirect, Lenexa, KS), and an elliptical measurement method using the standard formula (πab) for the calculation of the area of an …
Double Down for a Double Win
Authors: Pearl S. Huang
Journal: Clinical Cancer Research (2012)

The rationale for using multiple inhibitors between and within the phosphoinositide 3-kinase/AKT/mTOR and RAS/MEK/ERK pathways is scientifically compelling, and a limited number of experimental agents are currently being tested in phase I combinations. Patient subpopulations, whose tumors are defined by genetic lesions, are showing promising responses to this approach.