tbuckley/cabot-search huggingface dataset:
Coupling Data Mining and Laboratory Experiments to Discover Drug Interactions Causing QT Prolongation
Authors: Tal Lorberbaum, Kevin J. Sampson, Jeremy B. Chang, Vivek Iyer, Raymond L. Woosley, Robert S. Kass, Nicholas P. Tatonetti
Journal: Journal of the American College of Cardiology (2016)

QT interval-prolonging drug-drug interactions (QT-DDIs) may increase the risk of life-threatening arrhythmia. Despite guidelines for testing from regulatory agencies, these interactions are usually discovered after drugs are marketed and may go undiscovered for years. Using a combination of adverse event reports, electronic health records (EHR), and laboratory experiments, the goal of this study was to develop a data-driven pipeline for discovering QT-DDIs. 1.8 million adverse event reports were mined for signals indicating a QT-DDI. Using 1.6 million electrocardiogram results from 380,000 patients in our institutional EHR, these putative interactions were either refuted or corroborated. In the laboratory, we used patch-clamp electrophysiology to measure the human ether-à-go-go-related gene (hERG) channel block (the primary mechanism by which drugs prolong the QT interval) to evaluate our top candidate. Both direct and indirect signals in the adverse event reports provided evidence that the combination of ceftriaxone (a cephalosporin antibiotic) and lansoprazole (a proton-pump inhibitor) will prolong the QT interval. In the EHR, we found that patients taking both ceftriaxone and lansoprazole had significantly longer QTc intervals (up to 12 ms in white men) and were 1.4 times more likely to have a QTc interval above 500 ms. In the laboratory, we found that, in combination and at clinically relevant concentrations, these drugs blocked the hERG channel. As a negative control, we evaluated the combination of lansoprazole and cefuroxime (another cephalosporin), which lacked evidence of an interaction in the adverse event reports. We found no significant effect of this pair in either the EHR or in the electrophysiology experiments. Class effect analyses suggested this interaction was specific to lansoprazole combined with ceftriaxone but not with other cephalosporins. Coupling data mining and laboratory experiments is an efficient method for identifying QT-DDIs. Combination therapy of ceftriaxone and lansoprazole is associated with increased risk of acquired long QT syndrome.
Hemophilia B Gene Therapy Modelled in Null and Missense Mutant Mice: Kinetics of Transgenic Factor IX Expression Influences Tolerance to a Greater Extent Than Dose or Serotype of Adeno-Associated Virus (AAV) Vector.
Authors: Paul E. Monahan, Tai-Ping Zhang, Da-Yun Jin, Tong Gui, Darrel W. Stafford
Journal: Blood (2005)
TCT-71 Safety and Efficacy of Carotid Stenting With Proximal Embolic Protection Through Transradial/brachial Approach: Results in 60 Consecutive Patients
Authors: Piero Montorsi, Stefano Galli, Simone Tresoldi, Paolo M. Ravagnani, Giovanni Teruzzi, Daniela Trabattoni, Franco Fabbiocchi, Luca Grancini, Giuseppe Calligaris, Stefano De Martini, Antonio L. Bartorelli
Journal: Journal of the American College of Cardiology (2015)
Influence of first line treatment in the 5 (5yS) and 10-year (10yS) survival outcomes of patients with gastroenteropancreatic neuroendocrine tumors (GNETs): 2001–2005 Spanish task force GNET group
Authors: E. Vilar, M. Martinez, V. Alonso, M. Sevilla, J. Sastre, D. Castellano, M. Marazuela, J. Diaz, C. Villabona, R. Salazar
Journal: Journal of Clinical Oncology (2006)

14058 Background: Data on incidence, morbidity and mortality of GNETs is limited due to the low frequency of these tumors. However this survival data is critical to design studies with new agents. Methods: Data was obtained from medical records of 262 patients with GNETs and centralized in an online registry at www.retegep.net . Among the study parameters were histology, localization, stage, diagnostic workup, 1 st line and subsequent treatments, 5yS and 10yS for the whole dataset and for different stages, tumor types and 1 st line systemic treatment. Results: Mean age 58, 58% male. Primary tumors: 49% Carcinoids (C), 19% non-functioning pancreatic tumors (PT), 9% insulinomas, 6% gastrinomas and 8% unknown primary. Localizations: midgut (36%), head (17%) and body of pancreas (10%). Functioning symptoms led to diagnosis in 38% of cases. 4% were associated to MEN1. Stage at diagnosis was advanced (Adv) in 46%, localised (L) in 30% and locorregional (LR) in 13% (unknown in 11%). Diagnostic workup were CT Scan (84%), Octreoscan (52%) and US (52%) and serum hormone tests (65%). Treatments for Adv disease included somatostatin analogues (SA) (47%), surgery (S) (43%), chemotherapy (CT) (35%) and interferon (IFN) (34%), embolization (7%) and radiofrequency ablation (3%). 5yS and 10yS for the whole group was 61.6% (SD: 5.2%) and 49.8% (SD: 7.7%) respectively. 5yS and 10yS for the L/LR and Adv stages were 78.1% (SD: 7.3%) and 71% (SD: 10%), and 48.9% (SD: 7.7%) and 29% (SD: 12.4%), respectively. LR PT and C had similar 5 and 10yS but Adv PT did worse than Adv C (5yS of 36.2% and 61.1%, respectively). 1 st line systemic treatment for LR and Adv disease (n=90) included SA (39%), CT (34.4%), IFN (5.6%), combinations of SA+IFN (13.3%), A+CT (4.4%) and other combinations (3.3%), with a 10yS rate of 69%, 79%, 50%, 89%, 66% and 50%, respectively. Adv PT perform worse than C regardless of treatment choice. As second line systemic treatment (n=43) 30% received SA, 30% CT, 26% inmunotherapy and 14% combinations. Conclusions: An extensive use of systemic therapy and a scarce use of non-surgical LR treatments is observed in the Adv stages. Choice of 1 st line systemic treatment does not seem to influence survival outcomes. No significant financial relationships to disclose.
Detection of BCR-ABL Kinase Domain Mutations in Chronic Myeloid Leukemia Patients Treated with Tirosin-Kinase Inhibitors
Authors: Gonzalo Manrique, Roberta Bittencout, Verónica Pérez, Vanesa Sholl, Monica Cappetta, Noel Zubillaga, Rocio Hassan, Susana Boschi, Victoria Elizondo, Hector Seuanez, Ilana Zalcberg, Lem Martinez, M. Rosario Uri arte Escuder
Journal: Blood (2008)
GW27-e0696 Hemodynamic and Biology Response of a Fully Repositionable and Retrievable TAVI System in a Sheep Model
Authors: Dongming Hou, Jeannot Potvin, Elena Ladich, Barbara Huibregtse, Renu Virmani, Keith Dawkins, Amelie Bouchard, Guy Leclerc
Journal: Journal of the American College of Cardiology (2016)
Gene expression profile of endothelial cells during perturbation of the gut vascular barrier
Authors: Ilaria Spadoni, Alessandro Pietrelli, Graziano Pesole, Maria Rescigno
Journal: Gut Microbes (2016)

It has been widely demonstrated that tolerance against gut microbiota is compartmentalized to mucosal sites where microbes mostly reside. How the commensal bacteria are excluded from the entrance into the blood stream via intestinal capillaries that are located beneath the gut epithelium was not clear. We recently described the existence of a new anatomical structure, the 'gut vascular barrier' (GVB), both in murine and human intestines that plays a fundamental role in avoiding indiscriminate trafficking of bacteria from the gut into the blood circulation. The vascular barrier integrity could be altered by Salmonella typhimurium, a pathogen capable of systemic dissemination, through the modulation of the Wnt/β-catenin signaling pathway. Here we have analyzed the differences in gut endothelial gene expression profiles during Salmonella infection and have identified some interesting characteristics of endothelial to mesenchymal transition. These findings add new insights in the gut-liver axis.
TCT-156 Outcomes After Transcatheter Aortic Valve Implantation Using a Novel Balloon-Expandable Transcatheter Heart Valve: A Single Center Experience
Authors: Oliver Husser, Costanza Pellegrini, Thorsten Kessler, Christof Burgdorf, Hannah Thaller, Patrick Mayr, Ilka Ott, Markus Kasel, Heribert Schunkert, Adnan Kastrati, Christian Hengstenberg
Journal: Journal of the American College of Cardiology (2015)
Leishmania Uses Mincle to Target an Inhibitory ITAM Signaling Pathway in Dendritic Cells that Dampens Adaptive Immunity to Infection
Authors: Salvador Iborra, María Martínez-López, Francisco J. Cueto, Ruth Conde-Garrosa, Carlos Del Fresno, Helena M. Izquierdo, Clare L. Abram, Daiki Mori, Yolanda Campos-Martín, Rosa María Reguera, Benjamin Kemp, Sho Yamasaki, Matthew J. Robinson, Manuel Soto, Clifford A. Lowell, David Sancho
Journal: Immunity (2016)
TCT-243 Long-term residual risk according to optimal medical treatment in acute myocardial infarction treated with percutaneous coronary
Authors: Byung-Hee Hwang, Sungmin Lim, Eun Ho Choo, Ha-Wook Park, Young Soo Lee, Yoon Seok Koh, Hun Jun Park, Pum Joon Kim, Kiyuk Chang, Hee-Yeol Kim, Wook Sung Chung, Myung Ho Jeong, Ki-Bae Seung
Journal: Journal of the American College of Cardiology (2015)
Pegfilgrastim Use and Outcomes In Non-Hodgkin-Lymphoma Patients Receiving Chemotherapy In Clinical Practice: Combined Analysis Of The Austrian and Swiss E-Avare Studies
Authors: Wolfgang Willenbacher, Ferdinand Haslbauer, Peter Neumeister, Anton Guttmann, Roland Sperb, Andreas Lohri, Biagio Saldutto, Christine Jaeger, Carine Bast, Christoph Renner
Journal: Blood (2013)
The Immature Reticulocyte Fraction Predicts Marrow Recovery and Can Obviate the Need for Bone Marrow Examination in Persistently Neutropenic Cancer Patients
Authors: Sajjad Haider, Lakshmikanth Katragadda, Jameel Muzaffar, Monica Grazziutti, Muhammad R Akbar, Michele H. Cottler-Fox, Bart Barlogie, Elias J. Anaissie
Journal: Blood (2011)
TCT-91 Comparison of Portico® and CoreValveTM Self-expanding Transcatheter Heart Valves for the Treatment of Failed Surgical Aortic Bioprosthesis: Insights from the Valve in Valve International Data (VIVID) Registry
Authors: Sami Alnasser, Asim Cheema, Ran Kornowski, Matheus S. Santos, Thomas Walther, Azeem Latib, Luca Testa, Jean-Claude Laborde, David Hildick-Smith, Marco Barbanti, Won-Keun Kim, Francesco Bedogni, Hafid Amrane, A.J. van Boven, Marc Pelletier, Josep Rodes-Cabau, Joelle Kefer, Christian Frerker, Nicolas M. Van Mieghem, Ganesh Manoharan, Stephen G. Worthley, Anita W. Asgar, Carmelo Sgroi, Webb John, Danny Dvir
Journal: Journal of the American College of Cardiology (2015)
The effect of sunitinib on immune parameters and haemopoetic stem cell markers in patients with untreated clear cell renal cancer.
Authors: S. Chowdhury, T. S. O’Brien, N. Sarwar, J. Shamash, S. McGrath, S. Agrawal, L. Lim, S. M. Rudman, P. G. Harper, T. Powles
Journal: Journal of Clinical Oncology (2010)

4620 Background: Sunitinib is widely used as first line therapy for metastatic clear cell renal cancer. It is associated with myelosuppression, however its effects on specific immune parameters and haemopoetic stem cells (CD34 /CD133 -ve) is unknown. Methods: Peripheral blood total white count, neutrophil, CD3, CD4 T-cell, CD8 T-cell , CD19 B-cell, CD56 natural killer cell and haemopetic stem cell count (CD34 /+ve CD133 -ve) were prospectively measured on consecutive patients taking sunitinib therapy as part of a clinical trial. During this clinical trial patients had a period off sunitinib therapy (for 4 weeks after 18 weeks of treatment to allow a nephrectomy to take place). Blood was taken at baseline, at 6 weeks, 18 weeks, after the treatment free period during nephrectomy and 6 weeks after restarting therapy. Results: 43 consecutive patients were enrolled into the study. Significant declines in total WCC (48%), CD3 (31%), neutrophils (62%), T-helper cells (CD4) counts (32%) and T-cytotoxic cell (CD8) count (37%) were seen after 3 months of therapy (p<0.05 for each). CD34 level were markedly elevated in 74% of patients before therapy (significantly higher than healthy controls), while CD 133 (an endothelial cell progenitor marker) was absent in all samples, indicating the presence of haemopoetic stem cells rather than endothelial cells. Treatment was associated with a marked fall in this CD34 count (61% p<0.05). During the treatment free interval all of these parameters recovered to the baseline level. None of these falls had a significant effect on progression free survival (p>0.05). Sunitinib had no significant effect on natural killer cell (CD56 cells -18%) or B lymphocyte count (CD19 cells +1%). Conclusions: Sunitinib is associated with a significant inhibition of specific protagonists of the immune repertoire. This is reversible with cessation of therapy and has implications for both the development of infections and anti tumour immunogenic effects. The presence of CD34+ve/CD133-ve cells are intriguing, as is their fall will therapy. It indicates hyperactive bone marrow function in RCC which can be reversed with sunitinib therapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline, Novartis, Pfizer Pfizer
TCT-571 Clinical Outcomes of Biodegradable-Polymer Coated Sirolimus-Eluting Stent in Unselected Patients with Long Coronary Lesions: LONG-FLEX Registry
Authors: Prakash Chandwani, Puneet Verma, Sudheer Saxena, Atul Abhyankar, Manjinder Singh Sandhu, Nikhil Parikh, Jayesh Prajapati, Sharad Jain, Ashok N. Bhupali, Padma Kumar Ramachandran, Arohi Sarang, Ashok Thakkar
Journal: Journal of the American College of Cardiology (2015)
TCT-206 Effect of the α2A-Adrenergic Receptor Genetic Variants on Platelet Reactivity and Adverse Clinical Events in Chinese Patients with Dual Antiplatelet Therapy after Percutaneous Coronary Intervention
Authors: Ying Song, Xiao-Fang Tang, Jia-Hui Zhang, Yi Yao, Jing-Jing Xu, Run-Lin Gao, Bo Xu, Jin-Qing Yuan
Journal: Journal of the American College of Cardiology (2015)
in Philadelphia-Chromosome-Negative Acute Lymphoblastic Leukemia, Late Relapses Are Not Uncommon, Occur Mostly in Patients at Standard Risk and Have a Relatively Favorable Outcome. Results of the International ALL Trial: MRC Ukallxii/ECOG E2993
Authors: Chezi Ganzel, Wang Xin Victoria, Adele K. Fielding, Jacob M. Rowe, Susan M Richards, Georgina Buck, Rajesh Chopra, I. Jill Durrant, David Marks, Ian M. Franklin, Andrew K McMilan, Mark R Litzow, Elisabeth Paietta, Selina Luger, Peter H Wiernik, Dan Douer, Hillard M. Lazarus, Martin S Tallman, Anthony H. Goldstone
Journal: Blood (2015)
18F-FDG PET/CT in Metastatic Pilomatrix Carcinoma
Authors: Manuela Vadrucci, Laura Gilardi, Filippo Crivelli, Alberto Baroli, Giuseppe Lomuscio
Journal: Clinical Nuclear Medicine (2016)

We describe the FDG PET/CT findings in an exceedingly rare case of metastatic pilomatrix carcinoma (PC). A 76-year-old man, who underwent incisional biopsy of a soft-tissue mass in the frontal scalp that revealed PC, was referred for an 18F-FDG PET/CT scan for staging purposes. PET/CT showed areas of increased radiotracer uptake corresponding to frontal mass and unsuspected lung lesions, which were later confirmed as metastases from PC at histological analysis. Clinical condition deteriorated rapidly, and the patient died 3 months after the initial diagnosis.
Erythropoetin (EPO) and Granulocyte Colony Stimulating Factor (GCS-F) Based Therapy in Patients with Low Risk MDS: A Single Centre Experience from India.
Authors: Velu Nair, Deepak K. Mishra, Ajay Sharma, Satya N. Das, J. Kotwal, B. Mukerjee, M.B. Agarwal, S.R. Mehta
Journal: Blood (2006)
Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy
Authors: Alain Ravaud, Robert J. Motzer, Hardev S. Pandha, Daniel J. George, Allan J. Pantuck, Anup Patel, Yen-Hwa Chang, Bernard Escudier, Frede Donskov, Ahmed Magheli, Giacomo Carteni, Brigitte Laguerre, Piotr Tomczak, Jan Breza, Paola Gerletti, Mariajose Lechuga, Xun Lin, Jean-Francois Martini, Krishnan Ramaswamy, Michelle Casey, Michael Staehler, Jean-Jacques Patard
Journal: New England Journal of Medicine (2016)

Sunitinib, a vascular endothelial growth factor pathway inhibitor, is an effective treatment for metastatic renal-cell carcinoma. We sought to determine the efficacy and safety of sunitinib in patients with locoregional renal-cell carcinoma at high risk for tumor recurrence after nephrectomy.In this randomized, double-blind, phase 3 trial, we assigned 615 patients with locoregional, high-risk clear-cell renal-cell carcinoma to receive either sunitinib (50 mg per day) or placebo on a 4-weeks-on, 2-weeks-off schedule for 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. The primary end point was disease-free survival, according to blinded independent central review. Secondary end points included investigator-assessed disease-free survival, overall survival, and safety.The median duration of disease-free survival was 6.8 years (95% confidence interval [CI], 5.8 to not reached) in the sunitinib group and 5.6 years (95% CI, 3.8 to 6.6) in the placebo group (hazard ratio, 0.76; 95% CI, 0.59 to 0.98; P=0.03). Overall survival data were not mature at the time of data cutoff. Dose reductions because of adverse events were more frequent in the sunitinib group than in the placebo group (34.3% vs. 2%), as were dose interruptions (46.4% vs. 13.2%) and discontinuations (28.1% vs. 5.6%). Grade 3 or 4 adverse events were more frequent in the sunitinib group (48.4% for grade 3 events and 12.1% for grade 4 events) than in the placebo group (15.8% and 3.6%, respectively). There was a similar incidence of serious adverse events in the two groups (21.9% for sunitinib vs. 17.1% for placebo); no deaths were attributed to toxic effects.Among patients with locoregional clear-cell renal-cell carcinoma at high risk for tumor recurrence after nephrectomy, the median duration of disease-free survival was significantly longer in the sunitinib group than in the placebo group, at a cost of a higher rate of toxic events. (Funded by Pfizer; S-TRAC ClinicalTrials.gov number, NCT00375674 .).
The Evolution of Silicon Transport in Eukaryotes
Authors: Alan O. Marron, Sarah Ratcliffe, Glen L. Wheeler, Raymond E. Goldstein, Nicole King, Fabrice Not, Colomban de Vargas, Daniel J. Richter
Journal: Molecular Biology and Evolution (2016)

Biosilicification (the formation of biological structures from silica) occurs in diverse eukaryotic lineages, plays a major role in global biogeochemical cycles, and has significant biotechnological applications. Silicon (Si) uptake is crucial for biosilicification, yet the evolutionary history of the transporters involved remains poorly known. Recent evidence suggests that the SIT family of Si transporters, initially identified in diatoms, may be widely distributed, with an extended family of related transporters (SIT-Ls) present in some nonsilicified organisms. Here, we identify SITs and SIT-Ls in a range of eukaryotes, including major silicified lineages (radiolarians and chrysophytes) and also bacterial SIT-Ls. Our evidence suggests that the symmetrical 10-transmembrane-domain SIT structure has independently evolved multiple times via duplication and fusion of 5-transmembrane-domain SIT-Ls. We also identify a second gene family, similar to the active Si transporter Lsi2, that is broadly distributed amongst siliceous and nonsiliceous eukaryotes. Our analyses resolve a distinct group of Lsi2-like genes, including plant and diatom Si-responsive genes, and sequences unique to siliceous sponges and choanoflagellates. The SIT/SIT-L and Lsi2 transporter families likely contribute to biosilicification in diverse lineages, indicating an ancient role for Si transport in eukaryotes. We propose that these Si transporters may have arisen initially to prevent Si toxicity in the high Si Precambrian oceans, with subsequent biologically induced reductions in Si concentrations of Phanerozoic seas leading to widespread losses of SIT, SIT-L, and Lsi2-like genes in diverse lineages. Thus, the origin and diversification of two independent Si transporter families both drove and were driven by ancient ocean Si levels.
Platelet-Derived Microparticles Induce Angiogenesis In Vitro and In Vivo.
Authors: Bao-An Chen, Yue-Jiao Zhong, Cheng-Yin Huang, Feng Gao, Jian Chen, Chong Gao, Yun-Yu Sun, Jun Wang, Gang Zhao, Jia-Hua Ding, Ning-Na Chen, Xiao-Ping Pei
Journal: Blood (2007)
Foodborne (1973–2013) and Waterborne (1971–2013) Disease Outbreaks — United States
Authors: Daniel Dewey-Mattia, Virginia A. Roberts, Antonio Vieira, Kathleen E. Fullerton
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

CDC collects data on foodborne and waterborne disease outbreaks reported by all U.S. states and territories through the Foodborne Disease Outbreak Surveillance System (FDOSS) (http://www.cdc.gov/foodsafety/fdoss/surveillance/index.html) and the Waterborne Disease and Outbreak Surveillance System (WBDOSS) http://www.cdc.gov/healthywater/surveillance), respectively. These two systems are the primary source of national data describing the number of reported outbreaks; outbreak-associated illnesses, hospitalizations, and deaths; etiologic agents; water source or implicated foods; settings of exposure; and other factors associated with recognized foodborne and waterborne disease outbreaks in the United States.
Diabetes prescribing rises by a third over five years
Authors: Ingrid Torjesen
Journal: BMJ (2016)

The number of prescriptions for drugs that treat type 2 diabetes that were dispensed by pharmacies in England has risen by one third (33%) in five years, according to research carried out by analytic database provider EXASOL.

The researchers analysed a government dataset which included every prescription handed out by pharmacies since 2010, and found that in 2011 26 million type 2 diabetes drug prescriptions were dispensed, rising to 35 …
The Keloid Scars of Slavery
Authors: Neha Jariwala, Jules B. Lipoff
Journal: JAMA Dermatology (2016)

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Survival Comparability Between Thalassemia Major Versus Thalassemia Intermedia
Authors: Angela Vitrano, Giuseppina Calvaruso, Eliana Lai, Grazia Colletta, Alessandra Quota, Calogera Gerardi, Luciana Concetta Rigoli, Liana Cuccia, Francesco Gagliardotto, Aldo Filosa, Vincenzo Caruso, Crocetta Argento, Saveria Campisi, Michele Rizzo, Carmelo Fidone, Paolo Rigano, Massimiliano Sacco, Alessia Pepe, Rosario Di Maggio, Lorella Pitrolo, Aurelio Maggio
Journal: Blood (2015)