tbuckley/cabot-search huggingface dataset:
A dual role for integrin-linked kinase in platelets: regulating integrin function and α-granule secretion
Authors: Katherine L. Tucker, Tanya Sage, Joanne M. Stevens, Peter A. Jordan, Sarah Jones, Natasha E. Barrett, Rene St-Arnaud, Jonathan Frampton, Shoukat Dedhar, Jonathan M. Gibbins
Journal: Blood (2008)

Integrin-linked kinase (ILK) has been implicated in the regulation of a range of fundamental biological processes such as cell survival, growth, differentiation, and adhesion. In platelets ILK associates with beta1- and beta3-containing integrins, which are of paramount importance for the function of platelets. Upon stimulation of platelets this association with the integrins is increased and ILK kinase activity is up-regulated, suggesting that ILK may be important for the coordination of platelet responses. In this study a conditional knockout mouse model was developed to examine the role of ILK in platelets. The ILK-deficient mice showed an increased bleeding time and volume, and despite normal ultrastructure the function of ILK-deficient platelets was decreased significantly. This included reduced aggregation, fibrinogen binding, and thrombus formation under arterial flow conditions. Furthermore, although early collagen stimulated signaling such as PLCgamma2 phosphorylation and calcium mobilization were unaffected in ILK-deficient platelets, a selective defect in alpha-granule, but not dense-granule, secretion was observed. These results indicate that as well as involvement in the control of integrin affinity, ILK is required for alpha-granule secretion and therefore may play a central role in the regulation of platelet function.
Human leukocyte antigen-G (HLA-G) expression in biliary epithelial cells is associated with allograft acceptance in liver-kidney transplantation
Authors: Caroline Créput, Antoine Durrbach, Catherine Menier, Catherine Guettier, Didier Samuel, Jean Dausset, Bernard Charpentier, Edgardo D Carosella, Nathalie Rouas-Freiss
Journal: Journal of Hepatology (2003)
Emotions, not just decision-making processes, are critical to an evolutionary model of human behavior
Authors: Glenn E. Weisfeld, Peter LaFreniere
Journal: Behavioral and Brain Sciences (2007)

An evolutionary model of human behavior should privilege emotions: essential, phylogenetically ancient behaviors that learning and decision making only subserve. Infants and non-mammals lack advanced cognitive powers but still survive. Decision making is only a means to emotional ends, which organize and prioritize behavior. The emotion of pride/shame, or dominance striving, bridges the social and biological sciences via internalization of cultural norms.
Small-Molecule Multidrug Resistance–Associated Protein 1 Inhibitor Reversan Increases the Therapeutic Index of Chemotherapy in Mouse Models of Neuroblastoma
Authors: Catherine A. Burkhart, Fujiko Watt, Jayne Murray, Marina Pajic, Anatoly Prokvolit, Chengyuan Xue, Claudia Flemming, Janice Smith, Andrei Purmal, Nadezhda Isachenko, Pavel G. Komarov, Katerina V. Gurova, Alan C. Sartorelli, Glenn M. Marshall, Murray D. Norris, Andrei V. Gudkov, Michelle Haber
Journal: Cancer Research (2009)

Abstract The multidrug resistance–associated protein 1 (MRP1) has been closely linked to poor treatment response in several cancers, most notably neuroblastoma. Homozygous deletion of the MRP1 gene in primary murine neuroblastoma tumors resulted in increased sensitivity to MRP1 substrate drugs (vincristine, etoposide, and doxorubicin) compared with tumors containing both copies of wild-type MRP1, indicating that MRP1 plays a significant role in the drug resistance in this tumor type and defining this multidrug transporter as a target for pharmacologic suppression. A cell-based readout system was created to functionally determine intracellular accumulation of MRP1 substrates using a p53-responsive reporter as an indicator of drug-induced DNA damage. Screening of small-molecule libraries in this readout system revealed pyrazolopyrimidines as a prominent structural class of potent MRP1 inhibitors. Reversan, the lead compound of this class, increased the efficacy of both vincristine and etoposide in murine models of neuroblastoma (syngeneic and human xenografts). As opposed to the majority of inhibitors of multidrug transporters, Reversan was not toxic by itself nor did it increase the toxicity of chemotherapeutic drug exposure in mice. Therefore, Reversan represents a new class of nontoxic MRP1 inhibitor, which may be clinically useful for the treatment of neuroblastoma and other MRP1-overexpressing drug-refractory tumors by increasing their sensitivity to conventional chemotherapy. [Cancer Res 2009;69(16):6573–80]
Hyperfractionated Versus Conventional Radiotherapy Followed by Chemotherapy in Standard-Risk Medulloblastoma: Results From the Randomized Multicenter HIT-SIOP PNET 4 Trial
Authors: Birgitta Lannering, Stefan Rutkowski, Francois Doz, Barry Pizer, Göran Gustafsson, Aurora Navajas, Maura Massimino, Roel Reddingius, Martin Benesch, Christian Carrie, Roger Taylor, Lorenza Gandola, Thomas Björk-Eriksson, Jordi Giralt, Foppe Oldenburger, Torsten Pietsch, Dominique Figarella-Branger, Keith Robson, Marco Forni, Steven C. Clifford, Monica Warmuth-Metz, Katja von Hoff, Andreas Faldum, Véronique Mosseri, Rolf Kortmann
Journal: Journal of Clinical Oncology (2012)

To compare event-free survival (EFS), overall survival (OS), pattern of relapse, and hearing loss in children with standard-risk medulloblastoma treated by postoperative hyperfractionated or conventionally fractionated radiotherapy followed by maintenance chemotherapy.In all, 340 children age 4 to 21 years from 122 European centers were postoperatively staged and randomly assigned to treatment with hyperfractionated radiotherapy (HFRT) or standard (conventional) fractionated radiotherapy (STRT) followed by a common chemotherapy regimen consisting of eight cycles of cisplatin, lomustine, and vincristine.After a median follow-up of 4.8 years (range, 0.1 to 8.3 years), survival rates were not significantly different between the two treatment arms: 5-year EFS was 77% ± 4% in the STRT group and 78% ± 4% in the HFRT group; corresponding 5-year OS was 87% ± 3% and 85% ± 3%, respectively. A postoperative residual tumor of more than 1.5 cm(2) was the strongest negative prognostic factor. EFS of children with all reference assessments and no large residual tumor was 82% ± 2% at 5 years. Patients with a delay of more than 7 weeks to the start of RT had a worse prognosis. Severe hearing loss was not significantly different for the two treatment arms at follow-up.In this large randomized European study, which enrolled patients with standard-risk medulloblastoma from more than 100 centers, excellent survival rates were achieved in patients without a large postoperative residual tumor and without RT treatment delays. EFS and OS for HFRT was not superior to STRT, which therefore remains standard of care in this disease.
Redox Cycling for Passive Modification of Polypyrrole Surface Properties: Effects on Cell Adhesion and Proliferation
Authors: Kartik M. Sivaraman, Berna Özkale, Olgaç Ergeneman, Tessa Lühmann, Giuseppino Fortunato, Muhammad Arif Zeeshan, Bradley J. Nelson, Salvador Pané
Journal: Advanced Healthcare Materials (2012)

Abstract The surface properties of electrodeposited poly(pyrrole) (Ppy) doped with sodium dodecylbenzenesulphonate (NaDBS) are modified by two methods: addition of poly(ethylene glycol) (PEG) during the electrodeposition and through redox cycling post electrodeposition. X‐ray photoelectron spectroscopy (XPS) was used to ascertain PEG incorporation and to analyze the change in the oxidation state of the polymer. Anodic cycling resulted in the formation of micrometer‐sized surface cracks which increased the amount of Rhodamine‐B dye adsorbed onto the surface, and played a role in decreasing the wettability of the surface. The change in surface wettability caused by these cracks was mitigated by the presence of PEG in the Ppy matrix. Compared to the incorporation of PEG, redox cycling was more effective in passively modulating the adhesion of NIH 3T3 fibroblast cells on the Ppy surface. Based on the attenuation of surface polarity of the Ppy surfaces by the incorporated PEG, a mechanism is proposed to explain the observed cell adhesion behavior.
Effects of an acute exacerbation on nutritional and metabolic profile of patients with COPD
Authors: MA Vermeeren, AM Schols, EF Wouters
Journal: European Respiratory Journal (1997)

In this study, we investigated the influence of an acute disease exacerbation on the nutritional and metabolic status of patients with chronic obstructive pulmonary disease (COPD). The study group consisted of 23 patients acutely admitted to the hospital for standardized medical treatment. Dietary intake (dietary records and diet history), resting energy expenditure (ventilated hood), body composition (bioelectrical impedance spectroscopy) and disease symptoms (visual analogue scale) were assessed on admission, daily throughout the hospitalization period, at discharge and 3 months thereafter in stable clinical condition. Dietary intake, since aggravation of disease symptoms, prior to admission, (5,640+/-2,671 kJ) was significantly lower than habitual intake (7,863+/-2,005 kJ). The balance between dietary intake with measured resting energy expenditure and estimated diet-induced thermogenesis was severely impaired during the first 3 days of hospitalization, stabilizing thereafter to 145+/-24% at discharge. Resting energy expenditure decreased from 6,812+/-900 kJ (123+/-11%) on admission to 6,196+/-795 kJ (113+/-14%) at discharge (p&lt;0.001). During treatment, no significant shift in water compartments, fat-free mass and body weight was seen. Follow-up data were obtained from 10 out of 23 patients. Three months after admission, dietary intake was not significantly different from usual dietary intake (8,512+/-2,290 and 8,415+/-2,600 kJ, respectively), resting energy expenditure was similar to the value at discharge, and a significant body weight gain was seen. We conclude that an acute exacerbation of chronic obstructive pulmonary disease is accompanied by an impaired energy balance due to a decreased dietary intake and an increased resting energy expenditure.
Priorities for Research in Complementary Medicine
Authors: D Melchart, E Ernst
Journal: Journal of the Royal Society of Medicine (2001)

The House of Lords' report on complementary and alternative medicine (CAM) recommends that adequate research funds for CAM should be created in the UK. This raises the question about research priorities in this area. In 1996, we reported a (1995) survey of CAM researchers' views on this matter1. The same survey instrument was used again in 2000, at another international conference on CAM research (Evidence-based Complementary Medicine—State of the Evidence, Methodological Challenges, Technische Universitat, Munich, April 2000). Table 1 shows the three answers with the highest level of priority in both years. The remarkable stability of these results over 5 years suggests that assessment of efficacy and safety as well as development of research tools are true priorities for CAM research of the future.



Table 1

Survey responses
Decreased Non–Insulin-Dependent Glucose Clearance Contributes to the Rise in Fasting Plasma Glucose in the Nondiabetic Range
Authors: Rucha Jani, Marjorie Molina, Masafumi Matsuda, Bogdan Balas, Alberto Chavez, Ralph A. DeFronzo, Muhammad Abdul-Ghani
Journal: Diabetes Care (2008)

To assess the contribution of decreased glucose clearance to the rise in fasting plasma glucose (FPG) in the nondiabetic range.A total of 120 subjects with normal glucose tolerance received an oral glucose tolerance test and euglycemic insulin clamp with 3-[(3)H]glucose. The basal and insulin-stimulated rates of glucose appearance, glucose disappearance, and glucose clearance and the basal hepatic insulin resistance index were calculated. Simple Pearson's correlation was used to assess the relationship between variables.The increase in FPG (range 75-125 mg/dl) correlated (r = 0.32, P < 0.0001) with the increase in BMI (20-50 kg/m(2)). The fasting plasma insulin (FPI) concentration also increased progressively with the increase in BMI (r = 0.62, P < 0.0001). However, despite increasing FPI, the basal glucose clearance rate declined and correlated with the increase in BMI (r = -0.56, P < 0.0001). Basal hepatic glucose production (HGP) decreased with increasing BMI (r = -0.51, P < 0.0001) and correlated inversely with the increase in FPI (r = -0.32, P < 0.0001). The hepatic insulin resistance (basal HGP x FPI) increased with rising BMI (r = 0.52, P < 0.0001). During the insulin clamp, glucose disposal declined with increasing BMI (r = -0.64, P < 0.0001) and correlated with the basal glucose clearance (r = 0.39, P < 0.0001).These results demonstrate that in nondiabetic subjects, rising FPG is associated with a decrease (not an increase) in basal hepatic glucose production and is explained by a reduction in glucose clearance.
Premature vascular ageing in cystic fibrosis
Authors: W. MacNee
Journal: European Respiratory Journal (2009)

t is increasingly recognised that chronic inflammatory disorders of the lungs, such as chronic obstructive pulmonary disease (COPD), and other organs, such as rheumatoid arthritis, are associated with systemic effects that result in comorbidities [1,2].Cystic fibrosis (CF) has also been shown to have systemic effects, for example loss of muscle mass and decreased bone density associated with a systemic inflammatory response [3].A further systemic effect of chronic inflammatory conditions, such as COPD and rheumatoid arthritis, is the development of systemic vascular abnormalities with resultant cardiovascular comorbidity [4, 5], which has important adverse effects on morbidity and mortality in these conditions.Many of these comorbid conditions are a feature of ageing, and it has been suggested that the presence of these comorbidities reflects an accelerated ageing process in conditions such as COPD [6].
Inpatient care of mentally ill people in prison: results of a year's programme of semistructured inspections
Authors: J. L Reed
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To investigate the facilities for inpatient care of mentally disordered people in prison. <b>Design:</b> Semistructured inspections conducted by doctor and nurse. Expected standards were based on healthcare quality standards published by the Prison Service or the NHS. <b>Setting:</b> 13 prisons with inpatient beds in England and Wales subject to the prison inspectorate9s routine inspection programme during 1997-8. <b>Main outcomes measures:</b> Appraisals of quality of care against published standards. <b>Results:</b> The 13 prisons had 348 beds, 20% of all beds in prisons. Inpatient units had between 3 and 75 beds. No doctor in charge of inpatients had completed specialist psychiatric training. 24% of nursing staff had mental health training; 32% were non-nursing trained healthcare officers. Only one prison had occupational therapy input; two had input from a clinical psychologist. Most patients were unlocked for about 3.5 hours a day and none for more than nine hours a day. Four prisons provided statistics on the use of seclusion. The average length of an episode of seclusion was 50 hours. <b>Conclusion:</b> The quality of services for mentally ill prisoners fell far below the standards in the NHS. Patients9 lives were unacceptably restricted and therapy limited. The present policy dividing inpatient care of mentally disordered prisoners between the prison service and the NHS needs reconsideration.
5′-triphosphate-siRNA: turning gene silencing and Rig-I activation against melanoma
Authors: Hendrik Poeck, Robert Besch, Cornelius Maihoefer, Marcel Renn, Damia Tormo, Svetlana Shulga Morskaya, Susanne Kirschnek, Evelyn Gaffal, Jennifer Landsberg, Johannes Hellmuth, Andreas Schmidt, David Anz, Michael Bscheider, Tobias Schwerd, Carola Berking, Carole Bourquin, Ulrich Kalinke, Elisabeth Kremmer, Hiroki Kato, Shizuo Akira, Rachel Meyers, Georg Häcker, Michael Neuenhahn, Dirk Busch, Jürgen Ruland, Simon Rothenfusser, Marco Prinz, Veit Hornung, Stefan Endres, Thomas Tüting, Gunther Hartmann
Journal: Nature Medicine (2008)
Genetic and morphological findings in progressive familial intrahepatic cholestasis (Byler disease [PFIC-1] and Byler syndrome): Evidence for heterogeneity
Authors: L N Bull, V E Carlton, N L Stricker, S Baharloo, J A DeYoung, N B Freimer, M S Magid, E Kahn, J Markowitz, F J DiCarlo, L McLoughlin, J T Boyle, B B Dahms, P R Faught, J F Fitzgerald, D A Piccoli, C L Witzleben, N C O'Connell, K D Setchell, R M Agostini, S A Kocoshis, J Reyes, A S Knisely
Journal: Hepatology (1997)

Byler disease (ByD) is an autosomal recessive disorder in which cholestasis of onset in infancy leads to hepatic fibrosis and death. Children who have a clinically similar disorder, but are not members of the Amish kindred in which ByD was described, are said to have Byler syndrome (ByS). Controversy exists as to whether ByD and ByS (subtypes of progressive familial intrahepatic cholestasis [PFIC]) represent one clinicopathological entity. The gene for ByD has been mapped to a 19-cM region of 18q21-q22. PFIC caused by a lesion in this region, including ByD, can be designated PFIC-1. Examination of haplotypes in siblings with ByS in two unrelated non-Amish families showed that the gene(s) responsible for their disorder(s) did not lie in the PFIC-1 candidate region. On light microscopy and transmission electron microscopy (TEM), liver tissue differed between Amish children with PFIC-1, who had coarsely granular bile and at presentation had bland intracanalicular cholestasis, and the children with ByS in the two non-Amish families, who had amorphous or finely filamentous bile and at presentation had neonatal hepatitis. Bile acid composition of bile also differed: In the Amish children with PFIC-1 and in one ByS family, the proportional concentration of chenodeoxycholic acid (CDCA) in bile was low compared with normal bile; in the other ByS family, it was only slightly reduced. Genetic analysis and light microscopy and TEM of liver may help distinguish PFIC-1 from other forms of ByS.
Models of decision-making and the coevolution of social preferences
Authors: Joseph Henrich, Robert Boyd, Samuel Bowles, Colin Camerer, Ernst Fehr, Herbert Gintis, Richard McElreath, Michael Alvard, Abigail Barr, Jean Ensminger, Natalie Smith Henrich, Kim Hill, Francisco Gil-White, Michael Gurven, Frank W. Marlowe, John Q. Patton, David Tracer
Journal: Behavioral and Brain Sciences (2005)

We would like to thank the commentators for their generous comments, valuable insights and helpful suggestions. We begin this response by discussing the selfishness axiom and the importance of the preferences, beliefs, and constraints framework as a way of modeling some of the proximate influences on human behavior. Next, we broaden the discussion to ultimate-level (that is evolutionary) explanations, where we review and clarify gene-culture coevolutionary theory, and then tackle the possibility that evolutionary approaches that exclude culture might be sufficient to explain the data. Finally, we consider various methodological and epistemological concerns expressed by our commentators.
Maternal Exposure to Air Pollution and Birth Outcomes
Authors: Ebba Malmqvist, Anna Rignell-Hydbom, Håkan Tinnerberg, Jonas Björk, Emilie Stroh, Kristina Jakobsson, Ralf Rittner, Lars Rylander
Journal: Environmental Health Perspectives (2011)

The knowledge about air pollution effects on birth weight, prematurity, and small for gestational age (SGA) in low-exposure areas is insufficient.The aim of this birth cohort study was to investigate whether low-level exposure to air pollution was associated with prematurity and fetal growth and whether there are sex-specific effects.We combined high-quality registry information on 81,110 births with individually modeled exposure data at residence for nitrogen oxides (NO(x)) and proximity to roads with differing traffic density. The data were analyzed by logistic and linear regression with and without potential confounders.We observed an increased risk for babies being SGA when we compared highest and lowest NO(x) quartiles, adjusting for maternal age, smoking, sex, and year of birth. After additional adjustment for maternal country of origin and parity (which were highly intercorrelated), the increase was no longer statistically significant. However, in subgroup analyses when we compared highest and lowest NO(x) quartiles we still observed an increased risk for SGA for girls [odds ratio (OR)=1.12; 95% confidence interval (CI), 1.01-1.24); we also observed increased risk among mothers who had not changed residency during pregnancy (OR=1.09; 95% CI, 1.01-1.18). The confounders with the greatest impact on SGA were parity and country of origin. Concerning prematurity, the prevalence was lower in the three higher NO(x) exposure quartiles compared with the lowest category.For future studies on air pollution effects on birth outcomes, careful control of confounding is crucial.
Obituary: Henry A. Magnus
Authors: F. A. Jones
Journal: Gut (1967)

Animal models have demonstrated that mild hearing loss caused by acoustic trauma results in spontaneous hyperactivity in the central auditory pathways. This hyperactivity has been hypothesized to be involved in the generation of tinnitus, a phantom auditory sensation. We have recently shown that such hyperactivity, recorded in the inferior colliculus, is still dependent on cochlear neural output for some time after recovery (up to 6 weeks). We have now studied the capacity of an intrinsic efferent system, i.e., the olivocochlear system, to alter hyperactivity. This system is known to modulate cochlear neural output. Anesthetized guinea pigs were exposed to a loud sound and after 2 or 3 weeks of recovery, single-neuron recordings in inferior colliculus were made to confirm hyperactivity. Olivocochlear axons were electrically stimulated and effects on cochlear neural output and on highly spontaneous neurons in inferior colliculus were assessed. Olivocochlear stimulation suppressed spontaneous hyperactivity in the inferior colliculus. This result is in agreement with our earlier finding that hyperactivity can be modulated by altering cochlear neural output. Interestingly, the central suppression was generally much larger and longer lasting than reported previously for primary afferents. Blockade of the intracochlear effects of olivocochlear system activation eliminated some but not all of the effects observed on spontaneous activity, suggesting also a central component to the effects of stimulation. More research is needed to investigate whether these central effects of olivocochlear efferent stimulation are due to central intrinsic circuitry or to coactivation of central efferent collaterals to the cochlear nucleus.
Prospective transGEICAM study of the impact of the 21-gene Recurrence Score assay and traditional clinicopathological factors on adjuvant clinical decision making in women with estrogen receptor-positive (ER+) node-negative breast cancer
Authors: J. Albanell, A. González, M. Ruiz-Borrego, E. Alba, J.A. García-Saenz, J.M. Corominas, O. Burgues, V. Furio, A. Rojo, J. Palacios, B. Bermejo, M. Martínez-García, M.L. Limon, A.S. Muñoz, M. Martín, I. Tusquets, F. Rojo, R. Colomer, I. Faull, A. Lluch
Journal: Annals of Oncology (2011)

This study examined the impact of the Recurrence Score (RS) in Spanish breast cancer patients and explored the associations between clinicopathological markers and likelihood of change in treatment recommendations.