tbuckley/cabot-search huggingface dataset:
Abstract 12851: Clinical Significance of Myeloperoxidase, Neopterin, and High Sensitivity C-Reactive Protein as Independent Predictors of Cardiovascular Events
Authors: Tomotaka Yoshiyama, Kei Yunoki, Ryushi Komatsu, Kazuo Haze, Takahiko Naruko, Kenichi Sugioka, Masashi Nakagawa, Mayumi Inaba, Minoru Yoshiyama, Makiko Ueda
Journal: Circulation (2014)

Background: We previously demonstrated that inflammatory biomarkers such as myeloperoxidase (MPO), a member of the heme peroxidase superfamily, and neopterin (produced by activated macrophages after interferon-γ stimulation by T-lymphocytes) are important in the pathogenesis of coronary plaque instability. Additional evidence supports high sensitivity C-reactive protein (hs-CRP) as an independent predictor of increased coronary risk. We assessed the prognostic significance of plasma MPO and neopterin levels, and serum hs-CRP levels in patients with stable angina pectoris (SAP) and unstable angina pectoris (UAP). Methods: Plasma MPO, neopterin, and serum hs-CRP levels were measured in 219 SAP patients and 144 UAP patients at admission. Cardiovascular (CV) events were defined as sudden cardiac death, fatal or non-fatal myocardial infarction and other non-fatal events including unstable angina pectoris or coronary revascularization. Results: Over a mean follow-up of 27±14 months, 56 SAP patients (26%) had CV events. When SAP patients were stratified based on the median neopterin level (15.0 nmol/L), Kaplan-Meier analysis showed that the high-neopterin group (&gt;15.0 nmol/L) had significantly worse outcomes (P=0.015) than the low-neopterin group. Multivariate analysis showed that elevated neopterin was the only independent factor associated with CV events (OR, 2.19; 95% CI, 1.18-4.09; P=0.014). In contrast, over a mean follow-up of 30±24 months, 33 UAP patients (23%) had CV events. When UAP patients were divided based on the median MPO level (16.0 ng/mL), Kaplan-Meier analysis showed that the high-MPO group (&gt;16.0 ng/mL) had significantly worse outcomes (P=0.012) than the low-MPO group. Multivariate analysis showed that elevated MPO was the only independent factor associated with CV events (OR, 2.58; 95% CI, 1.07-6.23; P=0.035). With regard to hs-CRP levels, there were no significant differences in CV events between the two groups according to the median hs-CRP in both SAP and UAP patients. Conclusions: The clinical significance of elevated MPO and neopterin levels as independent predictors of CV events differs depending on the clinical condition of SAP and UAP patients, because of different production mechanisms of these biomarkers.
Contributors to antibiotic resistance
Authors: M J Cheesbrough, P. Godwin, M. Guslandi, A. J Smith, E. Dickson, K. M Roy, D. MacKenzie, M. S Jackson, J. Bagg
Journal: BMJ (1999)

Carriage of meningococci in contacts of patients with meningococcal disease"Kissing contacts" need to be defined Editor-In their study Kristiansen et al show high carriage rates of pathogenic strains of Neisseria menigitidis in household and kissing contacts of patients with invasive meningococcal disease. 1 While it is easy to define a household contact it may be more difficult to define a kissing contact.There are many types of kiss, ranging from a "peck on the cheek" to much more!In some cultures kissing is as common as shaking hands.In such situations widespread chemoprophylaxis to "kissing contacts" may not be appropriate.It would be valuable to know whether Kristiansen et al placed any restrictions on who was defined as a kissing contact.
Abstract 18577: Evaluation of Right Ventricular Function using Cardiac Computed Tomography in Patients with Left Ventricular Assist Devices
Authors: Ana Garcia-Alvarez, Leticia Leticia Fernandez-Friera, Joe F. Lau, Simonette T. Sawit, Jesus G Mirelis, Javier G. Castillo, Sean Pinney, Anelechi C. Anyanwu, Valentin Fuster, Javier Sanz, Mario J. Garcia
Journal: Circulation (2010)

Background: Right ventricular (RV) failure is a major contributor of morbidity and mortality after left ventricular assist device (LVAD) implantation. Accurate evaluation of RV function under LVAD support using echocardiography remains challenging. Hypothesis: The feasibility and reproducibility of RV evaluation in patients with LVAD with electrocardiographic-gated cardiac computed tomography (CCT) is higher compared to echocardiography. Methods: Twenty-five consecutive patients with an implanted LVAD underwent 2D-echocardiography and contrast-enhanced CCT with retrospective electrocardiographic gating. RV fractional area change, tricuspid annular plane systolic excursion (TAPSE) and RV end-diastolic short-to-long axis ratio were calculated by echocardiography. RV end-diastolic and end-systolic volumes and ejection fraction were quantified with CCT. Intraclass correlation coefficients (ICC) and Bland and Altman analysis were used to assess intra and inter-observer reproducibility for measurements. Results...
Evaluation of Changes in Renal Function in a Phase III Study of Maintenance (Mtc) Pemetrexed (Pem) Plus Best Supportive Care (Bsc) Versus Placebo (Plb) Plus Bsc After Induction Treatment (Tx) with Pem Plus Cisplatin for Advanced Nonsquamous Non-Small Cell Lung Cancer (Paramount)
Authors: G. Middleton, C. Gridelli, F. De Marinis, J. Pujol, M. Reck, R. Ramlau, M.B. Parente, T. Pieters, C.M. Visseren-Grul, B. San Antonio, W. John, A. Zimmermann, N. Chouaki, L. Paz-Ares
Journal: Annals of Oncology (2014)
Abstract P6-08-45: Predictive characteristics for extensive nodal involvement in patients with axillary lymph node metastases
Authors: Nicole C Verheuvel, Ingrid Van den Hoven, Hendrik WA Ooms, Vivianne CG Tjan-Heijnen, Rudi MH Roumen, Adri C Voogd
Journal: Cancer Research (2015)

Abstract Background Staging of axillary lymph nodes in invasive breast cancer is an important prognostic indicator. Various prediction models have been developed to predict the risk of not having additional axillary metastases in patients with a positive sentinel node, thereby disregarding patients with a positive ultrasound. However, it is important to identify all patients with extensive nodal involvement, defined as 3 or more positive axillary lymph nodes, in whom an axillary lymph node dissection cannot be omitted. Aim This study aims to identify factors predicting extensive nodal involvement in the axilla, with the emphasis on the method of axillary staging; ultrasound guided lymph node biopsy versus sentinel node procedure. Methods All patients diagnosed with invasive breast cancer in the period between January 2006 and December 2011 at the breast center of the Máxima Medical Center were studied. Univariate and multivariate regression analyses were performed. Variables with a p-value of ≤0.10 in univariate analyses were entered in the multivariate model where a p-value of ≤0.05 was considered statistically significant. Results We included 307 cases, representing 306 node positive patients, of whom 178 cases had 1 or 2 positive lymph nodes and 129 cases had 3 or more positive lymph nodes. Multivariate analyses showed that factors as a positive axillary ultrasound (OR=4.513; 95%CI=2.30-8.86), palpability of axillary lymph nodes (OR=2.143; 95%CI=1.04-4.42) and lymphovascular invasion (OR=3.622; 95%CI=1.63-7.81) are significantly associated with extensive nodal involvement in patients with invasive breast cancer. Conclusion This study has identified clinically important factors predicting extensive nodal involvement in patients with a positive lymph node biopsy by either a sentinel lymph node procedure or an ultrasound guided lymph node biopsy. Hence, the role of axillary staging by ultrasound should be redefined since it might play an important role in selecting patients with extensive nodal involvement who, in our opinion, may still benefit from axillary treatment. Citation Format: Nicole C Verheuvel, Ingrid Van den Hoven, Hendrik WA Ooms, Vivianne CG Tjan-Heijnen, Rudi MH Roumen, Adri C Voogd. Predictive characteristics for extensive nodal involvement in patients with axillary lymph node metastases [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-45.
Bcr-Abl regulates c-Myc expression in chronic myelogenous leukemia through a Bcr-Abl/Jak2 network of proteins involving Gab2, PI-3 kinase, NF-κB and GSK3β
Authors: Ajoy K. Samanta, Hui Lin, Tong Sun, Ralph B. Arlinghaus
Journal: Cancer Research (2006)

4116  The Bcr-Abl oncoprotein, a constitutively active tyrosine kinase, is derived from the BCR/ABL gene fusion produced by Philadelphia chromosome, which is found in most chronic myelogenous leukemia patients (CML). Imatinib mesylate, an inhibitor of Bcr-Abl kinase, is a very effective drug for CML. However in some of CML patients, drug resistance develops and the patients relapse. Thus, a better understanding of Bcr-Abl signaling pathways is needed, and alternative therapeutic targets need to be identified. We have shown that Bcr-Abl activates its downstream target Jak2 leading to the enhancement of c-Myc expression. How c-Myc is regulated by Jak2 activation in CML is not understood. In the current study we have shown that Bcr-Abl is associated with a cluster of signaling proteins including Jak2, Gab2, Akt and GSK3β. Treatment of CML cell lines and mouse BCR-ABL+ 32D cells (myeloid lineage) with the either Jak2 siRNA or the Jak2 kinase inhibitor AG490 caused inhibition of pTyr Gab2 formation, pSer Akt formation and the activation of NF-κB. Importantly, blocking Jak2 kinase activated the kinase activity of GSK3β leading to the reduction of c-Myc expression, and inhibited NF-κB activation causing the reduction of c-MYC transcripts. Similar results were obtained with the Bcr-Abl kinase inhibitor, imatinib mesylate. We conclude that Bcr-Abl enhances c-Myc expression through a Bcr-Abl/Jak2/Gab2/ Akt/GSK3β network of proteins by inducing activation of NF-κB and by inhibition of the GSK3β kinase activity. Importantly, mouse BaF3 hematopoietic cells expressing the T315I and E255K imatinib-resistant mutants of BCR-ABL underwent apoptosis upon exposure to the Jak2 inhibitor AG490 yet were resistant to imatinib. However, both imatinib and AG490 treatments induced wild-type BCR-ABL+ BaF3 cells to under apoptosis. These results identify Jak2 as a potentially important therapeutic target for CML drug design.
Clinical Significance of Obstruction of the First Major Septal Branch
Authors: Mareomi Hamada, Koji Kodama, Kunio Hiwada
Journal: Circulation (1998)

A primary rhythm in the central nervous system that entrains both heart rate, blood pressure, and ventilation 1 is suggested by profound effects on angina through consciously focusing on breathing and intervening pauses; adaptation to stress manifested by slower, deeper breathing, contributing to a 6.5-fold reduction in mortality; and the role of a slower rate of living in a lifespan increased 5-fold. 2 This hypothesis is supported by the association of the reduction of blood pressure with longer, less recurrent speech hesitation pauses 1 second or more in length, manifested by pauses averaging 1.18 seconds at Ͼ2 per minute and 1.93 seconds at 1 per minute, thus yielding a ratio of 0.611, approximating the golden section 0.618 (range, 0.534 to 0.833).It is also supported by the fact that even brief (1-5-second) spontaneous pauses in ongoing patterned behaviors are accompanied by an immediate reduction of 5-hydroxytryptamine neuronal activity to or below baseline levels, coordinating autonomic, motor, and sensory functions 3 and serotonergic modulation of dopamine 4 lateralized to the right hemisphere, thereby preventing disruption of brain stem cardiovascular control and lefthemisphere dominance associated with hazardous surges of sympathetic tone in abnormal awake respiratory patterns that are common in chronic heart failure manifested by cardiac dysrhythmia and vasoconstriction. 1,2
Abstract LB-177: Novel approaches for improving interpretation and predictive models of comparative genomic hybridization data
Authors: Daniel Rotroff, Matthew Breen, Alison Motsinger-Reif
Journal: Cancer Research (2015)

Abstract As costs of genome wide analyses decline and become more accessible, their use in both human and animal cancer studies are generating increasing information regarding underlying cancer etiology. Comparative genomic hybridization (CGH) is providing valuable information relating copy number aberrations (CNAs) to cancer mechanisms and clinical outcomes. However, challenges exist to interpreting and fully utilizing these data. First, without matched tumor and healthy tissue samples from individuals, distinguishing naturally occurring copy number variations (CNVs) from CNAs is difficult. Second, the large search space of genome wide analyses makes finding combinations of CNAs with improved predictive potential compared to single CNAs challenging. Here we provide novel methods to address these challenges associated with CGH data. Many new resources (e.g. The Cancer Genome Atlas (TCGA)), are making large volumes of genomic data publically accessible. However, most datasets do not have matched normal and tumor tissue samples between subjects. We tested matched normal and tissue samples from 30 patients with colorectal, lung, and pancreatic cancer and compared CNVs and CNAs to findings in larger, non-matched samples in TCGA. Even with limited matched samples, this approach allows for the differentiation of CNVs from CNAs discovered in analyses of non-matched samples. In some cases, combinations of CNAs can provide improved predictive capability compared to any single CNA. However, it is computationally intractable to exhaustively test combinations of CNAs in a genome-wide study. To address this limitation, we use a novel approach for CNA feature reduction that minimizes the variance within CNA segments across subjects, and Random Forest Ensemble Classification. This approach provides CNA combinations with balanced accuracies of 83.5% and 94.9% for distinguishing 52 cases of canine ALL/AML and 71 cases of B-CLL/T-CLL, respectively. These two approaches address frequent limitations in the interpretation CGH data. Better distinguishing CNVs and interrogating CNA combinations, can provide additional information about the role of CNAs in disease mechanisms and improve treatment decisions. Citation Format: Daniel Rotroff, Matthew Breen, Alison Motsinger-Reif. Novel approaches for improving interpretation and predictive models of comparative genomic hybridization data. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-177. doi:10.1158/1538-7445.AM2015-LB-177
Relationship of baseline or annual change of clinical parameters on mortality in patients with COPD
Authors: Hironi Makita, Masaru Suzuki, Katsura Nagai, Masaharu Nishimura
Journal: European Respiratory Journal (2013)

Background:  We have shown that the rate of annual change in FEV1 was varied widely among patients with COPD over 5 years (Nishimura, AJRCCM 2012).  Aim:  To examine how baseline or annual changes of clinical parameters are related to mortality.  Methods:  A total of 279 of clinically stable patients with COPD (GOLD 1, 26%; GOLD 2, 45%; GOLD 3/4, 29%) served as subjects. We collected BMI and spirometric data every 6 months, diffusing capacity (Kco), emphysema severity assessed by CT, and health-related QOL (SGRQ) every year, and monitored exacerbation frequency, smoking behavior, and any medications. Mortality of the subjects was continuously recorded by physicians, telephone interviews, and letters to their families. Annual changes in post-bronchodilator FEV1, BMI, Kco, and SGRQ until the 3 rd  year were determined by linear regression.  Results:  The median follow-up time was 8.2 years. Of the 265 patients, 98 died, with 38 classified as respiratory deaths. Age, emphysema score, BMI, FEV1 (%), Kco, SGRQ, exacerbations, and usage of respiratory medications were significantly related to mortality of all causes of death. By a multivariate logistic regression analysis, age (odds ratio [OR] 1.16; 95%CI 1.11-1.22; p Conclusion:  An annual decline in Kco, besides age, BMI, Kco at baseline, is an independent risk factor of mortality of any respiratory diseases in patients with COPD.
Network-Based Approaches to Understand the Roles of miR-200 and Other microRNAs in Cancer
Authors: Cameron P. Bracken, Yeesim Khew-Goodall, Gregory J. Goodall
Journal: Cancer Research (2015)

microRNAs (miRNA) are well suited to the task of regulating gene expression networks, because any given miRNA has the capacity to target dozens, if not hundreds, of genes. The simultaneous targeting of multiple genes within a pathway may enable miRNAs to more strongly regulate the pathway, or to achieve more subtle control through the targeting of distinct subnetworks of genes. Therefore, as our capacity to discover miRNA targets en masse increases, so must our consideration of the complex networks in which these genes participate. We highlight recent studies in which the comprehensive identification of targets has been used to elucidate miRNA-regulated gene networks in cancer, focusing especially upon miRNAs such as members of the miR-200 family that regulate epithelial-mesenchymal transition (EMT), a reversible phenotypic switch whereby epithelial cells take on the more invasive properties of their mesenchymal counterparts. These studies have expanded our understanding of the roles of miRNAs in EMT, which were already known to form important regulatory loops with key transcription factors to regulate the epithelial or mesenchymal properties of cells.
Abstract 16534: State Mandated Public Reporting of Percutaneous Coronary Intervention Outcomes is Associated with Better Outcomes: A report from the NCDR(R)
Authors: Matthew A Cavender, Karen E Joynt, Frederick S Resnic, Craig S Parzynski, John S Rumsfeld, Mauro Moscucci, Frederick A Masoudi, Jeptha P Curtis, Eric D Peterson, Hitinder S Gurm
Journal: Circulation (2012)

Introduction: The effectiveness of public reporting as a strategy to improve quality of care and outcomes is controversial. The data supporting an association between public reporting and outcomes ...
Abstract 3767: Bone Mineral Density and Bone Loss over Time in Men with Chronic Heart Failure, and their Determinants
Authors: Ewa A Jankowska, Aldona Cwynar, Justyna Jakubaszko, Jacek Majda, Kinga Wegrzynowska, Waldemar Banasiak, Piotr Ponikowski
Journal: Circulation (2006)

Background:  Bone metabolism has not been comprehensively studied in chronic heart failure (CHF). We evaluated the prevalence of reduced BMD (bone mineral density), BMC (bone mineral content) and bone loss over time in CHF men, and assessed their determinants.   Methods:  BMC and BMD in arms, legs, trunk and total body were measured using DEXA in 187 consecutive CHF men (age: 60±11 y [mean±SD], LVEF: 32±7 %, NYHA I/II/III/IV: 20/76/76/15).   Results:  In men with CHF, reduced BMD and BMC in all anatomical regions were detected mainly in NYHA IV patients (NYHA I/II/III/IV: BMD-total: 1.22±0.11/1.20±0.07/1.19±0.09/1.12±0.11 g/cm 2 , BMC-total: 3.1±0.5/3.0±0.3/2.9±0.4/2.6±0.5 kg, respectively, p 0.2). Reduced BMC and BMD were accompanied by diminished lean and fat tissue mass (p 2 y (mean time between 2 DEXA scans: 3±1 y). Significant bone loss over time (defined prospectively as a reduction in BMC-total >=1 %/y) occurred in 21 (35 %) CHF men (24/55 % of men in NYHA I-II/III-IV, p   Conclusions:  In men with CHF, reduced bone mass in mainly confined to the sickest patients, and is associated with fat and lean tissue wasting, hyperparathyroidism, enhanced bone resorption, and adrenal and gonadal anabolic deficiency. During a natural history of disease, a significant bone loss occurs in 1/3 of men with CHF, and is related predominantly to testosterone depletion, disease severity and hyperparathyroidism.
Regulation of the l-arabinose operon of Escherichia coli
Authors: Robert Schleif
Journal: Trends in Genetics (2000)

Over forty years of research on the L-arabinose operon of Escherichia coli have provided insights into the mechanism of positive regulation of gene activity. This research also discovered DNA looping and the mechanism by which the regulatory protein changes its DNA-binding properties in response to the presence of arabinose. As is frequently seen in focused research on biological subjects, the initial studies were primarily genetic. Subsequently, the genetic approaches were augmented by physiological and then biochemical studies. Now biophysical studies are being conducted at the atomic level, but genetics still has a crucial role in the study of this system.
Causes and Mortality in Patients Aged over 75 Years with Gastrointestinal Haemorrhage
Authors: K Kafetz, V Wijesuriya
Journal: Journal of the Royal Society of Medicine (1991)

One hundred and fifty-five patients aged 75 years and over with gastrointestinal haemorrhage were studied and compared with a series of patients aged under 75 years. The mortality in patients with gastric ulcer or gastric carcinoma was not affected by age. However, the mortality in patients with duodenal ulcer was greater in the over-75s (8/31 deaths in the over-75s, 4/77 deaths in the under-75s, P = 0.01). There was no reluctance to operate on the over-75s. These results can be used to help construct future trials to improve treatment.
Selection Criteria for Drug-Eluting Versus Bare-Metal Stents and the Impact of Routine Angiographic Follow-Up
Authors: Gregg W. Stone, Helen Parise, Bernhard Witzenbichler, Ajay Kirtane, Giulio Guagliumi, Jan Z. Peruga, Bruce R. Brodie, Dariusz Dudek, Martin Möckel, Alexandra J. Lansky, Roxana Mehran
Journal: Journal of the American College of Cardiology (2010)
Controlled discontinuation of benzodiazepine treatment for patients with panic disorder
Authors: R Noyes, M J Garvey, B Cook, M Suelzer
Journal: American Journal of Psychiatry (1991)

The purpose of this study was to compare the effects of discontinuing treatment with intermediate- and long-acting benzodiazepines.Fifty patients with panic disorder who had taken part in a double-blind treatment study and had responded to alprazolam, diazepam, or placebo for 8 months were asked to stop taking these medications gradually.After a relatively rapid dose reduction, the majority of patients relapsed. Rebound anxiety and withdrawal symptoms were identified in a substantial minority of patients. Those who were taking alprazolam showed earlier and more intense rebound anxiety and withdrawal symptoms than did the patients who received diazepam. Both the level of pretreatment anxiety and the drug the patient was taking predicted the level of anxiety when drug treatment was discontinued.The findings indicate that withdrawal phenomena commonly occur after patients stop taking benzodiazepines and that they are more frequent after discontinuation of treatment with shorter-acting drugs.
Global genetic carrier testing: a vision for the future
Authors: Arthur L. Beaudet
Journal: Genome Medicine (2015)

Expanded genetic carrier testing is changing clinical practice. Current experience highlights the need for rigorous curation of tens of thousands of variants as to their pathogenicity and phenotypic effects. There is an urgent need for strategies to present a range of options to families to enable them to make informed decisions. The potential exists to avoid the great majority of serious inherited, but not de novo, single-gene disabilities.