tbuckley/cabot-search huggingface dataset:
Abstract P059: The Association between Fruit and Vegetable Intake and Alanine Aminotransferase Levels in Children
Authors: Jina Choo, Hye-Jin Kim, Hwami Yang, Suyeon Kim, In-Young Lee
Journal: Circulation (2014)

Purpose: Increasing the intake of fruits and vegetables is recommended for the prevention of childhood obesity. Obesity in children affects the liver, causing conditions such as elevated alanine aminotransferase (ALT) levels. Elevated ALT levels in obese children may be associated with features of metabolic syndrome. Yet empirical evidence on the association between fruit and vegetable intake and ALT levels in children has been lacking. Methods: A cross-sectional study design was used. Participants were 115 children aged 6 to 12 years, who were recruited from community child care centers in a community of Seoul metropolitan area in South Korea. Eating and activity behaviors were obtained by questionnaire administration. ALT levels were analyzed as a dichotomous variable with normal vs. abnormal values (≥30 IU/dL in boys and ≥19 IU/dL in girls). According to body mass index (BMI) percentile, participants were categorized into a normal-weight group of below the 85 th percentile, an overweight group between the 85 th and &lt;95 th percentiles, and an obese group at or above the 95 th percentile. Eating behaviors were assessed via daily intake of fruits and vegetables as a dichotomous variable of 7 days vs. &lt;7 days per week, and frequent intake of fast foods and sweetened beverages as dichotomous variables of &lt; 3 days vs. ≥3 days per week. Daily physical activity was assessed as a dichotomous variable of 7 days vs. &lt; 7 days per week. A logistic regression analysis was performed with an outcome variable of abnormal ALT and a predictor variable of daily fruit and vegetable intake, after adjusting for age, sex, income, alcohol consumption, frequent intake of fast food, frequent beverage intake, daily activity, and obesity groups. Results: Participants were 53.0% female, with a mean age of 9.7 years and a mean BMI percentile of 49.4%. Of the total participants, 28.7% were overweight or obese, and 24.3% were in the abnormal range for ALT levels. In a multivariate-adjusted model, children with a daily intake of fruits and vegetables were significantly less likely to have abnormal ALT levels (odds ratio [OR]=0.27, p=.017). Moreover, the obese group was significantly more likely to have abnormal ALT levels than the normal-weight group (OR=9.6, p=.005). Conclusions: Among children aged 6 to 12 years, daily fruit and vegetable intake was significantly and inversely associated with abnormal ALT levels, even after adjusting for overall obesity levels. Moreover, obesity in children was significantly associated with abnormal ALT levels. Therefore, ALT levels may reflect healthy eating behavior, especially fruit and vegetable intake, and a risk for obesity in children.
927. Cell Therapy To Restore Perfusion and Cardiac Function in Infarcted Heart Is Improved by EPAS1 Gene Transfer
Authors: Yao Liang Tang, Yi Tang, Y. Clare Zhang, Keping Qian, M. Ian Phillips
Journal: Molecular Therapy (2004)

Background: Although constitutive expression of human heme oxygenase-1(hHO-1) could provide a useful approach for cellular protection in the ischemic heart. However, uncontrollable over-expression of hHO-1 can lead to unwanted side effects. We developed a novel vigilant vector system, which is composed of myosin light chain-2v promoter (MLC-2v) and a gene switch that is based on an oxygen dependent degradation domain (ODD) from the hypoxia inducible factor-1-alpha(HIF-1alpha). We hypothesis that vigilant system could control hHO-1 expression and protect ischemic myocardium from ischemic damage.
Four UK parliaments launch HIV handbook for legislators
Authors: Gavin Yamey
Journal: BMJ (1999)

A new international handbook on HIV and AIDS, aimed at helping parliamentarians to enact effective, HIV related law and policy reform, was launched this month simultaneously in the Houses of Parliament, the Scottish parliament, and the assemblies of Wales and Northern Ireland.

The handbook was prepared by the Joint United Nations Programme on HIV/AIDS and the Inter-Parliamentary Union, a global organisation of 139 national parliaments. It …
An in vitro model of colorectal liver metastases to study candidate factors which influence metastasizing cells
Authors: Jeremy I. Wilson, Stephen H. Leveson, Ludwik K. Trejdosiewicz, Jennifer Southgate
Journal: Cancer Research (2005)

5677  Colorectal cancer remains a leading cause of cancer death in the Western world. Many patients have synchronous liver metastases at the time of presentation, associated with a poorer prognosis. The cancer protective effects of non-steroidal anti-inflammatory drugs (NSAIDs) in colon cancer are well-documented and have led to clinical trials to assess any benefit in maintenance therapy. NSAIDs act on the cyclooxygenase (COX) and possibly lipoxygenase (LOX) pathways to inhibit the production of prostaglandins and other bioactive fatty acid metabolites. Although there are many animal models of liver metastases, their relevance to human cancer is restricted. The aim of our work was to develop an in vitro human organotypic model to investigate how COX/LOX activities might contribute to the attachment, survival and proliferation of metastasizing cells of colorectal carcinoma origins within the liver microenvironment. Established human colorectal cell lines (HT29, T84, SW480 and SW620) were assessed by Western blotting for modulation of COX and LOX enzyme expression in response to cytodifferentiation induced by sodium butyrate or to exposure to archetypal cytokines (TGFβ, IFNγ and TNFα). Tumor-free segments of human liver were obtained from patients undergoing liver resection for metastatic disease from colorectal cancer. Macroscopically-normal areas of liver were used for culture and representative areas were processed for histology to confirm the absence of micro-metastases. Colorectal cell lines were seeded onto fragments of normal human liver and maintained in suspension organ culture and assessed by immunohistochemistry for evidence of proliferation, apoptosis and invasion by tumor cells. We found that human liver can be maintained in suspension organ culture for up to 96 hours. All of the colorectal cell lines seeded onto liver attached and invaded. The expression of COX/LOX enzymes was influenced by pre-culture with 2mM sodium butyrate for 6 days; expression of 5-LOX was induced in HT29 and T84 cells, whilst COX-1 expression was down-regulated in T84, SW480 and SW620. MK-886, a specific 5-LOX inhibitor, induced a concentration- and time- dependent inhibition of cell proliferation in HT29 cells. Our model is thus relevant for the study of modulation of COX/LOX expression and its effect on metastasizing colorectal cancer cells.
The Relationship between Overweight in Adolescence and Premature Death in Women
Authors: Rob M. van Dam, Walter C. Willett, JoAnn E. Manson, Frank B. Hu
Journal: Annals of Internal Medicine (2006)

Background: The impact of adiposity in adolescence on death during adulthood is uncertain. Objective: To examine the relation between adiposity in adolescence and premature death in women. Design: Prospective cohort study. Setting: United States. Participants: 102 400 women from the Nurses' Health Study II who were 24 to 44 years of age and free of cancer at baseline. Ninety percent were of non-Hispanic white ethnicity. Measurements: In 1989, current weight and height and recalled weight at age 18 years were assessed by using validated questionnaires, and body mass index (BMI) was calculated. Hazard ratios for death and 95% CIs were adjusted for potential confounders, including cigarette smoking, alcohol use, and physical activity during adolescence. Results: During 12 years of follow-up, 710 participants died. Compared with a BMI of 18.5 to 21.9 kg/m2 at age 18 years, the hazard ratio for premature death was 0.98 (95% CI, 0.78 to 1.23) for a BMI less than 18.5 kg/m2, 1.18 (CI, 0.97 to 1.43) for a BMI of 22.0 to 24.9 kg/m2, 1.66 (CI, 1.31 to 2.10) for a BMI of 25.0 to 29.9 kg/m2, and 2.79 (CI, 2.04 to 3.81) for a BMI of 30 kg/m2 or greater. Among participants who never smoked, a BMI of 22.0 to 24.9 kg/m2 at age 18 years was also associated with increased premature death (hazard ratio, 1.50 [CI, 1.16 to 1.94]). Associations between BMI at age 18 years and death could only partly be explained by adult BMI measured in 1989. Limitations: Because of the observational study design, residual confounding by imperfectly measured or unknown confounders may still be present. Conclusion: Moderately higher adiposity at age 18 years is associated with increased premature death in younger and middle-aged U.S. women.
Abstract 16517: Atrial Natriuretic Peptide as a Marker for Early Rule-Out of Acute Myocardial Infarction
Authors: Anna Slagman, Julia Searle, Fabian Holert, Jörn Ole Vollert, Reinhold Muller, Martin Stockburger, Christian Müller, Martin Möckel
Journal: Circulation (2014)

Introduction: Mid-regional pro-ANP is mainly synthesized in the atria of the heart and it′s secretion is stimulated by ischemia and distension of the myocardium. Objective: To assess the utility of ANP for rule out NSTEMI in combination with cardiac troponin in unselected patients who attend the Emergency Department (ED) with acute cardiac chief complaints. Methods: Patients with chest pain and dyspnea were enrolled over a period of 30 months in the Emergency Department (n=537). Patients with STEMI were excluded from the analysis as diagnosis is ECG- and not biomarker-based (n=18). Blood samples were drawn within 2 hours after admission. Gold-Standard diagnoses were adjudicated by an independent cardiologist. ANP was measured using the BRAHMS Kryptor MR-proANP assay. The lower limit of detection is 2.1 pmol/l. The 97.5 th percentile of a normal population is 86.2 pmol/l and was applied as a cut-off value in this analysis. Troponin I was measured using the Stratus CS and a cut-off value of 0.1 μg/L was applied. Variables are shown as median (IQR) and 95%-CIs. Results: The median ANP-value in all patients (n=519) was 135 pmol/l. Patients with NSTEMI (n=58) had significantly higher ANP-values (244/104-350 pmol/l) as compared to patients with other diagnoses (126/74-256; p&lt;0.0001). In ROC-analysis ANP had an area under the curve of 0.648 (CI:0.582-0.715) for the diagnosis of NSTEMI. Of all patients, 74.2% were troponin negative at admission (n=385). Of these patients, 32.2% (n=124) were also ANP negative. The prevalence of AMI in this subgroup was 1.6% (n=2). The NPV for the combination of troponin and ANP was 98.4% (CI: 94.3-99.8%) and thus higher than for both markers alone (figure 1). In combination with Copeptin, the NPV increased to 100% (CI: 96.3-100%). Conclusions: ANP has potential for early rule-out of AMI in combination with troponin and, due to a different pathophysiological stimulus, it might be used as part of a triple-marker strategy with copeptin and troponin.
Protein Expression Profiling Identifies Subclasses of Breast Cancer and Predicts Prognosis
Authors: Jocelyne Jacquemier, Christophe Ginestier, Jacques Rougemont, Valérie-Jeanne Bardou, Emmanuelle Charafe-Jauffret, Jeannine Geneix, José Adélaïde, Alane Koki, Gilles Houvenaeghel, Jacques Hassoun, Dominique Maraninchi, Patrice Viens, Daniel Birnbaum, François Bertucci
Journal: Cancer Research (2005)

Breast cancer is a heterogeneous disease whose evolution is difficult to predict by using classic histoclinical prognostic factors. Prognostic classification can benefit from molecular analyses such as large-scale expression profiling. Using immunohistochemistry on tissue microarrays, we have monitored the expression of 26 selected proteins in more than 1,600 cancer samples from 552 consecutive patients with early breast cancer. Both an unsupervised approach and a new supervised method were used to analyze these profiles. Hierarchical clustering identified relevant clusters of coexpressed proteins and clusters of tumors. We delineated protein clusters associated with the estrogen receptor and with proliferation. Tumor clusters correlated with several histoclinical features of samples, including 5-year metastasis-free survival (MFS), and with the recently proposed pathophysiologic taxonomy of disease. The supervised method identified a set of 21 proteins whose combined expression significantly correlated to MFS in a learning set of 368 patients (P < 0.0001) and in a validation set of 184 patients (P < 0.0001). Among the 552 patients, the 5-year MFS was 90% for patients classified in the "good-prognosis class" and 61% for those classified in the "poor-prognosis class" (P < 0.0001). This difference remained significant when the molecular grouping was applied according to lymph node or estrogen receptor status, as well as the type of adjuvant systemic therapy. In multivariate analysis, the 21-protein set was the strongest independent predictor of clinical outcome. These results show that protein expression profiling may be a clinically useful approach to assess breast cancer heterogeneity and prognosis in stage I, II, or III disease.
Cheaper antiretrovirals to treat AIDS in South Africa
Authors: K. Zwi
Journal: BMJ (2000)

Many countries in sub-Saharan Africa are overwhelmed by a pandemic of HIV and AIDS that is reducing life expectancy by two decades, reversing gains made in infant mortality and increasing the burden on health resources that are already overstretched. South Africa is no exception. The government, AIDS activists, healthcare professionals, and communities are desperate to find a universal solution or “magic bullet.” Triple combination therapy has dramatically widened the gulf in people's experience of HIV and AIDS, depending on whether they live in the North or the South. Not surprisingly, activists, both local and international, have persistently called for a substantial lowering of the prices of antiretroviral and other expensive drugs needed to treat people with AIDS.

What would reducing the price of antiretrovirals mean for South Africa in its battle against HIV and AIDS? It is important to distinguish between using antiretroviral drugs to prevent mother to child transmission and to treat adults infected with HIV. Interventions to reduce vertical transmission are highly effective in preventing …
Rivaroxaban prevents painful cutaneous infarctions in livedoid vasculopathy
Authors: N. Kerk, A. Drabik, T.A. Luger, S.W. Schneider, T. Goerge
Journal: British Journal of Dermatology (2012)

Journal Article Rivaroxaban prevents painful cutaneous infarctions in livedoid vasculopathy Get access N. Kerk, N. Kerk Department of Dermatology Search for other works by this author on: Oxford Academic Google Scholar A. Drabik, A. Drabik Center for Clinical Studies, University Münster, Münster 48149, Germany Search for other works by this author on: Oxford Academic Google Scholar T.A. Luger, T.A. Luger Department of Dermatology Search for other works by this author on: Oxford Academic Google Scholar S.W. Schneider, S.W. Schneider Department of Dermatology, Venereology, and Allergology, Division of Experimental Dermatology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany Search for other works by this author on: Oxford Academic Google Scholar T. Goerge T. Goerge Department of Dermatology Tobias Goerge. E‐mail:tobias.goerge@ukmuenster.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 168, Issue 4, 1 April 2013, Pages 898–899, https://doi.org/10.1111/bjd.12100 Published: 01 April 2013
Erratum: Corrigendum: Potent inhibition of heterotopic ossification by nuclear retinoic acid receptor–γ agonists
Authors: Kengo Shimono, Wei-en Tung, Christine Macolino, Amber Hsu-Tsai Chi, Johanna H Didizian, Christina Mundy, Roshantha A Chandraratna, Yuji Mishina, Motomi Enomoto-Iwamoto, Maurizio Pacifici, Masahiro Iwamoto
Journal: Nature Medicine (2012)
Abstract 4982: Characterization of novel α-ketoamide derivatives as potent inhibitors against cathepsin S induced by acidic extracellular pH in pancreatic cancer cells
Authors: Wun-Shaing Wayne Chang, Tzu-Yuan Chang, Tzu-Chin Wu, Chien-Yu Liao, Chun-Cheng Lin
Journal: Cancer Research (2014)

Abstract Extracellular acidification is known to be a driving force in pancreatic cancer growth and metastasis. Thus, manipulation of acidic peritumoral pH or blockage of key proteins stimulated by acidic extracellular microenvironment may offer considerable potential for pancreatic cancer therapy. Cathepsin S, also known as CTSS or CatS, is a critical proteolytic enzyme found to be up-regulated in malignant cells and secreted into the extracellular milieu to degrade surrounding matrix components. By examining the effect of low pH (6.7) on various pancreatic tumor cell lines, we detected a consistently increased CTSS expression associated with augmented cell migration and invasion. Other features such as CTSS-mediated proteolysis and ECM degradation were also observed under mildly acidic condition. Based on these findings, we designed and synthesized some new small molecules bearing an α-ketoamide warhead to evaluate their ability to inhibit CTSS. Kinetic study revealed these compound inhibitors possess very low Ki values and high specificity against target CTSS enzyme. Further in vitro and in vivo analyses demonstrated these agents not only could protect fibronectin from CTSS-mediated degradation but also induce tumor cell autophagy under extracellular acidification. Together these results indicate the potential of α-ketoamide derivatives as antitumor agents against pancreatic cancer. Citation Format: Wun-Shaing Wayne Chang, Tzu-Yuan Chang, Tzu-Chin Wu, Chien-Yu Liao, Chun-Cheng Lin. Characterization of novel α-ketoamide derivatives as potent inhibitors against cathepsin S induced by acidic extracellular pH in pancreatic cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4982. doi:10.1158/1538-7445.AM2014-4982
Population Estimates of Household Firearm Storage Practices and Firearm Carrying in Oregon—Correction
Authors: J H Glaser
Journal: JAMA (1998)

medical schools that do not involve an excessive reliance on test scores and that can be applied to all students can be a mechanism for encouraging diversity and maintaining a broad social and racial mix in the medical profession.Arguably, application of explicit criteria is also not as divisive as present quota-based affirmative action policies since it can be applied to all students.Diversity in admissions criteria should be about encouraging students from disadvantaged socioeconomic groups as well as from ethnic minority groups, and while these 2 are frequently associated in the United States, this is not an exclusive relationship.Admissions committees should be trying to increase the pool of applicants to medical schools with flexible admissions policies that take account of the differing educational backgrounds of students, identify applicants with the potential to succeed, and give them the opportunity to study medicine.
642. In Vitro Rescue of Radiosensitive Phenotype Using a Novel Human Artificial Chromosome (HAC) Vector Containing DNA-PKcs Gene
Authors: W. Michael McCormack, Racel G. Cela, Christian Clarke, Viraj Mane, Kiran Ubhayakar, Brendan H. Lee
Journal: Molecular Therapy (2004)

Adenoviral vectors have the advantage of extremely effective transduction of target tissues and a large cloning capacity. In earlier studies, first generation adenoviral vectors achieved long-term expression of human alpha-1-antitrypsin (hAAT) in C3H/Hej mice only when the transgene was driven by a tissue-specific albumin promoter expressing in the liver. When a ubiquitously expressing promoter was used, expression was of short term lasting only a few weeks. These earlier adenoviral vectors were limited by intermediate and late toxicity due to expression of viral transgenes in host tissues and the potential for a host humoral response to the hAAT. To improve the toxicity profile, helper-dependant adenoviral vectors (HDV) devoid of all viral coding regions were developed. HDVs produce minimal intermediate and late toxicity. In this study we sought to compare three different promoters using the HDV system in C3H/Hej mice. (1) The albumin promoter (Alb) is tissue specific expressing only in liver. (2) The phosphoenolpyruvate carboxykinase promoter (PEPCK) is tissue restricted expressing largely in liver with some expression in other tissues including kidney. (3) The phosphoglycerate kinase promoter (PGK) expresses in a ubiquitous fashion. After intravenous injection (N=5 each group), the highest level of hAAT expression (18,000 ng/mL) was achieved with the PGK vector. The Alb and PEPCK expression peaked at levels of 12,000 ng/mL and 7,000 ng/mL respectively. The peak of expression in all three groups was at six weeks following vector administration. With all three promoters, there was long-term expression beyond 24 weeks. The final levels of hAAT were approximately one half to one third of peak levels. The finding of long-term expression in the PGK treated mice is interesting as mice treated with first generation PGK-hAAT vectors do not demonstrate long-term expression whereas first generation ALB-hAAT vectors do. These data support that the host humoral immune response can be determined by both tissue restricted gene expression in the case of first generation vectors or by abolishing viral gene expression in the case of helper-dependent vectors.
Abstract 2555: A cell based bioluminescent reporter assay for rapid measuring function of PD-1 or PD-L1 therapeutic antibodies
Authors: Mei Cong, Natasha Karassina, Jey Cheng, Frank Fan
Journal: Cancer Research (2014)

Abstract Programmed death-1(PD-1) and its ligand (PD-L1) are important immunotherapy targets for cancer. PD-1 serves as a negative costimulatory receptor on various cell types, including T and B cells as well as myeloid-derived cells. Its ligand PD-L1 (B7-H1) is not expressed by normal epithelial tissues, but it is aberrantly expressed on a wide array of human cancers including melanoma, non-small cell lung carcinoma, breast cancer, pancreatic cancer, etc. Engagement of PD-1 by its ligands PD-L1 expressed on tumor cells associated with poorer prognosis by disabling the host antitumor response. The most recent investigational anti-PD-1 immunotherapy drugs such as nivolumab from BMS and lambrolizumab (MK-3475) from Merck have all demonstrated significant overall survival rate in patients with advanced melanoma. Here we developed a cell based bioluminescent reporter assay that can be used for rapid quantifying function of PD-1 or PD-L1 therapeutic antibodies as measured by activation of NFAT signaling pathway. For this, Jurkat T-cell line stably expressing NFAT-luciferase reporter and human PD-1 was generated. Raji stably expressing human PD-L1 was generated as antigen presenting cells (APC). by co-cultivating the two cell lines in the present of CD3 and IgG, Raji cells fully activate Jurkat NFAT pathway via CD28 binding to CD80 (B7-1) and CD86 (B7-2) endogenously expressed on Raji cells. PD-1 signaling in Jurkat cells following engagement of PD-L1 ectopically expressed on Raji cells inhibits T cell function, and results in NFAT pathway inhibition. Blockade of PD-L1 using anti-PD-L1 mAb reversed NFAT pathway activation. Citation Format: Mei Cong, Natasha Karassina, Jey Cheng, Frank Fan. A cell based bioluminescent reporter assay for rapid measuring function of PD-1 or PD-L1 therapeutic antibodies. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2555. doi:10.1158/1538-7445.AM2014-2555