tbuckley/cabot-search huggingface dataset:
Cancer research papers with industry ties more likely to report favourable results
Authors: J. Hopkins Tanne
Journal: BMJ (2009)

Conflicts of interest are common in research papers on cancer, and papers with conflicts are more likely to report positive results, say researchers at the University of Michigan ( Cancer 2009 May 11, doi:10.1002/cncr.24315).

The study says that almost one in three of 1534 original papers in eight leading journals in 2006 had reported conflicts of interest, and 17% reported industry funding.

In studies where the authors reported a conflict of interest, 29% of the patients who had received the intervention had improved survival rates, and in studies whose authors had no reported conflict of interest that figure was only 14%.

Reshma Jagsi, an assistant professor of radiation oncology, and …
Interstitial lung disease in patients with mixed connective tissue disease
Authors: Harpreet K Lota
Journal: Thorax (2012)

Interstitial lung disease in patients with mixed connective tissue diseaseThis cross-sectional study evaluates the prevalence and severity of interstitial lung disease (ILD), with particular emphasis on CT evaluation, in an unselected, nationwide cohort of 126 Caucasian patients with mixed connective tissue disease (MCTD).Overall, high-resolution CT (HRCT) abnormalities were seen in half the number of patients.Although MCTD is characterised by overlap features between scleroderma (SSc), polymyositis/dermatomyositis (PM/DM) and systemic lupus erythematosus (SLE), the HRCT findings appeared remarkably homogenous.Reticular patterns were the most common, present in a third of patients, with coarse reticulation present only in a minority.As the authors discuss, the findings were consistent with a radiological pattern of non-specific interstitial pneumonia.Interestingly, although myositis occurred in the majority, areas of consolidation suggestive of organising pneumonia were absent, a feature frequently present in PM/DM.The HRCT features of MCTD, when tightly defined, would appear much more similar to a scleroderma-related ILD phenotype than to a PM/DM one.As the unifying feature for MCTD is anti-ribonucleoprotein antibody (anti-RNP) positivity, one could speculate that anti-RNP antibody associated ILD is in fact non-specific interstitial pneumonia, regardless of the associated clinical features, although this will require confirmation.After 4 years of follow-up, lung fibrosis was associated with increased mortality, highest in severe fibrosis (20.8%).Patients with severe fibrosis tended to be older, to have worse lung function/functional status, and to have shorter disease duration compared with those with minor/moderate fibrosis.This small but well-characterised cohort provides insight into the high prevalence and increased mortality of ILD in MCTD.Similar to ILD associated with other CTDs, patients with severe fibrosis likely represent a more progressive disease subset, and may benefit from early identification and timely immunosuppression.
Corn cereal sensitization in Maldivian children
Authors: Sukhbir Shahid
Journal: European Respiratory Journal (2013)

Background: Cereals form an important constituent of food. Corn is being increasingly used as an ingredient in a number of food preparations nowadays. It is known to be allergenic. There is to date no data on prevalence of corn allergy in allergic Maldivian children  Objective: We aimed to evaluate corn allergy in children presenting with allergy in our clinic  Methods: Children with allergic presentation were evaluated demographically. Their total serum IgE and specific IgE to 29 common food and aeroallergens including corn was estimated. Comparison was performed between children with positive corn IgE with those who proved negative to this test.  Results: 26/100 children was positive to corn allergen. There were significantly more females afflicted. Weight seemed unaffected by corn allergy. Presence of atopic dermatitis, eye and respiratory allergy did not differ between corn-sensitive and corn-stable children. Total IgE was also significantly raised in corn IgE positive children compared to those not allergic to corn (1893.60± 379.74 vs 248.61±40.25 IU/ml respectively). Food as well as aeroallergen index was higher in corn-allergic children. Wheat, milk, soyabean, coconut, egg white, dust and pollen allergy was commonly associated with corn allergy.  Conclusion: Corn allergy is seen in a quarter of allergic children in Maldives. Females suffer more from it and associated wheat allergy is common.
Antifibrillatory efficacy of ersentilide, a novel β-adrenergic and Ikr blocker, in conscious dogs with a healed myocardial infarction
Authors: Philip B. Adamson, Emilio Vanoli, Stephen S. Hull, Robert D. Foreman, Peter J. Schwartz
Journal: Cardiovascular Research (1998)

Objectives:IKr blockade is ineffective in preventing ventricular fibrillation elicited by the interaction between acute myocardial ischemia and elevated sympathetic activity. This depends in part on the fact that adrenergic activation offsets more than 50% of the action potential prolonging effect of IKr blockade, and thus impairs its primary mechanism of action. This study examined the antifibrillatory effect of ersentilide (CK-3579), a novel antiarrhythmic agent which combines blockade of the rapid component of the delayed rectifier potassium channel (IKr) with relatively weak β-adrenergic blockade, in a conscious canine model of lethal arrhythmias. Methods: Ersentilide was tested in 19 dogs with a healed myocardial infarction (MI) undergoing two minutes of circumflex artery occlusion (CAO) during sub-maximal treadmill exercise. Epicardial monophasic action potential duration was measured before and after ersentilide in 8 anesthetized open chest dogs at baseline and during stimulation of the left stellate ganglion at constant paced heart rate. Results: In the control tests 13 of the 19 dogs had ventricular fibrillation (VF) during the exercise and ischemia test, 6 did not. During a subsequent exercise test, ersentilide prevented VF in 85% (11 of 13) of the high risk animals and showed no proarrhythmic effects in the 6 dogs without arrhythmias in the initial test. Ersentilide lowered heart rate at all levels of exercise and during acute myocardial ischemia. The antifibrillatory effect was maintained in 3 of 4 dogs in which heart rate was kept at control levels by atrial pacing. Ersentilide prolonged left ventricular monophasic action potential duration by 30% (from 179±6 ms to 233±5 ms, p<0.001) at a 360 ms cycle length and completely prevented its shortening during sympathetic stimulation. Conclusions: The combination of IKr and weak β-adrenergic blockade, using ersentilide, represents a very effective and safe antiarrhythmic intervention able to overcome the limitations present in drugs devoid of any antiadrenergic effect. Such a combination may be very useful in the management of post-myocardial infarction patients at high arrhythmic risk.
mTOR Inhibitors Block Kaposi Sarcoma Growth by Inhibiting Essential Autocrine Growth Factors and Tumor Angiogenesis
Authors: Debasmita Roy, Sang-Hoon Sin, Amy Lucas, Raman Venkataramanan, Ling Wang, Anthony Eason, Veenadhari Chavakula, Isaac B. Hilton, Kristen M. Tamburro, Blossom Damania, Dirk P. Dittmer
Journal: Cancer Research (2013)

Abstract Kaposi sarcoma originates from endothelial cells and it is one of the most overt angiogenic tumors. In Sub-Saharan Africa, where HIV and the Kaposi sarcoma–associated herpesvirus (KSHV) are endemic, Kaposi sarcoma is the most common cancer overall, but model systems for disease study are insufficient. Here, we report the development of a novel mouse model of Kaposi sarcoma, where KSHV is retained stably and tumors are elicited rapidly. Tumor growth was sensitive to specific allosteric inhibitors (rapamycin, CCI-779, and RAD001) of the pivotal cell growth regulator mTOR. Inhibition of tumor growth was durable up to 130 days and reversible. mTOR blockade reduced VEGF secretion and formation of tumor vasculature. Together, the results show that mTOR inhibitors exert a direct anti-Kaposi sarcoma effect by inhibiting angiogenesis and paracrine effectors, suggesting their application as a new treatment modality for Kaposi sarcoma and other cancers of endothelial origin. Cancer Res; 73(7); 2235–46. ©2012 AACR.
A Novel Acetylenic Tricyclic <i>bis</i>-(Cyano Enone) Potently Induces Phase 2 Cytoprotective Pathways and Blocks Liver Carcinogenesis Induced by Aflatoxin
Authors: Karen Liby, Mark M. Yore, Bill D. Roebuck, Karen J. Baumgartner, Tadashi Honda, Chitra Sundararajan, Hidenori Yoshizawa, Gordon W. Gribble, Charlotte R. Williams, Renee Risingsong, Darlene B. Royce, Albena T. Dinkova-Kostova, Katherine K. Stephenson, Patricia A. Egner, Melinda S. Yates, John D. Groopman, Thomas W. Kensler, Michael B. Sporn
Journal: Cancer Research (2008)

A novel acetylenic tricyclic bis-(cyano enone), TBE-31, is a lead compound in a series of tricyclic compounds with enone functionalities in rings A and C. Nanomolar concentrations of this potent multifunctional molecule suppress the induction of the inflammatory protein, inducible nitric oxide synthase, activate phase 2 cytoprotective enzymes in vitro and in vivo, block cell proliferation, and induce differentiation and apoptosis of leukemia cells. Oral administration of TBE-31 also significantly reduces formation of aflatoxin-DNA adducts and decreases size and number of aflatoxin-induced preneoplastic hepatic lesions in rats by >90%. Because of the two cyano enones in rings A and C, TBE-31 may directly interact with DTT and protein targets such as Keap1 that contain reactive cysteine residues. The above findings suggest that TBE-31 should also be tested for chemoprevention and chemotherapy in relevant models of cancer and against other chronic, degenerative diseases in which inflammation and oxidative stress contribute to disease pathogenesis.
<i>TSC2</i> Loss in Lymphangioleiomyomatosis Cells Correlated with Expression of CD44v6, a Molecular Determinant of Metastasis
Authors: Gustavo Pacheco-Rodriguez, Wendy K. Steagall, Denise M. Crooks, Linda A. Stevens, Hiroshi Hashimoto, Shaowei Li, Ji-an Wang, Thomas N. Darling, Joel Moss
Journal: Cancer Research (2007)

Lymphangioleiomyomatosis (LAM), a rare multisystem disease found primarily in women of childbearing age, is characterized by the proliferation of abnormal smooth muscle-like cells, LAM cells, that form nodules in the pulmonary interstitium. Proliferation of LAM cells results, in part, from dysfunction in tuberous sclerosis complex (TSC) genes TSC1 (hamartin) and/or TSC2 (tuberin). Identification of LAM cells in donor lungs, their isolation from blood, and their presence in urine, chylous ascites, and pleural effusions are consistent with their ability to metastasize. Here, we investigated the presence on LAM cells of the hyaluronic acid receptor CD44 and its splice variants associated with metastasis. The heterogeneous populations of cells grown from lungs of 12 LAM patients contain cells expressing mRNA for the variant CD44v6. Histologically, CD44v6 was present in LAM lung nodules, but not in normal vascular smooth muscle cells. CD44v6-positive sorted cells showed loss of heterozygosity at the TSC2 locus; binding of CD44v6 antibody resulted in loss of cell viability. Levels of CD44 were higher in cultured Eker rat (Tsc2-/-) cells than in Tsc2+/+ cells, but unlike human LAM cells, the Tsc2-/- Eker rat cells did not contain CD44v6 splice variant mRNA. CD44 splicing and signaling is regulated by osteopontin. Plasma from LAM patients contained higher concentrations of osteopontin than plasma of healthy, age-, and sex-matched volunteers (P = 0.00003) and may be a biomarker for LAM. The cell surface receptor CD44 and its splice variant CD44v6 may contribute to the metastatic potential of LAM cells.
WITHDRAWN: The emerging role of Ca2+ sensitivity regulation in promoting myogenic vasoconstriction
Authors: R SCHUBERT, D LIDINGTON, S BOLZ
Journal: Cardiovascular Research (2007)

Growing evidence suggests that mechanisms which regulate the Ca2+ sensitivity of the contractile apparatus in vascular smooth muscle cells form the backbone of pressure-induced myogenic vasoconstriction. The modulation of Ca2+ sensitivity is suited to partially uncouple intracellular Ca2+ from constriction, thereby allowing the maintenance of tone with fully conserved function of other Ca2+-dependent processes. Following a brief review of 'classical' Ca2+-dependent signalling pathways involved in the myogenic response, the present review describes the emerging mechanisms that promote myogenic vasoconstriction via modulation of Ca2+ sensitivity. For the purpose of this review, Ca2+ sensitivity reflects the dynamic equilibrium between myosin light-chain kinase and myosin light-chain phosphatase activities in terms of its impact on vascular tone. Several signalling pathways (PKC, RhoA/Rho kinase, ROS) which have been identified as prominent regulators of Ca2+ sensitivity will be discussed. Although Ca2+ sensitivity modulation is clearly an important component of the myogenic response, attempts to integrate it into existing mechanistic models resulted in a two-phase model, with a predominant Ca2+-dependent 'initiation/trigger' phase followed by a Ca2+-independent 'maintenance' phase. We propose that the two-phase model is rather simplistic, because the literature reviewed here demonstrates that Ca2+-dependent and -independent mechanisms do not operate in isolation and are important at all stages of the response. The regulation of Ca2+ sensitivity, as an equal and complimentary partner of Ca2+-dependent processes, significantly enhances our understanding of the complex array of signalling pathways, which ultimately mediate the myogenic response.
S57 The Role of Vitamin D Deficiency in Regulating the Severity and Duration of Murine Lung Injury
Authors: S Lax, D Parekh, R Dancer, D Thickett
Journal: Thorax (2012)

<h3>Introduction</h3> Vitamin D has been shown to modulate both the innate and adaptive immune responses. Patients deficient have increased susceptibility to both infection and autoimmunity. Our research suggests patients with, or at risk of developing acute lung injury (ALI), are severely Vitamin D deficient/insufficient. As there are no licenced treatments for ALI, novel therapies need to be developed, therefore we investigated the effect of Vitamin D deficiency in a murine model of ALI to understand the mechanistic drivers of its action. <h3>Methods</h3> Using a diet completely devoid of Vitamin D, we established near complete Vitamin D deficiency in otherwise wild type C57Bl/6 mice. We combined this with intra-tracheal instillations of LPS (50µg), and analysed the inflammatory response within the lungs of these mice compared to those fed on a Vitamin D sufficient diet. In addition, systemic Vitamin D supplementation was assessed by intra-peritoneal injection of cholecalciferol 48hrs prior to LPS instillation. Cell infiltrates, expression of several inflammatory markers within bronchial lavage fluid (BALF), as well as tissue permeability were examined to evaluate the immune response and resulting lung damage. <h3>Results</h3> Dietary Vitamin D deficient mice (n=12) had elevated BALF protein concentration (p=0.0369) and red blood cell (RBC) extravasation (p=0.084) 48hrs post IT-LPS, suggestive of increased alveolar epithelial damage. BALF levels of VEGF (p=0.0023) and CXCL1/KC (p=0.0121) were significantly increased 48hrs post-LPS, indicating an increase in the inflammatory response in deficient mice. Moreover, inflammation was prolonged with both the total number of cells recruited into the BALF (p=0.0479), and the number of apoptotic neutrophils (p=0.034) significantly higher at 96hrs post LPS in Vitamin D deficient mice. Furthermore, wild type mice with normal Vitamin D levels pre-treated with cholecalciferol had reduced BALF cellular inflammation (p=0.0093), with a lower BALF protein concentration (p=0.076) and RBC accumulation in BALF (p=0.0274) 48hrs post-LPS. <h3>Conclusion</h3> Our data indicate that Vitamin D deficiency significantly augments both the severity and duration of murine lung injury and that exogenous Vitamin D reduces lung responses to LPS even in mice with normal Vitamin D levels. These data support the use of Vitamin D to both prevent and potentially treat established ALI.
Evidence of lung surfactant abnormality in respiratory failure. Study of bronchoalveolar lavage phospholipids, surface activity, phospholipase activity, and plasma myoinositol.
Authors: M Hallman, R Spragg, J H Harrell, K M Moser, L Gluck
Journal: Journal of Clinical Investigation (1982)

Autopsy findings suggest that lung surfactant is damaged in the adult respiratory distress syndrome. In the present study 225 bronchoalveolar lavage specimens (78 from 36 patients, 1-78 yr old with respiratory failure, 135 from another 128 patients with other respiratory disease, and 12 from healthy controls) were assayed for the lung profile [lecithin/sphingomyelin (L/S) ratio, saturated lecithin, phosphatidylinositol, and phosphatidylglycerol]. Bronchoalveolar lavage fluid was further analyzed for phospholipids and for phosphatidic acid phosphohydrolase, phospholipase A2, and phosphatidylinositol phosphodiesterase activities. A lipid-protein complex was isolated and analyzed for surface activity, and plasma was measured for myoinositol. There were only small differences seen in the recovery of total phospholipid between respiratory failure patients and normal controls. However, in respiratory failure, phospholipids in bronchoalveolar lavage were qualitatively different from those recovered either from normal controls or from patients with other lung disease: the LO/S ratio, phosphatidylglycerol, and disaturated lecithin were low, whereas sphingomyelin and phosphatidylserine were prominent. These abnormalities were present early in respiratory failure and tended to normalize during recovery. Low L/S ratio (less than 2), and low phosphatidylglycerol (1% or less of glycerophospholipids) in bronchoalveolar lavage was always associated with respiratory failure. Abnormal lavage phospholipids were not due to plasma contamination. The phospholipase studies revealed little evidence of increased catabolism of phospholipids. In respiratory failure, the lipid-protein complexes from lung lavage were not surface active, whereas that from healthy controls had surface properties similar to lung surfactant. Phospholipids from patients with respiratory failure were similar to those from respiratory distress syndrome in the newborn. However, the latter condition is characterized by fast recovery of surfactant deficiency and by high plasma myoinositol that suppresses the synthesis of surfactant phosphatidylglycerol and increases phosphatidylinositol (Pediatr. Res. 1981. 15: 720). On the other hand, in adult respiratory distress syndrome, the abnormality in surfactant phospholipids may last for weeks and in most cases is associated with low phosphatidylinositol, low phosphatidylglycerol, and low plasma myoinositol.
Burnout and Career Satisfaction Among US Oncologists
Authors: Tait D. Shanafelt, William J. Gradishar, Michael Kosty, Daniel Satele, Helen Chew, Leora Horn, Ben Clark, Amy E. Hanley, Quyen Chu, John Pippen, Jeff Sloan, Marilyn Raymond
Journal: Journal of Clinical Oncology (2014)

To evaluate the personal and professional characteristics associated with career satisfaction and burnout among US oncologists.Between October 2012 and March 2013, the American Society of Clinical Oncology conducted a survey of US oncologists evaluating burnout and career satisfaction. The survey sample included equal numbers of men and women and represented all career stages.Of 2,998 oncologists contacted, 1,490 (49.7%) returned surveys (median age of respondents, 52 years; 49.6% women). Among the 1,117 oncologists (37.3% of overall sample) who completed full-length surveys, 377 (33.8%) were in academic practice (AP) and 482 (43.2%) in private practice (PP), with the remainder in other settings. Oncologists worked an average of 57.6 hours per week (AP, 58.6 hours per week; PP, 62.9 hours per week) and saw a mean of 52 outpatients per week. Overall, 484 oncologists (44.7%) were burned out on the emotional exhaustion and/or depersonalization domain of Maslach Burnout Inventory (AP, 45.9%; PP, 50.5%; P = .18). Hours per week devoted to direct patient care was the dominant professional predictor of burnout for both PP and AP oncologists on univariable and multivariable analyses. Although a majority of oncologists were satisfied with their career (82.5%) and specialty (80.4%) choices, both measures of career satisfaction were lower for those in PP relative to AP (all P < .006).Overall career satisfaction is high among US oncologists, albeit lower for those in PP relative to AP. Burnout rates among oncologists seem similar to those described in recent studies of US physicians in general. Those oncologists who devote the greatest amount of their professional time to patient care seem to be at greatest risk for burnout.
Phase II Pethema Trial of Alternating Bortezomib and Dexamethasone As Induction Regimen Before Autologous Stem-Cell Transplantation in Younger Patients With Multiple Myeloma: Efficacy and Clinical Implications of Tumor Response Kinetics
Authors: Laura Rosiñol, Albert Oriol, Maria Victoria Mateos, Anna Sureda, Pedro García-Sánchez, Norma Gutiérrez, Adrián Alegre, Juan José Lahuerta, Javier de la Rubia, Carlos Herrero, Xiangyang Liu, Helgi Van de Velde, Jesús San Miguel, Joan Bladé
Journal: Journal of Clinical Oncology (2007)

This is the first study in which bortezomib and dexamethasone were administered on an alternating basis as up-front therapy in multiple myeloma (MM). We investigated the efficacy and kinetics of response to each drug and safety.Patients with newly diagnosed MM who were less than 66 years old were treated with bortezomib at 1.3 mg/m2 on days 1, 4, 8, and 11 (cycles 1, 3, and 5) and dexamethasone 40 mg orally on days 1 through 4, 9 to 12, and 17 to 20 (cycles 2, 4, and 6), followed by autologous stem-cell transplantation (ASCT). Responses were evaluated by modified European Bone Marrow Transplantation criteria. Random effects models were used to analyze the tumor response kinetics.Forty patients were enrolled. Partial response (PR) or greater was 65% (12.5% complete response [CR], 10% very good PR [VGPR], and 42.5% PR) plus 17.5% minor response. Time to response was rapid, with 82% serum M-protein reduction achieved within the first two cycles. The M-protein decrease was similar with dexamethasone and with bortezomib (P = .48). Chromosome 13 deletion, t(4;14), and t(14;16) did not have a negative impact on response. Toxicity was low, with no grade 3 to 4 peripheral neuropathy and no grade 2 to 4 thrombocytopenia. The response rate after ASCT was 88%, with 33% CR (negative immunofixation) plus 22% VGPR.Bortezomib alternating with dexamethasone is a highly effective induction regimen with low toxicity. The kinetic study has shown a high degree of heterogeneity in response and rapid effect from both agents, supporting the use of a short induction regimen before ASCT in MM.
Intracoronary injection of basic fibroblast growth factor enhances angiogenesis in infarcted swine myocardium
Authors: Alexander Battler, Mickey Scheinowitz, Amir Bor, David Hasdai, Zvi Vered, Elio Di Segni, Nira Varda-Bloom, Devorah Nass, Santiago Engelberg, Michael Eldar, Michael Belkin, Naphtali Savion
Journal: Journal of the American College of Cardiology (1993)