tbuckley/cabot-search huggingface dataset:
Effects on Coronary Heart Disease of Increasing Polyunsaturated Fat in Place of Saturated Fat: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Dariush Mozaffarian, Renata Micha, Sarah Wallace
Journal: PLoS Medicine (2010)

Reduced saturated fat (SFA) consumption is recommended to reduce coronary heart disease (CHD), but there is an absence of strong supporting evidence from randomized controlled trials (RCTs) of clinical CHD events and few guidelines focus on any specific replacement nutrient. Additionally, some public health groups recommend lowering or limiting polyunsaturated fat (PUFA) consumption, a major potential replacement for SFA.We systematically investigated and quantified the effects of increased PUFA consumption, as a replacement for SFA, on CHD endpoints in RCTs. RCTs were identified by systematic searches of multiple online databases through June 2009, grey literature sources, hand-searching related articles and citations, and direct contacts with experts to identify potentially unpublished trials. Studies were included if they randomized participants to increased PUFA for at least 1 year without major concomitant interventions, had an appropriate control group, and reported incidence of CHD (myocardial infarction and/or cardiac death). Inclusions/exclusions were adjudicated and data were extracted independently and in duplicate by two investigators and included population characteristics, control and intervention diets, follow-up duration, types of events, risk ratios, and SEs. Pooled effects were calculated using inverse-variance-weighted random effects meta-analysis. From 346 identified abstracts, eight trials met inclusion criteria, totaling 13,614 participants with 1,042 CHD events. Average weighted PUFA consumption was 14.9% energy (range 8.0%-20.7%) in intervention groups versus 5.0% energy (range 4.0%-6.4%) in controls. The overall pooled risk reduction was 19% (RR = 0.81, 95% confidence interval [CI] 0.70-0.95, p = 0.008), corresponding to 10% reduced CHD risk (RR = 0.90, 95% CI = 0.83-0.97) for each 5% energy of increased PUFA, without evidence for statistical heterogeneity (Q-statistic p = 0.13; I(2) = 37%). Meta-regression identified study duration as an independent determinant of risk reduction (p = 0.017), with studies of longer duration showing greater benefits.These findings provide evidence that consuming PUFA in place of SFA reduces CHD events in RCTs. This suggests that rather than trying to lower PUFA consumption, a shift toward greater population PUFA consumption in place of SFA would significantly reduce rates of CHD. Please see later in the article for the Editors' Summary.
Human fatalities from cyanobacteria: chemical and biological evidence for cyanotoxins.
Authors: W W Carmichael, S M Azevedo, J S An, R J Molica, E M Jochimsen, S Lau, K L Rinehart, G R Shaw, G K Eaglesham
Journal: Environmental Health Perspectives (2001)

An outbreak of acute liver failure occurred at a dialysis center in Caruaru, Brazil (8 degrees 17' S, 35 degrees 58' W), 134 km from Recife, the state capital of Pernambuco. At the clinic, 116 (89%) of 131 patients experienced visual disturbances, nausea, and vomiting after routine hemodialysis treatment on 13-20 February 1996. Subsequently, 100 patients developed acute liver failure, and of these 76 died. As of December 1996, 52 of the deaths could be attributed to a common syndrome now called Caruaru syndrome. Examination of phytoplankton from the dialysis clinic's water source, analyses of the clinic's water treatment system, plus serum and liver tissue of clinic patients led to the identification of two groups of cyanobacterial toxins, the hepatotoxic cyclic peptide microcystins and the hepatotoxic alkaloid cylindrospermopsin. Comparison of victims' symptoms and pathology using animal studies of these two cyanotoxins leads us to conclude that the major contributing factor to death of the dialyses patients was intravenous exposure to microcystins, specifically microcystin-YR, -LR, and -AR. From liver concentrations and exposure volumes, it was estimated that 19.5 microg/L microcystin was in the water used for dialysis treatments. This is 19.5 times the level set as a guideline for safe drinking water supplies by the World Health Organization.
Rational combinations of immunotherapeutics that target discrete pathways
Authors: Stefani Spranger, Thomas Gajewski
Journal: Journal for ImmunoTherapy of Cancer (2013)

An effective anti-tumor immune response requires the coordinated action of the innate and adaptive phases of the immune system. Critical processes include the activation of dendritic cells to present antigens, produce cytokines including type I interferons, and express multiple costimulatory ligands; induction of a productive T cell response within lymph nodes; migration of activated T cells to the tumor microenvironment in response to chemokines and homing receptor expression; and having effector T cells gain access to antigen-expressing tumor cells and maintain sufficient functionality to destroy them. However, tumors can become adept at escaping the immune response, developing multiple mechanisms to disrupt key processes. In general, tumors can be assigned into two different, major groups depending on whether the tumor there is an 'inflamed' or 'non-inflamed' tumor microenvironment. Improvements in our understanding of the interactions between the immune system and cancer have resulted in the development of various strategies to improve the immune-mediated control of tumors in both sub-groups. Categories of major immunotherapeutic intervention include methods to increase the frequency of tumor antigen-specific effector T cells in the circulation, strategies to block or uncouple a range of immune suppressive mechanisms within the tumor microenvironment, and tactics to induce de novo immune inflammation within the tumor microenvironment. The latter may be particularly important for eliciting immune recognition of non-inflamed tumor phenotypes. The premise put forth in this review is that synergistic therapeutic effects in vivo may be derived from combination therapies taken from distinct "bins" based on these mechanisms of action. Early data in both preclinical and some clinical studies provide support for this model. We also suggest that optimal application of these combinations may be aided by appropriate patient selection based on predictive biomarkers.
Mesenchymal stem cells alleviate bacteria‐induced liver injury in mice by inducing regulatory dendritic cells
Authors: Yi Zhang, Wei Cai, Qingrong Huang, Yuting Gu, Yufang Shi, Jiefang Huang, Fang Zhao, Qiang Liu, Xunbin Wei, Min Jin, Changping Wu, Qing Xie, Yi Zhang, Bing Wan, Yanyun Zhang
Journal: Hepatology (2013)

Fulminant hepatic failure (FHF) is a clinical syndrome characterized by sudden and severe impairment of liver function. Mesenchymal stem cells (MSCs) have been proposed as a promising therapeutic approach for FHF. In this study we used Propionibacterium acnes ( P. acnes )-primed, lipopolysaccharide (LPS)-induced liver injury in mice as an animal model of human FHF. We demonstrated that administration of MSCs significantly ameliorated liver injury and improved the survival rates of mice subjected to P. acnes plus LPS-induced FHF. Allogeneic MSCs showed similar treatment efficacy as autologous MSCs did in FHF. Treatment efficacy of MSCs could be attributed to decreased infiltration and activation of CD4+ T cells in the liver, inhibition of T helper 1 cells, and induction of regulatory T cells (Tregs). Moreover, decreased DNA copies of P. acnes were detected in the liver of MSC-treated mice. Intriguingly, a distinct liver population of CD11c+MHCIIhiCD80loCD86lo regulatory dendritic cells (DCs) was induced by MSCs. Moreover, these DCs induced Treg differentiation through transforming growth factor-β production. Further mechanistic studies demonstrated that MSC-derived prostaglandin E2 and one of its receptors, EP4, played essential roles in the differentiation of CD11c+B220− DC precursors into regulatory DCs in a phosphoinositide 3-kinase-dependent manner. Conclusion : MSCs induce regulatory DCs from CD11c+B220− DC precursors. This study elucidates an immunoregulatory mechanism of MSCs and lays a foundation for application of MSCs in FHF therapy. (Hepatology 2014;59:671–682)
ESTERASES OF TESTIS AND OTHER TISSUES
Authors: Charles Huggins, Stanley H. Moulton
Journal: The Journal of Experimental Medicine (1948)

The tissues most effective in the enzymatic hydrolysis of acyl esters of p-nitrophenol by tissue extracts of the rat and dog were the liver, lung, pancreas, renal cortex, and testis; in the dog tracheal and vesical mucosae were also esterase-rich and the lens had appreciable activity. Esterase was at low concentration in the tissues of the rat for 4 and 5 days after birth, but an increase to adult levels soon took place except in the testis where the rise was delayed until puberty. The esterase values of the blood of newborn children were also low. Two patterns of activity in tissues against these esters were found. A pattern in which propionate esters were hydrolyzed most rapidly was displayed regularly by liver, lung, renal cortex, and testis of the rat and also by dog, rabbit and human serum. A second pattern with progressive effectiveness in hydrolyzing fatty acid esters of 2-carbon to 5-carbon chain length was exhibited by the pancreas of the rat, rabbit, and dog and also by rat serum. Esterase of the testis of the rat is located in the interstitial cells and its concentration seems to be directly related to androgenic hormone production. The increase of testicular esterase during puberty paralleled the increase of prostatic weight. Hypophysectomy caused a profound decrease of testicular esterase which was restored in part by gonadoptrophin. Artificial cryptorchism in the rat, causing elimination of germinal epithelium, resulted in an increase of esterase concentration although the total content of the testis slowly decreased.
Increased NBS1 Expression Is a Marker of Aggressive Head and Neck Cancer and Overexpression of NBS1 Contributes to Transformation
Authors: Muh-Hwa Yang, Wei-Chung Chiang, Teh-Ying Chou, Shyue-Yih Chang, Po-Min Chen, Shu-Chun Teng, Kou-Juey Wu
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Head and neck squamous cell carcinoma (HNSCC) represents the sixth most frequent type of cancer worldwide. However, the molecular genetic alterations underlying its malignant behavior and progression are little known. We showed previously that c-MYC directly activates the expression of the DNA double-strand break repair gene NBS1, and NBS1 overexpression contributes to transformation. Here, we investigate the role of NBS1 overexpression in HNSCC. Experimental Design: Immunohistochemistry analysis of NBS1 expression was done in 81 locally advanced HNSCC patients. Real-time PCR and Western blot analysis were used to confirm immunohistochemistry results. Human hypopharyngeal cancer cell lines (FADU) with overexpressing NBS1 (FADUNBS) or inducible short interference RNA to repress endogenous NBS1 (FADUNBSi) were generated by stable transfection. Soft agar clonogenicity assay was used to determine the transformation activity. Western blot analysis and phosphatidylinositol 3-kinase (PI3K) assay were done to evaluate the signaling pathways that were involved. Results: NBS1 overexpression was identified in 45% of advanced HNSCC patients. It was an independent marker of poor prognosis. NBS1 expression levels correlated with the transformation activity of FADU clones and also correlated with the phosphorylation levels of Akt and its downstream target mammalian target of rapamycin (mTOR). PI3K activity was increased in NBS1-overexpressing FADU clones. NBS1 overexpression also correlated with increased Akt phosphorylation levels in tumor samples. Conclusions: Increased NBS1 expression is a significant prognostic marker of advanced HNSCC, and the underlying mechanism may involve the activation of the PI3K/Akt pathway.
Training tomorrow's doctors, in exercise medicine, for tomorrow's patients
Authors: Ann B Gates
Journal: British Journal of Sports Medicine (2015)

<h3>ABSTRACT</h3> MicroRNAs (miRNAs), which play critical roles in gene regulatory networks, have emerged as promising diagnostic and prognostic biomarkers for human cancer. In particular, circulating miRNAs that are secreted into circulation exist in remarkably stable forms, and have enormous potential to be leveraged as non-invasive biomarkers for early cancer detection. Novel and user-friendly tools are desperately needed to facilitate data mining of the vast amount of miRNA expression data from The Cancer Genome Atlas (TCGA) and large-scale circulating miRNA profiling studies. To fill this void, we developed CancerMIRNome, a comprehensive database for the interactive analysis and visualization of miRNA expression profiles based on 10,998 samples from 33 TCGA projects and 21,993 samples from 40 public circulating miRNome datasets. A series of cutting-edge bioinformatics tools and machine learning algorithms have been packaged in CancerMIRNome, allowing for the pan-cancer analysis of a miRNA of interest across multiple cancer types and the comprehensive analysis of miRNome profiles to identify dysregulated miRNAs and develop diagnostic or prognostic signatures. The data analysis and visualization modules will greatly facilitate the exploit of the valuable resources and promote translational application of miRNA biomarkers in cancer. The CancerMIRNome database is publicly available at http://bioinfo.jialab-ucr.org/CancerMIRNome.
Acute protection against exercise-induced bronchoconstriction by formoterol, salmeterol and terbutaline
Authors: K. Richter, S. Janicki, R.A. Jorres, H. Magnussen
Journal: European Respiratory Journal (2002)

The onset of bronchoprotection as obtained by various β<sub>2</sub>-agonists has not been examined in a comparitive study. In this study, the onset of bronchodilation and protection against exercise-induced bronchoconstriction in asthmatics after inhalation of the long-acting β<sub>2</sub>-agonists formoterol and salmeterol and the short-acting β<sub>2</sub>-agonist terbutaline were measured. Twenty-five subjects with asthma and a history of exercise-induced bronchoconstriction (mean baseline forced expiratory volume in one second (FEV<sub>1</sub>): 90% predicted; mean fall in FEV<sub>1</sub> after exercise: 31% from baseline) were enrolled in this double-blind, double-dummy, placebo-controlled, randomized, four-period crossover study. Exercise challenges were performed on 12 days at either 5, 30, or 60 min after inhalation of a single dose of formoterol (12 µg Turbuhaler®), salmeterol (50 µg Diskus®), terbutaline (500 µg Turbuhaler®) or placebo. Exercise-induced bronchoconstriction (maximum fall in FEV<sub>1</sub> or area under the curve) did not differ significantly between terbutaline, formorerol and salmeterol either 5, 30, or 60 min after inhalation of the study medication. In contrast, the onset of bronchodilation was slower after salmeterol compared to terbutaline and formoterol (p&lt;0.05, each), which both showed a similar time course. At all time points between 5 and 60 min, formoterol provided significantly greater bronchodilation than salmeterol (p&lt;0.05). These data indicate that equipotent doses of the bronchodilators salmeterol, formoterol and terbutaline were similarly effective with respect to their short-term protective potency against exercise-induced bronchoconstriction, despite the fact that the time course of bronchodilation was significantly different between the three β<sub>2</sub>-agonists.
Nifedipine – a Calcium Channel Blocker – in Asthmatic Patients Interaction with Terbutaline
Authors: Karin Svedmyr, Claes‐Goran Lofdahl, Nils Svedmyr
Journal: Allergy (1984)

Seven asthmatic patients were studied in a single‐blind randomized, crossover study after oral administration of 20 mg nifedipine or placebo Four increasing doses of i.v. terbutaline were then given with 30 min interval. The study was concluded with inhalation of five terbutaline puffs. FFAV 1 measurements 30 min after intake of nifedipine did not show any difference compared to placebo. During the terbutaline treatment, however, there was a more pronounced bronchodilation after nifedipine than after placebo (P &lt; 0.051. Terbualine‐induced skeletal muscle tremor was similar after nifedipine and placebo pretreatments. After nifedipine intake there was a decrease of diastolic blood pressure and a reflexogenic tachycardia. Thus, this study showed a small potentiation of the beta 2 ‐adrenoceptor mediated bronchodilation. which is of importance when treating patients with simultaneous asthma and hypertension or angina pectoris.
Longitudinal Assessment of Mental Health Problems Among Active and Reserve Component Soldiers Returning From the Iraq War
Authors: Charles S. Milliken, Jennifer L. Auchterlonie, Charles W. Hoge
Journal: JAMA (2007)

To promote early identification of mental health problems among combat veterans, the Department of Defense initiated population-wide screening at 2 time points, immediately on return from deployment and 3 to 6 months later. A previous article focusing only on the initial screening is likely to have underestimated the mental health burden.To measure the mental health needs among soldiers returning from Iraq and the association of screening with mental health care utilization.Population-based, longitudinal descriptive study of the initial large cohort of 88 235 US soldiers returning from Iraq who completed both a Post-Deployment Health Assessment (PDHA) and a Post-Deployment Health Re-Assessment (PDHRA) with a median of 6 months between the 2 assessments.Screening positive for posttraumatic stress disorder (PTSD), major depression, alcohol misuse, or other mental health problems; referral and use of mental health services.Soldiers reported more mental health concerns and were referred at significantly higher rates from the PDHRA than from the PDHA. Based on the combined screening, clinicians identified 20.3% of active and 42.4% of reserve component soldiers as requiring mental health treatment. Concerns about interpersonal conflict increased 4-fold. Soldiers frequently reported alcohol concerns, yet very few were referred to alcohol treatment. Most soldiers who used mental health services had not been referred, even though the majority accessed care within 30 days following the screening. Although soldiers were much more likely to report PTSD symptoms on the PDHRA than on the PDHA, 49% to 59% of those who had PTSD symptoms identified on the PDHA improved by the time they took the PDHRA. There was no direct relationship of referral or treatment with symptom improvement.Rescreening soldiers several months after their return from Iraq identified a large cohort missed on initial screening. The large clinical burden recently reported among veterans presenting to Veterans Affairs facilities seems to exist within months of returning home, highlighting the need to enhance military mental health care during this period. Increased relationship problems underscore shortcomings in services for family members. Reserve component soldiers who had returned to civilian status were referred at higher rates on the PDHRA, which could reflect their concerns about their ongoing health coverage. Lack of confidentiality may deter soldiers with alcohol problems from accessing treatment. In the context of an overburdened system of care, the effectiveness of population mental health screening was difficult to ascertain.
Setting Priorities for Cancer Control Programs&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: D M Eddy
Journal: JNCI Journal of the National Cancer Institute (1986)

This paper describes a simple method for comparing the effectiveness and costs of different cancer control activities and illustrates use of the method by evaluating priorities for controlling oral cancer in developing countries. The method estimates the long-term effect of prevention, screening, detection, treatment, and support activities (e.g., pain control) on morbidity, mortality, measures of quality of life, and cost for a specified population. It can be used to compare the cost effectiveness of various combinations of activities for one or more cancers and to help set priorities for cancer control programs. An analysis of two primary prevention activities, two screening activities, and three treatment activities to control oral cancer in Sri Lanka indicates that highest priority should be given to primary prevention activities such as anti-tobacco education and to screening.
TCT-533 Impact of High High-Density Lipoprotein-Cholesterol on 1-year Outcome of Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention
Authors: Yun-Kyeong Cho, Ji-Hyun Sohn, Hyun-Ok Cho, Hyoung-Seob Park, Hyuck-Jun Yoon, Hyungseop Kim, Chang-Wook Nam, Seung-Ho Hur, Yoon-Nyun Kim, Kwon-Bae Kim
Journal: Journal of the American College of Cardiology (2012)
Human lymphocytes bearing T cell receptor gamma/delta are phenotypically diverse and evenly distributed throughout the lymphoid system.
Authors: V Groh, S Porcelli, M Fabbi, L L Lanier, L J Picker, T Anderson, R A Warnke, A K Bhan, J L Strominger, M B Brenner
Journal: The Journal of Experimental Medicine (1989)

A direct quantitative and phenotypic cytofluorographic analysis of TCR-gamma/delta+ lymphocytes as well as an immunohistologic study of their tissue distribution and microanatomy was made possible by the availability of two mAbs (anti-TCR-delta 1 and anti-C gamma M1) specific for framework determinants on human TCR gamma and delta chains, respectively. TCR-gamma/delta+ lymphocytes, ranging between greater than 0.5 and 16% of CD3+ cells, were found in fetal and postnatal thymus, fetal and adult peripheral lymphoid organs, and adult peripheral blood. While TCR-gamma/delta+ lymphocytes comprised a small subpopulation of T cells (mean, approximately 4%) occasionally greater than 10-16% of CD3+ cells expressed TCR-gamma/delta. Virtually all TCR-gamma/delta+ thymocytes/lymphocytes expressed CD7, CD2, and CD5 but were heterogeneous with respect to their expression of CD1, CD4, CD8, CD28, CD11b, CD16, and Leu-7. Human TCR-gamma/delta+ cells populate both organized lymphoid tissues (thymus, tonsil, lymphnode, and spleen) as well as the gut- and skin-associated lymphoid systems at similar frequencies without obvious tropism for epithelial microenvironments. TCR-gamma/delta+ lymphocytes tend to be located within a given organ wherever TCR-alpha/beta+ lymphocytes are found. This study shows that TCR-gamma/delta+ lymphocytes constitute a small but numerically important, phenotypically diverse T cell population distributed throughout the body. These results support the concept that TCR-gamma/delta+ cells comprise a distinct, functionally heterogeneous, mature T cell sublineage that may substantially broaden the T cell repertoire at all immunologically relevant sites.