tbuckley/cabot-search huggingface dataset:
A Multicenter Phase I Study Evaluating Dual PI3K and BRAF Inhibition with PX-866 and Vemurafenib in Patients with Advanced BRAF V600–Mutant Solid Tumors
Authors: Clinton Yam, Xiaowei Xu, Michael A. Davies, Phyllis A. Gimotty, Jennifer J.D. Morrissette, Michael T. Tetzlaff, Khalida M. Wani, Shujing Liu, Wanleng Deng, Meghan Buckley, Jianhua Zhao, Ravi K. Amaravadi, Naomi B. Haas, Ragini R. Kudchadkar, Anna C. Pavlick, Jeffrey A. Sosman, Hussein Tawbi, Luke Walker, Lynn M. Schuchter, Giorgos C. Karakousis, Tara C. Gangadhar
Journal: Clinical Cancer Research (2017)

Purpose: The objectives of the study were to evaluate the safety of daily oral PX-866 in combination with twice daily vemurafenib and to identify potential predictive biomarkers for this novel combination.Experimental Design: We conducted a phase I, open-label, dose-escalation study in patients with advanced BRAF V600-mutant solid tumors. PX-866 was administered on a continuous schedule in combination with vemurafenib. Patients underwent a baseline and on-treatment biopsy after 1-week of PX-866 monotherapy for biomarker assessment.Results: Twenty-four patients were enrolled. The most common treatment-related adverse events were gastrointestinal side effects. One dose-limiting toxicity (DLT) of grade 3 rash and one DLT of grade 3 pancreatitis were observed in cohort 2 (PX-866 6 mg daily; vemurafenib 960 mg twice daily) and cohort 3 (PX-866 8 mg daily; vemurafenib 960 mg twice daily), respectively. Of 23 response-evaluable patients, seven had confirmed partial responses (PR), 10 had stable disease, and six had disease progression. Decreases in intratumoral pAKT expression were observed following treatment with PX-866. Patients who achieved PRs had higher rates of PTEN loss by IHC (80% vs. 58%) and pathogenic PTEN mutations and/or deletions (57% vs. 25%). Two patients with durable PRs had an increase in intratumoral CD8+ T-cell infiltration following treatment with PX-866.Conclusions: PX-866 was well tolerated at its maximum tolerated single-agent dose when given in combination with a modified dose of vemurafenib (720 mg twice daily). Response to treatment appeared to be associated with PTEN loss and treatment with PX-866 seemed to increase CD8+ T-cell infiltration in some patients. Clin Cancer Res; 24(1); 22-32. ©2017 AACR.
Genetics of human susceptibility to active and latent tuberculosis: present knowledge and future perspectives
Authors: Laurent Abel, Jacques Fellay, David W Haas, Erwin Schurr, Geetha Srikrishna, Michael Urbanowski, Nimisha Chaturvedi, Sudha Srinivasan, Daniel H Johnson, William R Bishai
Journal: The Lancet Infectious Diseases (2017)
Rede europeia de vigilância serológica
Authors: K Osborne, J Weinberg, E Miller
Journal: Eurosurveillance (1997)

O objectivo da vigilância serologica consiste em monitorizar os niveis de imunidade duma populacao, face a certas doencas, a fim de melhorar a qualidade das informacoes nas quais se baseiam as medidas de saude publica, como os programas de vacinacao. Em Inglaterra e no Pais de Gales, foi iniciada, em 1987, uma vigilância serologica para monitorizar os efeitos de um novo programa de vacinacao contra o sarampo, a parotidite e a rubeola (R O R) (1). A vigilância serologica demonstrou o seu valor pela identificacao dum aumento da proporcao de criancas em idade escolar susceptiveis ao sarampo. A partir desta observacao, tecnicas de modelacao matematica permitiram a predicao de uma importante epidemia de sarampo nestas criancas (2). Estas previsoes eram suportadas por evidencias epidemiologicas provenientes doutras fontes. Consequentemente, foi realizada uma campanha de vacinacao nacional, em 1994, para proteger estas criancas (3).
Experienced endoscopists improve Barrett’s surveillance outcomes independently of time allocation
Authors: John Schembri, Andrew Hopper, Mo Thoufeeq
Journal: Endoscopy (2017)

We read the article by Ooi et al. with interest, noting the positive outcomes when using extended time slots and specially trained endoscopists for surveillance of Barrett’s esophagus (BE) [1]. We conducted an audit over a 6-month period in 2015, which also demonstrated significantly better performance when BE surveillance was carried out by experienced endoscopists (previously unpublished data).
ACCF/ACR/AHA/NASCI/SCMR 2010 Expert Consensus Document on Cardiovascular Magnetic Resonance
Authors: W. Gregory Hundley, David A. Bluemke, J. Paul Finn, Scott D. Flamm, Mark A. Fogel, Matthias G. Friedrich, Vincent B. Ho, Michael Jerosch-Herold, Christopher M. Kramer, Warren J. Manning, Manesh Patel, Gerald M. Pohost, Arthur E. Stillman, Richard D. White, Pamela K. Woodard
Journal: Journal of the American College of Cardiology (2010)
Mast cells acquire MHCII from dendritic cells during skin inflammation
Authors: Jan Dudeck, Anna Medyukhina, Julia Fröbel, Carl-Magnus Svensson, Johanna Kotrba, Michael Gerlach, Ann-Christine Gradtke, Bernd Schröder, Stephan Speier, Marc Thilo Figge, Anne Dudeck
Journal: The Journal of Experimental Medicine (2017)

Mast cells (MCs) and dendritic cells (DCs) are essential innate sentinels populating host-environment interfaces. Using longitudinal intravital multiphoton microscopy of DCGFP/MCRFP reporter mice, we herein provide in vivo evidence that migratory DCs execute targeted cell-to-cell interactions with stationary MCs before leaving the inflamed skin to draining lymph nodes. During initial stages of skin inflammation, DCs dynamically scan MCs, whereas at a later stage, long-lasting interactions predominate. These innate-to-innate synapse-like contacts ultimately culminate in DC-to-MC molecule transfers including major histocompatibility complex class II (MHCII) proteins enabling subsequent ex vivo priming of allogeneic T cells with a specific cytokine signature. The extent of MHCII transfer to MCs correlates with their T cell priming efficiency. Importantly, preventing the cross talk by preceding DC depletion decreases MC antigen presenting capacity and T cell–driven inflammation. Consequently, we identify an innate intercellular communication arming resident MCs with key DC functions that might contribute to the acute defense potential during critical periods of migration-based DC absence.
PDGFRα polymorphisms influence risk of developing imatinib induced thrombocytopenia inchronic myeloid leukaemia patients
Authors: Sameer Ahmad Guru, Musadiq Ahmad Bhat, Abdul Rshid Mir, Imtiyaz Ahmad Najar, Mariyam Zuberi, Mamta Parveen Sumi, Naresh Kumar Gupta, Alpana Saxena
Journal: Annals of Oncology (2017)
Abstract 19438: Premature Ventricular Contractions and Cardiomyopathy: A Retrospective Cohort Study
Authors: Kevin Manocha, Surksha Sirichand, David Snipelisky, Siva Mulpuru, Suraj Kapa
Journal: Circulation (2016)

Introduction:  Premature Ventricular Contractions (PVC) are common with prevalence over 50% according to some studies. In the absence of an underlying cause and symptoms PVCs are considered benign and do not require therapy. Some have argued, however that increasing burden may be a risk factor for developing cardiomyopathy (CM). However, there are no studies looking at PVC burden and relationship to cardiomyopathy and the question remains unanswered.   Hypothesis:  Increased frequency of PVCs is associated with a higher risk of CM.   Methods:  Using the Olmsted County database, 696 patients were identified. In these patients we studied the overall prevalence of CM as a function of PVC burden. We also evaluated the incidence of CM, change in left ventricular ejection fraction (EF) and change in left ventricular end diastolic dimension (LVEDD) as a function of PVC burden over time. This was done in a 104 patient subset with a holter study an echocardiogram within 100 days of the holter study and a subsequent echocardiogram at least 100 days after the first echocardiogram. Significant EF change was a drop of EF greater than at least 10% and a significant LVEDD increase was a LVEDD increase of at least 1cm.   Results:  In all comers, there was a significant difference in the PVC burden of patients with known CM vs those without a CM (7.23% vs 4.39%, p=.0044) regardless of the time between diagnosis of cardiomyopathy and holter study. In patients with serial echocardiograms: There was no difference in mean PVC burden between patients who had a significant EF decrease compared to patients who did not (2.9% vs 6.1%, p=.3695). There was also no difference in the PVC burden between patients who had a significant LVEDD increase vs those without (4.3% vs 7.5%, p=.0892). In patients with >10% PVC burden, there was no difference in the mean change in EF (2.4% vs -.7%, p=.2145) or in mean change in LVEDD (-1.50 cm vs .14 cm, p=.1703) compared to patients w/ less than 10% PVC burden. 1/22 patients with PVC burden >10% had a 10% EF drop compared to 6/82 patients with PVC burden    Conclusions:  PVC burden is not directly related to significant EF or LVEDD changes and thus should not be targeted for treatment if they are otherwise asymptomatic and healthy.
The BRONCH‐AHF study: effects on short‐term outcome of nebulized bronchodilators in emergency department patients diagnosed with acute heart failure
Authors: Òscar Miró, Josep Tost, Víctor Gil, Francisco Javier Martín‐Sánchez, Pere Llorens, Pablo Herrero, Alexandre Mebazaa, Veli‐Pekka Harjola, José Ríos, Javier Marco‐Hernández, Sean P. Collins, W. Frank Peacock, Judd E. Hollander, María T. Lorca, Javier Jacob
Journal: European Journal of Heart Failure (2017)
TCT-393 Latin America Telemedicine Infarct Network (LATIN) - Telemedicine + STEMI Systems of Care to Hugely Expand Access to AMI Care in Emerging Countries
Authors: Sameer Mehta, Roberto Botelho, Francisco Fernandez, Marco Perin, Cesar Dusilek, Rodolfo Cardoso, Juan Carlos Perez Alva, Marco Alcocer-Gamba, Daniel Rodriguez, Isaac Yepes, Mario Torres
Journal: Journal of the American College of Cardiology (2017)
Subnotificação da doença do legionário em França: caso para uma vigilância mais activa
Authors: A Infuso, B Hubert, J Etienne
Journal: Eurosurveillance (1998)

A doenca do legionario e transmitida por inalacao de aerossois de agua infectada com Legionella spp. Estas bacterias encontram-se, frequentemente em reservatorios de agua construidos pelo homem e crescem optimamente em agua quente. Os sistemas de distribuicao de agua quente e as torres de arrefecimento do ar condicionado sao, frequentemente, identificadas como fontes de infeccao.
GLIS3 is indispensable for TSH/TSHR-dependent thyroid hormone biosynthesis and follicular cell proliferation
Authors: Hong Soon Kang, Dhirendra Kumar, Grace Liao, Kristin Lichti-Kaiser, Kevin Gerrish, Xiao-Hui Liao, Samuel Refetoff, Raja Jothi, Anton M. Jetten
Journal: Journal of Clinical Investigation (2017)

Deficiency in Krüppel-like zinc finger transcription factor GLI-similar 3 (GLIS3) in humans is associated with the development of congenital hypothyroidism. However, the functions of GLIS3 in the thyroid gland and the mechanism by which GLIS3 dysfunction causes hypothyroidism are unknown. In the current study, we demonstrate that GLIS3 acts downstream of thyroid-stimulating hormone (TSH) and TSH receptor (TSHR) and is indispensable for TSH/TSHR-mediated proliferation of thyroid follicular cells and biosynthesis of thyroid hormone. Using ChIP-Seq and promoter analysis, we demonstrate that GLIS3 is critical for the transcriptional activation of several genes required for thyroid hormone biosynthesis, including the iodide transporters Nis and Pds, both of which showed enhanced GLIS3 binding at their promoters. The repression of cell proliferation of GLIS3-deficient thyroid follicular cells was due to the inhibition of TSH-mediated activation of the mTOR complex 1/ribosomal protein S6 (mTORC1/RPS6) pathway as well as the reduced expression of several cell division-related genes regulated directly by GLIS3. Consequently, GLIS3 deficiency in a murine model prevented the development of goiter as well as the induction of inflammatory and fibrotic genes during chronic elevation of circulating TSH. Our study identifies GLIS3 as a key regulator of TSH/TSHR-mediated thyroid hormone biosynthesis and proliferation of thyroid follicular cells and uncovers a mechanism by which GLIS3 deficiency causes neonatal hypothyroidism and prevents goiter development.
TCT-28 A New Optical Coherence Tomography-Based Calcium Scoring System to Predict Stent Underexpansion
Authors: Akiko Fujino, Gary Mintz, Mitsuaki Matsumura, Myong Hwa Yamamoto, Cheolmin Lee, Masahiro Hoshino, Eisuke Usui, Yoshihisa Kanaji, Tadashi Murai, Taishi Yonetsu, Allen Jeremias, Ziad Ali, Fernando Sosa, Elizabeth Haag, Jeffrey Moses, Richard Shlofmitz, Tsunekazu Kakuta, Akiko Maehara
Journal: Journal of the American College of Cardiology (2017)
Three-Year Outcomes With the Absorb Bioresorbable Scaffold
Authors: Ziad A. Ali, Runlin Gao, Takeshi Kimura, Yoshinobu Onuma, Dean J. Kereiakes, Stephen G. Ellis, Bernard Chevalier, Minh-thien Vu, Zhen Zhang, Charles A. Simonton, Patrick W. Serruys, Gregg W. Stone
Journal: Circulation (2017)

Background: The Absorb bioresorbable vascular scaffold (BVS) completely resorbs within 3 years after coronary artery implantation. The safety and effectiveness of BVS through this critical 3-year period have not been characterized. Methods: We performed an individual-patient-data pooled meta-analysis of the 4 randomized ABSORB trials in which 3389 patients with coronary artery disease were randomly assigned to everolimus-eluting Absorb BVS (n=2164) or cobalt-chromium everolimus-eluting stents (n=1225). The primary efficacy outcome measure was target lesion failure (cardiac mortality, target vessel myocardial infarction, or ischemia-driven target lesion revascularization), and the primary safety outcome measure was device thrombosis. Results: BVS compared with cobalt-chromium everolimus-eluting stents resulted in higher 3-year rates of target lesion failure (11.7% versus 8.1%; risk ratio [RR], 1.38; 95% confidence interval [CI], 1.10–1.73; P =0.006), driven by greater target vessel myocardial infarction (7.8% versus 4.2%; RR, 1.72; 95% CI, 1.26–2.35; P =0.0006) and ischemia-driven target lesion revascularization (6.6% versus 4.4%; RR, 1.44; 95% CI, 1.05–1.98; P =0.02), with comparable cardiac mortality (1.1% versus 1.1%; RR, 0.93; 95% CI, 0.47–1.88; P =0.85). Device thrombosis rates through 3 years were also higher with BVS (2.4% versus 0.6%; RR, 3.71; 95% CI, 1.70–8.11; P =0.001). Between 1 and 3 years, target lesion failure rates (6.1% versus 3.9%; P =0.02) and device thrombosis rates (1.1% versus 0.0%; P &lt;0.0001) were higher with BVS than cobalt-chromium everolimus-eluting stents. Conclusions: In the present individual-patient-data pooled meta-analysis of the ABSORB trials, BVS was associated with increased rates of target lesion failure and device thrombosis between 1 and 3 years and cumulatively through 3 years of follow-up compared with everolimus-eluting stents. Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifiers: NCT01751906, NCT01844284, NCT01923740, and NCT01425281.
Abstract 19054: Yap Plays a Crucial Role in the Development of Cardiomyopathy in Lysosomal Storage Diseases
Authors: Shohei Ikeda, Akihiro Shirakabe, Peiyong Zhai, Junichi Sadoshima
Journal: Circulation (2016)

Lysosomal storage diseases (LSDs) cause severe cardiomyopathy. However, there is currently no effective treatment. Rag proteins play a critical role in regulating lysosomal functions. Muscle-specific deletion of RagA and RagB (RagA/B) suppresses autophagy and induces cardiomyopathy reminiscent of LSDs. Here, we aimed to investigate the molecular mechanism of cardiomyopathy in RagA/B knockout (KO) mice. We generated cardiac-specific RagA/BKO (RagA/BcKO) mice using αMHC-Cre. Like the muscle-specific KO mice, RagA/BcKO mice showed prominent cardiac hypertrophy (CH) (heart weight (HW)/ tibial length (TL): 12.35 ± 0.41 vs. 7.12 ± 0.15, p< 0.01) at 3 months of age. RagA/BcKO mice exhibited significantly more phospho-histone H3-positive cardiomyocytes (CMs) than control mice, suggesting that CM proliferation is stimulated. However, RagA/BcKO mice exhibited a significantly smaller fractional shortening (%FS: 23.0 ± 0.82 vs. 45.8 ± 1.06, p< 0.01) and significantly higher mortality than control mice (50% vs. 0%, p<...
Abstract 19802: Implantable Hemodynamic Monitoring Reduces Heart Failure Hospitalizations Due to Congestion Regardless of Perfusion Status
Authors: Alan B Miller, Edward M Gilbert, Eugene S Chung, Wayne C Levy, John R Teerlink, Peter Carson, Philip B Adamson, William T Abraham
Journal: Circulation (2015)

Introduction: Heart failure (HF) management guided by implantable hemodynamic monitoring systems reduces overall hospitalizations in NYHA Class III patients with a previous HF hospitalization. Hypothesis: Hemodynamic monitoring may reduce hospitalizations with accompanying low output status, as well as those resulting primarily from congestion. Methods: The CHAMPION Trial enrolled 550 NYHA Class III patients and randomly assigned them to a treatment group who were managed by hemodynamic monitoring using a permanently implanted pulmonary artery (PA) MEMS-based sensor or to a control group who were managed by standard clinical assessments (MEMS-sensors were implanted, but the uploaded pressures were not available to investigators). The primary endpoints were the comparison of HF hospitalization rates between the treatment and control groups assessed after 6 and 17 months of randomized follow-up. The blinded Clinical Events Committee prospectively adjudicated each HF hospitalization based on documented clinical hemodynamic characteristics: (1) well perfused/congested, (2) poorly perfused/congested or (3) poorly perfused without congestion. Group 3 events were rare and not different between groups. Results: Patients in the treatment group had fewer hospitalizations overall (182 hospitalizations, rate 0.46/patient/year treatment vs. 279 hospitalizations, rate 0.68/patient/year control; (HR 0.67 CI (0.55-0.80), p&lt;0.001). The majority of hospitalizations fit the perfused/congested profile, and were decreased in the treatment group compared with control (138 vs. 224 hospitalizations, HR 0.62, CI 0.50-0.77, p&lt;0.001). Poorly perfused/congested events were similarly reduced in the treatment group compared with control (29 vs. 44 hospitalizations, HR 0.63, CI 0.39-1.01, p=0.05). Conclusions: Compared to standard clinical assessments, HF managed with implantable hemodynamic monitoring results in significant reductions in heart failure hospitalization regardless of perfusion status.
TCT-558 Impact of an electrophysiology study guided PPM implantation strategy after TAVR
Authors: Toby Rogers, Athanasios Thomaides, Arie Steinvil, Edward Koifman, Michael Lipinski, M Chadi Alraies, Kyle Buchanan, Petros Okubagzi, Rebecca Torguson, Itsik Ben-Dor, Augusto Pichard, Lowell Satler, Ron Waksman
Journal: Journal of the American College of Cardiology (2017)
Multi-probe droplet digital PCR increased the detection efficiency of plasma EGFR exon 19 deletion mutation
Authors: Satoru Kitazono, Kazuko Sakai, Junji Koyama, Ryo Ariyasu, Shingo Nishikawa, Noriko Yanagitani, Atsushi Horiike, Makoto Nishio, Kazuto Nishio
Journal: Annals of Oncology (2017)
SmiNet-2 : descripción de un sistema de vigilancia por Internet de enfermedades transmisibles en Suecia
Authors: P Rolfhamre, A Janson, M Arneborn, K Ekdahl
Journal: Eurosurveillance (2006)

Los sistemas electronicos de vigilancia de enfermedades transmisibles mejoran la calidad de la vigilancia pues simplifican las notificaciones, perfeccionan la exhaustividad y aceleran el proceso. En este articulo, describimos los principios y tecnologias de SmiNet-2, el nuevo sistema regional y nacional de vigilancia de enfermedades transmisibles en Suecia. Con ese sistema, la notificacion puede ser hecha por los medicos (por medio de un formulario en la red) o por los laboratorios (directamente por el sistema de datos de laboratorios) usando Internet. Con un numero de identificacion personal unico, SmiNet-2 fusiona automaticamente las declaraciones clinicas y de laboratorio con los registros de casos. Los usuarios autorizados, a nivel nacional y regional, utilizan un servidor central comun que contiene todas las declaraciones y registros de casos. Ademas, SmiNet-2 tiene servidores a nivel provincial, con herramientas utiles para las investigaciones de brotes, la busqueda de contactos y el manejo de casos. 
SmiNet-2 se inicio en Septiembre de 2004. Las provincias reciben hasta el 90% de todas notificaciones electronicamente. Durante el primer ano, SmiNet-2 recibio 54.980 notificaciones clinicas y 32.765 declaraciones de laboratorios, que generaron 58.891 registros de casos. 
Dado que la mayoria de los medicos en Suecia acceden facilmente a Internet, se pueden generalizar las notificaciones por la web. Se puede prever que dentro de pocos anos, todas las notificaciones a SmiNet-2 se haran via Internet. En ese contexto, SmiNet-2, comparado con otros sistemas, presenta ciertas ventajas importantes : la rapidez en el flujo de datos (incluso al nivel nacional), la integracion de declaraciones clinicas y de laboratorios, y la capacidad de manejar mas de 50 enfermedades con formularios de notificacion a la medida en un sistema unico.
Abstract 15962: Age, Sex, and Race Differences in Statin Discontinuation and Side Effect Patterns. The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study
Authors: Lisandro D Colantonio, Rikki M Tanner, Keri L Monda, Ricardo Dent, Michael E Farkouh, Benjamin Taylor, Robert S Rosenson, Paul Muntner, Monika M Safford
Journal: Circulation (2016)

Introduction: Many people discontinue statin therapy, with side effects thought to be a common reason for discontinuation. Determining the frequency of, and the reasons for, statin discontinuation ...
TCT-17 Procedural characteristics, Outcomes and Complications in patients undergoing percutaneous coronary chronic total occlusion angioplasty: Pooled analysis from RECHARGE, Expert JCTO, EURO CTO, PROGRESS and OPEN CTO Registries
Authors: Sudhir Rathore, S.R.K. Seshasai, Alfredo Galassi, Marouane Boukhris, Etsuo Tsuchikane, Joseph Dens, Kambis Mashayekhi, J. Aaron Grantham, Emmanouil Brilakis, Gerald Werner
Journal: Journal of the American College of Cardiology (2017)