tbuckley/cabot-search huggingface dataset:
Human Atrial Action Potential and Ca <sup>2+</sup> Model
Authors: Eleonora Grandi, Sandeep V. Pandit, Niels Voigt, Antony J. Workman, Dobromir Dobrev, José Jalife, Donald M. Bers
Journal: Circulation Research (2011)

Rationale: Understanding atrial fibrillation (AF) requires integrated understanding of ionic currents and Ca 2+ transport in remodeled human atrium, but appropriate models are limited. Objective: To study AF, we developed a new human atrial action potential (AP) model, derived from atrial experimental results and our human ventricular myocyte model. Methods and Results: Atria versus ventricles have lower I K1 , resulting in more depolarized resting membrane potential (≈7 mV). We used higher I to,fast density in atrium, removed I to,slow , and included an atrial-specific I Kur . I NCX and I NaK densities were reduced in atrial versus ventricular myocytes according to experimental results. SERCA function was altered to reproduce human atrial myocyte Ca 2+ transients. To simulate chronic AF, we reduced I CaL , I to , I Kur and SERCA, and increased I K1 ,I Ks and I NCX . We also investigated the link between Kv1.5 channelopathy, [Ca 2+ ] i , and AF. The sinus rhythm model showed a typical human atrial AP morphology. Consistent with experiments, the model showed shorter APs and reduced AP duration shortening at increasing pacing frequencies in AF or when I CaL was partially blocked, suggesting a crucial role of Ca 2+ and Na + in this effect. This also explained blunted Ca 2+ transient and rate-adaptation of [Ca 2+ ] i and [Na + ] i in chronic AF. Moreover, increasing [Na + ] i and altered I NaK and I NCX causes rate-dependent atrial AP shortening. Blocking I Kur to mimic Kv1.5 loss-of-function increased [Ca 2+ ] i and caused early afterdepolarizations under adrenergic stress, as observed experimentally. Conclusions: Our study provides a novel tool and insights into ionic bases of atrioventricular AP differences, and shows how Na + and Ca 2+ homeostases critically mediate abnormal repolarization in AF.
Functional Effects of a Retained Ancestral Polymorphism in<i>Prestin</i>
Authors: Yuan-Yuan Li, Zhen Liu, Fei-Yan Qi, Xin Zhou, Peng Shi
Journal: Molecular Biology and Evolution (2016)

Molecular basis for mammalian echolocation has been receiving much concerns. Recent findings on the parallel evolution of prestin sequences among echolocating bats and toothed whales suggest that adaptations for high-frequency hearing have occurred during the evolution of echolocation. Here, we report that although the species tree for echolocating bats emitting echolocation calls with frequency modulated (FM) sweeps is paraphyletic, prestin exhibits similar functional changes between FM bats. Site-directed mutagenesis shows that the amino acid 308S in FM bats is responsible for the similar functional changes of prestin. We strongly support that the occurrence of serine at position 308 is a case of hemiplasy, caused by incomplete lineage sorting of an ancestral polymorphism. Our study not only reveals sophisticated molecular basis of echolocation in bats, but also calls for caution in the inference of molecular convergence in species experiencing rapid radiation.
TCT-628 Prospective Non-randomized Comparison Between Three Transcatheter Aortic Valve Replacement Devices: Accurate vs Corevalve vs Sapien XT. A Single Heart Team Experience in Patients With Severe Aortic Stenosis
Authors: Tannas Jatene, Antonio d Castro Filho, Rafael A. Meneguz-Moreno, Dimytri A. Siqueira, Alexandre Abizaid, Auristela I. Ramos, Magaly Arrais, David Le Bihan, Rodrigo B. Barreto, Adriana Moreira, J. Eduardo Sousa, Amanda Sousa
Journal: Journal of the American College of Cardiology (2015)
A novel signalling screen demonstrates that CALR mutations activate essential MAPK signalling and facilitate megakaryocyte differentiation
Authors: K Kollmann, W Warsch, C Gonzalez-Arias, F L Nice, E Avezov, J Milburn, J Li, D Dimitropoulou, S Biddie, M Wang, E Poynton, M Colzani, M R Tijssen, S Anand, U McDermott, B Huntly, T Green
Journal: Leukemia (2016)

Most myeloproliferative neoplasm (MPN) patients lacking JAK2 mutations harbour somatic CALR mutations that are thought to activate cytokine signalling although the mechanism is unclear. To identify kinases important for survival of CALR-mutant cells, we developed a novel strategy (KISMET) that utilizes the full range of kinase selectivity data available from each inhibitor and thus takes advantage of off-target noise that limits conventional small-interfering RNA or inhibitor screens. KISMET successfully identified known essential kinases in haematopoietic and non-haematopoietic cell lines and identified the mitogen activated protein kinase (MAPK) pathway as required for growth of the CALR-mutated MARIMO cells. Expression of mutant CALR in murine or human haematopoietic cell lines was accompanied by myeloproliferative leukemia protein (MPL)-dependent activation of MAPK signalling, and MPN patients with CALR mutations showed increased MAPK activity in CD34 cells, platelets and megakaryocytes. Although CALR mutations resulted in protein instability and proteosomal degradation, mutant CALR was able to enhance megakaryopoiesis and pro-platelet production from human CD34+ progenitors. These data link aberrant MAPK activation to the MPN phenotype and identify it as a potential therapeutic target in CALR-mutant positive MPNs.
Viral Insertion Safety in Patients with Glioblastoma Who Received a Novel Lentiviral MGMT-P140K Gene Therapy to Protect Bone Marrow from Chemotherapy: No Dominant Clonal Evolution Observed with Chemo-Selection
Authors: Hua Fung, Andrew E Sloan, Jane Reese, Basem M. William, Karen Lingas, Lisa R Rogers, Heather Embree, Hillard M. Lazarus, Donna Kane, Boro Dropulic, Stanton L. Gerson
Journal: Blood (2014)
From the authors
Authors: S. S. Birring, V. M. Mann, S. Matos, N. Yousaf, C. Wood, T. Fleming, D. H. Evans, A. H. Morice, I. D. Pavord
Journal: European Respiratory Journal (2008)

The sensitivity of the system falls from 91 to 86% when 6-h validation was performed.BIRRING et al. [1] state that the reduction in sensitivity is most likely due to a more robust measure of true cough frequency used for the 2-h recordings.An alternative explanation is that the 2-h validation is poorly representative of the performance of the device over longer time periods.The data is presented for 24-h recordings on 50 subjects.So where are the data on sensitivity and specificity validated over a full 24 h?Previous publications have manually counted cough over 24-h periods in larger numbers of patients [2].Furthermore, the title of the paper describes the Leicester Cough Monitor as an automated cough detection system.In fact, operator input is required to classify sounds that might have been wrongly identified as cough events in the first phase.Therefore, the system would be more accurately described as semi-automated.
Safety and Clinical Benefit of Lentiviral Hematopoietic Stem Cell Gene Therapy for Wiskott-Aldrich Syndrome
Authors: Francesca Ferrua, Maria Pia Cicalese, Stefania Galimberti, Samantha Scaramuzza, Stefania Giannelli, Roberta Pajno, Francesca Dionisio, Luca Biasco, Maria Carmina Castiello, Miriam Casiraghi, Marcella Facchini, Andrea Finocchi, Ayse Metin, Jordan S. Orange, Michael H. Albert, Carmen Petrescu, Marita Bosticardo, Anna Villa, Chris Dott, Koen van Rossem, Maria Grazia Valsecchi, Fabio Ciceri, Maria Grazia Roncarolo, Luigi Naldini, Alessandro Aiuti
Journal: Blood (2015)
Iron Overload Occurs Very Early In Newly-Diagnosed Patients With Congenital, Transfusion-Dependent Anemias
Authors: Antonios Kattamis, Polyxeni Delaporta, Ioannis Papassotiriou, Dimitra Kyriakopoulou, Natalia Tourkantoni, Stavroula Kostaridou
Journal: Blood (2013)
Non-Myeloablative Allogeneic Hematopoietic Transplantation in Relapsed/Primary Refractory Follicular Lymphoma.
Authors: Claire Fabre, Christian Recher, Anne Huynh, Françoise Rigal-Huguet, Michel Abbal, Nicole Dastugue, Talal Al Saati, Pierre Brousset, Michel Attal
Journal: Blood (2004)
Pharmacokinetic (PK) and Pharmacodynamics (PD) Study of Two Doses of Bortezomib (Btz) in Patients with Relapsed Multiple Myeloma (MM).
Authors: A. Keith Stewart, Dan Sullivan, Sagar Lonial, Ann F. Mohrbacher, Gurkamal Chatta, Chaim Shustik, Howard Burris, Michael Karol, Peter Zannikos, Donna E. Reece
Journal: Blood (2006)
High Risk Hairy Cell Leukemia (HCL) Treatment with Fludarabine: Report of Three Cases with Low Toxicity and Durable Responses.
Authors: Antonio A. Carrasco-Yalan, Olga M. López-Odría, Luis Riva-Gonzales, Pilar Quiñones-Avila, Fernando Cauvi-R, Sergio A. Murillo-Vizcarra, Jorge S. Valdés-Gómez, Julia Huamaní-Zavala, Jorge A. Castillo-Aguirre, Brady E. Beltrán-Gárate
Journal: Blood (2005)
TCT-24 Selection of Collateral Channel Guided by A Hierarchic Decision Algorithm Achieved High Technical Success Rate and Low Procedural Complication Rate in Real World Retrograde Percutaneous Coronary Intervention (PCI) for Chronic Total Occlusion (CTO)
Authors: Ching-Chang Huang, Chih-Kuo Lee, Shih-Wei Meng, Ying-Hsien Chen, Mao-Shin Lin, Chih-Fan Yeh, Chi-Sheng Hung, Paul Hsien-Li Kao
Journal: Journal of the American College of Cardiology (2015)
Contrast-enhanced ultrasound does not discriminate between community acquired pneumonia and lung cancer
Authors: Marco Sperandeo, Gaetano Rea, Maria Arcangela Grimaldi, Francesca Trovato, Lucia M C Dimitri, Vincenzo Carnevale
Journal: Thorax (2016)

We investigated if contrast-enhanced ultrasound (CEUS) may differentiate community acquired pneumonia (CAP) from lung cancer (LC). Among 1374 patients admitted in a 5-year period for lung opacities, 728 (329 CAP and 399 LC) were investigated by CEUS, comparing the time of appearance, disappearance, duration and pattern of distribution of contrast enhancement (CE). The patients with CAP and LC did not differ in terms of age, time of CE appearance, disappearance and duration or CE distribution. Our data show that the timing and pattern of CE detected by chest CEUS does not distinguish between CAP and LC and overly optimistic beliefs on this matter should be abandoned.
TCT-462 Utility of the Syntax Score in Long-Term Outcomes after Newer-Generation Drug Eluting Stents in a Real-World
Authors: Hiroyuki Jinnouchi, Shoichi Kuramitsu, Yohei Kobayashi, Takashi Hiromasa, Takashi Morinaga, Kenji Ando
Journal: Journal of the American College of Cardiology (2015)
The Histone Deacetylase Inhibitor Depsipeptide Mediates Distinct Patterns of Histone Acetylation in Cells Overexpressing Bcl-2.
Authors: David M. Lucas, Liwen Zhang, Melanie E. Davis, Xiaodan Su, Amy Sklenar, Mark R. Parthun, Michael A. Freitas, Shinichi Kitada, John C. Reed, Guido Marcucci, Michael R. Grever, John C. Byrd
Journal: Blood (2004)
Targeted Delivery of an Anti-inflammatory PDE4 Inhibitor to Immune Cells via an Antibody–drug Conjugate
Authors: Shan Yu, Aaron D Pearson, Reyna KV Lim, David T Rodgers, Sijia Li, Holly B Parker, Meredith Weglarz, Eric N Hampton, Michael J Bollong, Jiayin Shen, Claudio Zambaldo, Danling Wang, Ashley K Woods, Timothy M Wright, Peter G Schultz, Stephanie A Kazane, Travis S Young, Matthew S Tremblay
Journal: Molecular Therapy (2016)

Phosphodiesterase 4 (PDE4) inhibitors are approved for the treatment of some moderate to severe inflammatory conditions. However, dose-limiting side effects in the central nervous system and gastrointestinal tract, including nausea, emesis, headache, and diarrhea, have impeded the broader therapeutic application of PDE4 inhibitors. We sought to exploit the wealth of validation surrounding PDE4 inhibition by improving the therapeutic index through generation of an antibody-drug conjugate (ADC) that selectively targets immune cells through the CD11a antigen. The resulting ADC consisted of a human αCD11a antibody (based on efalizumab clone hu1124) conjugated to an analog of the highly potent PDE4 inhibitor GSK256066. Both the human αCD11a ADC and a mouse surrogate αCD11a ADC (based on the M17 clone) rapidly internalized into immune cells and suppressed lipololysaccharide (LPS)-induced TNFα secretion in primary human monocytes and mouse peritoneal cells, respectively. In a carrageenan-induced air pouch inflammation mouse model, treatment with the ADC significantly reduced inflammatory cytokine production in the air pouch exudate. Overall, these results provide compelling evidence for the feasibility of delivering drugs with anti-inflammatory activity selectively to the immune compartment via CD11a and the development of tissue-targeted PDE4 inhibitors as a promising therapeutic modality for treating inflammatory diseases.
Relationship Between Pulmonary Artery Pressure and Spleen Volume in Non-Splenectomized Hemoglobin E/β-Thalassemia Patients
Authors: Vichai Atichartakarn, Suporn Chuncharunee, Sukit Yamwong, Teerapat Yingchoncharoen, Sutipong Jongjirasiri, Napaporn Archararit, Umaporn Udomsubpayakul, Katcharin Aryurachai
Journal: Blood (2011)
Luspatercept Treatment Leads to Long Term Increases in Hemoglobin and Reductions in Transfusion Burden in Patients with Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS): Preliminary Results from the Phase 2 PACE-MDS Extension Study
Authors: Aristoteles Giagounidis, Uwe Platzbecker, Ulrich Germing, Katharina Götze, Philipp Kiewe, Karin Tina Mayer, Oliver Ottmann, Markus Radsak, Thomas Wolff, Detlef Haase, Monty Hankin, Dawn Wilson, Xiaosha Zhang, Adberrahmane Laadem, Matthew L. Sherman, Kenneth M. Attie
Journal: Blood (2015)
First-in-human phase I study of CetuGEX, a novel anti-EGFR monoclonal antibody (mAb) with optimized glycosylation and antibody dependent cellular cytotoxicity.
Authors: Walter Fiedler, Cristiana Sessa, Luca Gianni, Sara Cresta, Henning Schulze-Bergkamen, Jens Weidmann, Sara De Dosso, Anna Tessari, Marc Oliver Salzberg, Hans Baumeister, Antje Danielczyk, Bruno Dietrich, Johannes Nippgen, Steffen Goletz
Journal: Journal of Clinical Oncology (2013)

3008 Background: Epidermal growth factor receptor (EGFR) is a validated target in cancer. EGFR antagonists in clinical use do not exploit the full potential of this target. CetuGEX is an IgG1 mAb against EGFR. Fully human and optimized glycosylation lead to a 10- to 250-fold improvement of ADCC-mediated tumor cell killing in all FcγRIIIa allotypes and lack of immunogenic carbohydrate-chains, compared to cetuximab. Methods: Eligible patients with advanced solid tumors, progressing after standard treatment, were enrolled into this phase I, first-in-human, multicenter, single agent dose escalation trial. PK, PD and immunological parameters were assessed. Endpoints were safety and tolerability and secondarily pharmacokinetics, immunogenicity and anti-tumor activity. Results: 41 patients were treated on a q1w (8 dose levels from 12 to 1,370 mg flat dose), or q2w (990 mg flat) schedule. 25 pts had received at least 8 weekly doses (per protocol population [PP]).The most frequently observed drug-related AE were nausea (20%), vomiting (20%), hypertension (20%), almost all low grade and acneiform dermatitis (25%), only grade 1 or 2. Infusion-related reactions (IRR), virtually restricted to the first infusion, were associated with cytokine secretion: IL-6, IL-8, TNFα, IFNγ and IP-10 as marker of macrophage activation. Optimization of infusion scheme and premedication reduced IRRs in severity and frequency from 76% to 57% mainly of low grade. Blood NK cells were reduced as sign of redistribution. Activity was seen over all dose levels. One patient with NSCLC achieved a complete response. One patient with metastatic colorectal cancer had a partial response, another 2 patients with esophageal and gastric cancer without measurable disease at study entry had marked improvement of symptoms and normalization of tumor markers. Additional 15 pts had stable disease lasting from 8 weeks to over a year, including several minor responses, leading to a clinical benefit rate of 46% (19/41) in the overall and 76% (19/25) in the PP population. PK supports q1w and q2w dosing. Conclusions: CetuGEX shows clear signs of activity and acceptable toxicity. Phase II will soon be initiated. Clinical trial information: NCT01222637.
PTH-027 Review of faults and usage of two upper and lower gastrointestinal endoscopes suppliers in nhs lothian over a 40 month period: Abstract PTH-027 Table 1
Authors: S Inglis, N Kennedy, JN Plevris
Journal: Gut (2015)

<h3>Introduction</h3> Endoscopes are used for diagnostic and therapeutic applications in Gastroenterology (GI). The nature of these procedures, can subject endoscopes to hard use and stringent cleaning and decontamination procedures, leading to numerous faults developing over their lifespan. The aim was to review the service history of two upper and lower GI endoscopes suppliers within NHS Lothian, and usage, over a 40 month period. <h3>Method</h3> The service history of each GI endoscope owned by NHS Lothian was requested from each supplier’s service department, between January 2011 and April 2014. Usage data for each endoscope with a repair was extracted from the Endoscopy Reporting System (Unisoft). Each repair was reviewed and classified as either an angulation, damage, leak, blockage, image, electrical, or other fault. The fault and corresponding usage was split by type and supplier to calculate average number of repairs, usage and give a measure of reliability (average repairs per annum/average procedure per annum). A chi square was performed to see if there were significant differences between fault categories from each supplier. A p &lt; 0.05 was classed as significant. <h3>Results</h3> The results obtained from the analysis of the faults from supplier A and supplier B were: Angulation 2 and 4.4% (p = 0.10), Damage 9.3 and 6% (p = 0.15), Blockages 17.7 and 20% (p = 0.49), Image faults <b>21</b>and 29.6% (p = 0.02), Leaks 40.7 and <b>22.4</b>% (p &lt; 0.001), electrical failures <b>3.7</b>and 13.2% (p &lt; 0.001) and other of 5.7 and 4.4% (p = 0.50) respectively. A summary of the number of scopes, procedures and repairs from both suppliers are shown in Table 1. <h3>Conclusion</h3> A comprehensive registry of endoscopes with individual repair profiles can give extremely valuable information regarding endoscope reliability and durability. This ensures that hardware quality is maintained. It can facilitate the replacement process as well as help in the negotiation of maintenance contracts. Modern endoscopes in general are of similar high quality and have similar repair profiles. There are individual company differences in terms of vulnerable parts for different scopes but in general choice of endoscopes should be based on existing facilities, unit case mix and cost rather than on individual brand names. <h3>Disclosure of interest</h3> S. Inglis: None Declared, N. Kennedy: None Declared, J. Plevris Grant/ Research Support from: JN Plevris has received funding from Fujifilm in the past for endoscopic research.
Outcomes of Myeloablative Hematopoietic Stem Cell Transplantation for Patients with Acute Myelogenous Leukemia with Relapsed or Refractory Disease
Authors: Courtney D. DiNardo, Alison Loren, Steven Goldstein, Stephen J. Schuster, Alexander Perl, Donald Tsai, Noelle Frey, Elizabeth Hexner, Ran Reshef, Edward A. Stadtmauer, David L. Porter, Selina Luger
Journal: Blood (2010)
Bortezomib, Doxorubicin and Dexamethasone (PAD) Combination Therapy Followed by Thalidomide and Dexamethasone (TD) as a Salvage Treatment for Relapsed Multiple Myeloma (MM): Preliminary Analysis of Efficacy and Safety.
Authors: Sung Sook Lee, Cheolwon Suh, Bong-Seog Kim, Jooseop Chung, Young-Don Joo, Hun-Mo Ryoo, Young Rok Do, Jong-Youl Jin, Hye Jin Kang, Gyeong-Won Lee, Moon Hee Lee, Hyeok Shim, Kihyun Kim, Sung-Soo Yoon, Ho Young Kim, Dong Soon Lee, Jae-Hoon Lee
Journal: Blood (2007)
GW27-e0549 Absolute values of blood pressure fluctuation as an independent risk factor for postoperative delirium: secondary, exploratory analysis of the randomized controlled “Surgery Depth of anaesthesia and Cognitive Outcome”- (SuDoCO) trial
Authors: Bruno Neuner, Bjrn Weiss, Torsten Wulfekammer, Finn Radtke, Martin Franck, Claudia Spies
Journal: Journal of the American College of Cardiology (2016)
TCT-159 Transcatheter Mitral Valve Implantation: Six-Month Outcomes Of First-In-Man Experience with an Apically Tethered Device
Authors: Alison Duncan, Caesare Quarto, Philipp Blanke, Jonathon A. Leipsic, Paul Grayburn, Simon Davies, Neil Moat
Journal: Journal of the American College of Cardiology (2015)
Stretching the Limits of Renal Transplantation in Elderly Recipients of Grafts from Elderly Deceased Donors
Authors: Hessel Peters-Sengers, Stefan P. Berger, Martin B.A. Heemskerk, Doaa al Arashi, Jaap J. Homan van der Heide, Aline C. Hemke, Ineke J.M. ten Berge, Mirza M. Idu, Michiel G.H. Betjes, Arjan D. van Zuilen, Luuk B. Hilbrands, Aiko P.J. de Vries, Azam S. Nurmohamed, Maarten H. Christiaans, L.W. Ernest van Heurn, Johan W. de Fijter, Frederike J. Bemelman
Journal: Journal of the American Society of Nephrology (2016)

An increasing number of elderly patients (≥65 years) receive a donor kidney from elderly donors after brain death (DBD) or after circulatory death (DCD). These organs are allocated within the Eurotransplant Senior Program, but outcomes must be evaluated. From the Dutch Organ Transplantation Registry, we selected 3597 recipients (≥18 years) who received a first DBD or DCD kidney during 2002-2012, and categorized them as young or elderly recipients receiving a graft from either a young or elderly donor, stratified by donor type. In multiple logistic regression analysis, elderly recipients of elderly DCD kidneys experienced more delayed graft function and acute rejection than did elderly recipients of young DBD kidneys (odds ratios 10.43 [95% confidence interval (95% CI), 5.75 to 18.91] and 2.78 [95% CI, 1.35 to 5.73], respectively). In Cox regression analysis, elderly recipients of elderly DCD kidneys had a 5-year mortality risk higher than that of elderly recipients of young DBD kidneys (hazard ratio, 1.86; 95% CI, 1.15 to 3.02). Elderly recipients of elderly kidneys had a 5-year mortality rate comparable to that of waitlisted elderly patients remaining on dialysis. Among elderly recipients, 63.8% of those who received elderly DCD kidneys, 45.5% of those who received elderly DBD kidneys, and approximately 26% of those who received young DBD or DCD kidneys had an eGFR<30 ml/min per 1.73 m2 (including primary nonfunction) after 1 year. In conclusion, improving donor selection and preservation is warranted if the allocation of elderly DCD grafts to elderly recipients is to be expanded.
Inhibition of Let-7 Processing in Adult Murine Hematopoietic Stem Cells Induces a Fetal-Like High Self-Renewal Pattern in Their Progeny
Authors: Michael R. Copley, David G. Kent, Claudia Benz, Stefan Wohrer, Keegan M. Rowe, Chris W. Day, Connie J. Eaves
Journal: Blood (2011)
Outcome of Patients (pts) with Chronic Myeloid Leukemia (CML) After Failure to 2nd and 3rd Tyrosine Kinase Inhibitors (TKIs)
Authors: Liunan Li, Hagop Kantarjian, Meng Zhao, Susan O'Brien, MD, Elias Jabbour, Alfonso Quintás-Cardama, Elizabeth Burton, Stefan Faderl, Alessandra Ferrajoli, Jorge E. Cortes
Journal: Blood (2010)