tbuckley/cabot-search huggingface dataset:
ASCO Core Values: Essential to Progress in Innovative, Quality Cancer Care
Authors: Sandra J. Horning
Journal: Journal of Clinical Oncology (2006)

Advances in cancer diagnosis, treatment, and supportive care have converged to result in dramatic changes in cancer mortality.Despite population growth and aging, the past year marked the first decline in cancer deaths in the United States since cancer statistics were initially recorded in 1931, and both early detection and improved treatments have led to an increase in overall cancer survivorship.Today, the total number of cancer survivors in the United States exceeds 10 million, compared with 3 million in 1971.As a member of the oncology community, I am proud of these accomplishments.However, even in this era of great advances in basic and clinical science-and sometimes because of them-we face significant challenges.The rising costs of oncology treatment and the chasms created by health disparities can preclude equal access to treatment, and the commercial nature of the United States health care industry may create either the perception of or actual conflicts of interest that erode the public trust.We must ensure that these challenges do not slow the pace of research or delay the development and delivery of new oncology products to all cancer patients.Upholding the highest professional standards, ensuring equitable access to treatment, and maintaining the trust of our patients are essential if we are to maintain our momentum.With these objectives, the American Society of Clinical Oncology (ASCO) recently revised its Core Values to reflect the Society's aspirations and document the fundamental elements of professional ethical behavior in the realm of oncology care: commitment, integrity, competence, innovation, and inclusivity.By articulating these values, ASCO reaffirms its commitment to keep them central to our mission and activities.ASCO advises oncologists to adhere to these principles in their interactions with patients, colleagues and the health care industry.In this issue of the Journal of Clinical Oncology, readers will find a Special Article by Dr Rebecca Pentz et al 1 in which the authors discuss the history of physician codes, including ASCO's Core Values, and use examples to highlight how these values apply in daily oncology practice.ASCO strives to abide by these principles in its own work.Through initiatives like the Quality Oncology Practice Initiative (QOPI), which was recently expanded to all members, ASCO has
Interleukin (IL) 4 differentially regulates monocyte IL-1 family gene expression and synthesis in vitro and in vivo.
Authors: H L Wong, G L Costa, M T Lotze, S M Wahl
Journal: The Journal of Experimental Medicine (1993)

Interleukin (IL) 4 is a multifunctional T cell-derived cytokine that inhibits cytokine production and certain effector functions in human monocytes, while enhancing others. We show that IL-4 may contribute to the downregulation and resolution of an inflammatory response by selectively promoting expression of the IL-1 receptor antagonist (IL-1ra) that blocks the action of IL-1. IL-1ra specifically binds to the IL-1 receptor without initiating signal transduction. Peripheral blood monocytes obtained from cancer patients, before and immediately after a regimen of IL-4 immunotherapy, were examined for IL-1ra gene expression. After IL-4 therapy, monocytes from the patients showed a marked increase in IL-1ra mRNA. This selective induction of IL-1ra mRNA in circulating monocytes was reflected by significantly enhanced serum levels of IL-1ra (p < 0.01) during IL-4 therapy, which declined after IL-4 treatment. In vitro analysis of IL-4 regulation of monocytes from normal individuals revealed a dose-dependent induction of IL-1ra mRNA within 2-4 h after stimulation without a concomitant effect on the expression of IL-1 mRNA. Increased IL-1ra mRNA was not due to RNA stabilization, but occurred at the level of transcription. In the presence of LPS, IL-4 not only augmented IL-1ra levels, but markedly inhibited LPS-induced IL-1 mRNA expression. The selective upregulation of IL-1ra by resting or activated monocytes, coupled with inhibition of IL-1 production by activated monocytes, as we demonstrate both in vitro and in vivo, suggests that IL-4 may prove clinically useful as a systemic antiinflammatory agent.
A Population of Multipotent CD34-Positive Adipose Stromal Cells Share Pericyte and Mesenchymal Surface Markers, Reside in a Periendothelial Location, and Stabilize Endothelial Networks
Authors: Dmitry O. Traktuev, Stephanie Merfeld-Clauss, Jingling Li, Mikhail Kolonin, Wadih Arap, Renata Pasqualini, Brian H. Johnstone, Keith L. March
Journal: Circulation Research (2007)

It has been shown that stromal–vascular fraction isolated from adipose tissues contains an abundance of CD34 + cells. Histological analysis of adipose tissue revealed that CD34 + cells are widely distributed among adipocytes and are predominantly associated with vascular structures. The majority of CD34 + cells from freshly isolated stromal–vascular fraction were CD31 − /CD144 − and could be separated from a distinct population of CD34 + /CD31 + /CD144 + (endothelial) cells by differential attachment on uncoated plastic. The localization of CD34 + cells within adipose tissue suggested that the nonendothelial population of these cells occupied a pericytic position. Analysis of surface and intracellular markers of the freshly isolated CD34 + /CD31 − /CD144 − adipose-derived stromal cells (ASCs) showed that &gt;90% coexpress mesenchymal (CD10, CD13, and CD90), pericytic (chondroitin sulfate proteoglycan, CD140a, and CD140b), and smooth muscle (α-actin, caldesmon, and calponin) markers. ASCs demonstrated polygonal self-assembly on Matrigel, as did human microvascular endothelial cells. Coculture of ASCs with human microvascular endothelial cells on Matrigel led to cooperative network assembly, with enhanced stability of endothelial networks and preferential localization of ASCs on the abluminal side of cords. Bidirectional paracrine interaction between these cells was supported by identification of angiogenic factors (vascular endothelial growth factor, hepatocyte growth factor, basic fibroblast growth factor), inflammatory factors (interleukin-6 and -8 and monocyte chemoattractant protein-1 and -2), and mobilization factors (macrophage colony-stimulating factor and granulocyte/macrophage colony-stimulating factor) in media conditioned by CD34 + ASCs, as well a robust mitogenic response of ASCs to basic fibroblast growth factor, epidermal growth factor, and platelet-derived growth factor-BB, factors produced by endothelial cells. These results demonstrate for the first time that the majority of adipose-derived adherent CD34 + cells are resident pericytes that play a role in vascular stabilization by mutual structural and functional interaction with endothelial cells.
Brain Response to Empathy-Eliciting Scenarios Involving Pain in Incarcerated Individuals With Psychopathy
Authors: Jean Decety, Laurie R. Skelly, Kent A. Kiehl
Journal: JAMA Psychiatry (2013)

<h3>Importance</h3>A marked lack of empathy is a hallmark characteristic of individuals with psychopathy. However, neural processes associated with empathic processing have not yet been directly examined in psychopathy, especially in response to the perception of other people in pain and distress.<h3>Objective</h3>To identify potential differences in patterns of neural activity in incarcerated individuals with psychopathy and incarcerated persons serving as controls during the perception of empathy-eliciting stimuli depicting other people experiencing pain.<h3>Design</h3>In a case-control study, brain activation patterns elicited by dynamic stimuli depicting individuals being harmed and facial expressions of pain were compared between incarcerated individuals with psychopathy and incarcerated controls.<h3>Setting</h3>Participants were scanned on the grounds of a correctional facility using the Mind Research Network's mobile 1.5-T magnetic resonance imaging system.<h3>Participants</h3>Eighty incarcerated men were classified according to scores on the Hare Psychopathy Checklist–Revised (PCL-R) as high (27 men; PCL-R, ≥30), intermediate (28 men; PCL-R, 21-29), or low (25 men; PCL-R, ≤20) levels of psychopathy.<h3>Main Outcome Measure</h3>Neurohemodynamic response to empathy-eliciting dynamic scenarios revealed by functional magnetic resonance imaging.<h3>Results</h3>Participants in the psychopathy group exhibited significantly less activation in the ventromedial prefrontal cortex, lateral orbitofrontal cortex, and periaqueductal gray relative to controls but showed greater activation in the insula, which was positively correlated with scores on both PCL-R factors 1 and 2.<h3>Conclusions and Relevance</h3>In response to pain and distress cues expressed by others, individuals with psychopathy exhibit deficits in the ventromedial prefrontal cortex and orbitofrontal cortex regardless of stimulus type and display selective impairment in processing facial cues of distress in regions associated with cognitive mentalizing. A better understanding of the neural responses to empathy-eliciting stimuli in psychopathy is necessary to inform intervention programs.
Shear Stress–Mediated Arterial Remodeling in Atherosclerosis
Authors: Annemarie E. Silver, Joseph A. Vita
Journal: Circulation (2006)

nder physiological conditions, chronic changes in blood flow stimulate compensatory changes in arterial size.This arterial remodeling process occurs during normal growth and development and contributes to the adaptive response to a variety of clinical situations.For example, repetitive increases in blood flow during exercise may stimulate expansive remodeling of conduit arteries in the limbs and heart, 1 whereas chronic disuse of the lower extremities as a result of spinal cord injury is associated with constrictive remodeling of the femoral arteries. 2Uterine arteries display expansive remodeling during pregnancy and then undergo constrictive remodeling after delivery.Thus, dynamic remodeling of the arterial tree plays a critical role in maintaining the appropriate balance between tissue demand and blood supply throughout life.
PREDICTIVE VALUE OF GLASGOW COMA SCORE FOR AWAKENING AFTER OUT-OF-HOSPITAL CARDIAC ARREST
Authors: Arsène Mullie, Walter Buylaert, Noella Michem, Herman Verbruggen, Luc Corne, Rita De Cock, Jef Mennes, Agnes Quets, Paul Verstringe, Harry Houbrechts, Herman Delooz, Lut van den Broeck, Door Lauwaert, Mark Weeghmans, Leo Bossaert, Paul Lewi
Journal: The Lancet (1988)
Efficacy of Sertraline in Prevention of Depression Recurrence in Older Versus Younger Adults With Diabetes
Authors: Monique M. Williams, Ray E. Clouse, Billy D. Nix, Eugene H. Rubin, Gregory S. Sayuk, Janet B. McGill, Alan J. Gelenberg, Paul S. Ciechanowski, Irl B. Hirsch, Patrick J. Lustman
Journal: Diabetes Care (2007)

Sertraline maintenance therapy effectively delays recurrence of major depressive disorder in adult diabetic patients when data are examined across all age-groups. A secondary analysis was performed to assess this effect in younger and older subsets of patients.Younger (aged <55 years, n = 85) and older (aged > or =55 years, n = 67) subsets were identified from a multicenter, double-blind, placebo-controlled, maintenance treatment trial of sertraline in diabetic participants who achieved depression recovery with open-label sertraline treatment. Cox proportional hazards models were used to determine differences in time to depression recurrence between treatment arms (sertraline or placebo) for each age subset and between age subsets for each treatment.In younger subjects, sertraline conferred significantly greater prophylaxis against depression recurrence than placebo (hazard ratio 0.37 [95% CI 0.20-0.71]; P = 0.003). Benefits of sertraline maintenance therapy were lost in older participants (0.94 [0.39-2.29]; P = 0.89). There was no difference in time to recurrence for sertraline-treated subjects between age subsets (P = 0.65), but older subjects had a significantly longer time to recurrence on placebo than younger subjects (P = 0.03).While sertraline significantly increased the time to depression recurrence in the younger diabetic participants, there was no treatment effect in those aged > or =55 years because of a high placebo response rate. Further research is necessary to determine the mechanisms responsible for this effect and whether depression maintenance strategies specific for older patients with diabetes should be developed.
Efficacy and safety of lesogaberan in gastro-oesophageal reflux disease: a randomised controlled trial
Authors: Nicholas J Shaheen, Hans Denison, Karin Björck, Maria Karlsson, Debra G Silberg
Journal: Gut (2012)

<h3>Objective</h3> Lesogaberan (AZD3355) is a novel γ-aminobutyric acid B-type receptor agonist designed to treat gastro-oesophageal reflux disease (GERD) by inhibiting transient lower oesophageal sphincter relaxations. A randomised, double-blind, placebo-controlled, multi-centre phase IIb study was performed to assess the efficacy and safety of lesogaberan as an add-on to proton pump inhibitor (PPI) therapy in patients with GERD who are partially responsive to PPI therapy (ClinicalTrials.gov reference: NCT01005251). <h3>Design</h3> In total, 661 patients were randomised to receive 4 weeks of placebo or 60, 120, 180 or 240 mg of lesogaberan twice daily, in addition to ongoing PPI therapy. Symptoms were measured using the Reflux Symptom Questionnaire electronic Diary. Response to treatment was defined as having an average of ≥3 additional days per week of not more than mild GERD symptoms during treatment compared with baseline. <h3>Results</h3> In the primary analysis, 20.9%, 25.6%, 23.5% and 26.2% of patients responded to the 60, 120, 180 and 240 mg twice daily lesogaberan doses, respectively, and 17.9% responded to placebo. The response to the 240 mg twice daily dose was statistically significantly greater than the response to placebo using a one-sided test at the predefined significance level of p&lt;0.1. However, the absolute increases in the proportions of patients who responded to lesogaberan compared with placebo were low. Lesogaberan was generally well tolerated, although six patients receiving lesogaberan developed reversible elevated alanine transaminase levels. <h3>Conclusions</h3> In patients with GERD symptoms partially responsive to PPI therapy, lesogaberan was only marginally superior to placebo in achieving an improvement in symptoms.
Reduction of exercise-induced asthma in children by short, repeated warm ups
Authors: C de Bisschop, H Guenard, P Desnot, J Vergeret
Journal: British Journal of Sports Medicine (1999)

To study the effect of a warm up schedule on exercise-induced asthma in asthmatic children to enable them to engage in asthmogenic activities.In the first study, peak flows during and after three short, repeated warm up schedules (SRWU 1, 2, and 3), identical in form but differing in intensity, were compared in 16 asthmatic children. In the second study the efficiency of the best of these SRWU schedules was tested on 30 young asthmatic children. Children performed on different days a 7 minute run alone (EX1) or the same run after an SRWU (EX2).The second study showed that for most children (24/30) the fall in peak flow after EX2 was less than that after EX1. The percentage fall in peak flow after EX2 was significantly correlated with the percentage change in peak flow induced by SRWU2 (r = 0.68). The children were divided into three subgroups according to the change in peak flow after SRWU2: (G1: increase in peak flow; G2: < 15% fall in peak flow; G3: > 15% fall in peak flow). Only the children in the G3 subgroup did not show any gain in peak flow after EX2 compared with EX1.The alteration in peak flow at the end of the SRWU period was a good predictor of the occurrence of bronchoconstriction after EX2. An SRWU reduced the decrease in peak flow for most of the children (24/30) in this series, thus reducing subsequent post-exercise deep bronchoconstriction.
Informatic and Functional Approaches to Identifying a Regulatory Region for the Cardiac Sodium Channel
Authors: Thomas C. Atack, Dina Myers Stroud, Hiroshi Watanabe, Tao Yang, Lynn Hall, Susan B. Hipkens, John S. Lowe, Brenda Leake, Mark A. Magnuson, Ping Yang, Dan M. Roden
Journal: Circulation Research (2011)

Although multiple lines of evidence suggest that variable expression of the cardiac sodium channel gene SCN5A plays a role in susceptibility to arrhythmia, little is known about its transcriptional regulation.We used in silico and in vitro experiments to identify possible noncoding sequences important for transcriptional regulation of SCN5A. The results were extended to mice in which a putative regulatory region was deleted.We identified 92 noncoding regions highly conserved (>70%) between human and mouse SCN5A orthologs. Three conserved noncoding sequences (CNS) showed significant (>5-fold) activity in luciferase assays. Further in vitro studies indicated one, CNS28 in intron 1, as a potential regulatory region. Using recombinase-mediated cassette exchange (RMCE), we generated mice in which a 435-base pair region encompassing CNS28 was removed. Animals homozygous for the deletion showed significant increases in SCN5A transcripts, Na(V)1.5 protein abundance, and sodium current measured in isolated ventricular myocytes. ECGs revealed a significantly shorter QRS (10.7±0.2 ms in controls versus 9.7±0.2 ms in knockouts), indicating more rapid ventricular conduction. In vitro analysis of CNS28 identified a short 3' segment within this region required for regulatory activity and including an E-box motif. Deletion of this segment reduced reporter activity to 3.6%±0.3% of baseline in CHO cells and 16%±3% in myocytes (both P<0.05), and mutation of individual sites in the E-box restored activity to 62%±4% and 57%±2% of baseline in CHO cells and myocytes, respectively (both P<0.05).These findings establish that regulation of cardiac sodium channel expression modulates channel function in vivo, and identify a noncoding region underlying this regulation.
The relationship between ambient particulate matter and respiratory mortality: a multi-city study in Italy
Authors: A. Faustini, M. Stafoggia, G. Berti, L. Bisanti, M. Chiusolo, A. Cernigliaro, S. Mallone, R. Primerano, C. Scarnato, L. Simonato, M.A. Vigotti, F. Forastiere
Journal: European Respiratory Journal (2011)

The association of air pollutants with natural and respiratory mortality has been consistently reported. However, several aspects of the relationship between particulate matter with a 50% cut-off aerodynamic diameter of 10 μm (PM 10 ) and respiratory mortality require further investigation. The aim of the present study was to assess the PM 10 –respiratory mortality association in Italy and examine potentially susceptible groups. All deaths from natural (n=276,205) and respiratory (n=19,629) causes among subjects aged ≥35 yrs in 10 northern, central and southern Italian cities in 2001–2005 were included in the study. Pollution data for PM 10 , nitrogen dioxide and ozone were also obtained. A time-stratified case-crossover analysis was carried out. Different cumulative lags were selected to analyse immediate, delayed, prolonged and best-time effects of air pollution. The shape of the exposure–response curve was analysed. Age, sex, chronic conditions and death site were investigated as potential effect modifiers. We found a 2.29% (95% CI 1.03–3.58%) increase in respiratory mortality at 0–3 days lag. The increase in respiratory mortality was higher in summer (7.57%). The exposure–response curve had a linear shape without any threshold. Sex and chronic diseases modified the relationship between particular matter (PM) and respiratory mortality. The effect of PM on respiratory mortality was stronger and more persistent than that on natural mortality. Females and chronic disease sufferers were more likely to die of a respiratory disease caused by air pollution than males and healthy people.
Collateral Function in Chronic Total Coronary Occlusions Is Related to Regional Myocardial Function and Duration of Occlusion
Authors: Gerald S. Werner, Markus Ferrari, Stefan Betge, Oliver Gastmann, Barbara M. Richartz, Hans R. Figulla
Journal: Circulation (2001)

Collateral circulation can maintain myocardial function and viability in chronic total coronary occlusion (TCO). The present study evaluates the relation of myocardial function and duration of occlusion to collateral function.A total of 50 patients underwent a successful recanalization of a TCO (>4 weeks' duration). Collateral function was assessed by intracoronary Doppler and pressure recordings before the first balloon inflation and after PTCA had been completed. Collateral function was assessed by Doppler- (CFI(D)) and pressure-derived collateral flow indices (CFI(P)), as well as indices of collateral (R(Coll)) and peripheral resistance (R(P)). Patients with normokinesia had lower R(Coll) (4.9+/-2.5 versus 11.8+/-8.2 mm Hg. cm(-1). s(-1); P=0.033) and lower R(P) (3.8+/-1.9 versus 6.1+/-4.1 mm Hg. cm(-1). s(-1); P=0.031) than those with akinesia. Patients with akinesia and a TCO duration of </=3 months had the highest R(Coll) and R(P), whereas those with akinesia and a longer TCO duration had similar collateral function as patients with normokinesia. After PTCA, CFI(D) and CFI(P) decreased from 0.37+/-0.20 to 0.21+/-0.17 (P<0.001) and from 0.44+/-0.12 to 0.36+/-0.11 (P<0.001), respectively, with an increase in R(Coll) of 139+/-128% (P<0.001) and R(P) by 65+/-99% (P=0.003). This attenuation of collateral function was less pronounced with epicardial collaterals than with intramyocardial collaterals.Collateral function was better in patients with TCO and normal regional function than in those with impaired regional function. In the latter group, collateral function improvement was time dependent. After recanalization, the recruitable collateral function was attenuated because of an increase of R(Coll) and R(P).
Bacterial Endocarditis Following Cardiac Surgery
Authors: CLARENCE DENTON, ELIAS G. PAPPAS, JOSEPH F. URICCHIO, HARRY GOLDBERG, WILLIAM LIKOFF
Journal: Circulation (1957)

Intracardiac surgery for rheumatic and congenital heart disease entails direct trauma to both normal and abnormal endocardium. This communication inquires into the incidence and nature of the endocardial infections that develop subsequent to this injury. On the basis of an examination of 2,263 patients operated upon for acquired and congenital heart disease during a 5-year period terminating in November 1955, bacterial endocarditis appears to be an infrequent complication of surgery, is caused by organisms not so commonly encountered in unoperated patients, and is characterized by a clinical pattern quite different from that ordinarily associated with bacterial endocarditis. The rate of attrition in this group of patients is high, and unquestionably is related to the antibiotic resistance of the unusual organisms and the severity of the basic heart disease.