tbuckley/cabot-search huggingface dataset:
Cardiovascular and Noncardiovascular Mortality Among Patients Starting Dialysis
Authors: Dinanda J. de Jager
Journal: JAMA (2009)

Cardiovascular mortality is considered the main cause of death in patients receiving dialysis and is 10 to 20 times higher in such patients than in the general population.To evaluate if high overall mortality in patients starting dialysis is a consequence of increased cardiovascular mortality risk only or whether noncardiovascular mortality is equally increased.Using data from between January 1, 1994, and January 1, 2007, age-stratified mortality in a European cohort of adults starting dialysis and receiving follow-up for a mean of 1.8 (SD, 1.1) years (European Renal Association-European Dialysis and Transplant Association [ERA-EDTA] Registry [N = 123,407]) was compared with the European general population (Eurostat).Cause of death was recorded by ERA-EDTA codes in patients and matching International Statistical Classification of Diseases, 10th Revision codes in the general population. Standardized cardiovascular and noncardiovascular mortality rates, their ratio, difference, and relative excess of cardiovascular over noncardiovascular mortality were calculated.Overall all-cause mortality rates in patients and the general population were 192 per 1000 person-years (95% confidence interval [CI], 190-193) and 12.055 per 1000 person-years (95% CI, 12.05-12.06), respectively. Cause of death was known for 90% of the patients and 99% of the general population. In patients, 16,654 deaths (39%) were cardiovascular and 21,654 (51%) were noncardiovascular. In the general population, 7,041,747 deaths (40%) were cardiovascular and 10,183,322 (58%) were noncardiovascular. Cardiovascular and noncardiovascular mortality rates in patients were respectively 38.1 per 1000 person-years (95% CI, 37.2-39.0) and 50.1 per 1000 person-years (95% CI, 48.9-51.2) higher than in the general population. On a relative scale, standardized cardiovascular and noncardiovascular mortality were respectively 8.8 (95% CI, 8.6-9.0) and 8.1 (95% CI, 7.9-8.3) times higher than in the general population. The ratio of these rates, ie, relative excess of cardiovascular over noncardiovascular mortality in patients starting dialysis compared with the general population, was 1.09 (95% CI, 1.06-1.12). Relative excess in a sensitivity analysis in which unknown/missing causes of death were regarded either as noncardiovascular or cardiovascular varied between 0.90 (95% CI, 0.88-0.93) and 1.39 (95% CI, 1.35-1.43).Patients starting dialysis have a generally increased risk of death that is not specifically caused by excess cardiovascular mortality.
Single-Trial Analysis of Neuroimaging Data: Inferring Neural Networks Underlying Perceptual Decision-Making in the Human Brain
Authors: P. Sajda, M.G. Philiastides, L.C. Parra
Journal: IEEE Reviews in Biomedical Engineering (2009)

Advances in neural signal and image acquisition as well as in multivariate signal processing and machine learning are enabling a richer and more rigorous understanding of the neural basis of human decision-making. Decision-making is essentially characterized behaviorally by the variability of the decision across individual trials - e.g., error and response time distributions. To infer the neural processes that govern decision-making requires identifying neural correlates of such trial-to-trial behavioral variability. In this paper, we review efforts that utilize signal processing and machine learning to enable single-trial analysis of neural signals acquired while subjects perform simple decision-making tasks. Our focus is on neuroimaging data collected noninvasively via electroencephalograpy (EEG) and functional magnetic resonance imaging (fMRI). We review the specific framework for extracting decision-relevant neural components from the neuroimaging data, the goal being to analyze the trial-to-trial variability of the neural signal along these component directions and to relate them to elements of the decision-making process. We review results for perceptual decision-making and discrimination tasks, including paradigms in which EEG variability is used to inform an fMRI analysis. We discuss how single-trial analysis reveals aspects of the underlying decision-making networks that are unobservable using traditional trial-averaging methods.
Regional Patterns of Fat Distribution
Authors: PER BÖRNTORP
Journal: Annals of Internal Medicine (1985)

Long-term studies are needed to establish obesity itself as a risk factor for cardiovascular disease, even though other well-known risk factors are prevalent in obese persons. It is possible that the risk for cardiovascular disease is found in a subgroup of the total obesity population. Cross-sectional studies have shown abdominal obesity to be strongly associated with risk factors for cardiovascular disease. Prospective epidemiologic studies in men and women have shown that abdominal obesity is associated with increased risk for ischemic heart disease, stroke, and death independent of the total degree of obesity. Even limited abdominal obesity should be treated and patients examined carefully for complicating conditions.
CYTOTOXIC THYMUS-DERIVED LYMPHOCYTES IN CEREBROSPINAL FLUID OF MICE WITH LYMPHOCYTIC CHORIOMENINGITIS
Authors: R. M. Zinkernagel, P. C. Doherty
Journal: The Journal of Experimental Medicine (1973)

The fatal neurological disease occurring in adult mice injected intracerebrally (IC) with lymphocytic choriomeningitis (LCM) virus is apparently induced by massive invasion of leukocytes (1, 2) into the central nervous system (CNS).Dosing with antithymocyte serum or cyclophosphamide (2, 3) prevents cellular infiltration: mice survive as asymptomatic carriers.Adoptive induction of this inflammatory process, by injecting immune spleen cells into immunosuppressed recipients, depends on presence of specific thymus-derived lymphocytes (T cells) in the transferred cell population (4).Such lymphocytes can now be assayed in vitro by measuring release of radioactivity from 51Cr-labeled target cells infected with L C M virus (5, 6).The present paper gives evidence that these cytotoxic T cells are found in cerebrospinal fluid (CSF) of mice with clinical LCM.This is, to our knowledge, the first direct demonstration of specifically sensitized lymphocytes in a virus-induced inflammatory exudate.
Discrepancy between Dual-Energy Computed Tomography Lung Perfusion Blood Volume and Lung Perfusion Single-Photon Emission Computed Tomography/Computed Tomography Images in Pulmonary Embolism
Authors: Hirofumi Koike, Eijun Sueyoshi, Hiroki Nagayama, Kazuto Ashizawa, Ichiro Sakamoto, Masataka Uetani, Takashi Kudo, Satoshi Ikeda
Journal: American Journal of Respiratory and Critical Care Medicine (2014)
Brachial Artery Responses to Ambient Pollution, Temperature, and Humidity in People with Type 2 Diabetes: A Repeated-Measures Study
Authors: Antonella Zanobetti, Heike Luttmann-Gibson, Edward S. Horton, Allison Cohen, Brent A. Coull, Barbara Hoffmann, Joel D. Schwartz, Murray A. Mittleman, Yongsheng Li, Peter H. Stone, Celine de Souza, Brooke Lamparello, Petros Koutrakis, Diane R. Gold
Journal: Environmental Health Perspectives (2014)

Extreme weather and air pollution are associated with increased cardiovascular risk in people with diabetes.In a population with diabetes, we conducted a novel assessment of vascular brachial artery responses both to ambient pollution and to weather (temperature and water vapor pressure, a measure of humidity).Sixty-four 49- to 85-year-old Boston residents with type 2 diabetes completed up to five study visits (279 repeated measures). Brachial artery diameter (BAD) was measured by ultrasound before and after brachial artery occlusion [i.e., flow-mediated dilation (FMD)] and before and after nitroglycerin-mediated dilation (NMD). Ambient concentrations of fine particulate mass (PM2.5), black carbon (BC), organic carbon (OC), elemental carbon, particle number, and sulfate were measured at our monitoring site; ambient concentrations of carbon monoxide, nitrogen dioxide, and ozone were obtained from state monitors. Particle exposure in the home and during each trip to the clinic (home/trip exposure) was measured continuously and as a 5-day integrated sample. We used linear models with fixed effects for participants, adjusting for date, season, temperature, and water vapor pressure on the day of each visit, to estimate associations between our outcomes and interquartile range increases in exposure.Baseline BAD was negatively associated with particle pollution, including home/trip-integrated BC (-0.02 mm; 95% CI: -0.04, -0.003, for a 0.28 μg/m3 increase in BC), OC (-0.08 mm; 95% CI: -0.14, -0.03, for a 1.61 μg/m3 increase) as well as PM2.5, 5-day average ambient PM2.5, and BC. BAD was positively associated with ambient temperature and water vapor pressure. However, exposures were not consistently associated with FMD or NMD.Brachial artery diameter, a predictor of cardiovascular risk, decreased in association with particle pollution and increased in association with ambient temperature in our study population of adults with type 2 diabetes.Zanobetti A, Luttmann-Gibson H, Horton ES, Cohen A, Coull BA, Hoffmann B, Schwartz JD, Mittleman MA, Li Y, Stone PH, de Souza C, Lamparello B, Koutrakis P, Gold DR. 2014. Brachial artery responses to ambient pollution, temperature, and humidity in people with type 2 diabetes: a repeated-measures study. Environ Health Perspect 122:242-248; http://dx.doi.org/10.1289/ehp.1206136.
High Frequencies of Functional Tumor-Reactive T Cells in Bone Marrow and Blood of Pancreatic Cancer Patients
Authors: Friedrich H. Schmitz-Winnenthal, Christine Volk, Kaspar Z'graggen, Luis Galindo, Daniel Nummer, Yvonne Ziouta, Marianna Bucur, Jürgen Weitz, Volker Schirrmacher, Markus W. Büchler, Philipp Beckhove
Journal: Cancer Research (2005)

Abstract Pancreatic cancer is characterized by aggressive growth and treatment resistance. New approaches include immunotherapeutic strategies but the type and extent of spontaneous immune responses against tumor antigens remains unclear. A dominance of TH2 cytokines in patients' sera reported previously suggests systemic tumor-induced immunosuppression, potentially inhibiting the induction of tumor-reactive T cells. We characterized the localization, frequencies, and functional potential of spontaneously induced memory T cells specific for individual tumor antigens or the tumor-associated antigen mucin-1 in the peripheral blood and bone marrow of 41 pancreatic cancer patients. We found high numbers of tumor-reactive T cells in all bone marrow samples and in 50% of the blood samples. These cells secreted the TH1 cytokine IFN-γ rather than TH2 cytokines upon stimulation with tumor antigens. Although consistently induced during pancreatic cancer, T cells specific for pancreatic antigens were not detected during chronic pancreatitis, suggesting that their evaluation may be of diagnostic use in both diseases. Freshly isolated T cells from cancer patients recognized autologous tumor cells and rejected them in vitro and in a xenotransplant model in vivo, suggesting their therapeutic potential. Thus, tumor antigen–specific T cell responses occur regularly during pancreatic cancer disease and lead to enrichment of tumor cell–reactive memory T cells in the bone marrow. The bone marrow can therefore be considered an important organ for antitumor immune responses in pancreatic cancer.
Patterns of respiratory viral infections correspond closely with early childhood wheezing phenotypes
Authors: T.E. Pappas, K.T. Sullivan Dillie, E.L. Anderson, D.F. DaSilva, M.D. Evans, L.E. Pleiss, K.A. Roberg, C.J. Tisler, J.E. Gern, R.F. Lemanske
Journal: Journal of Allergy and Clinical Immunology (2005)
Comparative Pharmacokinetics and Glucodynamics of Two Human Insulin Mixtures 70/30 and 50/50 insulin mixtures
Authors: James R Woodworth, Daniel C Howey, Ronald R Bowsher, Rocco L Brunelle, Howard M Rowe, Joyce Compton, Benito Cerimele
Journal: Diabetes Care (1994)

OBJECTIVE To compare and contrast the pharmacokinetics and glucodynamics of two insulin mixtures, one of 50% NPH human insulin and 50% Regular human insulin (50/50) and one of 70% NPH human insulin and 30% Regular human insulin (70/30), in healthy male volunteers after subcutaneous administrations of 0.3 U/kg. RESEARCH DESIGN AND METHODS We administered single doses of 50/50 and 70/30 insulins to 18 volunteers in a randomized crossover fashion. All subjects received 0.3 U/kg of each mixture separated by at least 7 days. Each dose was given after an overnight fast and during a glucose clamp to maintain a euglycemic state. We measured serum insulin and Cpeptide concentrations through frequent blood sampling after each treatment. Pharmacokinetic measurements were calculated from insulin data corrected for C-peptide, including maximum insulin concentration (Cmax), time to maximum insulin concentration (tmax), terminal rate constant (β), area under the curve from 0 to ∞, (AUC x0), and mean residence time (MRT). Pharmacodynamic measurements were summarized from C-peptide concentrations (minimum C-peptide concentration [Cmin], time to minimum C-peptide concentration [tmin], area between the C-peptide baseline and the C-peptide suppression curve [AOCc], absolute maximal difference from baseline [Sdiff] and glucose clamp measurements. The glucose clamp measurements included maximum infusion rates (Rmax) and time to Rmax (TRmax) from glucose infusion rate (GIR) documentation, as well as cumulative glucose infused during the first 4 h (40Gtot) and total glucose infused (Gtot) during the study. RESULTS For the pharmacokinetic assessment, statistically greater values of insulin Cmax and β were found for the 50/50 mixture, whereas the 70/30 mixture had a greater MRT. Statistical differences were also detected in glucodynamics, with greater values of Rmax and (40Gtot) found with the 50/50 mixture. Notably, differences were not detected for insulin AUCx0 and Gtot values. CONCLUSIONS Higher insulin concentrations and a greater initial response were present with the 50/50 mixture, but the two mixtures had equivalent bioavailability and cumulative effects. These results support use of the 50/50 mixture in situations where greater initial glucose control is required.
Untreated Mild Hyperglycemia During Pregnancy and Anthropometric Measures of Obesity in Offspring at Age 5–7 Years
Authors: Parag K. Thaware, Sonia McKenna, Christopher C. Patterson, David R. Hadden, David J. Pettitt, David R. McCance
Journal: Diabetes Care (2015)

OBJECTIVE Obesity in the offspring of women with hyperglycemia during pregnancy has been reported, but the results are conflicting. This study examined the association of hyperglycemia during pregnancy and anthropometry in 5- to 7-year-old offspring whose mothers participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study at the Belfast Centre. RESEARCH DESIGN AND METHODS Women in the HAPO study underwent a 75-g oral glucose tolerance test (OGTT) at approximately 28 weeks of gestation. Mothers and caregivers remained blinded to the results unless the fasting plasma glucose (FPG) concentration was &amp;gt;5.8 mmol/L or the 2-h plasma glucose (2hPG) concentration was &amp;gt;11.1 mmol/L. Offspring weight, height, and skinfold thicknesses (triceps, subscapular, and suprailiac) were measured at age 5–7 years. Overweight, obesity, and extreme obesity were defined as a BMI z score ≥85th, ≥95th, and ≥99th percentile, respectively, based on the 1990 British Growth Standard. RESULTS Belfast HAPO offspring (n = 1,320, 82%) aged 5–7 years attended for follow-up. With use of multiple regression, maternal FPG, 1h PG, and 2hPG did not show any relation to offspring BMI z score or offspring skinfold sum independent of maternal BMI at OGTT and offspring birth weight z score. This lack of association with maternal glycemia persisted with the offspring BMI z score expressed as ≥85th, ≥95th, or 99th percentile and the sum of skinfolds expressed as ≥90th percentile specific for sex. The initially significant relation between FPG and all offspring adiposity measures was explained by maternal BMI at the OGTT. CONCLUSIONS After adjustment for maternal BMI at the OGTT, higher maternal FPG concentration during pregnancy (short of diabetes) is no longer a risk factor for obesity, as reflected by BMI and the sum of skinfolds in offspring aged 5–7 years.
Cholesterol modulates rat renal brush border membrane phosphate transport.
Authors: M Levi, B M Baird, P V Wilson
Journal: Journal of Clinical Investigation (1990)

In dietary phosphate (Pi) deprivation and in aging there is an inverse correlation between renal proximal tubular brush border membrane (BBM) cholesterol (Chol) content, BBM fluidity, and BBM sodium gradient-dependent Pi transport activity (Na-Pi cotransport). The purpose of this study was to determine whether in vitro enrichment of renal BBM with Chol has a direct modulating effect on Na-Pi cotransport. 12 and 24 mol % increases in Chol content caused dose-dependent decreases in Na-Pi cotransport activity, 2,000 in control, vs. 1,450 in Chol (+12%), vs. 900 pmol/5 s/mg BBM protein in Chol (+24%), all P less than 0.01, which was paralleled by dose-dependent increases in the fluorescence anisotropy of diphenylhexatriene, rDPH, i.e., decrease in BBM fluidity, 0.203 in control, vs. 0.210 in Chol (+12%), vs. 0.219 in Chol (+24%), all P less than 0.01. We found that increasing ambient temperature, which increases BBM fluidity independent of changes in Chol content, increased Na-Pi cotransport. When Na-Pi cotransport was analyzed as a function of BBM fluidity, 1/rDPH, we found that at an equivalent BBM fluidity BBM Chol enrichment still resulted in a dose-dependent decrease in Na-Pi cotransport. Finally, in BBM isolated from rats fed a low Pi diet in vitro enrichment with Chol completely reversed the adaptive increases in Na-Pi cotransport and fluidity. Our study therefore, indicates that Chol is a direct modulator of renal BBM Na-Pi cotransport activity, and that in vivo alterations in BBM Chol content most likely plays an important role in the regulation of renal tubular Pi transport.
Relationship between aspirin taking and gastroduodenal haemorrhage.
Authors: D J Parry, P H Wood
Journal: Gut (1967)

EDITORIAL COMMENT The causal relationship between aspirin and gastroduodenal haemorrhage is critically examined.Occult bleeding showed that as a group patients who had had a severe gastrointestinal bleed were not strikingly different from a group of people with normal digestive tracts.It seems likely that overt bleeding may be due to an idosyncratic response developing only in particular circumstances.
ERRα Is a Marker of Tamoxifen Response and Survival in Triple-Negative Breast Cancer
Authors: Subrata Manna, Josefine Bostner, Yang Sun, Lance D. Miller, Anya Alayev, Naomi S. Schwartz, Elin Lager, Tommy Fornander, Bo Nordenskjöld, Jane J. Yu, Olle Stål, Marina K. Holz
Journal: Clinical Cancer Research (2015)

Estrogen-related receptor alpha (ERRα) signaling has recently been implicated in breast cancer. We investigated the clinical value of ERRα in randomized cohorts of tamoxifen-treated and adjuvant-untreated patients.Cox proportional hazards regression was used to evaluate the significance of associations between ERRα gene expression levels and patient DMFS in a previously published microarray dataset representing 2,000 breast tumor cases derived from multiple medical centers worldwide. The 912 tumors used for immunostaining were from a tamoxifen-randomized primary breast cancer trial conducted in Stockholm, Sweden, during 1976-1990. Mouse model was used to study the effect of tamoxifen treatment on lung colonization of MDA-MB-231 control cells and MDA-MB-231 cells with stable knockdown of ERRα. The phenotypic effects associated with ERRα modulation were studied using immunoblotting analyses and wound-healing assay.We found that in ER-negative and triple-negative breast cancer (TNBC) adjuvant-untreated patients, ERRα expression indicated worse prognosis and correlated with poor outcome predictors. However, in tamoxifen-treated patients, an improved outcome was observed with high ERRα gene and protein expression. Reduced ERRα expression was oncogenic in the presence of tamoxifen, measured by in vitro proliferation and migration assays and in vivo metastasis studies.Taken together, these data show that ERRα expression predicts response to tamoxifen treatment, and ERRα could be a biomarker of tamoxifen sensitivity and a prognostic factor in TNBC.
An epigenetic role for PRL-3 as a regulator of H3K9 methylation in colorectal cancer
Authors: Yongxia Liu, Ping Zheng, Yuhong Liu, Tianhai Ji, Xunhua Liu, Su Yao, Xing Cheng, Ying Li, Lin Chen, Zhengquan Xiao, Jun Zhou, Jianming Li
Journal: Gut (2012)

<h3>Objective</h3> This study investigated the epigenetic role of PRL-3, a key metastasis gene in colorectal cancer (CRC), as a regulator of histone demethylation and the functions of Jumonji domain-containing protein 1B (JMJD1B) and JMJD2B in the progression of CRC. <h3>Methods</h3> PRL-3-associated proteins were analysed using functional distribution and category enrichment analysis. Western blotting and immunofluorescence were used to detect nuclear PRL-3. The relationship between PRL-3 and JMJD1B or JMJD2B and the roles of JMJD1B, JMJD2B and PRL-3 in histone demethylation were determined after these proteins were knocked down using RNA interference. Case–control studies on JMJD1B and JMJD2B in patients with CRC were performed using immunohistochemical analysis. The in vitro functional effects of JMJD2B and JMJD1B were examined further. <h3>Results</h3> JMJD1B and JMJD2B, two histone demethylases, were enriched among PRL-3-associated proteins. Nuclear PRL-3 was observed in CRC cells and clinical samples of CRC. The expression of nuclear PRL-3 was increased in patients with CRC at more advanced Dukes9 stages. PRL-3 was involved in the regulation of histone methylation by affecting the activities of JMJD1B and JMJD2B. A low expression of the JMJD1B protein was positively correlated with the lymph node status (p=0.032), Dukes9 classification (p=0.008) and TNM staging (p=0.022) of patients with CRC. A high expression of JMJD2B was positively correlated with the lymph node status (p=0.03), Dukes9 classification (p=0.036) and tumour invasion (p=0.003) of patients with CRC. A loss-of-function analysis confirmed that JMJD2B promoted the proliferation, colony formation and migration of human CRC cells. <h3>Conclusion</h3> Our data reveal a new role for PRL-3 as a key regulator of histone demethylation. JMJD1B seems to be a candidate tumour suppressor and JMJD2B seems to be a potential oncoprotein in the development and progression of CRC.