tbuckley/cabot-search huggingface dataset:
A phase I study of bevacizumab in children with refractory solid tumors: A Children’s Oncology Group study
Authors: J. L. Glade Bender, P. C. Adamson, S. Baruchel, Y. Shaked, H. X. Chen, J. M. Reid, A. M. Ingle, S. M. Blaney, J. J. Kandel, D. J. Yamashiro
Journal: Journal of Clinical Oncology (2006)

9017 Background: Bevacizumab is a humanized monoclonal antibody targeting the vascular endothelial growth factor (VEGF-A) that has demonstrated significant growth inhibition in several pre-clinical models of pediatric solid tumors. However, the agent has never been tested in pediatric patients. Methods: A phase I dose escalation study in children with refractory solid tumors was conducted to define the dose limiting toxicities (DLTs), and to determine the pharmacokinetics (PK) and recommended phase II dose of bevacizumab administered by IV infusion every 2 weeks in 28-day cycles. Cohorts were enrolled at dose levels of 5, 10, and 15 mg/kg; the final dose level was expanded to include at least 3 children &lt;6 years of age. Serial blood samples were collected for PK, plasma VEGF concentration, and circulating mature and progenitor endothelial cells (CECs/CEPs). Results: 20 patients (10 male), median age 13 yrs (range 1–21), were enrolled at dose levels 5 (n=3), 10 (n=3), and 15 (n=14) mg/kg. 18 patients were fully evaluable for toxicity (one withdrew consent prior to treatment and the second was removed for rapid disease progression). A total of 67 cycles were administered with a median of 3 per patient (range 1–16). Treatment was well tolerated and no DLTs were observed. Only one grade 3 toxicity, lymphopenia, was attributed to drug. Non-dose limiting, grade 1–2 toxicities included infusional reaction (n=3), rash (n=3), mucositis (n=2), and proteinuria (n=3). There was no hypertension, hemorrhage or thrombosis reported. There were no partial or complete responses; 3 pts with Ewings and 2 pts with soft tissue sarcoma had disease stabilization for &gt; 3 months. The serum exposure to bevacizumab as measured by AUC appeared to increase in proportion to dose. The median clearance of bevacizumab was 4.1 ml/day/kg (range 3.2–15.9), and the median T 1/2 was 11.8 days (range 3.9–14.6). In some patients, a rapid rate of rise in plasma VEGF, increase in mature CECs or decrease in CEPs was observed. Conclusion: Bevacizumab at doses up to 15mg/kg every two weeks is well tolerated in children with solid tumors. No significant financial relationships to disclose.
Balanced Crystalloids versus Saline in the Intensive Care Unit. The SALT Randomized Trial
Authors: Matthew W. Semler, Jonathan P. Wanderer, Jesse M. Ehrenfeld, Joanna L. Stollings, Wesley H. Self, Edward D. Siew, Li Wang, Daniel W. Byrne, Andrew D. Shaw, Gordon R. Bernard, Todd W. Rice, Gordon R. Bernard, Matthew W. Semler, Michael J. Noto, Todd W. Rice, Daniel W. Byrne, Henry J. Domenico, Li Wang, Jonathan P. Wanderer, Jesse M. Ehrenfeld, Andrew D. Shaw, Antonio Hernandez, Avinash B. Kumar, Wesley H. Self, Edward D. Siew, Debra F. Dunlap, Joanna L. Stollings, Mark Sullivan, Molly Knostman, David P. Mulherin, Fred R. Hargrove, David R. Janz, Seth Strawbridge
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Saline is the intravenous fluid most commonly administered to critically ill adults, but it may be associated with acute kidney injury and death. Whether use of balanced crystalloids rather than saline affects patient outcomes remains unknown.To pilot a cluster-randomized, multiple-crossover trial using software tools within the electronic health record to compare saline to balanced crystalloids.This was a cluster-randomized, multiple-crossover trial among 974 adults admitted to a tertiary medical intensive care unit from February 3, 2015 to May 31, 2015. The intravenous crystalloid used in the unit alternated monthly between saline (0.9% sodium chloride) and balanced crystalloids (lactated Ringer's solution or Plasma-Lyte A). Enrollment, fluid delivery, and data collection were performed using software tools within the electronic health record. The primary outcome was the difference between study groups in the proportion of isotonic crystalloid administered that was saline. The secondary outcome was major adverse kidney events within 30 days (MAKE30), a composite of death, dialysis, or persistent renal dysfunction.Patients assigned to saline (n = 454) and balanced crystalloids (n = 520) were similar at baseline and received similar volumes of crystalloid by 30 days (median [interquartile range]: 1,424 ml [500-3,377] vs. 1,617 ml [500-3,628]; P = 0.40). Saline made up a larger proportion of the isotonic crystalloid given in the saline group than in the balanced crystalloid group (91% vs. 21%; P < 0.001). MAKE30 did not differ between groups (24.7% vs. 24.6%; P = 0.98).An electronic health record-embedded, cluster-randomized, multiple-crossover trial comparing saline with balanced crystalloids can produce well-balanced study groups and separation in crystalloid receipt. Clinical trial registered with www.clinicaltrials.gov (NCT 02345486).
Zika virus is set to spread through Asia, WHO says
Authors: Owen Dyer
Journal: BMJ (2016)

Zika virus infection is “highly likely” to continue spreading through Asia, the World Health Organization predicted this week, as evidence grows that babies infected in the womb show a constellation of abnormalities, not just microcephaly.

A six month follow-up of 11 babies born to mothers diagnosed with the Zika virus in Brazil, published in JAMA Neurology , found a range of anomalies in addition to small head circumference. Amilcar Tanuri, of the Universidade Federal do Rio de Janeiro, Brazil, and coauthors have suggested naming the condition “congenital Zika syndrome.”1

Three …
GW26-e1582 The Relation between Glycosylated Hemoglobin and Severity of Coronary Artery Lesions in Patients with Coronary Heart Disease and Type 2 Diabetes Mellitus
Authors: Jianrui Zheng, Zhenda Zheng, Xing Shui, Dinghui Liu, Zheqi Wen, Chen Lin
Journal: Journal of the American College of Cardiology (2015)
TCT-145 Rheolytic Thrombectomy for Acute Myocardial Infarction Complicated by Cardiogenic Shock
Authors: Ruben Vergara, Renato Valenti, Angela Migliorini, Guido Parodi, Roberto Rondine, Maria Grazia De gregorio, Eleonora Gabrielli, Elena De Vito, Sofia Morini, David Antoniucci
Journal: Journal of the American College of Cardiology (2016)
TCT-601 Serial Optical coherence tomography assessment of natural history of silent plaque rupture
Authors: Teruyoshi Kume, Ryotaro Yamada, Kenzo Fukuhara, Terumasa Koyama, Yutaka Goryo, Hiroshi Okamoto, Yusuke Kobayashi, Yoji Neishi, Shiro Uemura
Journal: Journal of the American College of Cardiology (2016)
TCT-301 Outcomes of Percutaneous Coronary Intervention in Chronic Total Occlusions Caused by In-Stent Restenosis: Insights from a U.S. Multicenter Registry
Authors: Aya Alame, Dimitri Karmpaliotis, Khaldoon Alaswad, Farouc Jaffer, Robert Yeh, R. Michael Wyman, Mitul Patel, John Bahadorani, William Lombardi, J. Aaron Grantham, David Kandzari, Nicholas Lembo, Jeffrey Moses, Ajay Kirtane, Catalin Toma, Anthony Doing, James Choi, Barry Uretsky, Judit Karacsonyi, Erica Resendes, Phuong-Khanh Nguyen-Trong, Jose Roberto Martinez-Parachini, Aris Karatasakis, Barbara Anna Danek, Bavana Rangan, Craig Thompson, Subhash Banerjee, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2016)
TCT-679 Diabetes and Clinical Outcomes in Intermediate Risk Patients Randomized to Transcatheter Versus Surgical Aortic Valve Replacement: An Analysis of the PARTNER 2A Trial
Authors: Brian Lindman, Yigal Abramowitz, Philippe Pibarot, Nishath Quader, Hersh Maniar, Alan Zajarias, Suzanne Arnold, Rebecca Hahn, Sammy Elmariah, Rakesh Suri, Torsten Vahl, Lars Svensson, Vinod Thourani, Claire Litherland, Maria Alu, Martin Leon, Raj Makkar
Journal: Journal of the American College of Cardiology (2016)
CBIO-24GLIOBLASTOMA MULTIFORME CELLS ARE ADDICTED TO THE ONCOGENIC SURVIVAL FACTOR BCL6
Authors: Melanie McConnell, Marie-Sophie Fabre, Nicole Jones, Matthew Rowe, Noelyn Hung, Ari Melnick, Tania Slatter
Journal: Neuro-Oncology (2015)

The reluctance of GBM cells to apoptose is the primary hurdle in drug and radiation-mediated killing, which suggests an overriding antiapoptotic mechanism in GBM mediates survival. A prime candidate for that survival factor is BCL6, a zinc finger transcription factor that prevents apoptosis in response to DNA damage. In maturation of normal lymphocytes, BCL6 expression allows cells to survive DNA breakage and recombination, the process used to generate genetic diversity in antibody and immune receptor genes. However, ectopic BCL6 expression in lymphoma, leukemia and breast cancer similarly bypasses death in response to DNA damage induced by therapy. BCL6 transcript was elevated in glioma compared to normal brain tissue, and expression increased with grade. Consistent with this, BCL6 protein was variably expressed in >60% of GBM specimens examined. We examined BCL6 expression and activity in a panel of GBM cell lines. A low basal level of BCL6 protein was present under normal growth conditions, and consistent with induction by DNA damage, was substantially increased by the genotoxic drugs doxorubicin, temozolomide and ionising radiation, both in vitro and in an intra-cranial tumour model. Co-immunoprecipitation showed that BCL6 was associated with its co-repressors SMRT and NCOR in GBM cell lines, and a BCL6 reporter assay indicated that BCL6 had transcriptional repression activity. Inhibition of BCL6 activity by either siRNA, a specific peptide mimetic inhibitor, or by over-expression of dominant negative BCL6 notably decreased viability, and reduced the clonogenic potential, of GBM cells. Induction of BCL6 in the presence of inhibitors restored the clonogenic activity. Finally, GBM cells with a BCL6 somatic knock-out were non-viable, dying within 48 hours of genome editing. Together, these data imply that BCL6 is essential for on-going survival of GBM cells in vitro, and that DNA damage induced by therapy upregulates the oncogene, further facilitating the addiction.
TCT-509 Utilisation of 320-Slice Multidetector CT in Assessing the Aortic Root Geometry in Bicuspid Aortic Valves and its Implications for Transcatheter Aortic Valve Replacement
Authors: Hashrul Rashid, Ameera Amiruddin, Satish Ramkumar, Kawa Haji, Simon Steele, Nitesh Nerlekar, Ian Meredith, Arthur Nasis, Philip Mottram, Stuart Moir
Journal: Journal of the American College of Cardiology (2016)
<i>Retracted:</i> Redox‐dependent regulation of hepatocyte absent in melanoma 2 inflammasome activation in sterile liver injury in mice
Authors: Qian Sun, Patricia Loughran, Richard Shapiro, Indira H. Shrivastava, Daniel J. Antoine, Tunliang Li, Zhengzheng Yan, Jie Fan, Timothy R. Billiar, Melanie J. Scott
Journal: Hepatology (2016)

Sterile liver inflammation, such as liver ischemia-reperfusion, hemorrhagic shock after trauma, and drug-induced liver injury, is initiated and regulated by endogenous mediators including DNA and reactive oxygen species. Here, we identify a mechanism for redox-mediated regulation of absent in melanoma 2 (AIM2) inflammasome activation in hepatocytes after redox stress in mice, which occurs through interaction with cytosolic high mobility group box 1 (HMGB1). We show that in liver during hemorrhagic shock in mice and in hepatocytes after hypoxia with reoxygenation, cytosolic HMGB1 associates with AIM2 and is required for activation of caspase-1 in response to cytosolic DNA. Activation of caspase-1 through AIM2 leads to subsequent hepatoprotective responses such as autophagy. HMGB1 binds to AIM2 at a non-DNA-binding site on the hematopoietic interferon-inducible nuclear antigen domain of AIM2 to facilitate inflammasome and caspase-1 activation in hepatocytes. Furthermore, binding of HMGB1 to AIM2 is stronger with fully reduced all-thiol HMGB1 than with partially oxidized disulfide-HMGB1, and binding strength corresponds to caspase-1 activation. These data suggest that HMGB1 redox status regulates AIM2 inflammasome activation. Conclusion: These findings suggest a novel and important mechanism for regulation of AIM2 inflammasome activation in hepatocytes during redox stress and may suggest broader implications for how this and other inflammasomes are activated and how their activation is regulated during cell stress, as well as the mechanisms of inflammasome regulation in nonimmune cell types. (Hepatology 2017;65:253-268).
High Fasting Plasma Glucose, Diabetes, and Its Risk Factors in the Eastern Mediterranean Region, 1990–2013: Findings From the Global Burden of Disease Study 2013
Authors: Maziar Moradi-Lakeh, Mohammad Hossein Forouzanfar, Charbel El Bcheraoui, Farah Daoud, Ashkan Afshin, Sarah Wulf Hanson, Theo Vos, Mohsen Naghavi, Christopher J.L. Murray, Ali H. Mokdad
Journal: Diabetes Care (2016)

OBJECTIVE The prevalence of diabetes in the Eastern Mediterranean Region (EMR) is among the highest in the world. We used findings from the Global Burden of Disease 2013 study to calculate the burden of diabetes in the EMR. RESEARCH DESIGN AND METHODS The burden of diabetes and burden attributable to high fasting plasma glucose (HFPG) were calculated for each of the 22 countries in the EMR between 1990 and 2013. A systematic analysis was performed on mortality and morbidity data to estimate prevalence, deaths, and disability-adjusted life years (DALYs). RESULTS The diabetes death rate increased by 60.7%, from 12.1 per 100,000 population (95% uncertainty interval [UI]: 11.2–13.2) in 1990 to 19.5 per 100,000 population (95% UI: 17.4–21.5) in 2013. The diabetes DALY rate increased from 589.9 per 100,000 (95% UI: 498.0–698.0) in 1990 to 883.5 per 100,000 population (95% UI: 732.2–1,051.5) in 2013. In 2013, HFPG accounted for 4.9% (95% UI: 4.4–5.3) of DALYs from all causes. Total DALYs from diabetes increased by 148.6% during 1990–2013; population growth accounted for a 62.9% increase, and aging and increase in age-specific DALY rates accounted for 31.8% and 53.9%, respectively. CONCLUSIONS Our findings show that diabetes causes a major burden in the EMR, which is increasing. Aging and population growth do not fully explain this increase in the diabetes burden. Programs and policies are urgently needed to reduce risk factors for diabetes, increase awareness of the disease, and improve diagnosis and control of diabetes to reduce its burden.
Electric Plasma–generated Nitric Oxide: Hemodynamic Effects in Patients with Pulmonary Hypertension
Authors: Lorenzo Berra, Josanna Rodriguez-Lopez, Emanuele Rezoagli, Binglan Yu, Daniel F. Fisher, Marc J. Semigran, Donald B. Bloch, Richard N. Channick, Warren M. Zapol
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

observation provides potential mechanisms for reverse triggering that were previously unknown, such as the role of thoracic or diaphragmatic stretch receptors, a spinal reflex phenomenon, or the existence of a more complex spinal pattern generator.
PS01.45: Intraoperative Blood Loss is an Independent Predictor of Poor Disease Free Survival for Patients Undergoing VATS Lobectomy for Lung Cancer
Authors: M. Rahouma, Mohamed Kamel, Galal Ghaly, Abu Nasar, Sebron Harrison, Brednon Stiles, Nasser Altorki, Jeffrey L. Port
Journal: Journal of Thoracic Oncology (2016)
Potential Benefit of Low-Dose Candesartan in Trastuzumab-Induced Cardiotoxic Effects
Authors: Seongseok Yun, Rostam Khoubyari, Ivo Abraham
Journal: JAMA Oncology (2016)

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TCT-682 Predictors and Impact of Cerebrovascular Events 4 Years after Transcatheter Aortic Valve Implantation
Authors: David Jochheim, Magda Zadrozny, Tobias Mir Sadry, Hans Theiss, Florian Schwarz, Axel Bauer, Alexander Khandoga, Moritz Baquet, Philipp Lange, Jörg Hausleiter, Steffen Massberg, Julinda Mehilli
Journal: Journal of the American College of Cardiology (2016)
Roadmap for tuberculosis elimination in Latin American and Caribbean countries: a strategic alliance
Authors: Adrian Rendon, Zhenia Fuentes, Carlos A. Torres-Duque, Mirtha del Granado, Jorge Victoria, Raquel Duarte, Giovanni Battista Migliori
Journal: European Respiratory Journal (2016)

On July 4–5, 2016, representatives of the Asociación Latinoamericana de Tórax (ALAT), the European Respiratory Society (ERS) and of the Panamerican Health Organization (PAHO) met in Santiago de Chile to attend the VIII Regional Meeting of American Low Tuberculosis Incidence Countries. This meeting took place in connection with the 2016 ALAT Congress. Among the meeting attendees there were managers of national tuberculosis (TB) programmes and pulmonologists belonging to the ALAT Tuberculosis Dept. Joint ALAT/ERS/PAHO strategic alliance develops roadmap for TB elimination in Latin American and Caribbean countries <http://ow.ly/RbHH3034gY6> The Authors with to thank Lia D'Ambrosio and Rosella Centis (WHO Collaborating Centre for TB and Lung Disease, Tradate, Italy) for their technical support in finalising the manuscript. In addition, the authors thank the participants of first meeting of the GILA-TB as part of the ERS/ALAT LATSINTB Project (Adriana Maria Montoya Salazar, Colombia; Alfredo Cruz Lagunas, Mexico; Ana Putruelle, Argentina; Carlos Awad García, Colombia; Carlos Peña Mantinetti, Chile; Cartos Torres, Colombia; Domingo Palmero, Argentina; Edilberto Gonzalez Ochoa, Cuba; Edwin Herrera Flores, Peru; Gabriela Manonelles, Argentina; Giovanni Battista Migliori, Italy; Joaquin Zúñiga, Mexico; Kareen Suarez, Chile; Adrian Rendon, Mexico; Marcela Muñoz, Mexico; Margareth Dalcolmo, Brazil; Mario Chavez, Chile; Miguel Angel Salazar, Mexico; Mónica Sanchez, Chile; Nelly Cavieres, Chile; Raquel Duarte, Portugal; Roberto Accinelli Tanaka, Lima; Sandra Ariza Matiz, Colombia; Selene Manga, Peru; Tania Herrera, Chile; Tulio Torres, Guatemala; and Zhenia Fuentes, Venezuela) and the VIII Reunión Regional de Países de Baja Incidencia de Tuberculosis, Las Americas (Adrian Rendon, México; Adriana Maria Montoya Salazar, Colombia; Alvaro Díaz, Chile; Alvaro Yañez del Villar, Chile; Carlos Awad García, Colombia; Carlos A. Torres Duque, Colombia; Cecilia Coitinho Azevedo, Uruguay; Chris Archibald, Canada; Edilberto González Ochoa, Cuba; Ernesto Moreno Naranjo, Colombia; Fabiola Arias, Chile; Getahun Gebre Haileyesus, Switzerland; Giovanni Battista Migliori, Italy; Gonzalo Solis, Chile; Jorge Victoria, Panama; Jorge Rodríguez De Marco, Uruguay; José Raúl de Armas Fernández, Cuba; Karla Kohan, Chile; Marcela Moreno Lunes, Chile; Marcelo Vila, Argentina; Marcos Gallardo, Chile; Mariela Contrera, Uruguay; Martha Angelica García Avilés, México; Miguel Salazar, Mexico; Mirtha Del Granado, USA; Paula Lasserra Echenique, Uruguay; Raquel Duarte Portugal; Raúl Diaz Rodríguez, Cuba; Roberto Del Aguila, Chile; Rosario Lepe Lepe, Chile; Sandra Ariza Matiz, Colombia; Tania Herrera, Chile; Zeidy Mata Azofeifa, Costa Rica; Zhenia Fuentes, Venezuela; and Zulema Torres Gaete, Chile).
TCT-106 Outcomes after Revascularization with Sirolimus-eluting and Birolimus-Eluting Stents with biodegradable polymer In Patients with Acute Coronary Syndromes. From the SORT OUT VII Trial
Authors: None christian oliver fallesen, Evald Christiansen, Hans Erik Bøtker, Bent Raungaard, Michael Maeng, Anders Junker, None lars jakobsen, Svend Eggert Jensen, Johnny Kahlert, Lisette Okkels Jensen
Journal: Journal of the American College of Cardiology (2016)
O113 : HLA DPB1 rs9277535 polymorphism strongly predicts HBsAg clearance in IFN treated genotype D HBeAg-negative patients with chronic hepatitis B
Authors: P. Lampertico, E. Galmozzi, F. Facchetti, C. Cheroni, F. Invernizzi, V. Valveri, R. Soffredini, M. Viganò, S. Abrignani, R. De Francesco, M. Colombo
Journal: Journal of Hepatology (2015)
ORAL01.01: A Prospective, Multi-Institutional Assessment of Four Assays for PD-L1 Expression in NSCLC by Immunohistochemistry
Authors: David Rimm, Gang Han, Janis M. Taube, Eunhee S. Yi, Julia A. Bridge, Douglas B. Flieder, Robert Homer, William W. West, Hong Wu, Anja C. Roden, Junya Fujimoto, Hui Yu, Robert Anders, Ashley Kowalewski, Christopher Rivard, Jamaal Rehman, Fred Hirsch, Ignacio I. Wistuba
Journal: Journal of Thoracic Oncology (2016)
TCT-566 Association Between Lesion Remodeling and Plaque Morphology Assessed By Intravascular Ultrasound and Optical Coherence Tomography
Authors: Mitsuaki Matsumura, Gary Mintz, WENBIN ZHANG, Yang Cao, Cheolmin Lee, Tsunekazu Kakuta, Akiko Maehara
Journal: Journal of the American College of Cardiology (2016)
TCT-77 Association of Residual Mitral Regurgitation after Transcatheter Aortic Valve Replacement with Readmission for Acute Heart Failure: An Analysis from PARTNER 1
Authors: John Petersen, Eugene H. Blackstone, Jeevanantham Rajeswaran, David Cohen, Pamela Douglas, Rebecca Hahn, Susheel Kodali, Lars Svensson, Martin Leon
Journal: Journal of the American College of Cardiology (2016)
ORAL01.03: CheckMate 012: Safety and Efficacy of First-Line Nivolumab and Ipilimumab in Advanced NSCLC
Authors: Scott J. Antonia, Scott N. Gettinger, Jonathan Goldman, Julie Brahmer, Hossein Borghaei, Laura Q. Chow, Neal E. Ready, David E. Gerber, Rosalyn Juergens, Frances Shepherd, Scott A. Laurie, Tina Young, William J. Geese, Shruti Agrawal, Xuemei Li, Matthew D. Hellmann
Journal: Journal of Thoracic Oncology (2016)
Constitutive B-Cell Maturation Antigen (BCMA) Activation In Human Multiple Myeloma Cells Promotes Myeloma Cell Growth and Survival In The Bone Marrow Microenvironment Via Upregulated MCL-1 and NFκB Signaling
Authors: Yu-Tzu Tai, Chirag Acharya, Mike Y Zhong, Michele Cea, Antonia Cagnetta, Paul G. Richardson, Nikhil C. Munshi, Kenneth C. Anderson
Journal: Blood (2013)