tbuckley/cabot-search huggingface dataset:
Higher Rates of Cigarette Smoking in Male Adolescents Before the Onset of Schizophrenia: A Historical-Prospective Cohort Study
Authors: Mark Weiser, Abraham Reichenberg, Itamar Grotto, Ross Yasvitzky, Jonathan Rabinowitz, Gad Lubin, Daniella Nahon, Haim Y Knobler, Michael Davidson
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The prevalence of cigarette smoking among schizophrenia patients is significantly higher than in the general population; this may reflect self-medication of symptoms and/or adverse effects of neuroleptics. The authors examined the prevalence of cigarette smoking in apparently healthy adolescents later hospitalized for schizophrenia. METHOD: Each year, a random sample of male Israeli military recruits, who have been screened and found not to be suffering from major psychopathology, complete a smoking questionnaire. Through the Israeli National Psychiatric Hospitalization Case Registry, 14,248 of these adolescents were followed to determine later psychiatric hospitalization. RESULTS: Of the 14,248 adolescents assessed, 4,052 (28.4%) reported smoking at least one cigarette a day. Over a 4–16-year follow-up, the prevalence of schizophrenia in the entire cohort was 0.3% (N=44). Smokers were at greater risk for later schizophrenia; the adjusted relative risk was 1.94, and the 95% confidence interval (CI) was 1.05–3.58. The number of cigarettes smoked was significantly associated with the risk for schizophrenia. Compared to nonsmokers, adolescents who smoked 1–9 cigarettes/day were 1.38 times (95% CI=0.48–4.00) as likely to be hospitalized later for schizophrenia, and adolescents who smoked 10 cigarettes/day or more were 2.28 times (95% CI=1.19–4.34) as likely; the latter difference was statistically significant. CONCLUSIONS: Taken together with the existing data on abnormalities in nicotinic transmission in patients and their relatives, this higher prevalence of smoking in future schizophrenia patients, before the onset of their illness, might indicate that impaired nicotinic neurotransmission is involved in the pathophysiology of schizophrenia.
The comparison of exercise test in patients with lung resection candidates
Authors: Sevgi Ozalevli, Duygu Ilgin, Hasan Ersoz, Aydin Sanli, Can Sevinc, Nezih Ozdemir
Journal: European Respiratory Journal (2011)

Aim:  It has been aimed at investigating the consistency of the maximal cardiopulmonary exercise test (CPET), 6-minute walking test (6MWT), and stair climbing test (SCT) results with each other and discussing the applicability of these submaximal field tests in patients with lung resection surgery indication.   Material-method:  The maximal cycle ergometry, 6MWT, and SCT tests were done in 22 lung cancer patients (6F, 16M) followed with lung resection surgery indication. maxVO 2  value was calculated indirectly using indirect formulas for 6MWT and SCT. Peripheral oxygen saturation (SpO 2 ) and heart rate values were recorded using pulse oximetry during tests.   Results:  The mean maxVO 2  values were 16.07±2.70ml/kg/min (for CPET), 24.44±4.09 ml/kg/min (for SCT), and 18.38±2.83 ml/kg/min (for 6MWT). It was determined that heart rate increased (heart rate differerence; for CPET=38.20±14.67, 6MWT=20.48±9.06, SCT=49.86±11.56, p 2  reduced (SpO 2  difference; for SCT=3.14±1.56 and 6MWT= 1.48±2.52 icin p 2  was correlated with 6MWT and SCT maxVO 2  (between CPET and SCT, rho=0.59, p=0.01; between CPET and 6MWT, rho=0.53, p=0.02). In addition, it was determined that there were correlations only between CPET and SCT in respect to load and work values (rho=0.70, p=0.001).   Conclusion:  Due to correlation between indirectly calculated maxVO 2  value with SCT and CPET maxVO 2  value, our results suggest that SCT and SCT maxVO 2  value may be applicable during patient follow up and treatment. Also, 6MWT can be used related to lower hemodynamical stres level in conditions the application of CPET and SCT are not possible.
Counteracting breast-cancer induced immune suppression by reactivating lymph node-resident conventional dendritic cells (LNR-cDC)
Authors: Rieneke van de Ven, Kim van Pul, Shaghayegh Aliabadi, Petrousjka van den Tol, Lisette A te Velde, Emiel JTh Rutgers, Ronald JCLM Vuylsteke, Hein BAC Stockmann, Christopher Dubay, Chris Harrington, Bernard A Fox, Tanja D de Gruijl
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Breast cancer (BrC)-derived factors inhibit proper development and activation of dendritic cells (DC), which in turn promote the expansion of regulatory T cells (Tregs), thus contributing to tumor progression and spread. In two separate BrC sentinel lymph node (SLN) cohorts, one
Prevalence and Functional Consequence of <i>TP53</i> Mutations in Pediatric Adrenocortical Carcinoma: A Children's Oncology Group Study
Authors: Jonathan D. Wasserman, Ana Novokmet, Claudia Eichler-Jonsson, Raul C. Ribeiro, Carlos Rodriguez-Galindo, Gerard P. Zambetti, David Malkin
Journal: Journal of Clinical Oncology (2015)

Purpose Adrenocortical carcinoma (ACC) is a rare pediatric malignancy. It occurs in excess among individuals with the Li-Fraumeni syndrome, which results primarily from germline mutations in the TP53 gene. Prior series exploring frequencies of germline TP53 mutation among children with ACC have been small, geographically limited, or subject to referral bias. The functional consequence of mutations has not been related to phenotype. We provide a genotype-phenotype analysis of TP53 mutations in pediatric ACC and propose a model for tissue-specific effects based on adrenocortical ontogeny. Patients and Methods Eighty-eight consecutive, unrelated children with ACC, unselected for family history, underwent germline TP53 sequencing. Rate and distribution of mutations were identified. Functional analysis was performed for novel TP53 variants. Correlation with the International Agency for Research on Cancer p53 database further delineated mutational distribution, association with family history, and risk for multiple primary malignancies (MPMs). Results Germline mutations were present in 50% of children. These mutations did not correspond to the conventional hotspot mutations. There was a wide range of mutant protein function. Patients bearing alleles encoding protein with higher functionality were less likely to have a strong family cancer history, whereas those with greater loss of function had MPMs and/or positive family history. In patients with MPMs, ACC was the most frequent initial malignancy. Finally, we demonstrated age-dependent rates of TP53 mutation positivity. Conclusion TP53 mutations are prevalent in children with ACC but decline with age. Mutations result in a broad spectrum of functional loss. Effect of individual mutations may predict carrier and familial disease penetrance with potentially broad implications for clinical surveillance and counseling.
Generation of fibrinolytic activity by infusion of activated protein C into dogs.
Authors: P C Comp, C T Esmon
Journal: Journal of Clinical Investigation (1981)

Bovine-activated protein C, administered intravenously to dogs, increases the rate of lysis of whole blood clots. Protein C, bovine prothrombin, and diisopropylfluorophosphate-inactivated protein Ca do not increase the rate of lysis. Repeated infusions of protein Ca sustain rapid blood clot lysis, but neither elevate circulating fibrin-split products nor decrease circulating plasminogen levels. The administration of protein Ca results in the elevation of the levels of lysine-adsorbable plasminogen activator activity in the plasma. When partially purified concentrates of this activator are added to normal dog blood at the levels seen following protein Ca injection, the rate of clot lysis is similar to that seen after protein Ca injection. The addition of protein Ca to citrated whole blood in vitro, with the subsequent neutralization of protein Ca with antibodies, results in increased rates of lysis when plasma made from the treated blood is reinjected into the animal. The generation of fibrinolytic activity is dependent on both cellular and plasma components of blood. A model of protein Ca fibrinolytic activity has a minimum of two components: a secondary messenger formed by protein Ca action on blood cells and plasma, and the subsequent appearance of plasminogen activator in the animal in response to that messenger.
Anti-reflux surgery in lung transplant recipients: outcomes and effects on quality of life
Authors: A.G.N. Robertson, A. Krishnan, C. Ward, J.P. Pearson, T. Small, P.A. Corris, J.H. Dark, D. Karat, J. Shenfine, S.M. Griffin
Journal: European Respiratory Journal (2011)

Fundoplication may improve survival after lung transplantation. Little is known about the effects of fundoplication on quality of life in these patients. The aim of this study was to assess the safety of fundoplication in lung transplant recipients and its effects on quality of life. Between June 1, 2008 and December 31, 2010, a prospective study of lung transplant recipients undergoing fundoplication was undertaken. Quality of life was assessed before and after surgery. Body mass index (BMI) and pulmonary function were followed up. 16 patients, mean± sd age 38±11.9 yrs, underwent laparoscopic Nissen fundoplication. There was no peri-operative mortality or major complications. Mean± sd hospital stay was 2.6±0.9 days. 15 out of 16 patients were satisfied with the results of surgery post fundoplication. There was a significant improvement in reflux symptom index and DeMeester questionnaires and gastrointestinal quality of life index scores at 6 months. Mean BMI decreased significantly after fundoplication (p=0.01). Patients operated on for deteriorating lung function had a statistically significant decrease in the rate of lung function decline after fundoplication (p=0.008). Laparoscopic fundoplication is safe in selected lung transplant recipients. Patient benefit is suggested by improved symptoms and satisfaction. This procedure is acceptable, improves quality of life and may reduce deterioration of lung function.
TRIBUTE: A Phase III Trial of Erlotinib Hydrochloride (OSI-774) Combined With Carboplatin and Paclitaxel Chemotherapy in Advanced Non–Small-Cell Lung Cancer
Authors: Roy S. Herbst, Diane Prager, Robert Hermann, Lou Fehrenbacher, Bruce E. Johnson, Alan Sandler, Mark G. Kris, Hai T. Tran, Pam Klein, Xin Li, David Ramies, David H. Johnson, Vincent A. Miller
Journal: Journal of Clinical Oncology (2005)

Erlotinib is a potent reversible HER1/epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor with single-agent activity in patients with non-small-cell lung cancer (NSCLC). Erlotinib was combined with chemotherapy to determine if it could improve the outcome of patients with NSCLC.TRIBUTE randomly assigned patients with good performance status and previously untreated advanced (stage IIIB/IV) NSCLC to erlotinib 150 mg/d or placebo combined with up to six cycles of carboplatin and paclitaxel, followed by maintenance monotherapy with erlotinib. Random assignment was stratified by stage, weight loss in the previous 6 months, measurable disease, and treatment center. The primary end point was overall survival (OS). Secondary end points included time to progression (TTP), objective response (OR), and duration of response.There were 1,059 assessable patients (526 erlotinib; 533 placebo). Median survival for patients treated with erlotinib was 10.6 v 10.5 months for placebo (hazard ratio, 0.99; 95% CI, 0.86 to 1.16; P = .95). There was no difference in OR or median TTP. Patients who reported never smoking (72 erlotinib; 44 placebo) experienced improved OS in the erlotinib arm (22.5 v 10.1 months for placebo), though no other prespecified factors showed an advantage in OS with erlotinib. Erlotinib and placebo arms were equivalent in adverse events (except rash and diarrhea).Erlotinib with concurrent carboplatin and paclitaxel did not confer a survival advantage over carboplatin and paclitaxel alone in patients with previously untreated advanced NSCLC. Never smokers treated with erlotinib and chemotherapy seemed to experience an improvement in survival and will undergo further investigation in future randomized trials.
AUTOANTIBODIES AGAINST NEUTROPHILS AND MONOCYTES: TOOL FOR DIAGNOSIS AND MARKER OF DISEASE ACTIVITY IN WEGENER'S GRANULOMATOSIS
Authors: F.J. Van Der Woude, S. Lobatto, H. Permin, M. Van Der Giessen, N. Rasmussen, A. Wiik, L.A. Van Es, G.K. Van Der Hem, T.H. The
Journal: The Lancet (1985)
FLIM-FRET Imaging of Caspase-3 Activity in Live Cells Using Pair of Red Fluorescent Proteins
Authors: Alexander P. Savitsky, Alexander L. Rusanov, Victoria V. Zherdeva, Tatiana V. Gorodnicheva, Maria G. Khrenova, Alexander V. Nemukhin
Journal: Theranostics (2012)

We report a new technique to detect enzyme activity inside cells. The method based on Fluorescence Lifetime Imaging (FLIM) technology allows one to follow sensor cleavage by proteolytic enzyme caspase-3. Specifically, we use the FLIM FRET of living cells via the confocal fluorescence microscopy. A specially designed lentivector pLVT with the DNA fragment of TagRFP-23-KFP was applied for transduction of A549 cell lines. Computer simulations are carried out to estimate FRET efficiency and to analyze possible steric restrictions of the reaction between the substrate TagRFP-23-KFP and caspase-3 dimer. Successful use of the fuse protein TagRFP-23-KFP to register the caspase-3 activation based on average life-time measurements is demonstrated. We show that the average life-time distribution is dramatically changed for cells with the modified morphology that is typical for apoptosis. Namely, the short-lived component at 1.8-2.1 ns completely disappears and the long-lived component appears at 2.4-2.6 ns. The latter is a fingerprint of the TagRFP molecule released after cleavage of the TagRFP-23-KFP complex by caspase-3. Analysis of life-time distributions for population of cells allows us to discriminate apoptotic and surviving cells within single frame and to peform statistical analysis of drug efficiency. This system can be adjusted for HTS by using special readers oriented on measurements of fluorescence life-time.
Television Watching and Other Sedentary Behaviors in Relation to Risk of Obesity and Type 2 Diabetes Mellitus in Women
Authors: Frank B. Hu, Tricia Y. Li, Graham A. Colditz, Walter C. Willett, JoAnn E. Manson
Journal: JAMA (2003)

Current public health campaigns to reduce obesity and type 2 diabetes have largely focused on increasing exercise, but have paid little attention to the reduction of sedentary behaviors.To examine the relationship between various sedentary behaviors, especially prolonged television (TV) watching, and risk of obesity and type 2 diabetes in women.Prospective cohort study conducted from 1992 to 1998 among women from 11 states in the Nurses' Health Study. The obesity analysis included 50 277 women who had a body mass index (BMI) of less than 30 and were free from diagnosed cardiovascular disease, diabetes, or cancer and completed questions on physical activity and sedentary behaviors at baseline. The diabetes analysis included 68 497 women who at baseline were free from diagnosed diabetes mellitus, cardiovascular disease, or cancer.Onset of obesity and type 2 diabetes mellitus.During 6 years of follow-up, 3757 (7.5%) of 50 277 women who had a BMI of less than 30 in 1992 became obese (BMI > or =30). Overall, we documented 1515 new cases of type 2 diabetes. Time spent watching TV was positively associated with risk of obesity and type 2 diabetes. In the multivariate analyses adjusting for age, smoking, exercise levels, dietary factors, and other covariates, each 2-h/d increment in TV watching was associated with a 23% (95% confidence interval [CI], 17%-30%) increase in obesity and a 14% (95% CI, 5%-23%) increase in risk of diabetes; each 2-h/d increment in sitting at work was associated with a 5% (95% CI, 0%-10%) increase in obesity and a 7% (95% CI, 0%-16%) increase in diabetes. In contrast, standing or walking around at home (2 h/d) was associated with a 9% (95% CI, 6%-12%) reduction in obesity and a 12% (95% CI, 7%-16%) reduction in diabetes. Each 1 hour per day of brisk walking was associated with a 24% (95% CI, 19%-29%) reduction in obesity and a 34% (95% CI, 27%-41%) reduction in diabetes. We estimated that in our cohort, 30% (95% CI, 24%-36%) of new cases of obesity and 43% (95% CI, 32%-52%) of new cases of diabetes could be prevented by adopting a relatively active lifestyle (<10 h/wk of TV watching and > or =30 min/d of brisk walking).Independent of exercise levels, sedentary behaviors, especially TV watching, were associated with significantly elevated risk of obesity and type 2 diabetes, whereas even light to moderate activity was associated with substantially lower risk. This study emphasizes the importance of reducing prolonged TV watching and other sedentary behaviors for preventing obesity and diabetes.
Measuring Preventable Harm
Authors: Peter J Pronovost, Elizabeth Colantuoni
Journal: JAMA (2009)

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Psychometric Properties of the Hypoglycemia Fear Survey-II for Adults With Type 1 Diabetes
Authors: Linda A. Gonder-Frederick, Karen M. Schmidt, Karen A. Vajda, Megan L. Greear, Harsimran Singh, Jaclyn A. Shepard, Daniel J. Cox
Journal: Diabetes Care (2011)

OBJECTIVE To perform the first comprehensive psychometric evaluation of the Hypoglycemia Fear Survey-II (HFS-II), a measure of the behavioral and affective dimensions of fear of hypoglycemia, using modern test-theory methods, including item-response theory (IRT). RESEARCH DESIGN AND METHODS Surveys completed in four previous studies by 777 adults with type 1 diabetes were aggregated for analysis, with 289 subjects completing both subscales of the HFS-II and 488 subjects completing only the Worry subscale. The aggregated sample (53.3% female, 44.4% using insulin pumps) had a mean age of 41.9 years, diabetes duration of 23.8 years, HbA1c value of 7.7%, and 1.4 severe hypoglycemic episodes in the past year. Data analysis included exploratory factor analysis using polychoric correlations and IRT. Factors were analyzed for fit, trait-level locations, point-measure correlations, and separation values. RESULTS Internal and test-retest reliability was good, as well as convergent validity, as demonstrated by significant correlations with other measures of psychological distress. Scores were significantly higher in subjects who had experienced severe hypoglycemia in the past year. Factor analyses validated the two subscales of the HFS-II. Item analyses showed that 12 of 15 items on the Behavior subscale, and all of the items on the Worry subscale had good-fit statistics. CONCLUSIONS The HFS-II is a reliable and valid measure of the fear of hypoglycemia in adults with type 1 diabetes, and factor analyses and IRT support the two separate subscales of the survey.
The muscarinic M1-receptor-selective antagonist, telenzepine, had no bronchodilatory effects in COPD patients
Authors: D Ukena, C Wehinger, R Engelstatter, V Steinijans, GW Sybrecht
Journal: European Respiratory Journal (1993)

In a double-blind, placebo-controlled, randomized, cross-over trial, we studied the effects of the muscarinic M1-receptor-selective antagonist (+/-)-telenzepine (3 mg orally at 6 p.m. for 5 days) in 21 patients with chronic obstructive pulmonary disease (COPD). At enrollment all patients showed at least a 50% decrease in airway resistance (Raw) after inhalation of 400 micrograms fenoterol or 200 micrograms oxitropium bromide. Telenzepine did not have a significant effect on forced expiratory volume in one second (FEV1) or forced vital capacity (FVC). Also, no significant changes could be detected in daily spirometric profiles or Raw. The results indicate that short-term treatment with the M1-selective antagonist, telenzepine, does not improve airway function in COPD patients, at least after administration by the oral route.
Ras-induced Modulation of CXCL10 and Its Receptor Splice Variant CXCR3-B in MDA-MB-435 and MCF-7 Cells: Relevance for the Development of Human Breast Cancer
Authors: Dipak Datta, Jesse A. Flaxenburg, Sreenivas Laxmanan, Christopher Geehan, Martin Grimm, Ana Maria Waaga-Gasser, David M. Briscoe, Soumitro Pal
Journal: Cancer Research (2006)

Interactions between chemokines and chemokine receptors have been proposed recently to be of importance in the development and progression of cancer. Human breast cancer cells express the chemokine CXCL10 (IP-10) and also its receptor CXCR3. In this study, we have investigated the role of Ras activation in the regulation of CXCL10 and its receptor splice variant CXCR3-B in two human breast cancer cell lines MDA-MB-435 and MCF-7. In cotransfection assays, using a full-length CXCL10 promoter-luciferase construct, we found that the activated form of Ras, Ha-Ras(12V), promoted CXCL10 transcriptional activation. Ras significantly increased CXCL10 mRNA and protein expression as observed by real-time PCR, fluorescence-activated cell sorting analysis, and ELISA. Selective inhibition of Ha-Ras by small interfering RNA (siRNA) decreased CXCL10 mRNA expression in a dose-dependent manner. Further, using effector domain mutants of Ras, we found that Ras-induced overexpression of CXCL10 is mediated primarily through the Raf and phosphatidylinositol 3-kinase signaling pathways. We also observed that the expression of the splice variant CXCR3-B, known to inhibit cell proliferation, was significantly down-regulated by Ras. Selective inhibition of CXCR3-B using siRNA resulted in an increase in CXCL10-mediated breast cancer cell proliferation through G(i) proteins and likely involving CXCR3-A. Finally, we observed intense expression of CXCL10 and CXCR3 in association with human breast cancer in situ, indicating that these observations may be of pathophysiologic significance. Together, these results suggest that activation of Ras plays a critical role in modulating the expression of both CXCL10 and CXCR3-B, which may have important consequences in the development of breast tumors through cancer cell proliferation.