tbuckley/cabot-search huggingface dataset:
Colchicine in Addition to Conventional Therapy for Acute Pericarditis
Authors: MassimoImazio, MarcoBobbio, EnricoCecchi, DanielaDemarie, BrunellaDemichelis, FrancoPomari, MauroMoratti, GianniGaschino, MassimoGiammaria, AldoGhisio, RiccardoBelli, RitaTrinchero
Journal: Circulation (2005)

Background— Colchicine is effective and safe for the treatment and prevention of recurrent pericarditis and might ultimately serve as the initial mode of treatment, especially in idiopathic cases. The aim of this work was to verify the safety and efficacy of colchicine as an adjunct to conventional therapy for the treatment of the first episode of acute pericarditis. Methods and Results— A prospective, randomized, open-label design was used. A total of 120 patients (mean age 56.9±18.8 years, 54 males) with a first episode of acute pericarditis (idiopathic, viral, postpericardiotomy syndromes, and connective tissue diseases) were randomly assigned to conventional treatment with aspirin (group I) or conventional treatment plus colchicine 1.0 to 2.0 mg for the first day and then 0.5 to 1.0 mg/d for 3 months (group II). Corticosteroid therapy was restricted to patients with aspirin contraindications or intolerance. The primary end point was recurrence rate. During the 2873 patient-month follow-up, colchicine ...
Abstract 17093: Long-term Survival After Off-pump Coronary Artery Bypass Graft Surgery: A Cohort Study
Authors: Nishith N Patel, Francesca Fiorentino, Mansour T Sharabiani, Gianni D Angelini
Journal: Circulation (2015)

Introduction: Randomised controlled trials demonstrate that Off-Pump Coronary Artery Bypass (OPCAB) is equivalent to On-Pump Coronary artery bypass graft (ONCAB) for in-hospital and short-term outcomes. Recent observational data, however, suggests that OPCAB may be associated with increased mid-term mortality although there are several conflicting studies. There is little data on long-term survival after OPCAB. The objective of this study was to determine the impact of OPCAB on long-term survival compared to ONCAB. Methods: We conducted a retrospective cohort study using the Bristol PATS database of all patients who underwent primary isolated CABG surgery from 1996 to 2011. Mortality data was obtained from the Office of National Statistics. Multivariate regression models were used to estimate the association between OPCAB and long-term survival. Results: We evaluated long-term survival in 11,981 patients (mean age 65.5±9.3 years, 2202 females) who underwent CABG (OPCAB, n=6133; ONCAB, n=5848). Survival data was complete in 99.2% of patients, with a median follow-up duration of 8 years (interquartile range: 4.8 to 11.8 years; maximum 17.3 years). Both groups were similar in terms of baseline characteristics and intraoperative variables. Euroscore was 3.7 (0.03) and 3.8 (0.03) and number of distal anastomoses performed were 2.53 (0.81) and 2.92 (0.78) in the OPCAB and ONCAB groups, respectively. Long-term survival was similar between patients undergoing OPCAB and ONCAB (HR for death: 0.94, 95%CI 0.87 - 1.01, p=0.087). Conclusions: In patients undergoing coronary revascularisation both ONCAB and OPCAB offer excellent long-term survival.
Abstract 2128: Autocrine fibronectin inhibits breast cancer metastasis
Authors: Aparna Shinde, Ammara Abdullah, Luis Solorio, Michael Wendt
Journal: Cancer Research (2018)

Abstract The processes of the epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) are strongly linked to breast cancer metastasis via their ability to generate cells of increased invasive capacity and enhanced tumor-initiating phenotypes. Numerous growth factors, cytokines and chemotherapies present in the tumor microenvironment are capable of inducing EMT, but the role of extracellular matrix (ECM) components in this process remains less well understood. Analysis of the METABRIC dataset strongly linked high-level FN expression to decreased patient survival. However, in vitro analysis of the MCF-10A progression series indicated that autocrine FN expression was associated with nonmetastatic cells. Therefore, we utilized differential bioluminescent imaging to track the metastasis of these isogenic epithelial and mesenchymal cells within heterogeneous primary tumors. Using this approach, we demonstrate that tumor cells expressing autocrine FN display a constitutively mesenchymal phenotype and are incapable of completing the metastatic process, even when grown within a tumor containing epithelial tumor cells. Importantly, depletion of FN allows tumor cells to exit their mesenchymal state, regain epithelial characteristics and initiate tumor growth in a metastatic microenvironment. Using a tessellated three-dimensional polymer scaffolding, we show that depletion of FN or pharmacologic inhibition of focal adhesion kinase prevents mesenchymal tumor cells from producing structural fibrils and thus supporting the growth and migration of metastatic-competent epithelial tumor cells. Finally, dynamic FN coating of this 3D growth scaffold resulted in formation of a functionalized fibrillar FN network that was sufficient to induce transient EMT events as metastatic cells migrated along FN fibrils. Taken together, our data indicate that autocrine expression of FN by tumor cells supports a stable mesenchymal phenotype limiting their metastatic potential. Instead, this tumor cell-derived production of fibrillar FN acts in a paracrine fashion to support transient EMT events in metastatic competent cells within a heterogeneous tumor microenvironment. Citation Format: Aparna Shinde, Ammara Abdullah, Luis Solorio, Michael Wendt. Autocrine fibronectin inhibits breast cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2128.
Value-Based Health Care Meets Cost-Effectiveness Analysis
Authors: Joel Tsevat, Christopher Moriates
Journal: Annals of Internal Medicine (2018)

Value-based health care (VBHC) has recently emerged as a prominent movement within health care. Value-based health care focuses on maximizing outcomes achieved per dollar spent. As such, it bears many similarities to a well-established method, cost-effectiveness analysis (CEA), which provides a framework for comparing the relative value of different diagnostic or treatment interventions. Both approaches address "bang for the health care buck," but although they overlap in many ways, VBHC and CEA differ with regard to their main applications, their perspective, and the types of costs and outcomes they consider. For example, CEA generally considers costs and benefits from the societal or health care sector perspectives, whereas VBHC is intended to adopt the patient perspective. As such, CEA is intended to inform coverage decisions at a group or population level and VBHC is intended to be implemented at the level of clinician-patient interactions. Meanwhile, value-based payment has emerged as a visible component of VBHC and is gaining a foothold in the United States in various forms, particularly bundled payments and accountable care organizations, in an effort to reward high-value care and disincentivize low-value care. Differences aside, as the worlds of VBHC and CEA begin to intersect, each discipline can learn from the other.
CRISPR-SKIP: programmable gene splicing with single base editors
Authors: Michael Gapinske, Alan Luu, Jackson Winter, Wendy S. Woods, Kurt A. Kostan, Nikhil Shiva, Jun S. Song, Pablo Perez-Pinera
Journal: Genome biology (2018)

CRISPR gene editing has revolutionized biomedicine and biotechnology by providing a simple means to engineer genes through targeted double-strand breaks in the genomic DNA of living cells. However, given the stochasticity of cellular DNA repair mechanisms and the potential for off-target mutations, technologies capable of introducing targeted changes with increased precision, such as single-base editors, are preferred. We present a versatile method termed CRISPR-SKIP that utilizes cytidine deaminase single-base editors to program exon skipping by mutating target DNA bases within splice acceptor sites. Given its simplicity and precision, CRISPR-SKIP will be broadly applicable in gene therapy and synthetic biology.
Abstract 12979: A Key Role of Transient Receptor Potential Canonical (TRPC) Channels in the Regulation of Ventricular Electrical Activity of the Developing Heart
Authors: Jessica Sabourin, Elodie Robin, Eric Raddatz
Journal: Circulation (2011)

It is well established that ventricular electrical activity is controlled by a series of voltage-dependent channels in the fetal and adult heart. However, the involvement of voltage-insensitive cationic TRPC channels remains unclear. We assessed the hypothesis that TRPC channels play a crucial role in the ventricular spontaneous activity of the developing heart. The TRPC channels expression and their role were investigated in isolated hearts obtained from 4-day-old chick embryos. Using RT-PCR, western blot and co-immunoprecipitation, we report for the first time that TRPC1, 3, 4, 5, 6 and 7 isoforms are expressed at the mRNA and protein levels and that they can form a macromolecular complex with the α1C subunit of the L-type voltage-gated calcium channel (LCC, Cav1.2) in ventricle. Using ex vivo electrocardiogram and electrogram of isolated ventricles, we found that inhibition of TRPC channels by SKF-96365 (SKF) provokes ventricular arrhythmias characterised by tachycardia (+31%), prolonged QT interval (+...
Abstract 14233: A Simple Risk Stratification Model for Acute Myocardial Infarction using the Combination of Blood Examination: Acute Myocardial Infarction-Kyoto Multi-Center Risk Study Group
Authors: Kenji Yanishi, Takeshi Nakamura, Naohiko Nakanishi, Kan Zen, Tetsuhiro Yamano, Hirokazu Shiraishi, Takeshi Shirayama, Satoaki Matoba
Journal: Circulation (2016)

Background: Acute myocardial infarction (AMI) is a disease associated with poor in-hospital prognosis. Although the thrombolysis in myocardial infarction (TIMI) risk score and TIMI risk index could...
Abstract 5165: Patterning of individual cellular behavior in collective invasion
Authors: Chin-Lin Guo, Emilio Sanchez, Eileen Fong
Journal: Cancer Research (2018)

Abstract Collective invasion is one of the most important factors accounting for the aggressiveness of solid tumors. Such behavior depends on interactions between tumor cells and between tumor and its surrounding miroenvironment, including stroma cells and extracellular matrix (ECM), which to a certain extent, can be observed in normal cells. Previously we have shown that epithelial cells can use cell-ECM-cell interaction to develop long-range (&amp;gt; 600 microns) invasive patterns. Here, using artificial wounding assay, we show that normal epithelial cells can develop two coexisting, orthogonal migration patterns at the tissue boundary, leading to a periodic patterning of invasion. Such patterning depends on microtubule dynamic instability and results in ROCK activation and YAP1 nuclear translocation, a process to induce epithelial-mesenchymal transition (EMT). Surprisingly, we found that both overexpression and knockdown of an EMT marker, vimentin, can enhance collective invasion, suggesting that the role of vimentin in EMT might be context dependent and needs to be revisited. Citation Format: Chin-Lin Guo, Emilio Sanchez, Eileen Fong. Patterning of individual cellular behavior in collective invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5165.
Erratum. Mediterranean Diet, Retinopathy, Nephropathy, and Microvascular Diabetes Complications: A Post Hoc Analysis of a Randomized Trial. Diabetes Care 2015;38:2134–2141
Authors: Andrés Díaz-López, Nancy Babio, Miguel A. Martínez-González, Dolores Corella, Antonio J. Amor, Montse Fitó, Ramon Estruch, Fernando Arós, Enrique Gómez-Gracia, Miquel Fiol, José Lapetra, Lluís Serra-Majem, Josep Basora, F. Javier Basterra-Gortari, Vicente Zanon-Moreno, Miguel Ángel Muñoz, Jordi Salas-Salvadó
Journal: Diabetes Care (2018)

Some imperfections in the randomization procedures affecting a small subset of participants in the Prevencion con Dieta Mediterranea (PREDIMED) trial (at most 14%) have been reported in a recent republication of the main PREDIMED article (see Estruch et al. Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med 2018;378:e34). For this reason, the authors wish to make the …
Coronary Vasoconstriction During Myocardial Ischemia Induced by Rises in Metabolic Demand in Patients With Coronary Artery Disease
Authors: GianmarioSambuceti, MarioMarzilli, PaoloMarraccini, JanSchneider-Eicke, EnriGliozheni, OberdanParodi, AntonioL'Abbate
Journal: Circulation (1997)

Background In patients with coronary artery disease, a maximal vasodilation of the coronary microcirculation is generally assumed to occur during myocardial ischemia induced by rises in metabolic demand. However, vasoconstriction has been documented during severe prolonged ischemia in animals. The aim of this study was to investigate coronary vasomotor tone during pacing-induced ischemia in humans. Methods and Results The study included 11 patients with exercise-induced ischemia and single-vessel disease of the left anterior descending artery and 7 control subjects with normal coronary arteries. Blood flow velocity was monitored with a Doppler catheter in the left anterior descending artery. Coronary resistance index was calculated as the ratio between mean arterial pressure and flow velocity. Measurements were obtained at baseline, after intracoronary adenosine (2 mg), and during maximal atrial pacing in the absence and presence of adenosine. After adenosine administration at rest, coronary resistance de...
Evolutionarily conserved partial gene duplication in the Triticeae tribe of grasses confers pathogen resistance
Authors: Jeyaraman Rajaraman, Dimitar Douchkov, Stefanie Lück, Götz Hensel, Daniela Nowara, Maria Pogoda, Twan Rutten, Tobias Meitzel, Jonathan Brassac, Caroline Höfle, Ralph Hückelhoven, Jörn Klinkenberg, Marco Trujillo, Eva Bauer, Thomas Schmutzer, Axel Himmelbach, Martin Mascher, Barbara Lazzari, Nils Stein, Jochen Kumlehn, Patrick Schweizer
Journal: Genome biology (2018)

The large and highly repetitive genomes of the cultivated species Hordeum vulgare (barley), Triticum aestivum (wheat), and Secale cereale (rye) belonging to the Triticeae tribe of grasses appear to be particularly rich in gene-like sequences including partial duplicates. Most of them have been classified as putative pseudogenes. In this study we employ transient and stable gene silencing- and over-expression systems in barley to study the function of HvARM1 (for H. vulgare Armadillo 1), a partial gene duplicate of the U-box/armadillo-repeat E3 ligase HvPUB15 (for H. vulgare Plant U-Box 15). The partial ARM1 gene is derived from a gene-duplication event in a common ancestor of the Triticeae and contributes to quantitative host as well as nonhost resistance to the biotrophic powdery mildew fungus Blumeria graminis. In barley, allelic variants of HvARM1 but not of HvPUB15 are significantly associated with levels of powdery mildew infection. Both HvPUB15 and HvARM1 proteins interact in yeast and plant cells with the susceptibility-related, plastid-localized barley homologs of THF1 (for Thylakoid formation 1) and of ClpS1 (for Clp-protease adaptor S1) of Arabidopsis thaliana. A genome-wide scan for partial gene duplicates reveals further events in barley resulting in stress-regulated, potentially neo-functionalized, genes. The results suggest neo-functionalization of the partial gene copy HvARM1 increases resistance against powdery mildew infection. It further links plastid function with susceptibility to biotrophic pathogen attack. These findings shed new light on a novel mechanism to employ partial duplication of protein-protein interaction domains to facilitate the expansion of immune signaling networks.
Airway smooth muscle may drive mucus hypersecretion in asthma
Authors: James G. Martin
Journal: European Respiratory Journal (2018)

The contribution of airway smooth muscle (ASM) to asthma is critical but the multiple ways in which it may contribute to its pathobiology is still an active area of exploration. Contractile, proliferative and secretory properties relevant to asthma have been assessed. To date, studies of the contractile properties of isolated ASM have failed to demonstrate alterations in contractile properties that could explain excessive airway narrowing and airway hyperresponsiveness [1, 2], however tempting it is to attribute these features of asthma to intrinsic abnormalities of the muscle. In contrast to studies of tissue strips, cultured ASM cells demonstrate a range of "pro-asthmatic" properties that differ between cells derived from asthmatic subjects and healthy controls. For example, cultured ASM cells show enhanced stiffening when stimulated with contractile agonists [3] and proliferate more rapidly when treated with growth factors [4, 5], a property that would potentially favour a predisposition to remodelling. The pro-inflammatory phenotype is manifest as the expression of cytokines such as the neutrophilic chemoattractant CXCL8, attributable to enhanced NF-κB binding to the promoter site of CXCL8 [6]. Matrix proteins affecting ASM function and other cellular phenotypes are also secreted by ASM and are determinant of the ASM phenotype (reviewed in [7]). New insights into a potential property of airway smooth muscle cells with relevance to asthma <http://ow.ly/uVe030kPoNN>
Abstract LB-311: Inhibition of ubiquitin-specific protease 34 (USP34) regenerates mammary glands via induction of epithelial-mesenchymal transition (EMT) and stemness
Authors: Eunhye Oh, Daeil Sung, Yoon-Jae Kim, Tae-Min Cho, Seojin Jang, Ji Young Kim, Jae Hong Seo
Journal: Cancer Research (2018)

Abstract Mammary stem cells (MaSCs) possess specific biological properties including self-renewal capacity and the ability to differentiate into two primary cell lineages; luminal cells and myoepithelial cells. Epithelial-mesenchymal transition (EMT) is a key process during mammary gland development. Recent study demonstrates that ubiquitin-specific protease 34 (USP34), as a member of the USP family plays a critical role in Wnt/b-catenin signaling pathway. Our objective was to investigate possible roles of USP34 on induction of EMT and properties of mammary epithelial stem cells as well as mammary gland regeneration. We observed that USP34 level was relatively lower in mesenchymal-like phenotype MDA-MB-231 and 4T1 cells, compared to epithelial-like phenotype cells. Inhibition of USP34 induced EMT in NMuMG cells, which was accompanied with upregulation of EMT markers, such as N-cadherin, phospho-smad3, snail and active-β-catenin as well as downregulation of E-cadherin. NMuMG cells exhibited a typical epithelial phenotype with an absence of invasive behavior, while USP34 knockdown NMuMG cells acquired an invasive property. This observation was associated with a significant increased MMP2 level. Furthermore, inhibition of USP34 promotes stemness as evidenced by increased mammosphere-forming ability, concomitant with upregulation of Nanog, Oct4 and Sox2 mRNA levels in NMuMG cells. To examine the importance observations of our in vitro studies physiologically, the CTL-KD or USP34-KD cells were transplanted into the cleared mammary fat pads (CFP), and then mammary gland regeneration was observed for 10 months. Our in vivo data showed that USP34-KD cells regenerated elongated ductal branching and TEB of mammary gland in CFP. Our findings suggest that USP34 may be potentially involved in development of mammary glands. Citation Format: Eunhye Oh, Daeil Sung, Yoon-Jae Kim, Tae-Min Cho, Seojin Jang, Ji Young Kim, Jae Hong Seo. Inhibition of ubiquitin-specific protease 34 (USP34) regenerates mammary glands via induction of epithelial-mesenchymal transition (EMT) and stemness [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-311.
Vascular Extracellular Superoxide Dismutase Activity in Patients With Coronary Artery Disease
Authors: UlfLandmesser, RolandMerten, StephanSpiekermann, KarstenBüttner, HelmutDrexler, BurkhardHornig
Journal: Circulation (2000)

Background—Increased inactivation of nitric oxide by oxygen free radicals contributes to endothelial dysfunction in patients with coronary artery disease (CAD). We therefore determined the activity of extracellular superoxide dismutase (EC-SOD), the major antioxidant enzyme system of the vessel wall, and its relation to flow-dependent, endothelium-mediated dilation (FDD) in patients with CAD. Methods and Results—SOD isoenzyme activity was determined in coronary arteries from 10 patients with CAD and 10 control subjects. In addition, endothelium-bound EC-SOD activity (eEC-SOD), released by heparin bolus injection, and FDD of the radial artery were measured in 35 patients with CAD and 15 control subjects. FDD, determined by high-resolution ultrasound, was assessed at baseline, after intra-arterial infusion of vitamin C, N-monomethyl-l-arginine, and combination of both. EC-SOD activity in coronary arteries (control subjects: 126±14; CAD: 63±11 U/mg protein; P<0.01) and eEC-SOD activity in vivo (control subje...