tbuckley/cabot-search huggingface dataset:
Increased nitric oxide metabolites in exhaled breath condensate after exposure to tobacco smoke
Authors: B Balint
Journal: Thorax (2001)

Background-Cigarette smoking reduces the level of exhaled nitric oxide (NO) in healthy subjects, although the mechanism is unclear.NO is a highly reactive molecule which can be oxidised or complexed with other biomolecules, depending on the microenvironment.The stable oxidation end products of NO metabolism are nitrite and nitrate.This study investigated the eVect of smoking on NO metabolites in exhaled breath condensate.Methods-Fifteen healthy current smokers were recruited together with 14 healthy non-smokers.Measurement of exhaled NO, lung function, and collection of exhaled breath condensate were performed.Nitrite, nitrite + nitrate, S-nitrosothiols, and nitrotyrosine levels were measured.The eVect of inhaling two cigarettes in smokers was also evaluated.The mean level of exhaled NO in smokers was significantly lower than in nonsmokers (4.3 (0.3) ppb v 5.5 (0.5) ppb, p<0. 05).Results-There was no diVerence in the levels of nitrite, nitrite + nitrate, S-nitrosothiols, and nitrotyrosine in the exhaled breath condensate at the baseline visit between smokers and non-smokers.After smoking, nitrite + nitrate levels were significantly but transiently increased (from 20.2 (2.8) µM to 29.8 (3.4) µM, p<0.05).There was no significant change in the levels of exhaled NO, nitrite, S-nitrosothiols, or nitrotyrosine 30 and 90 minutes after smoking.Conclusions-These findings suggest that acute smoking can increase the level of nitrate, but not nitrite, S-nitrosothiols, or nitrotyrosine in breath condensate.The deleterious eVect of oxidant radicals induced by smoking may contribute to the epithelial damage of airways seen in smokers.
Subgenual Cingulate Cortex Volume in First-Episode Psychosis
Authors: Yoshio Hirayasu, Martha E. Shenton, Dean F. Salisbury, Jun Soo Kwon, Cynthia G. Wible, Iris A. Fischer, Deborah Yurgelun-Todd, Carlos Zarate, Ron Kikinis, Ferenc A. Jolesz, Robert W. McCarley
Journal: American Journal of Psychiatry (1999)

Gray matter volume and glucose utilization have been reported to be reduced in the left subgenual cingulate of subjects with familial bipolar or unipolar depression. It is unclear whether these findings are secondary to recurrent illness or are part of a familial/genetic syndrome. The authors' goal was to clarify these findings.Volumetric analyses were performed by using magnetic resonance imaging in 41 patients experiencing their first episode of affective disorder or schizophrenia and in 20 normal comparison subjects.The left subgenual cingulate volume of the patients with affective disorder who had a family history of affective disorder was smaller than that of patients with affective disorder with no family history of the illness and the normal comparison subjects. Patients with schizophrenia did not differ from comparison subjects in left subgenual cingulate volume.Left subgenual cingulate abnormalities are present at first hospitalization for psychotic affective disorder in patients who have a family history of affective disorder.
Endoscopic Pancreatic Duct Stents Reduce the Incidence of Post–Endoscopic Retrograde Cholangiopancreatography Pancreatitis in High-Risk Patients
Authors: Atsushi Sofuni, Hiroyuki Maguchi, Tsuyoshi Mukai, Hiroshi Kawakami, Atsushi Irisawa, Kensuke Kubota, Shinji Okaniwa, Masataka Kikuyama, Hiromu Kutsumi, Keiji Hanada, Toshiharu Ueki, Takao Itoi
Journal: Clinical Gastroenterology and Hepatology (2011)
Effectiveness of an e-learning course in evidence-based medicine for foundation (internship) training
Authors: Julie Hadley, Regina Kulier, Javier Zamora, Sjors FPJ Coppus, Susanne Weinbrenner, Berrit Meyerrose, Tamas Decsi, Andrea R Horvath, Eva Nagy, Jose I Emparanza, Theodoros N Arvanitis, Amanda Burls, Juan B Cabello, Marcin Kaczor, Gianni Zanrei, Karen Pierer, Regina Kunz, Veronica Wilkie, David Wall, Ben WJ Mol, Khalid S Khan
Journal: Journal of the Royal Society of Medicine (2010)

Summary Aim To evaluate the educational effectiveness of a clinically integrated e-learning course for teaching basic evidence-based medicine (EBM) among postgraduate medical trainees compared to a traditional lecture-based course of equivalent content. Methods We conducted a cluster randomized controlled trial to compare a clinically integrated e-learning EBM course (intervention) to a lecture-based course (control) among postgraduate trainees at foundation or internship level in seven teaching hospitals in the UK West Midlands region. Knowledge gain among participants was measured with a validated instrument using multiple choice questions. Change in knowledge was compared between groups taking into account the cluster design and adjusted for covariates at baseline using generalized estimating equations (GEE) model. Results There were seven clusters involving teaching of 237 trainees (122 in the intervention and 115 in the control group). The total number of postgraduate trainees who completed the course was 88 in the intervention group and 72 in the control group. After adjusting for baseline knowledge, there was no difference in the amount of improvement in knowledge of EBM between the two groups. The adjusted post course difference between the intervention group and the control group was only 0.1 scoring points (95% CI −1.2–1.4). Conclusion An e-learning course in EBM was as effective in improving knowledge as a standard lecture-based course. The benefits of an e-learning approach need to be considered when planning EBM curricula as it allows standardization of teaching materials and is a potential cost-effective alternative to standard lecture-based teaching.
Tight control in the treatment of rheumatoid arthritis: efficacy and feasibility
Authors: M F Bakker, J W G Jacobs, S M M Verstappen, J W J Bijlsma
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> To evaluate the available evidence on the efficacy and feasibility of the new concept of tight control in randomised trials in patients with rheumatoid arthritis (RA). Tight control is a treatment strategy tailored to the individual patient with RA, which aims to achieve a predefined level of low disease activity or remission within a certain period of time. <h3>Methods:</h3> The literature database PubMed was searched and yielded four trials: the FIN-RACo trial, the TICORA study, the BeSt study and the CAMERA study. <h3>Results:</h3> Tight control resulted in greater improvement and a higher percentage of patients meeting the preset aim of low disease activity or remission when compared to the control intervention. In the FIN-RACo trial, aimed at DAS28&lt;2.6, 51% of patients in the tight control group achieved remission versus 16% in the contrast group (p&lt;0.001). In the TICORA study, 65% of patients in the tight control group versus 16% of the contrast group achieved remission, based on DAS&lt;1.6 (p&lt;0.0001). In the CAMERA study, 50% of patients in the tight control group using a computer decision model achieved remission, versus 37% in the contrast group (p = 0.029). The BeSt study consisted of only tight control groups aimed at a DAS&lt;1.6; remission was achieved in 38–46% of patients. This is higher than the range of remission in earlier trials of 13–36%. <h3>Conclusion:</h3> Tight control aiming for low disease activity or even better still, remission, seems a promising option in treating patients with RA in clinical trials and probably also in daily practice.
Effects of Olympic-style taekwondo kicks on an instrumented head-form and resultant injury measures
Authors: Gabriel P Fife, David M O'Sullivan, Willy Pieter, David P Cook, Thomas W Kaminski
Journal: British Journal of Sports Medicine (2012)

Objective The objective of this study was to assess the effect of taekwondo kicks and peak foot velocity (FVEL) on resultant head linear acceleration (RLA), head injury criterion (HIC15) and head velocity (HVEL). Methods Each subject (n=12) randomly performed five repetitions of the turning kick (TK), clench axe kick (CA), front leg axe kick, jump back kick (JB) and jump spinning hook kick (JH) at the average standing head height for competitors in their weight division. A Hybrid II Crash Test Dummy head was fitted with a protective taekwondo helmet and instrumented with a triaxial accelerometer and fixed to a height-adjustable frame. Resultant head linear acceleration, HVEL, FVEL data were captured and processed using Qualysis Track Manager. Results The TK (130.11±51.67 g) produced a higher RLA than the CA (54.95±20.08 g, p&lt;0.001, d=1.84) and a higher HIC15 than the JH (672.74±540.89 vs 300.19±144.35, p&lt;0.001, ES=0.97). There was no difference in HVEL of the TK (4.73±1.67 m/s) and that of the JB (4.43±0.78 m/s; p=0.977, ES&lt;0.01). Conclusions The TK is of concern because it is the most common technique and cause of concussion in taekwondo. Future studies should aim to understand rotational accelerations of the head.
Self-control and impulsiveness: Resolution of apparent contradictions in choice behavior
Authors: A. W. Logue
Journal: Behavioral and Brain Sciences (1996)

Abstract Choosing the smaller, less delayed reinforcers of drug abuse (including cessation of withdrawal) over the larger, more delayed reinforcers of a healthy life can be described as impulsiveness (the opposite of self-control). Examination of drug abuse using a self-control/impulsiveness framework can help explain many of the puzzles about this behavior, while tying drug abuse into a large research database.
Ascorbic Acid Enhances Differentiation of Embryonic Stem Cells Into Cardiac Myocytes
Authors: Tomosaburo Takahashi, Bernadette Lord, P. Christian Schulze, Ryan M. Fryer, Satinder S. Sarang, Steven R. Gullans, Richard T. Lee
Journal: Circulation (2003)

Embryonic stem (ES) cells are capable of self-renewal and differentiation into cellular derivatives of all 3 germ layers. In appropriate culture conditions, ES cells can differentiate into specialized cells, including cardiac myocytes, but the efficiency is typically low and the process is incompletely understood.We evaluated a chemical library for its potential to induce cardiac differentiation of ES cells in the absence of embryoid body formation. Using ES cells stably transfected with cardiac-specific alpha-cardiac myosin heavy chain (MHC) promoter-driven enhanced green fluorescent protein (EGFP), 880 compounds approved for human use were screened for their ability to induce cardiac differentiation. Treatment with ascorbic acid, also known as vitamin C, markedly increased the number of EGFP-positive cells, which displayed spontaneous and rhythmic contractile activity and stained positively for sarcomeric myosin and alpha-actinin. Furthermore, ascorbic acid induced the expression of cardiac genes, including GATA4, alpha-MHC, and beta-MHC in untransfected ES cells in a developmentally controlled manner. This effect of ascorbic acid on cardiac differentiation was not mimicked by the other antioxidants such as N-acetylcysteine, Tiron, or vitamin E.Ascorbic acid induces cardiac differentiation in ES cells. This study demonstrates the potential for chemically modifying the cardiac differentiation program of ES cells.
Tumor-Directed Radiation and the Immunotoxin SS1P in the Treatment of Mesothelin-Expressing Tumor Xenografts
Authors: Raffit Hassan, Juanita Williams-Gould, Seth M. Steinberg, David J. Liewehr, Junko Yokokawa, Kwong Y. Tsang, Robert J. Surawski, Tamalee Scott, Kevin Camphausen
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Mesothelin is a cell surface protein overexpressed in mesotheliomas and pancreatic and ovarian cancers. The goal of this study was to determine if radiation therapy in combination with the antimesothelin immunotoxin SS1(dsFv)PE38 (SS1P) would result in enhanced antitumor activity against mesothelin-expressing xenografts in nude mice. Experimental Design: Female athymic nude mice bearing s.c. mesothelin-expressing xenografts were treated with SS1P alone, tumor-focused radiation alone, or the combination of the two. Two different regimens of the combination therapy were tested. In the low-dose combination schedule, mice were treated with either 5 Gy radiation alone, 0.2 mg/kg SS1P alone, or the same doses of radiation and SS1P in combination. In the high-dose combination experiments, mice were treated with either 15 Gy radiation alone, 0.3 mg/kg SS1P alone, or the combination of radiation and SS1P. Results: In the low-dose radiation and SS1P combination studies, mice treated with the combination of radiation and SS1P had a statistically significant prolongation in time to tumor doubling or tripling compared with control, SS1P, or radiation alone. A similar increase in time to tumor doubling or tripling was seen in mice treated with high-dose radiation and SS1P combination. Conclusions: Combination of SS1P with tumor-directed radiation results in enhanced antitumor activity against mesothelin-expressing tumor xenografts. This effect was seen when either low or high doses of radiation were used.
Volume-pressure curve of the respiratory system predicts effects of PEEP in ARDS: "occlusion" versus "constant flow" technique.
Authors: V M Ranieri, R Giuliani, T Fiore, M Dambrosio, J Milic-Emili
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

The effects of positive end-expiratory pressure (PEEP) on static ("rapid airway occlusion" technique) and dynamic ("constant flow" technique) volume-pressure (V-P) curves were studied in 19 patients with adult respiratory distress syndrome (ARDS). To describe the shape of both curves, the nonlinear coefficient of a second-order polynomial equation fitted to the static (static nonlinear coefficient) and dynamic (dynamic nonlinear coefficient) V-P curves on zero end-expiratory pressure (ZEEP) was used. Two distinct patterns were observed: (1) in ten patients, the static and dynamic V-P curves on ZEEP exhibited a convex shape with a progressive decrease in slope with increasing inflation volume (nonlinear coefficients: negative). In these patients PEEP induced a volume displacement along the static and dynamic V-P curves on ZEEP (hyperinflation). (2) In nine patients, the static and dynamic V-P curves on ZEEP showed a concave shape with a progressive increase in slope with increasing volume (nonlinear coefficients: positive) and PEEP shifted both curves upward along the volume axis (alveolar recruitment). A correlation (p < 0.0001) between static and dynamic nonlinear coefficients was found at all levels of PEEP. Both static and dynamic nonlinear coefficients on ZEEP were correlated (p < 0.0001) with the amount of lung volume recruited with PEEP, and the variations of cardiac index (CI), O2 delivery (DO2), right-to-left venous admixture (Qs/Qt), and PaO2 with PEEP. Besides, the effects of PEEP on Cl, DO2, Qs/Qt, and PaO2 were less pronounced (p < 0.001) in patients with convex V-P curves than in patients with concave V-P curves.(ABSTRACT TRUNCATED AT 250 WORDS)
Gene Expression Divergence and Hybrid Misexpression between Lake Whitefish Species Pairs (Coregonus spp. Salmonidae)
Authors: S. Renaut, A.W. Nolte, L. Bernatchez
Journal: Molecular Biology and Evolution (2009)

Genomewide analyses of the transcriptome have confirmed that gene misexpression may underlie reproductive isolation mechanisms in interspecific hybrids. Here, using a 16,006 features cDNA microarray, we compared and contrasted gene expression divergence at two ontogenetic stages in incipient species of normal and dwarf whitefish (Coregonus clupeaformis) with that of first generation (normal × dwarf) and second-generation hybrid crosses (backcross: [normal × dwarf] × normal]. Our goal was to identify the main mode of action responsible for gene transcription and to discover key genes misexpressed in hybrids. Very few transcripts (five of 4,950 expressed) differed in mean expression level between parentals and hybrids at the embryonic stage, in contrast to 16-week-old juvenile fish for which 617 out of 5,359 transcripts differed significantly. We also found evidence for more misexpression in backcross hybrids whereby nonadditivity explained a larger fraction of hybrid inheritance patterns in backcross (54%) compared with F1-hybrids (9%). Gene expression in hybrids was more variable than in pure crosses and transgressive patterns of expression were ubiquitous in hybrids. In backcross embryos in particular, the expression of three key developmental genes involved in protein folding and mRNA translation was severely disrupted. Accordingly, gene misexpression in hybrids adds to other factors previously identified as contributing to the reproductive isolation of incipient species of lake whitefish.
Superparamagnetic Nanoparticle Clusters for Cancer Theranostics Combining Magnetic Resonance Imaging and Hyperthermia Treatment
Authors: Koichiro Hayashi, Michihiro Nakamura, Wataru Sakamoto, Toshinobu Yogo, Hirokazu Miki, Shuji Ozaki, Masahiro Abe, Toshio Matsumoto, Kazunori Ishimura
Journal: Theranostics (2013)

Superparamagnetic nanoparticles (SPIONs) could enable cancer theranostics if magnetic resonance imaging (MRI) and magnetic hyperthermia treatment (MHT) were combined. However, the particle size of SPIONs is smaller than the pores of fenestrated capillaries in normal tissues because superparamagnetism is expressed only at a particle size <10 nm. Therefore, SPIONs leak from the capillaries of normal tissues, resulting in low accumulation in tumors. Furthermore, MHT studies have been conducted in an impractical way: direct injection of magnetic materials into tumor and application of hazardous alternating current (AC) magnetic fields. To accomplish effective enhancement of MRI contrast agents in tumors and inhibition of tumor growth by MHT with intravenous injection and a safe AC magnetic field, we clustered SPIONs not only to prevent their leakage from fenestrated capillaries in normal tissues, but also for increasing their relaxivity and the specific absorption rate. We modified the clusters with folic acid (FA) and polyethylene glycol (PEG) to promote their accumulation in tumors. SPION clustering and cluster modification with FA and PEG were achieved simultaneously via the thiol-ene click reaction. Twenty-four hours after intravenous injection of FA- and PEG-modified SPION nanoclusters (FA-PEG-SPION NCs), they accumulated locally in cancer (not necrotic) tissues within the tumor and enhanced the MRI contrast. Furthermore, 24 h after intravenous injection of the NCs, the mice were placed in an AC magnetic field with H = 8 kA/m and f = 230 kHz (Hf = 1.8×10(9) A/m∙s) for 20 min. The tumors of the mice underwent local heating by application of an AC magnetic field. The temperature of the tumor was higher than the surrounding tissues by ≈6°C at 20 min after treatment. Thirty-five days after treatment, the tumor volume of treated mice was one-tenth that of the control mice. Furthermore, the treated mice were alive after 12 weeks; control mice died up to 8 weeks after treatment.
Circulating Nucleosomes Predict the Response to Chemotherapy in Patients with Advanced Non–Small Cell Lung Cancer
Authors: Stefan Holdenrieder, Petra Stieber, Joachim von Pawel, Hannelore Raith, Dorothea Nagel, Knut Feldmann, Dietrich Seidel
Journal: Clinical Cancer Research (2004)

Abstract Purpose: We investigated the potential of circulating, nucleosomal DNA for the early prediction of the efficacy of chemotherapy in patients with advanced lung cancer. Experimental Design: In serum of 212 patients with newly diagnosed non–small cell lung cancer (stages III and IV) undergoing chemotherapy, nucleosomes (ELISA, Roche) were measured at days 1, 3, 5, and 8 of the first cycle and before each new therapeutic cycle. Additionally, carcinoembryonic antigen and cytokeratin 19 fragments (CYFRA 21–1; Elecsys, Roche) were determined before each cycle. The therapeutic success was classified by computed tomography before start of the third cycle according to the World Health Organization criteria. Results: In univariate analysis, responders (patients with remission) showed significantly (P &amp;lt; 0.05) lower values for the area under the curve of days 1 to 8 (AUC 1–8) of nucleosomes, the pretherapeutic baseline values of cycle 2 (BV2) and cycle 3 (BV3) of nucleosomes, and higher decreases of the baseline values from cycle 1 to 2 (BV1–2) and from cycle 1 to 3 (BV1–3) compared with nonresponders (patients with stable or progressive disease). Additionally, CYFRA 21–1 (BV1, BV2, BV3, BV1–2, BV1–3) and carcinoembryonic antigen (BV1–2) discriminated significantly between both groups. In multivariate analysis including all parameters available until end of the first therapeutic cycle, nucleosomes (AUC 1–8), CYFRA 21–1 (BV1), stage, and age were independent predictors of therapy response with nucleosomes (AUC 1–8) having the strongest impact. Conclusion: Circulating nucleosomes in combination with oncological biomarkers are valuable for the early estimation of the efficacy of chemotherapy in patients with lung cancer.
Cognitive intervention with elite performers: reversal theory.
Authors: J H Kerr
Journal: British Journal of Sports Medicine (1987)

Noticeable in the literature associated with the application of psychology to the area of sport and sports performance in particular has been the increasing frequency of references to the use of cognitive intervention in the sports context. Currently utilised in clinical psychology and behavioural medicine, and receiving increasing attention in sports psychology, are a number of intervention techniques primarily oriented towards altering the individual's level of arousal. These techniques, which have been advocated for use by sports performers as an aid to adapting and coping during competition, have been largely concerned with arousal reduction. This paper presents an alternative approach, the case of reversal theory, a new general theory of psychology concerned with motivation, and emphasises the conceptual implications of this new approach for the use of cognitive intervention techniques in sport.
Update on Metastatic Gastric and Esophageal Cancers
Authors: Manish A. Shah
Journal: Journal of Clinical Oncology (2015)

Cancers of the stomach and esophagus are among the most challenging cancers of the GI tract to treat, associated with poor median survivals for metastatic disease and significant, sometimes prolonged, deteriorations in patient performance status as the diseases progress. However, in the past decade, we have begun to better understand disease biology and carcinogenesis, leading to the identification of subtypes of these diseases. There is also an increasing awareness of the global heterogeneity of disease and its impact on drug development. Our improved understanding of the molecular underpinnings of gastric and esophageal cancers has been accompanied with the development of novel therapeutic strategies. Recent actively investigated targets in this disease include human epidermal growth factor receptor 2, angiogenesis, MET, and immune checkpoint inhibition, with approvals of two new targeted agents, trastuzumab and ramucirumab. Improvements in our ability to deliver cytotoxic therapy, which is better tolerated and allows patients an opportunity to benefit from second- and more advanced lines of therapy, have also been observed. In this review, the current state-of-the-art management of advanced and metastatic gastric and esophageal adenocarcinomas, specifically highlighting the development of targeted therapies in these diseases, is described.