tbuckley/cabot-search huggingface dataset:
Reporting of Noninferiority and Equivalence Randomized Trials
Authors: Gilda Piaggio, Diana R Elbourne, Douglas G Altman, Stuart J Pocock, Stephen J W Evans
Journal: JAMA (2006)

The CONSORT (Consolidated Standards of Reporting Trials) Statement, including a checklist and a flow diagram, was developed to help authors improve their reporting of randomized controlled trials. Its primary focus was on individually randomized trials with 2 parallel groups that assess the possible superiority of one treatment compared with another but is now being extended to other trial designs. Noninferiority and equivalence trials have methodological features that differ from superiority trials and present particular difficulties in design, conduct, analysis, and interpretation. Although the rationale for such trials occurs frequently, those designed and described specifically as noninferiority or equivalence trials appear less commonly in the medical literature. The quality of reporting of those that are published is often inadequate. In this article, we present an adapted CONSORT checklist for reporting noninferiority and equivalence trials and provide illustrative examples and explanations for those items amended from the original CONSORT checklist. The intent is to improve reporting of noninferiority and equivalence trials, enabling readers to assess the validity of their results and conclusions.
Abstract 154: Transcriptomic Analysis Reveals Upregulation of The Pro-Apoptotic, Extracellular Matrix-Degrading Granzyme System in Human Aortic Valve Calcification
Authors: Pauli Ohukainen, Tuomas Peltonen, Juha Näpänkangas, Panu Taskinen, Pasi Ohtonen, Heikki Ruskoaho, Jaana Rysä
Journal: Circulation Research (2013)

Background: Calcific Aortic Valve Stenosis (CAVS) is a major valvular disease that leads to myocardial hypertrophy and heart failure. It shares many hallmarks with atherosclerosis, however, many of the specific mechanisms remain to be discovered. We used a DNA-microarray to study the transcriptomic changes in human aortic valve tissue during different stages of stenosis. Methods and Results: RNA was extracted from severely stenotic aortic valves of patients undergoing valve replacement surgery (n=5) and non-sclerotic control valves from patients with aortic insufficiency (n=5). A GeneChip Human Genome U133 Plus 2.0 Array (Affymetrix) was used to study the transcriptomic changes. Among the most upregulated genes were pro-apoptotic Granzymes, which are an integral part of the T-cell-mediated cytotoxic reaction. They have also been shown to be able to degrade the extracellular matrix (ECM). These findings were validated in a larger sample population (n=26) using qRT-PCR. Indeed, significantly increased expression of Granzymes A, B, H, K and M as well as granzyme co-effector Perforin 1 (PRF1) was detected in stenotic valves compared to normal valves. The most significant increase was seen in Granzyme B mRNA levels (7.1-fold; P&lt;0.001) and the gene expression of PRF1 was also markedly upregulated (3.6-fold; P&lt;0.001). Furthermore, the localization of granzymes within the valves and the effect of statin medication on their expression were studied. Conclusions: To our knowledge, this is the first time that the upregulation of the Granzyme system has been studied in human aortic valves. Its involvement indicates an active T-cell-mediated cytotoxic response as well as active degradation of the ECM. This opens up novel possibilities for the treatment and diagnosis of CAVS.
Pregnancy Outcomes in Women With Rare Autoimmune Diseases
Authors: Jian S. Chen, Christine L. Roberts, Judy M. Simpson, Lyn M. March
Journal: Arthritis & Rheumatology (2015)

To examine pregnancy outcomes and pregnancy-related health service utilization among women with rare autoimmune diseases.This population-based cohort study of an Australian obstetric population (2001-2011) used birth records linked to hospital records for identification of rare autoimmune diseases including systemic vasculitis, vasculitis limited to the skin, Sjögren's syndrome, systemic sclerosis, Behçet's disease, polymyositis/dermatomyositis, and other systemic involvement of connective tissue. We excluded births in women with systemic lupus erythematosus or rheumatoid arthritis as well as births occurring ≥6 months before the diagnosis of the rare autoimmune disease. Modified Poisson regression was used to compare study outcomes between women with autoimmune diseases and the general obstetric population.There were 991,701 births, including 409 births (0.04%) in 293 women with rare autoimmune diseases. Of the 409 births, 202 (49%) were delivered by cesarean section and 72 (18%) were preterm; these rates were significantly higher than those in the general obstetric population (28% and 7%, respectively). Compared to the general population, women with autoimmune diseases had higher rates of hypertensive disorders, antepartum hemorrhage, and severe maternal morbidity and required longer hospitalization at delivery, more hospital admissions, and tertiary obstetric care. Compared to other infants, those whose mothers had a rare autoimmune disease were at increased risk of admission to a neonatal intensive care unit, severe neonatal morbidity, and perinatal death.While the majority of women with rare autoimmune diseases delivered healthy infants, they were at increased risk of having both maternal complications and adverse neonatal outcomes, suggesting that their pregnancies should be closely monitored.
A cocktail of humanized anti–pertussis toxin antibodies limits disease in murine and baboon models of whooping cough
Authors: Annalee W. Nguyen, Ellen K. Wagner, Joshua R. Laber, Laura L. Goodfield, William E. Smallridge, Eric T. Harvill, James F. Papin, Roman F. Wolf, Eduardo A. Padlan, Andy Bristol, Michael Kaleko, Jennifer A. Maynard
Journal: Science Translational Medicine (2015)

A humanized antibody cocktail alleviates the high white blood cell count associated with severe pertussis infection and increases bacterial clearance in murine and baboon models.
A Comparison of Phylogenies Based on Structural and Tissue-Expressional Differences of Enzymes in a Family of Telecost Fishes (Salmoniformes: Umbridae)
Authors: Michelle Kettler, Arthur Ghent, Gregory Whitt
Journal: Molecular Biology and Evolution (1986)

Differences in tissue patterns of enzyme-locus expression were used to infer the extent of divergence among species.Enzyme activities, at 27 loci in six tissues of 15 individuals in four species of Umbridae (Salmoniformes), were estimated on the basis of starch-gel electrophoresis of tissue extracts subjected to twofold serial dilutions and subsequent histochemical staining to determine the visual endpoints.Some locus-tissue expressions diverged markedly among species, while other locustissue expressions were conserved.Differences in activity for a given enzyme among tissues, as well as for different enzymes within the same tissue, were sufficiently independent to permit each locus-tissue expression of a species to be treated as a separate character.Statistically significant differences in levels of tissue-enzyme activities among species were then used to construct a phylogeny.The phylogeny constructed using tissue-enzyme expressional differences was similar to that based on enzyme structural differences (genetic distances) and to one of the morphologically based phylogenies.This congruence suggests that species differences in tissue patterns of enzyme-locus expression can be used to test a variety of systematic and evolutionary hypotheses.
Phase I evaluation of all-trans retinoic acid with and without ketoconazole in adults with solid tumors.
Authors: J S Lee, R A Newman, S M Lippman, F V Fossella, M Calayag, M N Raber, I H Krakoff, W K Hong
Journal: Journal of Clinical Oncology (1995)

PURPOSE All-trans retinoic acid (RA) induces accelerated plasma all-trans RA clearance, presumably via cytochrome P450 enzymes. This accelerated metabolism has been shown to be inhibited in the short term by the cytochrome P450 inhibitor ketoconazole. This study was conducted to evaluate the efficacy of ketoconazole in maintaining plasma all-trans RA levels over time. PATIENTS AND METHODS Using a randomized crossover study design, we randomly assigned six patients to receive all-trans RA (45 mg/m2 orally twice per day for 14 days of a 21-day cycle) for cycle 1 and the same dose of all-trans RA plus ketoconazole (400 mg orally for one dose, then 200 mg orally three times per day for 14 days) for cycle 2, and seven patients to receive the same treatment in the reverse order. Plasma all-trans RA levels were measured during the initial 8-hour period after all-trans RA ingestion on days 1 and 15 of cycles 1 and 2. RESULTS There was a marked decrease in plasma all-trans RA levels after 14 days of treatment, as measured by the area under the concentration-time curve (AUC), regardless of whether ketoconazole was given (from a baseline value of 857 to 44 ng/mL/h; P = .025) or not (from 1,355 to 308 ng/mL/h; P = .123). This lack of effect on plasma all-trans RA levels was not due to inadequate plasma ketoconazole levels. Ketoconazole administration was associated with more toxicity. No objective tumor responses were observed. CONCLUSION Ketoconazole does not appear to maintain adequate plasma all-trans RA levels over time.
Effect of Clinical Decision-Support Systems
Authors: Tiffani J. Bright, Anthony Wong, Ravi Dhurjati, Erin Bristow, Lori Bastian, Remy R. Coeytaux, Gregory Samsa, Vic Hasselblad, John W. Williams, Michael D. Musty, Liz Wing, Amy S. Kendrick, Gillian D. Sanders, David Lobach
Journal: Annals of Internal Medicine (2020)

Evidence to support widespread use of clinical decision-support systems (CDSSs) is lacking. This review summarizes trials of CDSSs implemented in clinical settings to aid decision making at the poi...
Abstract #5571: Vascular disrupting activity of ABI-011
Authors: Vuong Trieu, Osmond D'Cruz, Chunlin Tao, Neil Desai
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Background: The tumor vasculature is an established target for anticancer therapies. ABI-011 is a novel thiocolchicine dimer with antitubulin and topisomerase 1 inhibitor properties. In this study, ABI-011 was examined for antiangiogenic as well as vascular disrupting activities (VDA). Methods: The antiangiogenic and VDA effects of ABI-011 were examined in vitro using tubule formation assay with human umbilical vein endothelial cells (HUVEC) and in vivo using the standard chick embryonic chorioallantoic membrane (CAM) assay with 3-day old embryos (n = 18). The shell-less quail embryonic CAM assay was used to determine the time course of VDAs (ABI-011 vs. combretastatin A4 Phosphate [CA4P]). Quail embryos (n = 36) were exposed to ABI-011 (1 to 16 µg/ml) on day 7 and digital CAM images were acquired over a 60 min period for scoring VDA. Subcutaneous human colon (HT29) tumors were grown in athymic nude mice and treated intravenously (IV) with ABI-011 (20-40 mg/kg; q4dx3, IV) or CA4P (200 mg/kg; qdx4, IV). The animal weights and tumor measurements were recorded three times weekly and adverse observations recorded. Results: In the tubule formation assay, ABI-011 significantly inhibited new microvessel formation and disrupted established microvessels even at the dose of 0.01 µg/ml. In the chicken embryonic CAM assay, ABI-011 demonstrated potent antiangiogenic activity in a concentration-dependent manner, with over 90% inhibition at 5 µg without affecting viability. In the quail embryonic CAM assay, ABI-011 exerted potent VDA in a concentration- and time-dependent manner. ABI-011 at concentration as low as 2 µg/CAM caused visible disruption of CAM vasculature at 60 min post-treatment, with the IC50 calculated to be 1.8 µg/ml. Higher concentrations caused increasing embryonic mortalities with an LD50 of 3.4 µg/ml. In contrast, the vascular disrupting agent CA4P demonstrated only modest VDA at concentrations much higher than the effective dose of ABI-011, with the IC50 of CA4P determined to be 13.1 µg/ml- close to its LD50 of 12.8 µg/ml. Against HT29 tumor model, ABI-011 was highly effective with greater than 80% tumor growth inhibition versus CA4P being ineffective. Conclusion: ABI-011 exhibited potent and specific antiangiogenic and vascular disrupting activities both in vitro and in vivo . ABI-011 was determined to be a more potent vascular disrupting antitumor agent with better therapeutic index than CA4P.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5571.
Obesity’s Effects on the Extracellular Matrix May Fuel Breast Cancer
Authors: Tracy Hampton
Journal: JAMA (2015)

A recent study suggests that obesity may alter the composition of breast adipose tissue and promote extracellular matrix stiffness, in turn increasing the tumorigenic potential of breast epithelial cells (Seo BR et al. Sci Transl Med. 2015;7[301]:301ra130).
Interdigitating Dendritic Cell Sarcoma
Authors: Venkata K. Pokuri, Mihai Merzianu, Shipra Gandhi, Junaid Baqai, Thom R. Loree, Seema Bhat
Journal: Journal of the National Comprehensive Cancer Network (2015)

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare dendritic cell tumor with slightly more than 100 cases reported in the English literature. This report discusses a case of localized IDCS involving cervical lymph nodes and provides a literature review of clinicopathologic aspects and treatment outcomes.
Bradykinin B1 Receptor-Mediated Changes in Renal Hemodynamics during Endotoxin-Induced Inflammation
Authors: JOOST P. SCHANSTRA, MARIA E. MARIN-CASTAN[Combining Tilde]O, FRANC[COMBINING CEDILLA]OISE PRADDAUDE, IVAN TACK, JEAN-LOUIS ADER, JEAN-PIERRE GIROLAMI, JEAN-LOUP BASCANDS, BENOIT JEUNIER
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Kinins have been shown to influence renal hemodynamics and function. Under physiologic conditions, most kinin effects involve bradykinin B 2 receptors, but bradykinin B 1 receptors are often induced during inflammation. The purpose of this study was to examine in vivo the effects of bradykinin B 1 receptor activation on renal hemodynamics under normal and inflammatory conditions. In anesthetized rats, activation of bradykinin B 1 receptors by arterial infusion of bradykinin B 1 receptor agonist des-Arg 9 -bradykinin reduced renal plasma flow and GFR. Prior administration (18 h) of lipopolysaccharide to induce inflammation resulted in a larger bradykinin B 1 receptor-induced reduction in renal plasma flow. Values of other parameters remained unchanged, thus resulting in an increased filtration fraction. The presence and the functionality of the bradykinin B 1 receptor at the level of glomerular afferent and efferent arterioles were studied by mRNA expression analysis and intracellular calcium ([Ca 2+ ] i ) mobilization studies. Stimulation with des-Arg 9 -bradykinin of microdissected afferent arterioles from control and lipopolysaccharide-treated rats induced [Ca 2+ ] i mobilization without any significant difference in amplitude between control and lipopolysaccharidetreated rats. However, des-Arg 9 -bradykinin only induced [Ca 2+ ] i mobilization in efferent arterioles from lipopolysaccharide-treated rats. It is suggested that activation of bradykinin B 1 receptors located along the efferent arteriole may participate in the modification of renal hemodynamics in inflammatory states.
Production of proinflammatory and regulatory monokines in hemodialysis patients shown at a single-cell level.
Authors: M Girndt, U Sester, H Kaul, H Köhler
Journal: Journal of the American Society of Nephrology (1998)

Immunologic complications of chronic renal failure are associated with the overproduction of proinflammatory cytokines by monocytes. This is partly due to renal failure itself but is further enhanced by hemodialysis treatment with frequent contact between blood and dialyzer membranes. Previous studies have shown an imbalance of proinflammatory and regulatory monokines in these patients. This study examines monokine production in hemodialysis patients using for the first time a very sensitive method of cytokine detection at a single-cell level by flow cytometry ("cytoflow technique"). Monocytes were stained intracellularly for the production of interleukin-6 (IL-6) and IL-10 after 20 h of culture with lipopolysaccharide. It was shown that high levels of proinflammatory IL-6 in hemodialysis patients are due to an increased number of monocytes producing this cytokine, while IL-6 synthesis per cell remains unchanged. In contrast, elevated levels of regulatory IL-10 are due to an increased synthesis per cell. This study demonstrates that in healthy subjects there is a population of monocytes producing exclusively IL-10 after 20 h of stimulation by lipopolysaccharide. This distinct population of regulatory monocytes is infrequent in dialysis patients, in whom most of the IL-10-positive monocytes also produce IL-6. These findings indicate that overproduction of proinflammatory factors in dialysis patients is at least in part due to a loss of cytokine-specific differentiation in monocytes.
Pyruvate kinase M2 may be a therapeutic target in a mouse model of human non-small cell lung cancer
Authors: Akiko Suzuki, Sachin Puri, Bharat H Joshi, Pamela Leland, Bernard A Fox, Raj K Puri
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Non-small cell lung cancer (NSCLC) is the most common cause of cancer related mortality worldwide and in need of new treatment options. Previously, we have shown that 97 genes are overexpressed in 9 primary NSCLC cell lines by DNA microarray technology. Pyruvate kinase M2 (PKM2),
Decreased lung function in 7-year-old children with early-life organophosphate exposure
Authors: Rachel Raanan, John R Balmes, Kim G Harley, Robert B Gunier, Sheryl Magzamen, Asa Bradman, Brenda Eskenazi
Journal: Thorax (2015)

<h3>Background</h3> Organophosphate pesticides are heavily used in agriculture, and adverse associations with respiratory health in occupational settings have been reported. However, most of the evidence comes from studies where there were no biomarkers of exposure and no objective outcome measurement. Non-occupational chronic effects among residents living in agricultural communities are less well described. <h3>Objective</h3> To evaluate associations between early-life organophosphate exposure and lung function of children living in an agricultural community. <h3>Methods</h3> Participants were 279 children from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) longitudinal birth cohort. The area under the curve for organophosphate exposure was determined by urinary diethyl and dimethyl dialkylphosphate metabolites of organophosphate pesticides, which were measured five times during childhood (6–60 months). Spirometry was performed at age 7 years. Regression models controlled for maternal smoking during pregnancy, season of birth, particulate matter concentrations with aerodynamic diameter ≤2.5 μm (PM<sub>2.5</sub>), breast feeding duration, mould and pets at home, distance of home from a highway, food insecurity, maternal education, season of spirometry, sex, height and technician. <h3>Results</h3> Childhood diethyl, dimethyl and total dialkylphosphate concentrations were associated with significant decreases in lung function at age 7. Specifically, we found lower FEV<sub>1</sub>, (L/s) (ß=−0.16, 95% CI −0.30 to −0.02, p=0.03) and FVC (L) (ß=−0.17, 95% CI −0.34 to 0.01, p=0.06) per 10-fold increase of total dialkylphosphate levels. <h3>Conclusions</h3> Early-life organophosphate exposure as assessed by dialkylphosphate concentrations was adversely associated with 7-year-old children9s lung function.
Clinical and Immunological Factors in Emphysema Progression. Five-Year Prospective Longitudinal Exacerbation Study of Chronic Obstructive Pulmonary Disease (LES-COPD)
Authors: Sivasubramanium Bhavani, Chu-Lin Tsai, Sarah Perusich, Sean Hesselbacher, Harvey Coxson, Lavannya Pandit, David B. Corry, Farrah Kheradmand
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Cross-sectional studies of T-cell responses to self-antigens correlate with baseline emphysema severity.Objectives: We investigated whether clinical and/or immunological factors could predict disease progression, such as emphysema, FEV1, and 6-minute-walk distance (6MWD), in former and active smokers in a 5-year prospective study.Methods: We recruited 224 ever smokers over 40 years of age and with greater than a 15 pack-year smoking history.Measurements and Main Results: Repeated spirometry, 6MWD, and peripheral blood T-cell cytokine responses to lung elastin fragments were measured. Baseline and repeat chest computed tomography (CT) scans (34 to 65 mo apart) were used to quantify emphysema progression. Of the 141 ever-smokers with baseline and repeat CT scans, the mean (SD) annual rate of change in percent emphysema was +0.46 (0.92), ranging from −1.8 to +4.1. In multivariable analyses, the rate of emphysema progression was greater in subjects who had lower body mass index (BMI) (+0.15 per 5-unit decrease in BMI; 95% confidence interval, +0.03 to +0.29). In active smokers, increased IFN-γ and IL-6 T-cell responses had a positive association with the annual rate of emphysema progression. Male sex and IL-6 T-cell responses to elastin fragments were significantly associated with annual 6MWD decline, whereas IL-13 was associated with an increase in annual 6MWD.Conclusions: The rate of emphysema progression quantified by CT scans among ever-smokers was highly variable; clinical factors and biomarkers explained only some of the variability. Aggressive clinical care that targets active smokers with autoreactive T cells and low BMI may temporize progression of emphysema.
Interracial rDNA Variation in the Grasshopper, Podisma pedestris
Authors: JF Dallas, NH Barton, GA Dover
Journal: Molecular Biology and Evolution (1988)

The structural basis and distribution of variation in the ribosomal RNA multigene family ( rDNA) was studied in the X0 and neo-XY races of the Alpine grasshopper Podisma pedestris. Restriction-enzyme sites in the gene region of the rDNA repeat were identical in both races and homogeneous in the rDNA family. In contrast, sites for Hind111 and PvuII in the intergenic spacer (IGS) region showed racial divergence and variation within the rDNA family and within populations. A short insertion in the 28s gene region was present in a minority of repeats in both races. The distributions of four polymorphic IGS Hind111 fragments were surveyed at 43 locations in and around the hybrid zone. Two of these fragments appear to be distributed as clines, one of which is strongly associated with the neo-X chromosome. The other two fragments show considerable variation in both races and show negative association. It is proposed that the clinally distributed variants arise from processes of amplification and divergence of IGS sequence variants and that such divergence may contribute to hybrid inviability.
Tobacco marketing hits poor countries hardest
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

People living in poor countries are exposed to more intense and aggressive tobacco marketing than those in affluent countries, a study has found.1

The study, published in the Bulletin of the World Health Organization , compared levels of tobacco marketing in 16 countries since 2005, when countries signed up to the WHO Framework Convention on Tobacco Control (WHO FCTC) that required them to adopt strict tobacco control measures, including marketing …
Pharmacokinetics (Pk) of Oral Etoposide (Oe) in Kenyans with Hiv-Related Kaposi'S Sarcoma (Ks) on Anti-Retroviral Therapy (Art)
Authors: R.M. Strother, N. Busakhala, E. Njiru, D. Jones, A. Masters, P. Loehrer
Journal: Annals of Oncology (2014)