tbuckley/cabot-search huggingface dataset:
Bosutinib Versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: Results From the Randomized BFORE Trial
Authors: Jorge E. Cortes, Carlo Gambacorti-Passerini, Michael W. Deininger, Michael J. Mauro, Charles Chuah, Dong-Wook Kim, Irina Dyagil, Nataliia Glushko, Dragana Milojkovic, Philipp le Coutre, Valentin Garcia-Gutierrez, Laurence Reilly, Allison Jeynes-Ellis, Eric Leip, Nathalie Bardy-Bouxin, Andreas Hochhaus, Tim H. Brümmendorf
Journal: Journal of Clinical Oncology (2017)

Purpose Bosutinib is a potent dual SRC/ABL kinase inhibitor approved for adults with Philadelphia chromosome–positive chronic myeloid leukemia (CML) resistant and /or intolerant to prior therapy. We assessed the efficacy and safety of bosutinib versus imatinib for first-line treatment of chronic-phase CML. Methods In this ongoing, multinational, phase III study, 536 patients with newly diagnosed chronic-phase CML were randomly assigned 1:1 to receive 400 mg of bosutinib once daily (n = 268) or imatinib (n = 268). Per protocol, efficacy was assessed in patients who were Philadelphia chromosome–positive with typical (e13a2/e14a2) transcripts (bosutinib, n = 246; imatinib, n = 241). Patients with Philadelphia chromosome–negative–/ BCR-ABL1–positive status and those with unknown Philadelphia chromosome status and/or atypical BCR-ABL1 transcript type were excluded from this population. Results The major molecular response (MMR) rate at 12 months (primary end point) was significantly higher with bosutinib versus imatinib (47.2% v 36.9%, respectively; P = .02), as was complete cytogenetic response (CCyR) rate by 12 months (77.2% v 66.4%, respectively; P = .0075). Cumulative incidence was favorable with bosutinib (MMR: hazard ratio, 1.34; P = .0173; CCyR: hazard ratio, 1.38; P &lt; .001), with earlier response times. Four patients (1.6%) receiving bosutinib and six patients (2.5%) receiving imatinib experienced disease progression to accelerated/blast phase. Among treated patients, 22.0% of patients receiving bosutinib and 26.8% of patients receiving imatinib discontinued treatment, most commonly for drug-related toxicity (12.7% and 8.7%, respectively). Grade ≥ 3 diarrhea (7.8% v 0.8%) and increased ALT (19.0% v 1.5%) and AST (9.7% v 1.9%) levels were more common with bosutinib. Cardiac and vascular toxicities were uncommon. Conclusion Patients who received bosutinib had significantly higher rates of MMR and CCyR and achieved responses faster than those who received imatinib. Consistent with the known safety profile, GI events and transaminase elevations were more common with bosutinib. Results indicate bosutinib may be an effective first-line treatment for chronic-phase CML.
TCT-610 Direct Stenting Versus Pre-Stent Balloon Dilatation in Patients Treated with Orbital Atherectomy: An ORBIT II Sub-analysis
Authors: Evan Shlofmitz, Michael Lee, Brad Martinsen, Ann Behrens, Joseph Puma, Richard Shlofmitz, Jeffrey Chambers
Journal: Journal of the American College of Cardiology (2017)
Il progetto EUVAC-NET: creazione e funzionamento di un network comunitario di sorveglianza delle malattie prevenibili da vaccino
Authors: S Glismann, T Rønne, A E Tozzi
Journal: Eurosurveillance (2001)

Il network EUVAC-NET si occupa della sorveglianza epidemiologica e del controllo delle malattie prevenibili da vaccino. E' coordinato dallo Statens Serum Institut in Danimarca, in collaborazione con l'Istituto Superiore di Sanita in Italia. Le principali malattie bersaglio del network sono il morbillo e la pertosse. E' in programma una collaborazione con il Public Health Laboratory Service per il monitoraggio dell'Haemophilus influenzae b. Fanno parte dell'EUVAC-NET i paesi membri della Unione Europea, piu l'Islanda, la Norvegia e la Svizzera.
How Low to Go With Glucose, Cholesterol, and Blood Pressure in Primary Prevention of CVD
Authors: Kimberly N. Hong, Valentin Fuster, Robert S. Rosenson, Clive Rosendorff, Deepak L. Bhatt
Journal: Journal of the American College of Cardiology (2017)

Diabetes, hyperlipidemia, and hypertension are modifiable risk factors that predict cardiovascular disease events. The effect of these risk factors on incident cardiovascular disease increases with progressively higher levels of glucose, low-density lipoprotein cholesterol, and blood pressure. The thresholds for initiating treatment of these modifiable risk factors and the optimal goals of risk factor modification are a focus of primary prevention research. Although an aggressive approach is appealing, adverse events may occur, and potential physiological barriers may exist. This paper discusses primary prevention of coronary heart disease that may be achieved through modification of diabetes, hyperlipidemia, and hypertension by summarizing current guidelines and pertinent clinical trial data from intervention trials that included a primary prevention cohort.
TCT-540 Percutaneous Mitral Valve Repair: Refining Selection Criteria
Authors: Juliëtte Velu, Friso Kortlandt, Tom Hendriks, Remco Schurer, Ad van Boven, Ben Van Den Branden, Jan van der Heyden, Berto Bouma, Benno Rensing, Jan Baan
Journal: Journal of the American College of Cardiology (2017)
Progress in Childhood Vaccination Data in Immunization Information Systems — United States, 2013–2016
Authors: Neil Murthy, Loren Rodgers, Laura Pabst, Amy Parker Fiebelkorn, Terence Ng
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

In 2016, 55 jurisdictions in 49 states and six cities in the United States* used immunization information systems (IISs) to collect and manage immunization data and support vaccination providers and immunization programs. To monitor progress toward achieving IIS program goals, CDC surveys jurisdictions through an annual self-administered IIS Annual Report (IISAR). Data from the 2013-2016 IISARs were analyzed to assess progress made in four priority areas: 1) data completeness, 2) bidirectional exchange of data with electronic health record systems, 3) clinical decision support for immunizations, and 4) ability to generate childhood vaccination coverage estimates. IIS participation among children aged 4 months through 5 years increased from 90% in 2013 to 94% in 2016, and 33 jurisdictions reported ≥95% of children aged 4 months through 5 years participating in their IIS in 2016. Bidirectional messaging capacity in IISs increased from 25 jurisdictions in 2013 to 37 in 2016. In 2016, nearly all jurisdictions (52 of 55) could provide automated provider-level coverage reports, and 32 jurisdictions reported that their IISs could send vaccine forecasts to providers via Health Level 7 (HL7) messaging, up from 17 in 2013. Incremental progress was made in each area since 2013, but continued effort is needed to implement these critical functionalities among all IISs. Success in these priority areas, as defined by the IIS Functional Standards (1), bolsters clinicians' and public health practitioners' ability to attain high vaccination coverage in pediatric populations, and prepares IISs to develop more advanced functionalities to support state/local immunization services. Success in these priority areas also supports the achievement of federal immunization objectives, including the use of IISs as supplemental sampling frames for vaccination coverage surveys like the National Immunization Survey (NIS)-Child, reducing data collection costs, and supporting increased precision of state-level estimates.
Gonadotrophins and Ovarian Cancer Risk: Reply
Authors: Daniel Cramer, M.D.
Journal: JNCI Journal of the National Cancer Institute (1985)

Gonadotrophins and Ovarian Cancer Risk: Reply Get access Daniel Cramer, M.D. Daniel Cramer, M.D. Department of Obstetrics and Gynecology Brigham and Women's Hospital, Boston, MA 02115 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 75, Issue 1, July 1985, Pages 179–180, https://doi.org/10.1093/jnci/75.1.179 Published: 01 July 1985
Comparative epigenomics in the Brassicaceae reveals two evolutionarily conserved modes of PRC2-mediated gene regulation
Authors: Claudia Chica, Alexandra Louis, Hugues Roest Crollius, Vincent Colot, François Roudier
Journal: Genome biology (2017)

Polycomb Repressive Complexes 2 (PRC2) are multi-protein chromatin modifiers that are evolutionarily conserved among eukaryotes and play key roles in the regulation of gene expression, notably through the trimethylation of lysine 27 of histone H3 (H3K27me3). Although PRC2-mediated gene regulation has been studied in many organisms, few studies have explored in depth the evolutionary conservation of PRC2 targets.Here, we compare the H3K27me3 epigenomic profiles for the two closely related species Arabidopsis thaliana and Arabidopsis lyrata and the more distant species Arabis alpina, three Brassicaceae that diverged from each other within the past 24 million years. Using a robust set of gene orthologs present in the three species, we identify two classes of evolutionarily conserved PRC2 targets, which are characterized by either developmentally plastic or developmentally constrained H3K27me3 marking across species. Constrained H3K27me3 marking is associated with higher conservation of promoter sequence information content and higher nucleosome occupancy compared to plastic H3K27me3 marking. Moreover, gene orthologs with constrained H3K27me3 marking exhibit a higher degree of tissue specificity and tend to be involved in developmental functions, whereas gene orthologs with plastic H3K27me3 marking preferentially encode proteins associated with metabolism and stress responses. In addition, gene orthologs with constrained H3K27me3 marking are the predominant contributors to higher-order chromosome organization.Our findings indicate that developmentally plastic and constrained H3K27me3 marking define two evolutionarily conserved modes of PRC2-mediated gene regulation that are associated with distinct selective pressures operating at multiple scales, from DNA sequence to gene function and chromosome architecture.
Role of tumor suppressor p53 and micro-RNA interplay in multiple myeloma pathogenesis
Authors: Jahangir Abdi, Nasrin Rastgoo, Lihong Li, Wenming Chen, Hong Chang
Journal: Journal of Hematology & Oncology (2017)

The molecular mechanisms underlying dysregulated wild type (wt) p53 in multiple myeloma (MM) have been subjects of intense investigation for years. Indeed, correlation of rarely occurring TP53 gene mutations or deletions with adverse clinical outcomes in MM patients is strongly established, while in majority of cases wtp53 seems to be non-functional or dysregulated bearing a high clinical impact. Interestingly, findings from recent investigations show that micro-RNAs (miRNAs) may contribute to suppression of wtp53 in MM, as they are now known to function as key regulatory elements in the p53 network. This area is shedding new light on understanding the biologic effects of dysregulated p53 in MM pathogenesis especially drug resistance. miRNAs such as miR-125b (oncomiR) or miR-34a (tumor suppressor-miR) can be negative or positive regulators of wtp53 function, respectively, with specific effects on MM cell viability. On the other hand, our knowledge of miRNA interaction with mutant (mt) p53 in MM, which is rather related to disease progression and resistance to therapy, is limited which demands in-depth exploration. Here, we will put forward the current knowledge on miRNA-p53 interaction in MM and its role in MM pathogenesis including drug resistance. We will also highlight the pre-clinical approaches for therapeutic application of miRNAs targeting p53 pathway.
Actividad gripal heterogénea en Europa durante el invierno de 2002-2003
Authors: W J Paget, T J Meerhoff, H Rebelo de Andrade
Journal: Eurosurveillance (2003)

La actividad gripal en Europa vario segun el pais durante la temporada 2002-2003, tanto en intensidad de la actividad clinica como en los tipos y subtipos del virus en circulacion. En las regiones occidentales de Europa hubo predominio general de la gripe B (Portugal, Espana, Reino Unido e Irlanda), mientras que en las regiones central y oriental (Alemania, Italia, Dinamarca, Suiza, Polonia, Eslovenia, Eslovaquia y Paises Bajos) prevalecio la gripe A (H3N2). Varios paises experimentaron temporadas mixtas, primero con una actividad asociada a la gripe B seguida de la gripe A (Belgica, Francia y Espana). En general, los paises con predominio de la gripe B presentaron niveles de intensidad bajos (comparados con los datos historicos) (temporada leve) y periodos de actividad gripal mas prolongados, comparados con los de paises con predominio de la gripe A (H3N2). Varios paises, todos ellos con predominio de gripe A (H3N2), declararon niveles de intensidad elevados comparados con los datos historicos: Republica Checa, Dinamarca, Alemania y Polonia. En los seis paises que ofrecieron tasas de incidencia especificas por edad, las mas elevadas se observaron en personas de 0-14 anos. Las cepas del virus gripal en circulacion por Europa coincidian en gran medida con las cepas viricas de la vacuna antigripal. Al finalizar la temporada se declaro un numero reducido de aislamientos (A/Fujian/411/2002 (H3N2)-like) con una reaccion baja a los antisueros de la cepa vacunal. La composicion de la vacuna antigripal 2003-2004 es la misma que la de la temporada 2002-2003.
Phase II multicenter study of imatinib in patients with chemorefractory germ cell tumors that express c-kit.
Authors: JM Piulats, X Garcia del Muro, R Huddart, J Aparicio, L Paz-Ares, M Sanchez, D Olmos, M Garcia, JR Germa-Lluch
Journal: Cancer Research (2007)

2648  Background: Imatinib has shown activity in tumors that depends on c-kit or PDGFRα pathway for their tumorogenesis. Germ cell tumors, mostly seminomas, express c-kit. Furthermore some of these tumors carry activating mutations that may be relevant to their tumor induction and progression. The purpose of this study is to assess the activity and toxicity of imatinib in patients with cisplatin refractory germ cell tumors.  Methods: Patients with germ cell tumors in progression indicated by CT scan or tumor markers, following cisplatin, ifosfamide and paclitaxel containing regimens and having tumor expression of c-kit, assessed by immunohistochemistry,were eligible for this phase II trial. Imatinib was administered orally at a dose of 400 mg/day continuously. Planned sample size was 26 patients. At the same time c-kit inmunohistochemistry was assessed in a tissue array that include 98 patients with metastatic germ cell tumors with a hight representation as hight as 28% of chemorefractory patients. PDGFRα and PDGFRβ has been assessed in the same sample.  Results: From February/03 to February/05, 7 male patients were included into the study at 6 centres. The study was closed early due to the low rate of c-kit expression (  Conclusions: This study evaluates the efficacy of imatinib in patients with refractory germ cell tumors. To summarize, imatinib as a single agent at this dose has no activity in this subset of patients. This may be related to recent findings that showed that mutations seen in germ cell tumors use to be in the kinase domain and are less sensitive to imatinib blockade.
Predicting Response to Intravesical Bacillus Calmette-Guérin Immunotherapy: Are We There Yet? A Systematic Review
Authors: Ashish M. Kamat, Roger Li, Michael A. O’Donnell, Peter C. Black, Morgan Roupret, James W. Catto, Eva Comperat, Molly A. Ingersoll, Wim P. Witjes, David J. McConkey, J. Alfred Witjes
Journal: European Urology (2018)
Bypassing Troubles: Relation of Exhaustion, Viral Burden, and Inflammation to Depressive Symptoms After Cardiac Surgery
Authors: Pamela S Miller, Lorraine S Evangelista, Joyce Newman Giger, Otoniel Martinez-Maza, Teresita Corvera-Tindel, Lynn Doering
Journal: Circulation (2011)

CORE 2. EPIDEMIOLOGY AND PREVENTION OF CV DISEASE: PHYSIOLOGY, PHARMACOLOGY AND LIFESTYLE SESSION TITLE: FATIGUE AND CARDIAC PATIENTS: SICK AND TIRED Abstract 14769: Bypassing Troubles: Relation of Exhaustion, Viral Burden, and Inflammation to Depressive Symptoms After Cardiac Surgery Pamela S Miiier, Lorraine S Evangelista, Joyce Newman Giger, Otonlel Martinez-Maza, Teresita Corvera-Tindel and Lynn V Doering Published: November 22, 2011 Artlcle Info & Metrics eLetters ,,. Jump to Abstract Background: Inflammation is a mechanism by which depressive symptoms and vital exhaustion (VE) may confer increased risk of adverse cardiac outcomes. Objective: To elucidate the relationship of post- bypass {CABG) depressive symptoms to VE, immune-mediated inflammation and pathogen burden (PB), defined as cumulative seropositive exposure to infectious pathogens. Methods: In a secondary analysis of 42 patients {age 67.5 ± 12.6 years, 90.5% male, 66.7% Caucasian, nonsmokers, and without malignancy, autoimmune disease or infection), depressive symptoms (Patient Health Questionnaire-9 [PHQ-9]), VE (Maastricht Interview), CBC and lipids were assessed before and 4-8 weeks aft.er CABG. Immune markers (interleukin [IL]-6, IL-10, soluble intercellular adhesion molecule-1) and serum lgG antibodies (Herpes Simplex Virus-1 and -2, Cytomegalovirus, Epstein Barr Virus) were measured by ELISA. PB was defined as low {0-1 exposures), moderate {2-3 exposures) and high (4 exposures). Analyses included Mann- Whitney U test and logistic regression.
Vigilancia del paludismo en Italia: análisis de los datos correspondientes a 1986-1996 y datos provisionales para 1997
Authors: G Sabatinelli, G Majori
Journal: Eurosurveillance (1998)

Durante siglos, el paludismo fue endemico en las regiones italianas de grandes marismas. Las obras hidraulicas que se llevaron a cabo contribuyeron enormemente a reducir la transmision del paludismo, pero la enfermedad era aun frecuente al principio de la segunda guerra mundial en ciertas zonas de marismas situadas a menos de 800 metros por encima del nivel del mar y las perturbaciones caracteristicas de los tiempos de guerra causaron un marcado incremento en la transmision del paludismo.
Bioterrorismo: crimine e opportunità
Authors: D Byrne
Journal: Eurosurveillance (2001)

I attacchi terroristici senza precedenti avvenuti negli Stati Uniti (SU) hanno gettato ondate di panico sulle amministrazioni nazionali, che a livello di sanita pubblica sono normalmente piu abituate a combattere guerre di costi nell'area sanitaria che a coordinare la vigilanza e la capacita di rispondere prontamente alle emergenze. A giudicare dalle immediate reazioni agli orrori e alle minacce dell'autunno 2001, sembra che in termini di salute e sicurezza, i governi hanno finora misurato i loro successi essenzialmente dal grado di calma e assenza di incidenti osservati dai responsabili della salute. Il paradosso a proposito di salute e sicurezza e che il momento vincente e quello in cui non succede niente: qualsiasi pubblicita e destinata ad essere cattiva pubblicita.
Abstract 16204: Knock-down of 24-dehydrocholesterol Reductase Suppresses SREBP2: A Novel Approach to Reduce PCSK9 in vivo
Authors: Saj Parathath, Ray Rosa, Heather Zhou, Sheng-ping Wang, Lazar A Bojic, Stephen Previs, Thomas F Vogt, Douglas G Johns
Journal: Circulation (2015)

Introduction: Current therapeutic approaches to suppress the actions of proprotein convertase subtilisin/kexin type 9 (PCSK9) primarily involve monoclonal antibody. An alternative approach could be to suppress the SREBP2 pathway. Inhibition of sterol regulatory element-binding protein cleacage-activating protein (SCAP) will prevent SREBP mediated transcription of sterol biogenesis genes and PCSK9.24-dehydrocholesterol reductase (DHCR24) catalyzes the last step of cholesterol synthesis, converting desmosterol to cholesterol. Desmosterol is a strong LXR agonist and an inhibitor of SCAP. Hypothesis: We tested our hypothesis that reduction of DHCR24 expression would result in an increase in desmosterol, resulting in the suppression of SCAP and reduction of PCSK9 in vivo. Methods: In these studies, we used AAVshRNA to knock-down DHCR24 in the livers of CETP transgenic mice and WT mice. Results: Animals injected with AAVshRNA-DHCR24 resulted in 85% knockdown of DHCR24, with a concomitant 75% suppression of cholesterol synthesis, as measured by deuterium incorporation into newly made cholesterol. Knock-down of DHCR24 was also associated with up-regulation of fatty acid oxidation genes and suppression of fatty acid biosynthetic and SREBP-2 cholesterol biosynthetic pathways. Interestingly, DHCR24 knockdown was associated with a 60% decrease in plasma PCSK9 levels in CETP Tg mice (n=10, P&lt;0.001) and similar results were observed in WT mice. Conclusions: To our knowledge, this is the first in vivo study to demonstrate that PCSK9 levels can be decreased via suppression of DHCR24 in vivo . These results suggest that DHCR24 might represent a novel therapeutic target for reducing LDL-cholesterol.
TCT-503 Large Multicenter Evaluation of Clinical Outcomes of Transcatheter Valve-in-Valve Procedures Performed for Failed Mitroflow/Trifecta (externally mounted leaflets) Bioprostheses and Comparison with Conventional Stented Bioprostheses
Authors: Jörg Kempfert, Axel Unbehaun, Matheus Simonato dos Santos, Sabine Bleiziffer, Gabriel Aldea, Lukas Capek, Tanja Rudolph, Jochen Wöhrle, Nicolas Van Mieghem, Konstantinos Spargias, Marco Barbanti, Stephan Windecker, Danny Dvir
Journal: Journal of the American College of Cardiology (2017)
Differentiated and anaplastic thyroid carcinoma: Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual
Authors: Nancy D. Perrier, James D. Brierley, R. Michael Tuttle
Journal: CA A Cancer Journal for Clinicians (2017)

ABSTRACT Answer questions and earn CME/CNE This is a review of the major changes in the American Joint Committee on Cancer staging manual, eighth edition, for differentiated and anaplastic thyroid carcinoma. All patients younger than 55 years have stage I disease unless they have distant metastases, in which case, their disease is stage II. In patients aged 55 years or older, the presence of distant metastases confers stage IVB, while cases without distant metastases are further categorized based on the presence/absence of gross extrathyroidal extension, tumor size, and lymph node status. Patients aged 55 years or older whose tumor measures 4 cm or smaller (T1‐T2) and is confined to the thyroid (N0, NX) have stage I disease, and those whose tumor measures greater than 4 cm and is confined to the thyroid (T3a) have stage II disease regardless of lymph node status. Patients aged 55 years or older whose tumor is confined to the thyroid and measures 4 cm or smaller (T1‐T2) with any lymph node metastases present (N1a or N1b) have stage II disease. In patients who demonstrate gross extrathyroidal extension, the disease is considered stage II if only the strap muscles are grossly invaded (T3b); stage III if there is gross invasion of the subcutaneous tissue, larynx, trachea, esophagus, or recurrent laryngeal nerve (T4a); or stage IVA if there is gross invasion of the prevertebral fascia or tumor encasing the carotid artery or internal jugular vein (T4b). The same T definitions will be used for both differentiated and anaplastic thyroid cancer, but the basic premise of the anatomic stage groups will remain the same. CA Cancer J Clin 2018;68:55‐63. © 2017 American Cancer Society.