tbuckley/cabot-search huggingface dataset:
Abstract 18548: Rapid Linear Ventricular Ablation Using a Novel Irrigated Multipolar Radiofrequency Ablation Catheter
Authors: Babak Nazer, Tomos E Walters, Srikant Duggirala, Edward P Gerstenfeld
Journal: Circulation (2016)

Introduction: A common strategy for ablation of scar-based VT is delivering multiple lesions in a linear pattern. We tested the efficacy of a novel linear irrigated multipolar ablation catheter (nMARQ, Biosense-Webster) capable of creating linear lesions with a single application. Methods: Healthy swine (n = 7) underwent endocardial (endo) and epicardial (epi) linear (LIN) ablation; control animals (n = 5) underwent focal (FOC) lesions in a linear pattern with an irrigated RF catheter (Thermocool). The LIN catheter contained 7 irrigated electrodes spaced over 3.5 cm and could deliver up to 25 W energy to each electrode (Fig 1A). Control FOC lesions were delivered contiguously over a 3.5 cm length from 20-35 W to achieve a >10 ohm impedence drop for each lesion (Fig 1B). In 2 additional swine, ablation was performed 1 month after an infarct was created using LAD balloon occlusion. Endo and epi LIN ablation was performed over the scar border zone. After sacrifice, hearts were sectioned for gross pathology, ...
The effect of acute morphine on obstructive sleep apnoea: a randomised double-blind placebo-controlled crossover trial
Authors: Luke Rowsell, Keith K H Wong, Brendon J Yee, Danny J Eckert, Andrew A Somogyi, James Duffin, Ronald R Grunstein, David Wang
Journal: Thorax (2018)

Objective Anaesthesiology guidelines suggest that opioids worsen obstructive sleep apnoea (OSA) despite no randomised controlled trial evidence. We therefore conducted a randomised controlled trial to evaluate the effects of a common clinical dose of morphine on OSA, and to identify clinical phenotype and genotype vulnerability to opioid-respiratory depression. Methods Under a double-blind, randomised, crossover design, 60 male patients with OSA attended two visits to the hospital sleep laboratory, at least 1 week apart. Either 40 mg controlled-release oral morphine or placebo was administered. Awake ventilatory chemoreflex tests were performed post dose and prior to overnight polysomnography monitoring. Blood was sampled before sleep and the next morning for toxicology and genotype analyses. Sleep time with oxygen saturation (SpO 2 ) &lt;90% (T90) was the primary outcome. Results Despite a large inter-individual variability, 40 mg morphine did not worsen T90 and apnoea–hypopnoea index, and only decreased the SpO 2 nadir by 1.3%. In patients with severe OSA, a lower baseline CO 2 ventilatory response threshold correlated with the worsening of T90, apnoea–hypopnoea index and oxygen desaturation index with morphine use. Patients with OSA and the A118G OPRM1 polymorphism of A/A and A/G had a significantly different morphine effect on awake ventilatory chemosensitivity and T90 during sleep. Conclusions 40 mg oral controlled-release morphine did not worsen OSA in men, challenging traditional thinking that OSA will be worsened by opioids. Individual opioid response in patients with OSA may relate to baseline CO 2 response threshold and OPRM1 genotype. Our study findings may pave the way for a precision medicine approach to avoid opioid-related risks. Trial registration number The Australian and New Zealand Clinical Trial Registry, ACTRN12613000858796.
Abstract 17235: Trends in Endocarditis Hospitalizations at US Children's Hospitals From 2003-2014: Impact of the 2007 American Heart Association Antibiotic Prophylaxis Guidelines
Authors: Katherine E Bates, Matthew Hall, Samir S Shah, Kevin D Hill, Sara K Pasquali
Journal: Circulation (2015)

Introduction: Over the past decade, national organizations in several countries have released more restrictive guidelines for infective endocarditis (IE) prophylaxis, including the American Heart Association (AHA) 2007 guidelines. Multiple initial studies demonstrated no change in IE rates over time following release of these guidelines, however a more recent analysis over a longer time period in the UK suggested an increase in IE. This prior study primarily included adults. Current IE trends in the pediatric population are unknown. Methods: Children (&lt;18 years) hospitalized with IE at 29 US centers participating in the Pediatric Health Information Systems Database from 2003-2014 were eligible for inclusion. Our primary analysis focused on IE most directly related to the change in the AHA guidelines, and included community-acquired IE cases (antibiotics covering oral streptococcal species started within 7 days of admission) in those &gt;5 years of age (most likely to be receiving dental care). Interrupted time series analysis was used to evaluate IE rates over time indexed to total hospital admissions. Results: A total of 841 IE cases were identified. Median age was 13 years (interquartile range 9-15 years). In the pre-guideline period, the IE rate increased slightly over time (+0.013 IE cases/1000 hospitalizations per 6-month period, see Figure). In the post-guideline period there was a similar trend in IE rates (+0.012 IE cases/1000 hospitalizations per 6-month period) with no significant difference in slope in the pre vs. post period (p=0.9). Additional analyses in those with congenital heart disease, and in those hospitalized with any type of IE (not limited to oral streptococci) at any age, revealed similar results. Conclusions: In contrast to a recent UK study, we found no evidence of a change in IE hospitalization rates associated with revised IE prophylaxis guidelines over an 11 year period across 29 US children’s hospitals.
Folk-economic beliefs as “evidential fiction”: Putting the economic public discourse back on track
Authors: Alberto Acerbi, Pier Luigi Sacco
Journal: Behavioral and Brain Sciences (2018)

Folk-economic beliefs may be regarded as "evidential fictions" that exploit the natural tendency of human cognition to organize itself in narrative form. Narrative counter-arguments are likely more effective than logical debunking. The challenge is to convey sound economic reasoning in narratively conspicuous forms - an opportunity for economics to rethink its role and agency in public discourse, in the spirit of its old classics.
RUNX1 upregulation via disruption of long-range transcriptional control by a novel t(5;21)(q13;q22) translocation in acute myeloid leukemia
Authors: Chi-Keung Cheng, Terry H. Y. Wong, Thomas S. K. Wan, Angela Z. Wang, Natalie P. H. Chan, Nelson C. N. Chan, Chi-Kong Li, Margaret H. L. Ng
Journal: Molecular Cancer (2018)

RUNX1 encodes a Runt-related transcription factor that is critical for hematopoiesis. In this study, through a combinatorial molecular approach, we characterized a novel t(5;21)(q13;q22) translocation involving RUNX1 that was acquired during the progression of myelodysplastic syndrome to acute myeloid leukemia (AML) in a pediatric patient. We found that this translocation did not generate RUNX1 fusion but aberrantly upregulated RUNX1. This upregulation was attributed to the disruption of long-range chromatin interactions between the RUNX1 P2 promoter and a silencer in the first intron of the gene. Characterization of the silencer revealed a role of SNAG repressors and their corepressor LSD1/KDM1A in mediating the effect. Our findings suggest that chromosomal rearrangements may activate RUNX1 by perturbing its transcriptional control to contribute to AML pathogenesis, in keeping with an emerging oncogenic role of RUNX1 in leukemia.
Comparison of HDV mono-infection with genotype 1 and 3 in CRPISPR/Cas generated humanized NTCP mice and human liver chimeric mice
Authors: K. Giersch, T. Volz, O.D. Bhadra, J. Kah, L. Allweiss, A.W. Lohse, J. Petersen, J. Casey, C. Sureau, M. Dandri, M. Luetgehetmann
Journal: Journal of Hepatology (2017)
Affibody-derived drug conjugates: Potent cytotoxic molecules for treatment of HER2 over-expressing tumors
Authors: Mohamed Altai, Hao Liu, Haozhong Ding, Bogdan Mitran, Per-Henrik Edqvist, Vladimir Tolmachev, Anna Orlova, Torbjörn Gräslund
Journal: Journal of Controlled Release (2018)
SCID genotype and 6-month posttransplant CD4 count predict survival and immune recovery
Authors: Elie Haddad, Brent R. Logan, Linda M. Griffith, Rebecca H. Buckley, Roberta E. Parrott, Susan E. Prockop, Trudy N. Small, Jessica Chaisson, Christopher C. Dvorak, Megan Murnane, Neena Kapoor, Hisham Abdel-Azim, Imelda C. Hanson, Caridad Martinez, Jack J. H. Bleesing, Sharat Chandra, Angela R. Smith, Matthew E. Cavanaugh, Soma Jyonouchi, Kathleen E. Sullivan, Lauri Burroughs, Suzanne Skoda-Smith, Ann E. Haight, Audrey G. Tumlin, Troy C. Quigg, Candace Taylor, Blachy J. Dávila Saldaña, Michael D. Keller, Christine M. Seroogy, Kenneth B. Desantes, Aleksandra Petrovic, Jennifer W. Leiding, David C. Shyr, Hélène Decaluwe, Pierre Teira, Alfred P. Gillio, Alan P. Knutsen, Theodore B. Moore, Morris Kletzel, John A. Craddock, Victor Aquino, Jeffrey H. Davis, Lolie C. Yu, Geoffrey D. E. Cuvelier, Jeffrey J. Bednarski, Frederick D. Goldman, Elizabeth M. Kang, Evan Shereck, Matthew H. Porteus, James A. Connelly, Thomas A. Fleisher, Harry L. Malech, William T. Shearer, Paul Szabolcs, Monica S. Thakar, Mark T. Vander Lugt, Jennifer Heimall, Ziyan Yin, Michael A. Pulsipher, Sung-Yun Pai, Donald B. Kohn, Jennifer M. Puck, Morton J. Cowan, Richard J. O'Reilly, Luigi D. Notarangelo
Journal: Blood (2018)
One-Year Safety and Clinical Outcomes of a Transcatheter Interatrial Shunt Device for the Treatment of Heart Failure With Preserved Ejection Fraction in the Reduce Elevated Left Atrial Pressure in Patients With Heart Failure (REDUCE LAP-HF I) Trial
Authors: Sanjiv J. Shah, Ted Feldman, Mark J. Ricciardi, Rami Kahwash, Scott Lilly, Sheldon Litwin, Chris D. Nielsen, Pim van der Harst, Elke Hoendermis, Martin Penicka, Jozef Bartunek, Peter S. Fail, David M. Kaye, Anthony Walton, Mark C. Petrie, Niki Walker, Anupam Basuray, Steven Yakubov, Scott L. Hummel, Stanley Chetcuti, Rhondalyn Forde-McLean, Howard C. Herrmann, Daniel Burkhoff, Joseph M. Massaro, John G. F. Cleland, Laura Mauri
Journal: JAMA Cardiology (2018)

In patients with heart failure (HF) and left ventricular ejection fraction (LVEF) equal to or greater than 40%, a transcatheter interatrial shunt device (IASD; Corvia Medical) reduces exercise pulmonary capillary wedge pressure (PCWP) and is safe compared with sham control treatment at 1 month of follow-up. The longer-term safety and patency of the IASD has not yet been demonstrated in the setting of a randomized clinical trial (RCT).To evaluate the 1-year safety and clinical outcomes of the IASD compared with a sham control treatment.This phase 2, double-blind, 1-to-1 sham-controlled multicenter RCT of IASD implantation vs a sham procedure (femoral venous access and imaging of the interatrial septum without IASD) was conducted in 22 centers in the United States, Europe, and Australia on patients with New York Heart Association (NYHA) class III or ambulatory class IV HF, LVEF equal to or greater than 40%, exercise PCWP equal to or greater than 25 mm Hg, and PCWP-right atrial pressure gradient equal to or greater than 5 mm Hg.Safety was assessed by major adverse cardiac, cerebrovascular, or renal events (MACCRE). Exploratory outcomes evaluated at 1 year were hospitalizations for HF, NYHA class, quality of life, a 6-minute walk test, and device patency.After 1 year, shunts were patent in all IASD-treated patients; MACCRE did not differ significantly in the IASD arm (2 of 21 [9.5%]) vs the control arm (5 of 22 [22.7%]; P = .41), and no strokes occurred. The yearly rate of hospitalizations for HF was 0.22 in the IASD arm and 0.63 in the control arm (P = .06). Median improvement in NYHA class was 1 class in the IASD arm (IQR, -1 to 0) vs 0 in the control arm (IQR, -1 to 0; P = .08). Quality of life and 6-minute walk test distance were similar in both groups. At 6 months, there was an increase in right ventricular size in the IASD arm (mean [SD], 7.9 [8.0] mL/m2) vs the control arm (-1.8 [9.6] mL/m2; P = .002), consistent with left-to-right shunting through the device; no further increase occurred in the IASD arm at 12 months.The REDUCE LAP-HF I phase 2, sham-controlled RCT confirms the longer-term patency of the IASD. Through 1 year of follow-up, IASD treatment appears safe, with no significant differences in MACCRE in patients receiving IASD compared with those who received sham control treatment.ClinicalTrials.gov identifier: NCT02600234.
Not all folk-economic beliefs are best understood through our ancestral past
Authors: Amit Bhattacharjee, Jason Dana
Journal: Behavioral and Brain Sciences (2018)

Abstract We applaud Boyer &amp; Petersen's (B&amp;P's) approach to a fascinating topic. Their arguments against understanding folk-economic beliefs (FEBs) in terms of economic ignorance or specific biases, however, are overly pessimistic. Economic theory is the reason beliefs about such disparate phenomena are labeled “economic” and “folk.” More importantly, some FEBs are better understood by examining current rather than ancestral contexts of exchange.
Functional Gut Microbiota Remodeling Contributes to the Caloric Restriction-Induced Metabolic Improvements
Authors: Salvatore Fabbiano, Nicolas Suárez-Zamorano, Claire Chevalier, Vladimir Lazarević, Silas Kieser, Dorothée Rigo, Stefano Leo, Christelle Veyrat-Durebex, Nadia Gaïa, Marcello Maresca, Doron Merkler, Mercedes Gomez de Agüero, Andrew Macpherson, Jacques Schrenzel, Mirko Trajkovski
Journal: Cell Metabolism (2018)

Caloric restriction (CR) stimulates development of functional beige fat and extends healthy lifespan. Here we show that compositional and functional changes in the gut microbiota contribute to a number of CR-induced metabolic improvements and promote fat browning. Mechanistically, these effects are linked to a lower expression of the key bacterial enzymes necessary for the lipid A biosynthesis, a critical lipopolysaccharide (LPS) building component. The decreased LPS dictates the tone of the innate immune response during CR, leading to increased eosinophil infiltration and anti-inflammatory macrophage polarization in fat of the CR animals. Genetic and pharmacological suppression of the LPS-TLR4 pathway or transplantation with Tlr4−/− bone-marrow-derived hematopoietic cells increases beige fat development and ameliorates diet-induced fatty liver, while Tlr4−/− or microbiota-depleted mice are resistant to further CR-stimulated metabolic alterations. These data reveal signals critical for our understanding of the microbiota-fat signaling axis during CR and provide potential new anti-obesity therapeutics.
Crimean-Congo haemorrhagic fever in a Greek worker returning from Bulgaria, June 2018
Authors: Anna Papa, Filothei Markatou, Helena C. Maltezou, Elpida Papadopoulou, Eirini Terzi, Sarantoula Ventouri, Danai Pervanidou, Sotirios Tsiodras, Efstratios Maltezos
Journal: Eurosurveillance (2018)

We report a tick-borne case of severe Crimean-Congo haemorrhagic fever (CCHF) imported into Greece from Bulgaria. The patient presented severe thrombocytopenia, hemophagocytosis, haemodynamic instability, large haematomas and altered mental status. Supportive treatment and ribavirin were administered. Symptoms started one day after the tick was removed; the patient was discharged from the hospital 26 days after symptom onset. No secondary cases were observed. Phylogenetically the CCHF virus strain belongs to clade Europe 1.
Abstract 15093: Feasibility of Dobutamine Stress Echocardiography as a Screening Modality for Evaluating Coronary Artery Disease Prior to Orthotopic Liver Transplantation
Authors: Akanksha Agrawal, Andre Dias, Aditi Kalla, Vinicius Jorge, Stalin Campos, Vincent Figueredo
Journal: Circulation (2016)

Background: Dobutamine stress echocardiography (DSE) is commonly used to screen coronary artery disease (CAD) and risk stratify patients before orthotopic liver transplantation (OLT). The purpose o...
Abstract 12566: Receptor for Activated Protein Kinase C1 Competes With GATA4 for p300 and Represses Hypertrophic Responses in Cardiomyocyte
Authors: Hidetoshi Suzuki, Yoichi Sunagawa, Yasufumi Katanasaka, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
Journal: Circulation (2014)

Introduction: The zinc finger protein GATA4 is one factor involved in transcriptional regulation during myocardial cell hypertrophy, and forms a complex with an intrinsic histone acetyltransferase (HAT), p300. HAT activity of p300 is required for acetylation and the transcriptional activity of GATA4, as well as for cardiomyocyte hypertrophy and the development of heart failure in vivo . We recently identified Receptor for Activated Protein Kinase C1 (RACK1), a multi-functional scaffold protein, as a novel GATA4-binding partner, and revealed that RACK1 regulates the p300/GATA4-dependent transcriptional pathway and hypertrophic responses in cardiomyocytes. However, the molecular mechanism by which RACK1 suppresses p300/GATA4-dependent gene transcription remains unknown. Hypothesis: We hypothesized that RACK1 reduces the phenylephrine (PE)-induced increase of the interaction between GATA4 and p300 in cardiacmyocytes. Methods and Results: To examine the effect of RACK on the binding activity of p300 to GATA4, expression plasmids encoding these proteins were used to co-transfect HEK293 cells. Nuclear extracts from these cells were subjected to immunoprecipitation, followed by Western blotting. Overexpression of RACK1 inhibited p300-induced GATA4 acetylation and the association with p300/GATA4. Based on chromatin immunoprecipitation and reporter assays, RACK1 inhibited not only p300-induced DNA binding activity of GATA4 on atrial natriuretic factors (ANF) and endothelin-1 (ET-1) promoters but also p300/GATA4-induced ANF and ET-1 promoter activities. In cultured neonatal rat ventricular cardiomyocytes, overexpression of RACK1 significantly inhibited PE-induced GATA4 acetylation, activation of ANF and ET-1 promoters, and myocardial cell hypertrophy. Also, PE decreased binding between GATA4 and RACK1. Finally, PE stimulation increased tyrosine phosphorylation of RACK1. This phosphorylation was inhibited by a tyrosine kinase inhibitor, Dasatinib. Conclusions: The findings demonstrated that RACK1 disrupted the p300/GATA4 complex and inhibited hypertrophic responses in cardiomyocytes. Tyrosine phosphorylation of RACK1 may trigger the dissociation of RACK1 from p300/GATA4.
Abstract 18332: Trends in Incidence, Management and Outcomes of Cardiogenic Shock Complicating Thyroid Storm in the United States
Authors: Divyanshu Mohananey, Pedro Villablanca, Nirmanmoh Bhatia, Sahil Agrawal, Jose C Murrieta, Malini Ganesh, Tanuja Salim, Jaskaran Sethi, Anushka Baruah, Muhammad S Ali, Ashish Angl, Aswathi Chandran, Harish Ramakrishna
Journal: Circulation (2016)

Introduction: Thyroid storm (TS) accounts for approximately 1-2% of admissions for thyrotoxicosis and is accompanied by profound hemodynamic derangements and development of atrial fibrillation (AF)...
Abstract 20393: End Stage Renal Disease After Pediatric Heart Transplantation: A 25-Year National Cohort Study
Authors: Swati Choudhry, Chesney D Castleberry, Vikas R Dharnidharka, Charles Goss, Kathleen E Simpson, Kenneth Schechtman, Charles E Canter
Journal: Circulation (2016)

Background: End stage renal disease (ESRD) is a known complication after heart transplant (HTx); however risk factors associated with ESRD are not well elucidated. The objectives of this study were...
Sepsis as a Cause of Infectious Disease Mortality—Reply
Authors: Charbel el Bcheraoui, Mohsen Naghavi, Christopher J. L. Murray
Journal: JAMA (2018)

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Abstract 18444: TRAF5 Deficiency Aggravates Diet-Induced Obesity in Mice
Authors: Florian Willecke, Mark C Gissler, Nathaly Anto Michel, Carmen Härtner, Ingo Hilgendorf, Peter Stachon, Dennis Wolf, Andreas Zirlik
Journal: Circulation (2016)

Objective: Accumulation of inflammatory leukocytes is a prerequisite of adipose tissue inflammation during cardiometabolic disease. We recently reported that genetic deficiency of the intracellular signaling adaptor TRAF5 accelerates atherogenesis in mice by increasing inflammatory cell recruitment. Since the latter is instrumental in metabolic disease, we tested the hypothesis that TRAF5 contributes to diet-induced obesity (DIO) in mice. Methods & Results: To induce metabolic syndrome, wild-type or TRAF5-/- mice consumed a high fat diet (45%kcal) for 20 weeks. TRAF5-/- mice showed an increased weight gain (78,8 ± 1,8% vs. 32,4 ±2,7 % wild-type), impaired insulin tolerance, and increased fasting blood glucose. Weight of liver and peripheral fat pats except epididymal fat were increased in TRAF5-/- mice. Analysis of the peripheral blood revealed leukocytosis driven by a relative increase in B-cells and monocytes. Analysis of inflammatory cells in the stromal vascular fraction revealed an increase in T-cell...
Abstract 19404: Effect of Medical Emergency Teams in Pediatric Hospitals on Hospital Mortality
Authors: Shelby Kutty, Philip Jones, Quentin Karels, Navya Joseph, John Spertus, Paul S Chan
Journal: Circulation (2016)

Introduction: Medical emergency teams (METs) have been promoted as a strategy to reduce preventable hospital deaths. Studies of METs on hospital mortality have been limited to single center studies...
Shedding of bevacizumab in tumour cells-derived extracellular vesicles as a new therapeutic escape mechanism in glioblastoma
Authors: Thomas Simon, Sotiria Pinioti, Pascale Schellenberger, Vinothini Rajeeve, Franz Wendler, Pedro R. Cutillas, Alice King, Justin Stebbing, Georgios Giamas
Journal: Molecular Cancer (2018)

Glioblastoma (GBM) is the most aggressive type of primary brain tumours. Anti-angiogenic therapies (AAT), such as bevacizumab, have been developed to target the tumour blood supply. However, GBM presents mechanisms of escape from AAT activity, including a speculated direct effect of AAT on GBM cells. Furthermore, bevacizumab can alter the intercellular communication of GBM cells with their direct microenvironment. Extracellular vesicles (EVs) have been recently described as main acts in the GBM microenvironment, allowing tumour and stromal cells to exchange genetic and proteomic material. Herein, we examined and described the alterations in the EVs produced by GBM cells following bevacizumab treatment. Interestingly, bevacizumab that is able to neutralise GBM cells-derived VEGF-A, was found to be directly captured by GBM cells and eventually sorted at the surface of the respective EVs. We also identified early endosomes as potential pathways involved in the bevacizumab internalisation by GBM cells. Via MS analysis, we observed that treatment with bevacizumab induces changes in the EVs proteomic content, which are associated with tumour progression and therapeutic resistance. Accordingly, inhibition of EVs production by GBM cells improved the anti-tumour effect of bevacizumab. Together, this data suggests of a potential new mechanism of GBM escape from bevacizumab activity.