tbuckley/cabot-search huggingface dataset:
Results of a phase 1 study of quizartinib as maintenance therapy in subjects with acute myeloid leukemia in remission following allogeneic hematopoietic stem cell transplant
Authors: Brenda M. Sandmaier, Samer Khaled, Betül Oran, Guy Gammon, Denise Trone, Olga Frankfurt
Journal: American Journal of Hematology (2017)

FLT3-ITD-mutated acute myeloid leukemia (AML) has very high risk of relapse and is associated with poor outcome following allogeneic hematopoietic-cell transplant (allo-HCT). This two-part, phase 1, multicenter, open-label, sequential-group, dose-escalation study aimed to determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and safety/tolerability of quizartinib, a selective and highly potent FLT3 inhibitor, when administered as maintenance therapy after allo-HCT. Thirteen subjects with documented FLT3-ITD-mutated AML in morphological remission following allo-HCT received one of two quizartinib dihydrochloride dose levels (DL): 40 mg/d (DL1; n = 7) and 60 mg/d (DL2; n = 6), administered orally in 28-day cycles for up to 24 cycles. Median age of participants was 43 years. All subjects received human leukocyte antigen (HLA)-matched allo-HCT. One subject treated at DL1 and 1 treated at DL2 had DLTs that required drug interruption (grade 3 gastric hemorrhage and grade 3 anemia, respectively). Ten subjects (77%) received quizartinib for >1 year; 5 (38%) completed 24 cycles. Four subjects (31%) discontinued quizartinib due to adverse events. One subject (8%) experienced relapse during cycle 1 and discontinued treatment. Most common grade 3/4 adverse events were neutropenia (23%), anemia (15%), leukopenia (15%), lymphopenia (15%), and thrombocytopenia (15%). This study demonstrated acceptable tolerability and early evidence of reduced relapse rate following allo-HCT with quizartinib maintenance compared to historical cohorts. No MTD was identified, but 60 mg daily was selected as highest dose for continuous daily administration based on randomized comparison of daily 30 and 60 mg doses in relapsed/refractory AML.
Neuroplastin and Basigin Are Essential Auxiliary Subunits of Plasma Membrane Ca2+-ATPases and Key Regulators of Ca2+ Clearance
Authors: Nadine Schmidt, Astrid Kollewe, Cristina E. Constantin, Sebastian Henrich, Andreas Ritzau-Jost, Wolfgang Bildl, Anja Saalbach, Stefan Hallermann, Akos Kulik, Bernd Fakler, Uwe Schulte
Journal: Neuron (2017)
TCT-182 Outcomes Following Left Main PCI vs. CABG in Patients With Cerebrovascular Disease: Results From the EXCEL Trial
Authors: Jamie Diamond, Mahesh Madhavan, Joseph Sabik, Patrick Serruys, A. Pieter Kappetein, Martin Leon, Jacques Berland, Marie-Claude Morice, Bernard Gersh, David Kandzari, Ovidiu Dressler, Gregg Stone
Journal: Journal of the American College of Cardiology (2017)
Ectopic lymphoid tissues support local immunoglobulin production in patients with chronic rhinosinusitis with nasal polyps
Authors: Jia Song, Hai Wang, Ya-Na Zhang, Ping-Ping Cao, Bo Liao, Zhe-Zheng Wang, Li-Li Shi, Yin Yao, Guan-Ting Zhai, Zhi-Chao Wang, Li-Meng Liu, Ming Zeng, Xiang Lu, Heng Wang, Xiang-Ping Yang, Di Yu, Claus Bachert, Zheng Liu
Journal: Journal of Allergy and Clinical Immunology (2017)
Pharmacodynamics and proteomic analysis of acalabrutinib therapy: similarity of on-target effects to ibrutinib and rationale for combination therapy
Authors: V K Patel, B Lamothe, M L Ayres, J Gay, J P Cheung, K Balakrishnan, C Ivan, J Morse, M Nelson, M J Keating, W G Wierda, J R Marszalek, V Gandhi
Journal: Leukemia (2017)
TCT-767 Predictors of Pacemaker Dependency After Transcatheter Aortic Valve Implantation
Authors: Javier Lopez-Pais, Juan Francisco Oteo Dominguez, Carlos Arellano Flores, Silvia Vilches-Soria, Jorge Manuel Solano López Morel, Carlos Gustavo Martinez Peredo, Arturo Garcia-Touchard, Jose Antonio Fernandez Diaz, Victor Castro, Jorge Toquero, Javier Goicolea
Journal: Journal of the American College of Cardiology (2017)
TCT-679 Intravascular ultrasound for stent graft sizing in emergency thoracic endovascular aortic repair
Authors: Julia Lortz, Konstantinos Tsagakis, Christos Rammos, Kim Rogmann, Michael Horacek, Thomas Schlosser, Heinz Jakob, Tienush Rassaf, Rolf Alexander Janosi
Journal: Journal of the American College of Cardiology (2017)
Une épidémie urbaine de Fièvre Q, Briançon, France, mars - juin 1996
Authors: A Armengaud, N Kessalis, J C Desenclos, E Maillot, P Brousse, P Brouqui, H Tixier-Dupont, D Raoult, P Provensal, Y Obadia
Journal: Eurosurveillance (1997)

La fievre Q, zoonose ubiquitaire due a une ricksettsie, Coxiella burnetii, sevit sous la forme de cas sporadiques en zones d'elevage de moutons et de chevres et peut etre responsable d'epidemies humaines (1). Le mode de transmission predominant est l'inhalation d'aerosols infectes provenant de l'environnement (sols, paille, laine), durablement contamines lors de la periode de mise bas, par le betail ovin, caprin ou bovin (1). Dans cet article, nous decrivons une epidemie urbaine de fievre Q survenue de mars a mai 1996 a Briancon, une ville de 12 000 habitants situee dans une zone d'elevage des Hautes Alpes.
Demographic and practice factors predicting repeated non-attendance in primary care: a national retrospective cohort analysis
Authors: David A Ellis, Ross McQueenie, Alex McConnachie, Philip Wilson, Andrea E Williamson
Journal: The Lancet Public Health (2017)

BackgroundAddressing the causes of low engagement in health care is a prerequisite for reducing health inequalities. People who miss multiple appointments are an under-researched group who might have substantial unmet health needs. Individual-level patterns of missed general practice appointments might thus provide a risk marker for vulnerability and poor health outcomes. We sought to ascertain the contributions of patient and practice factors to the likelihood of missing general practice appointments.MethodsFor this national retrospective cohort analysis, we extracted UK National Health Service general practice data that were routinely collected across Scotland between Sept 5, 2013, and Sept 5, 2016. We calculated the per-patient number of missed appointments from individual appointments and investigated the risk of missing a general practice appointment using a negative binomial model offset by number of appointments made. We then analysed the effect of patient-level factors (including age, sex, and socioeconomic status) and practice-level factors (including appointment availability and geographical location) on the risk of missing appointments.FindingsThe full dataset included information from 909 073 patients, of whom 550 083 were included in the analysis after processing. We observed that 104 461 (19·0%) patients missed more than two appointments in the 3 year study period. After controlling for the number of appointments made, patterns of non-attendance could be differentiated, with patients who were aged 16–30 years (relative risk ratio [RRR] 1·21, 95% CI 1·19–1·23) or older than 90 years (2·20, 2·09–2·29), and of low socioeconomic status (Scottish Index of Multiple Deprivation decile 1: RRR 2·27, 2·22–2·31) significantly more likely to miss multiple appointments. Men missed fewer appointments overall than women, but were somewhat more likely to miss appointments in the adjusted model (1·05, 1·04–1·06). Practice factors also substantially affected attendance patterns, with urban practices in affluent areas that typically have appointment waiting times of 2–3 days the most likely to have patients who serially miss appointments. The combination of both patient and practice factors to predict appointments missed gave a higher pseudo R2 value (0·66) than models using either group of factors separately (patients only R2=0·54; practice only R2=0·63).InterpretationThe findings that both patient and practice characteristics contribute to non-attendance of general practice appointments raise important questions for both the management of patients who miss multiple appointments and the effectiveness of existing strategies that aim to increase attendance. Addressing these issues should lead to improvements in provision of services and public health.FundingScottish Government Chief Scientist Office and Data Sharing and Linkage Service of the Scottish Government.
Trends in Breast, Colorectal, and Cervical Cancer Incidence Following the Affordable Care Act
Authors: Maxine Sun, Alexander P. Cole, Stuart L. Lipsitz, Quoc-Dien Trinh
Journal: JAMA Oncology (2017)

This observational study uses incidence rates before and after adoption of the Affordable Care Act (ACA) to assess whether adoption of the ACA increased screening for breast, colorectal, and cervical cancer.
OA01.04 A Comparability Study Verifying the Analytic Performance of a Blood-based Gene Expression Classifier to Identify Benign Pulmonary Nodules
Authors: L. Friedman, P. Mcquary, M. Shahbazian, S. Ravuri, K. Copeland, N. Sheibani, L. Hesterberg
Journal: Journal of Thoracic Oncology (2017)
Livestock-associated meticillin-resistant Staphylococcus aureus (MRSA) among human MRSA isolates, European Union/European Economic Area countries, 2013
Authors: Pete Kinross, Andreas Petersen, Robert Skov, Evelyn Van Hauwermeiren, Annalisa Pantosti, Frédéric Laurent, Andreas Voss, Jan Kluytmans, Marc J Struelens, Ole Heuer, Dominique L Monnet
Journal: Eurosurveillance (2017)

Currently, surveillance of livestock-associated meticillin-resistant Staphylococcus aureus (LA-MRSA) in humans in Europe is not systematic but mainly event-based. In September 2014, the European Centre for Disease Prevention and Control (ECDC) initiated a questionnaire to collect data on the number of LA-MRSA from human samples (one isolate per patient) from national/regional reference laboratories in European Union/European Economic Area (EU/EEA) countries in 2013. Identification of LA-MRSA as clonal complex (CC) 398 by multilocus sequence typing (MLST) was preferred, although surrogate methods such as spa-typing were also accepted. The questionnaire was returned by 28 laboratories in 27 EU/EEA countries. Overall, LA-MRSA represented 3.9% of 13,756 typed MRSA human isolates, but it represented ≥ 10% in five countries (Belgium, Denmark, Spain, the Netherlands and Slovenia). Seven of the reference laboratories did not type MRSA isolates in 2013. To monitor the dispersion of LA-MRSA and facilitate targeted control measures, we advocate periodic systematic surveys or integrated multi-sectorial surveillance.
Enfermedad de Creutzfeldt-Jakob y otras enfermedades afines en Francia de 1998 a 2000
Authors: L Capek, V Vaillant
Journal: Eurosurveillance (2003)

En Francia, el numero de declaraciones de casos sospechosos de ECJ aumento de 1998 a 2000, probablemente debido al incremento en las peticiones de pruebas biologicas: respectivamente, 459 en 1998, 590 en 1999 y 823 en 2000. La distribucion por sexo es similar en los tres anos, con una razon entre sexos (V/M) de 1,05. La proporcion de casos sospechosos menores de cincuenta anos permanecio estable (16% de todas las declaraciones en 1998-2000). El numero de casos esporadicos de ECJ, confirmados o probables, fue estable, con una tasa de mortalidad de 1,38 por millon en 1998, 1,56 en 1999 y 1,41 en 2000.
TCT-801 Peri-stent evaginations with bioresorbable everolimus-eluting vascular scaffolds and different metallic drug-eluting stents with bioabsorbable polymers at 6 and 12 months: Incidence, magnitude, associated factors and evaluation of device or patient-specificity
Authors: Jose de la Torre Hernandez, Nieves Gonzalo, Imanol Otaegui, Jose Ramon Rumoroso, Hipolito Gutierrez, Gerard Marti, Salvatore Brugaletta, Felipe Hernandez, Bruno Garcia, Pablo Salinas, Tomas Canton, Iñigo Lozano, Juan Antonio Franco Pelaez, Javier Zueco, Fernando Alfonso, Javier Escaned
Journal: Journal of the American College of Cardiology (2017)
Significance of estrogen receptor in thyroid cancer: Molecular link of epidemiologic observations
Authors: Shilpi Rajoria, Parminder Parmar, Stimson Schantz, Steven Schaefer, Devyani Chaudhuri, Raj Tiwari, Robert Suriano
Journal: Cancer Research (2008)

4254  The incidence of thyroid cancer is three times higher in women than in men. Women of childbearing age are at highest risk for non medullary thyroid cancer. Given the preponderance of thyroid cancer in women, we examined the significance of estrogen receptor (ER) in thyroid cancer using cell culture models. Our experimental model consisted of an immortalized normal thyroid cell line (NTHY-1), two papillary thyroid cancer cell lines (BCPAP and 8505-C), two follicular thyroid cancer cell lines (CGTHW-1 and ML-1) and a goiter cancer cell line (KAT50TS). We examined the cellular localization of ER, estrogen metabolism and responsiveness of these cells to estrogen and its metabolites. Our data using western blot analysis and electrophoretic mobility shift assay (EMSA) suggest that both ER-α and ER-β are present in the normal and thyroid cancer cell lines. The ER is localized in the cytoplasm as well as in the nucleus without any estradiol stimulation. However the nuclear ER in the cancer cells bind to the estrogen response element (ERE) whereas in the NTHY-1 cells, the nuclear or cytoplasmic ER did not bind to the ERE. All the cell lines were capable of metabolizing estradiol (E2) into its two key metabolites, 2-hydroxyestrone and 16 -hydroxyestrone, suggesting that thyroid cells are similar to estrogen responsive tissues and they do not lack the functional machinery necessary for estradiol metabolism. Binding of ER-Hsp90 although present in all thyroid cancer cell lines, showed cell- specific variations. These studies linking the cellular activity of ER together with the structural analysis of ER in thyroid cancer cells may provide the experimental rationale for the observed gender bias of thyroid cancer prevalence.
CD169+ macrophages are critical for osteoblast maintenance and promote intramembranous and endochondral ossification during bone repair
Authors: Lena Batoon, Susan Marie Millard, Martin Eduard Wullschleger, Corina Preda, Andy Chiu-Ku Wu, Simranpreet Kaur, Hsu-Wen Tseng, David Arthur Hume, Jean-Pierre Levesque, Liza Jane Raggatt, Allison Robyn Pettit
Journal: Biomaterials (2017)
Il nuovo programma di vaccinazione italiano ha ridotto la copertura contro la poliomielite nella città di Napoli
Authors: M. G. Panico, N M Trinchese, B Serpieri, F Attena
Journal: Eurosurveillance (2000)

Il 7 aprile 1999, il Ministero della Sanita italiano ha introdotto dei cambiamenti nei programmi di vaccinazione infantile, modificando anche quello contro la poliomielite. I cambiamenti comprendono la sostituzione delle prime due dosi di vaccino antipoliomielitico orale (OPV) con il vaccino antipoliomielitico inattivato e iniettabile (IPV). Questa misura e stata adottata dopo avere confrontato il rischio di contrarre la poliomielite di tipo selvaggio con quello di sviluppare paralisi poliomielitica causata del vaccino (rischio relativo 0/10). In Italia, l'ultimo caso di poliomielite indigena si e verificato nel 1983 e l'ultimo di poliomielite importata nel 1988 (1). Questo articolo descrive come la nuova legge ha influito sul tasso di vaccinazioni contro la poliomielite nei quartieri di Napoli afferenti all'Azienda Sanitaria Locale (ASL) NA4, costituita da 11 distretti sanitari e dove, nel 1988, sono nati 7500 bambini.
TCT-11 Association Between Scaffold Under-Expansion and Late Lumen Loss after Bioresorbable Scaffold Implantation: IVUS and Angiographic Insights from the ABSORB Japan Trial
Authors: Kozo Okada, Yasuhiro Honda, Hideki Kitahara, M. Brooke Hollak, Paul G. Yock, Jeffrey J. Popma, Hajime Kusano, Wai-Fung Cheong, Krishna Sudhir, Peter J. Fitzgerald, Takeshi Kimura
Journal: Journal of the American College of Cardiology (2017)
WP744, a novel anthracycline highly apoptotic in breast cancer cells
Authors: Michelle A. Fanale, Yanna Liu, Tamra McKenzie, Izabela Fokt, Waldemar Priebe, Kelly K. Hunt
Journal: Cancer Research (2004)

3843    Background : Anthracycline-based therapy with doxorubicin is a mainstay of both adjuvant and neoadjuvant therapy for breast cancer patients. Accumulation of doxorubicin in sufficient concentrations in breast cancer cells is needed to achieve anti-tumor efficacy. The emergence of multidrug resistance (MDR) mechanisms that cause drug efflux have led to increased clinical resistance to therapy. The two most studied forms of MDR in human tumors are secondary to overexpression of the MDR1 gene or the MRP1 gene. Both genes encode for proteins that act as drug efflux pumps, with MDR1 producing plasma membrane glycoprotein P-gp. WP744, a doxorubicin analog benzylated at the C-4’ hydroxyl, has increased lipophilicity and steric hindrance at C-4’. We believe that these properties of WP744 may help to circumvent the P-gp mediated drug efflux. We have shown in previous studies that WP744 is highly active  in vitro  against a wide range of tumors including MDR1 and MRP1 phenotypes and has demonstrated activity  in vivo  in leukemia and orthotopic glioblastoma models.  Methods and Results : In our current study, we compared the cell growth inhibitory activity and proapoptotic activity of WP744 versus doxorubicin using both doxorubicin-resistant (MCF-7, 231-GFP) and doxorubicin-sensitive (MCF-Her-18) breast cancer cells. Cells were plated at 1 x 10 4  cells/well, and then incubated with doxorubicin and WP744 at concentrations ranging from 0.05 to 0.5 μg/ml. At 72 h MTT assay was performed to assess growth inhibition, and the IC 50  was determined using data points from 6 replicate samples. WP744 was noted to be more potent (p = 0.007) in all cell lines as compared to doxorubicin, respectively: MCF-7 (IC 50  0.1 vs. >0.5 μg/ml), 231-GFP (IC 50  0.05 vs. 0.375 μg/ml), MCF-Her-18 (IC 50  0.1 vs. 0.175 μg/ml). Apoptosis was analyzed in duplicate after 72 h of incubation with concentrations of 0, 0.075, and 0.1 μg/ml with WP744 or doxorubicin, respectively. For 231-GFP apoptotic cell populations were: 30 % vs. 14 % for 0.1 μg/ml (p = 0.013). For MCF-Her-18 apoptotic cell populations were: 20 % vs. 11 % for 0.1 μg/ml (p = 0.005).  Conclusions : WP744 was superior to doxorubicin at inducing both growth inhibition and apoptosis for both doxorubicin-sensitive and resistant breast cancer cell lines. Therefore, we believe that WP744 has substantial promise in future clinical development as an antitumor agent that could be significantly more efficacious that doxorubicin for the treatment of breast cancer.
Next-generation sequencing technologies and their application to the study and control of bacterial infections
Authors: J. Besser, H.A. Carleton, P. Gerner-Smidt, R.L. Lindsey, E. Trees
Journal: Clinical Microbiology and Infection (2017)

With the efficiency and the decreasing cost of next-generation sequencing, the technology is being rapidly introduced into clinical and public health laboratory practice.The historical background and principles of first-, second- and third-generation sequencing are described, as are the characteristics of the most commonly used sequencing instruments.Peer-reviewed literature, white papers and meeting reports.Next-generation sequencing is a technology that could potentially replace many traditional microbiological workflows, providing clinicians and public health specialists with more actionable information than hitherto achievable. Examples of the clinical and public health uses of the technology are provided. The challenge of comparability of different sequencing platforms is discussed. Finally, the future directions of the technology integrating it with laboratory management and public health surveillance systems, and moving it towards performing sequencing directly from the clinical specimen (metagenomics), could lead to yet another fundamental transformation of clinical diagnostics and public health surveillance.
La tuberculosis en Portugal: evolución hasta 1994
Authors: M L Antunes, A Fonseca-Antunes
Journal: Eurosurveillance (1996)

Portugal construyo su primer hospital para el tratamiento de la tuberculosis (TB) en Funchal, Madeira, en 1862. En 1899, la reina Amelia propuso y patrocino una fundacion privada, con clinicas, hospitales, sanatorios y preventorios, donde familiares y otros allegados de los pacientes de TB eran ingresados para su control y tratamiento si era preciso. La fundacion se convirtio en una entidad publica en 1946. La lucha contra la TB siempre ha contado con la aceptacion politica, social y publica en general asi como con un generoso apoyo economico, ofreciendose todos los servicios, incluidos los farmacos mas modernos, sin cargo: en 1949 se introdujo la estreptomicina, en 1966 la rifampicina, y en 1979 la quimioterapia de tratamiento breve.
Specific MT1-MMP silencing reduces prostate cancer cell proliferation and bone matrix degradation
Authors: Zhong Dong, R. Daniel Bonfil, J. Carlos Trindade Filho, Sreenivasa Chinni, Wan-Ming Zhang, Sanaa Nabha, Rafael Fridman, Michael L. Cher
Journal: Cancer Research (2005)

2926  Membrane type 1- matrix metalloproteinase (MT1-MMP, also known as MMP-14) was originally identified as an activator of pro-MMP-2, but recent studies demonstrated its type I collagenolytic activity. We reported that MT1-MMP expression is associated with the transition from benign prostate epithelium to prostatic intraepithelial neoplasia in radical prostatectomy specimens (Clin Cancer Res 5: 4105, 1999). MT1-MMP has also been shown to be highly expressed in various human prostate cancer (PC) cell lines. Type I collagen is the major component of the bone extracellular matrix (ECM), and remodeling of the bone ECM is a hallmark of PC metastasis. We hypothesized that metastatic PC cells use proteases such as MT1-MMP to degrade bone ECM thereby promoting secondary tumor growth. In the current study, an expression vector with a DNA insert encoding human MT1-MMP siRNA was designed based on preliminary transfection experiments with MT1-MMP siRNA oligonucleotides. DU145 PC cells, which express relatively high levels of MT1-MMP, were stably transfected with either the MT1-MMP siRNA vector or a control vector containing a scrambled DNA insert. RT-PCR and immunoblot showed a substantial downregulation of MT1-MMP expression at both the gene and protein levels in cloned populations of MT1-MMP siRNA expressing cells. A specific MT1-MMP activity assay revealed a 78% reduction of MT1-MMP enzymatic activity (P
TCT-292 Everolimus eluting biorresorbable vascular scaffold: impact of lesions complexity on clinical outcome and predictors of adverse cardiac events at long term follow up
Authors: Javier Suarez De Lezo, Pedro Martin, Jorge Chavarria, Soledad Ojeda, José Segura, Damaso Valeron, Jose Novoa, Francisco Hidalgo, Miguel Romero, Manuel Pan
Journal: Journal of the American College of Cardiology (2017)
Adaptive Evolution of the GDH2 Allosteric Domain Promotes Gliomagenesis by Resolving IDH1R132H-Induced Metabolic Liabilities
Authors: Matthew S. Waitkus, Christopher J. Pirozzi, Casey J. Moure, Bill H. Diplas, Landon J. Hansen, Austin B. Carpenter, Rui Yang, Zhaohui Wang, Brian O. Ingram, Edward D. Karoly, Robert P. Mohney, Ivan Spasojevic, Roger E. McLendon, Henry S. Friedman, Yiping He, Darell D. Bigner, Hai Yan
Journal: Cancer Research (2017)

Hotspot mutations in the isocitrate dehydrogenase 1 (
Retour de la diphtérie en Europe
Authors: M Rey, O Patey, F Vincent-Ballereau
Journal: Eurosurveillance (1996)

Depuis la generalisation de la vaccination infantile, la diphterie a ete eliminee dans la plupart des pays europeens et la survenue recente d'une epidemie importante dans les Nouveaux Etats Independants (NEI) de l'ex-URSS etait inattendue. La reemergence de la diphterie dans les NEI souleve les questions suivantes : cette epidemie va-t-elle se repandre ? Comment la controler ? Menace-t-elle les autres pays europeens ? Ces pays sont-ils suffisamment proteges contre une reapparition de la diphterie ?