tbuckley/cabot-search huggingface dataset:
Health Care Use and Costs Associated With Use of a Health Club Membership Benefit in Older Adults with Diabetes
Authors: Huong Q. Nguyen, Matthew L. Maciejewski, Sue Gao, Elizabeth Lin, Barbara Williams, James P. LoGerfo
Journal: Diabetes Care (2008)

The purpose of this study was to determine whether elective use of a health plan-sponsored health club membership had an impact on health care use and costs among older adults with diabetes.Administrative claims for 2,031 older adults with diabetes enrolled in a Medicare Advantage plan were obtained for this retrospective cohort study. Participants (n = 618) in the plan-sponsored health club benefit (Silver Sneakers [SS]) and control subjects (n = 1,413) matched on SS enrollment index date were enrolled in the plan for at least 1 year before the index date. Two-year health care use and costs of SS participants and control subjects were estimated in regressions adjusting for baseline differences.SS participants were more likely to be male, had a lower chronic disease burden, used more preventive services, and had a lower prevalence of arthritis (P <or= 05). SS participants had lower adjusted total health care costs than control subjects in the first year after enrollment (-$1,633 [95% CI -$2,620 to -$646], P = 0.001), and adjusted total costs in year 2 trended lower (-$1,230 [-$2,494 to $33], P = 0.06). Participants who made on average >or=2 SS visits/week in year 1 had lower total costs in year 2 ($2,141 [-$3,877 to -$405], P = 0.02) than participants who made <2 visits/week.Use of a health club benefit by older adults with diabetes was associated with slower growth in total health care costs over 2 years; greater use of the benefit was actually associated with declines in total costs.
Molecular Mechanisms of Diuretic Agents
Authors: J Breyer, H R Jacobson
Journal: Annual Review of Medicine (1990)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
When a Decision Must Be Made: Role of Computer Modeling in Clinical Cancer Research
Authors: Rebecca A. Miksad
Journal: Journal of Clinical Oncology (2011)

Every day, multidisciplinary oncology teams make dozens of treatment decisions that may have a tremendous impact on a patient’s survival and quality of life. Made with the best of intentions, these decisions are informed by basic science and clinical research findings, clinical experience, and health policy. All too often, results from the gold standard of clinical trial research, a randomized controlled trial (RCT), that fit the specific details of the patient’s situation are not
G Protein-Coupled Receptor APJ and Its Ligand Apelin Act Downstream of Cripto to Specify Embryonic Stem Cells Toward the Cardiac Lineage Through Extracellular Signal-Regulated Kinase/p70S6 Kinase Signaling Pathway
Authors: Cristina D'Aniello, Enza Lonardo, Salvatore Iaconis, Ombretta Guardiola, Anna Maria Liguoro, Giovanna L. Liguori, Monica Autiero, Peter Carmeliet, Gabriella Minchiotti
Journal: Circulation Research (2009)

Pluripotent stem cells represent a powerful model system to study the early steps of cardiac specification for which the molecular control is largely unknown. The EGF-CFC (epidermal growth factor-Cripto/FRL-1/Cryptic) Cripto protein is essential for cardiac myogenesis in embryonic stem cells (ESCs).Here, we study the role of apelin and its G protein-coupled receptor, APJ, as downstream targets of Cripto both in vivo and in ESC differentiation.Gain-of-function experiments show that APJ suppresses neuronal differentiation and restores the cardiac program in Cripto(-/-) ESCs. Loss-of-function experiments point for a central role for APJ/apelin in the gene regulatory cascade promoting cardiac specification and differentiation in ESCs. Remarkably, we show for the first time that apelin promotes mammalian cardiomyogenesis via activation of mitogen-activated protein kinase/p70S6 through coupling to a Go/Gi protein.Together our data provide evidence for a previously unrecognized function of APJ/apelin in the Cripto signaling pathway governing mesoderm patterning and cardiac specification in mammals.
The Pharmacogenetics of Type 2 Diabetes: A Systematic Review
Authors: Nisa M. Maruthur, Matthew O. Gribble, Wendy L. Bennett, Shari Bolen, Lisa M. Wilson, Poojitha Balakrishnan, Anita Sahu, Eric Bass, W.H. Linda Kao, Jeanne M. Clark
Journal: Diabetes Care (2014)

OBJECTIVE We performed a systematic review to identify which genetic variants predict response to diabetes medications. RESEARCH DESIGN AND METHODS We performed a search of electronic databases (PubMed, EMBASE, and Cochrane Database) and a manual search to identify original, longitudinal studies of the effect of diabetes medications on incident diabetes, HbA1c, fasting glucose, and postprandial glucose in prediabetes or type 2 diabetes by genetic variation. Two investigators reviewed titles, abstracts, and articles independently. Two investigators abstracted data sequentially and evaluated study quality independently. Quality evaluations were based on the Strengthening the Reporting of Genetic Association Studies guidelines and Human Genome Epidemiology Network guidance. RESULTS Of 7,279 citations, we included 34 articles (N = 10,407) evaluating metformin (n = 14), sulfonylureas (n = 4), repaglinide (n = 8), pioglitazone (n = 3), rosiglitazone (n = 4), and acarbose (n = 4). Studies were not standalone randomized controlled trials, and most evaluated patients with diabetes. Significant medication–gene interactions for glycemic outcomes included 1) metformin and the SLC22A1, SLC22A2, SLC47A1, PRKAB2, PRKAA2, PRKAA1, and STK11 loci; 2) sulfonylureas and the CYP2C9 and TCF7L2 loci; 3) repaglinide and the KCNJ11, SLC30A8, NEUROD1/BETA2, UCP2, and PAX4 loci; 4) pioglitazone and the PPARG2 and PTPRD loci; 5) rosiglitazone and the KCNQ1 and RBP4 loci; and 5) acarbose and the PPARA, HNF4A, LIPC, and PPARGC1A loci. Data were insufficient for meta-analysis. CONCLUSIONS We found evidence of pharmacogenetic interactions for metformin, sulfonylureas, repaglinide, thiazolidinediones, and acarbose consistent with their pharmacokinetics and pharmacodynamics. While high-quality controlled studies with prespecified analyses are still lacking, our results bring the promise of personalized medicine in diabetes one step closer to fruition.
Epidemiological, Neurobiological, and Genetic Clues to the Mechanisms Linking Cannabis Use to Risk for Nonaffective Psychosis
Authors: Ruud van Winkel, Rebecca Kuepper
Journal: Annual Review of Clinical Psychology (2014)

Epidemiological studies have shown that the association between cannabis and psychosis is robust and consistent across different samples, with compelling evidence for a dose-response relationship. Because longitudinal work indicates that cannabis use precedes psychotic symptoms, it seems reasonable to assume a causal relationship. However, more work is needed to address the possibility of gene-environment correlation (for example, genetic risk for psychosis causing onset of cannabis use). Moreover, knowledge about underlying biological mechanisms linking cannabis use and psychosis is still relatively limited. In order to understand how cannabis use may lead to an increased risk for psychosis, in the present article we (a) review the epidemiological, neurobiological, and genetic evidence linking cannabinoids and psychosis, (b) assess the quality of the evidence, and finally (c) try to integrate the most robust findings into a neurodevelopmental model of cannabis-induced psychosis and identify the gaps in knowledge that are in need of further investigation.
Integrative Data Analysis in Clinical Psychology Research
Authors: Andrea M. Hussong, Patrick J. Curran, Daniel J. Bauer
Journal: Annual Review of Clinical Psychology (2013)

Integrative data analysis (IDA), a novel framework for conducting the simultaneous analysis of raw data pooled from multiple studies, offers many advantages including economy (i.e., reuse of extant data), power (i.e., large combined sample sizes), the potential to address new questions not answerable by a single contributing study (e.g., combining longitudinal studies to cover a broader swath of the lifespan), and the opportunity to build a more cumulative science (i.e., examining the similarity of effects across studies and potential reasons for dissimilarities). There are also methodological challenges associated with IDA, including the need to account for sampling heterogeneity across studies, to develop commensurate measures across studies, and to account for multiple sources of study differences as they impact hypothesis testing. In this review, we outline potential solutions to these challenges and describe future avenues for developing IDA as a framework for studies in clinical psychology.
A double-blind controlled trial of Rumalon in the treatment of painful osteoarthrosis of the hip.
Authors: A S Dixon, G D Kersley, R Mercer, M Thompson, R M Mason, C Barnes, G Wenley, E Lewis-Faning
Journal: Annals of the Rheumatic Diseases (1970)

Heberden Society 193dosage in all these patients, and were successful in about half of them.We noted an interesting fall in lymphocyte count, comparing the lymphocyte count with the total white cell count at the beginning of treatment and after one year.Whether or not immunosuppressives have any part to play in treatment of rheumatoid arthritis requires further study; we are at the present engaged in a double- blind controlled trial.*DR.G. D. K ER S L EY (Bath) In my experience in rheumatoid arthritis, the drug has often had to be stopped on account of side-effects.On the other hand we have had very good results in two cases which previously required a large dosage of steroids to control their disease.DR.T. BITTER (Bad Ragaz) I should like to add one minor comment.The effect on a secondary immune response of a so-called immunosuppressive drug is far from proven.The cytostatic effect is potent and the indications are probably best in highly cellular disease, in which we want to suppress cells.If the cells are sufficiently suppressed, a secondary immune response might appear to be suppressed without actual evidence of an immunosuppression.
Role of cancer stem cells in hepatocarcinogenesis
Authors: Bo Wang, Samson T Jacob
Journal: Genome Medicine (2011)

There has been considerable interest in cancer stem cells (CSCs) among cancer biologists and clinicians, most likely because of their role in the heterogeneity of cancer and their potential application in cancer therapeutics. Recent studies suggest that CSCs play a key role in liver carcinogenesis. A small subpopulation of cancer cells with CSC properties has been identified and characterized from hepatocellular carcinoma (HCC) cell lines, animal models and human primary HCCs. Considering the high mortality and ineffectiveness of current therapies for HCC, understanding the characteristics and function of CSCs is likely to lead to development of new therapies resulting in improvement of patient survival. This review summarizes recent progress in liver cancer stem cell research with regard to the identification, cell origin, regulation of self-renewal capacity, and therapeutic implications of liver CSCs.
First somatic mutation of E2F1 in a critical DNA binding residue discovered in well-differentiated papillary mesothelioma of the peritoneum
Authors: Willie Yu, Waraporn Chan-On, Melissa Teo, Choon Kiat Ong, Ioana Cutcutache, George E Allen, Bernice Wong, Swe Swe Myint, Kiat Hon Lim, P Mathijs Voorhoeve, Steve Rozen, Khee Chee Soo, Patrick Tan, Bin Tean Teh
Journal: Genome biology (2011)

Abstract Background Well differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare variant of epithelial mesothelioma of low malignancy potential, usually found in women with no history of asbestos exposure. In this study, we perform the first exome sequencing of WDPMP. Results WDPMP exome sequencing reveals the first somatic mutation of E2F1, R166H, to be identified in human cancer. The location is in the evolutionarily conserved DNA binding domain and computationally predicted to be mutated in the critical contact point between E2F1 and its DNA target. We show that the R166H mutation abrogates E2F1's DNA binding ability and is associated with reduced activation of E2F1 downstream target genes. Mutant E2F1 proteins are also observed in higher quantities when compared with wild-type E2F1 protein levels and the mutant protein's resistance to degradation was found to be the cause of its accumulation within mutant over-expressing cells. Cells over-expressing wild-type E2F1 show decreased proliferation compared to mutant over-expressing cells, but cell proliferation rates of mutant over-expressing cells were comparable to cells over-expressing the empty vector. Conclusions The R166H mutation in E2F1 is shown to have a deleterious effect on its DNA binding ability as well as increasing its stability and subsequent accumulation in R166H mutant cells. Based on the results, two compatible theories can be formed: R166H mutation appears to allow for protein over-expression while minimizing the apoptotic consequence and the R166H mutation may behave similarly to SV40 large T antigen, inhibiting tumor suppressive functions of retinoblastoma protein 1.
Validation of lung function prediction equations from patient survival data
Authors: Helen Ward, Brendan Cooper, Martin R. Miller
Journal: European Respiratory Journal (2011)

Diagnosing and managing pulmonary disease usually requires judging lung function against predicted values. We explored patient survival data to help identify the best equations for our population. The earliest spirometry, lung volumes and gas transfer data for all Caucasian patients were extracted from our database. Survival status was available for 8,139 patients. Lung function as standardised residuals (SR) from various prediction equations was used in Cox regression to predict the hazard ratio (HR) for death. The best lung function predictor of all-cause mortality was diffusing capacity of the lung for carbon monoxide ( D L,CO ), followed by forced vital capacity (FVC). These were best with the equations of Miller, derived from a US population, with Chi-squared values of 1,468 and 1,043 for D L,CO and FVC, respectively, having taken age, sex, smoking status and body mass index into account. The HR (95% CI) for SR &lt; -3 were 8.5 (6.0–12.1) and 2.9 (2.3–3.5), respectively. Spirometric equation prediction models varied less than those for D L,CO , with the Miller equations being slightly better than Lambda-Mu-Sigma (LMS) equations. Some D L,CO equations introduced sex bias (male sex HR of 3.0 versus 1.5 for other equations). We conclude that LMS or Miller spirometry equations and Miller’s D L,CO equations were best for our patient population. Using patient survival data is a new approach to help select which lung function prediction equations to use.
Talking to ourselves: The intelligibility of inner speech
Authors: Peter P. Slezak
Journal: Behavioral and Brain Sciences (2002)

The possible role of language in intermodular communication and non-domain-specific thinking is an empirical issue that is independent of the “vehicle” claim that natural language is “constitutive” of some thoughts. Despite noting objections to various forms of the thesis that we think in language, Carruthers entirely neglects a potentially fatal objection to his own preferred version of this “cognitive conception.”
ANGPTL4 Induction by Prostaglandin E2 under Hypoxic Conditions Promotes Colorectal Cancer Progression
Authors: Sun-Hee Kim, Yun-Yong Park, Sang-Wook Kim, Ju-Seog Lee, Dingzhi Wang, Raymond N. DuBois
Journal: Cancer Research (2011)

Prostaglandin E(2) (PGE(2)), the most abundant COX-2-derived prostaglandin found in colorectal cancer, promotes tumor cell proliferation and survival via multiple signaling pathways. However, the role of PGE(2) in tumor hypoxia is not well understood. Here, we show a synergistic effect of PGE(2) and hypoxia on enhancing angiopoietin-like protein 4 (ANGPTL4) expression and that elevation of ANGPTL4 promotes colorectal cancer growth. PGE(2) induces ANGPTL4 expression at both the mRNA and protein levels under hypoxic conditions. Moreover, hypoxia induces one of the PGE(2) receptors, namely EP1. Activation of EP1 enhances ANGPTL4 expression, whereas blockage of EP1 by an antagonist inhibits PGE(2) induction of ANGPTL4 under hypoxic conditions. Importantly, overexpression of ANGPTL4 promotes cell proliferation and tumor growth in vitro and in vivo. In addition, treatment with ANGPTL4 recombinant protein increases colorectal carcinoma cell proliferation through effects on STAT1 signaling. The MAP kinase and Src pathways mediate ANGPTL4-induced STAT1 expression and activation. These results are relevant to human disease because we found that the expression of ANGPTL4 and STAT1 are elevated in 50% of human colorectal cancers tested and there is a positive correlation between COX-2 and ANGPTL4 as well STAT1 expression in colorectal carcinomas. Collectively, these findings suggest that PGE(2) plays an important role in promoting cancer cell proliferation via ANGPTL4 under hypoxic conditions.
Turnover of Plasma Esterified Cholesterol in Normocholesterolemic and Hypercholesterolemic Subjects and Its Relation to Body Build*
Authors: P. J. Nestel, E. A. Monger
Journal: Journal of Clinical Investigation (1967)

The turnover rate of plasma total esterified cholesterol was measured after the intravenous injection of tritiated mevalonic acid in 16 men with coronary heart disease. Four subjects were normocholesterolemic and 12 were hypercholesterolemic; among the latter, 3 suffered from familial hypercholesterolemia and 6 were overweight. The turnover rate of plasma esterified cholesterol was highest among the overweight hypercholesterolemic subjects and least among the subjects with familial hypercholesterolemia. Hypercholesterolemic subjects of normal weight had turnover rates similar to those found in normocholesterolemic men. Significant correlations were found between body surface or body weight and the turnover rate of plasma esterified cholesterol. We conclude that the factors which determine the development of hypercholesterolemia are not identical in all hypercholesterolemic subjects and that when hypercholesterolemia is associated with overweight there is an increased formation of at least plasma esterified cholesterol.
Ets-1 regulates intracellular glutathione levels: key target for resistant ovarian cancer
Authors: Meghan L Verschoor, Gurmit Singh
Journal: Molecular Cancer (2013)

Ovarian cancer is characterized by high rates of metastasis and therapeutic resistance. Many chemotherapeutic agents rely on the induction of oxidative stress to cause cancer cell death, thus targeting redox regulation is a promising strategy to overcome drug resistance.We have used a tetracycline-inducible Ets-1 overexpression model derived from 2008 ovarian cancer cells in the present study. To examine the role of Ets-1 in glutathione regulation we have measured intracellular reactive oxygen species and glutathione levels, as well as glutathione peroxidase enzyme activity. Glutathione synthesis was limited using transsulfuration or Sx(c)- pathway blocking agents, and glutamate release was measured to confirm Sx(c)- blockade. Cell viability following drug treatment was assessed via crystal violet assay. Oxidative stress was induced through glucose oxidase treatment, which produces hydrogen peroxide by glucose oxidation. The protein expressions of redox-related factors were measured through western blotting.Overexpression of Ets-1 was associated with decreased intracellular ROS, concomitantly with increased intracellular GSH, GPX antioxidant activity, and Sx(c)- transporter activity. Under basal conditions, inhibition of the transsulfuration pathway resulted in decreased GSH levels and GPX activity in all cell lines, whereas inhibition of Sx(c)- by sulfasalazine decreased GPX activity in Ets-1-expressing cells only. However, under oxidative stress the intracellular GSH levels decreased significantly in correlation with increased Ets-1 expression following sulfasalazine treatment.In this study we have identified a role for proto-oncogene Ets-1 in the regulation of intracellular glutathione levels, and examined the effects of the anti-inflammatory drug sulfasalazine on glutathione depletion using an ovarian cancer cell model. The findings from this study show that Ets-1 mediates enhanced Sx(c)- activity to increase glutathione levels under oxidative stress, suggesting that Ets-1 could be a promising putative target to enhance conventional therapeutic strategies.
Measurement, Characterization, and Source of Somatostatin-like Immunoreactivity in Human Amniotic Fluid
Authors: David Fitz-Patrick, Yogesh C. Patel
Journal: Journal of Clinical Investigation (1979)

Somatostatin-like immunoreactivity (SLI) is widely distributed in tissues and biological fluids. To determine whether SLI is also present in amniotic fluid, samples obtained by amniocentesis from 30 normal and 27 abnormal pregnancies were studied by radioimmunoassay. Direct incubation of [125I-Tyr1]tetradecapeptide somatostatin (SRIF) with amniotic fluid resulted in 89% tracer degradation. Damage was reduced to <5% when samples were acidified and boiled before the assay. With this technique, SLI was detectable in all normal amniotic fluid samples; the mean level at 15-20 wk of gestation (320±55 pg/ml, n = 15) being 4.5 times higher than the mean at 32-43 wk (70±12 pg/ml, n = 15) (P < 0.001). In cases of preeclampsia (n = 6), gestational diabetes (n = 5), anencephaly (n = 1), and meningomyelocele (n = 1), SLI values were in the normal range, but in one juvenile diabetic and one patient with chronic renal failure, SLI was undetectable (<10 pg/ml). In a pair of monochorionic diamniotic twins, SLI levels were very different (33 and 197 pg/ml), which suggests that fetal factors are more important than materno-placental ones in determining amniotic fluid SLI. Serial dilutions of amniotic fluid showed parallelism with standard SRIF. When concentrates of pooled amniotic fluid were chromatographed on Sephadex G-25 columns, all SLI eluted in the void volume ahead of SRIF even after treatment with 8 M urea and dithiothreitol. This “big” SLI incubated in amniotic fluid showed 100% stability over 24 h at 37°C, whereas SRIF was rapidly inactivated (t½ ≅ 7 min). Extracts of placenta and fetal membranes contained no SLI, but small amounts (6-20% of total amniotic fluid SLI) were found in cells from fresh fluid. Radioimmunoassay of SLI in extracts of seven paired cord arterial and venous plasma samples showed no arteriovenous gradient consistent with fetal origin of cord blood SLI. It is concluded that (a) amniotic fluid contains SLI which is of fetal origin and (b) normal levels vary with gestational age. The SLI has a higher molecular weight (≥5,000) and is more stable in amniotic fluid than SRIF.