tbuckley/cabot-search huggingface dataset:
ACTR-26. TOXICITY AND EFFICACY OF LOMUSTINE PLUS BEVACIZUMAB IN RECURRENT GLIOBLASTOMA PATIENTS
Authors: Jan Nyrop Jakobsen, Thomas Urup, Kirsten Grunnet, Ib Jarle Christensen, Mette Villingshøj, Hans Skovgaard Poulsen
Journal: Neuro-Oncology (2017)

Bevacizumab combined with chemotherapy has shown high response rates in recurrent glioblastoma patients and responding patients have improved survival and quality of life. The Danish treatment recommendations for recurrent glioblastoma patients were recently changed by replacing irinotecan with lomustine in the bevacizumab combination regimen. To evaluate the toxicity and efficacy of lomustine plus bevacizumab in recurrent glioblastoma patients by comparing the treatment with irinotecan plus bevacizumab. The study included recurrent glioblastoma patients treated according to two different treatment protocols at Rigshospitalet. Cohort 1: Seventy consecutive, non-selected patients treated with lomustine 60 mg/m2 every 6 weeks and bevacizumab 10 mg/kg every 2 weeks (Lom-Bev). Cohort 2: A total of 219 patients treated with irinotecan 125 mg/m2 (if EIAED 340 mg/m2) and bevacizumab 10 mg/kg every 2 weeks (Iri-Bev). Comparison analyses of toxicity and efficacy between the two treatment regimens were performed by the Fisher’s Exact test and Kaplan-Meier method. To compare survival outcome between responding patients of the two treatment regimens a landmark analysis was performed. Clinical and molecular factors were screened for association with response, progression-free survival (PFS) and overall survival (OS) using logistic and Cox regression analyses. Lom-Bev patients had a significantly higher frequency of hematological toxicity and less gastrointestinal toxicity compared to Iri-Bev. The response rate was 37% for Lom-Bev and 30% for Iri-Bev. Median PFS was 23 weeks for Lom-Bev and 21 weeks for Iri-Bev (P=0.86). Median OS was 37 weeks for Lom-Bev and 32 weeks for Iri-Bev (P=0.47). In recurrent glioblastoma patients treated outside clinical trials lomustine plus bevacizumab is safe. However, hematological toxicity is a dose limiting factor. No significant difference between Lom-Bev and Iri-Bev were observed with regard to progression-free survival or overall survival when considering the whole group of recurrent glioblastoma patients. Updated results will be presented.
Actividades de vigilancia de la sensibilidad de los antivirales antigripales en relación con las reservas nacionales de antivirales en Europa durante la temporada invernal 2006-07
Authors: A Meijer, A Lackenby, A Hay, M Zambon
Journal: Eurosurveillance (2007)

Ante la amenaza de una pandemia gripal, muchos paises estan acaparando antivirales con la esperanza de reducir sus consecuencias. Es probable que la resistencia a los antivirales altere notablemente su eficacia, por lo que los programas de vigilancia para controlar la aparicion de resistencias cobran una especial importancia.
HOUT-05. THE ELEVATED PRETREATMENT ASPARTATE AMINOTRANSFERASE TO LYMPHOCYTE RATIO INDEX PREDICTS POOR PROGNOSIS IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME
Authors: Jie Zhang, Zhenqiang He, Yong Gao Mou
Journal: Neuro-Oncology (2017)

This study aimed to determine the prognostic value of pretreatment aspartate aminotransferase to lymphocyte ratio index (ALRI) in patients with newly diagnosed glioblastoma multiforme (GBM) treated with surgery as well as adjuvant radiotherapy and chemotherapy. We retrospectively analyzed 91 newly diagnosed GBM patients treated at Sun Yat-sen University Cancer Center between June 2001 and July 2014. The optimal cut-off value of ALRI was determined using Receiver operating characteristic (ROC) curve analysis. Univariate and multivariate analysis using cox regression model was applied to evaluate the independent prognostic value of ALRI for overall survival (OS) and progression-free survival (PFS) in GBM patients. The optimal cut-off value of ALRI was 6.928 (U/109). No significant correlation between ALRI and other clinicopathological parameters was observed. The Kaplan-Meier analysis demonstrated that both PFS (p=0.01) and OS (p=0.002) were significantly worse in GBM patients with high ALRI level. Multivariate analysis further demonstrated ALRI as a predictive factor for both PFS (HR: 2.010, 95%CI: 1.068-3.748, p=0.031) and OS (HR: 2.667, 95%CI: 1.262-5.634, p=0.01), independent of age and extent of resection. The result suggested that the pretreatment ALRI may be a simple and useful prognostic marker for GBM patients.
P3.04-009 Stereotactic Body Radiotherapy to All Sites of Oligometastatic Non-Small Cell Lung Cancer (NSCLC) Combined with Durvalumab and Tremelimumab
Authors: M. Bassetti, J. Lang, Z. Morris, B. Morris, J. Eickhoff, A. Traynor, T. Campbell, K. Matkowskyj, A. Baschnagel, T. Leal
Journal: Journal of Thoracic Oncology (2017)
METB-10. EVALUATION OF NON-SUPERVISED MATRIX-ASSISTED LASER DESORPTION / IONIZATION MASS SPECTROMETRY IMAGING (MALDI) MASS SPECTROMETRY IMAGING (MSI) COMBINED WITH MICROPROTEOMICS FOR DETERMINATION OF GLIOBLASTOMA HETEROGENEITY
Authors: Emilie Le Rhun, Marie Duhamel, Lauranne Drelich, Fahed Zairi, Nicolas Reyns, Maxence Wisztoski, Claude Alain Maurage, Fabienne Escande, Michel Salzet, Isabelle Fournier
Journal: Neuro-Oncology (2017)

The aim of the GLIOMIC study (NCT 02473484) is to identify prognostic subgroups of glioblastoma by Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) followed by tissue micro-extraction and unsupervised clustering. In this analysis, lipid MALDI imaging was performed for 18 glioblastoma samples, peptide MALDI imaging for 29 samples and microproteomic analysis for 6 samples. Frozen tissue sections of 12 µm thickness were obtained followed by trypsin digestion and by matrix deposition with a sprayer. Tissues were prepared for imaging of peptides and lipids. Tumor-specific mass spectra were acquired with 70 µm spatial resolution. After molecular image acquisition, matrix was removed, and tissues were stained and annotated by a pathologist. The imaging datasets were spatially segmented by clustering all spectra by their molecular profile similarity. Then the regions of interest were determined and tissue microextraction was performed followed by shot gun analysis for the identification of proteins and molecular pathways. There was intratumoral heterogeneity as well as a heterogeneity between pathologist annotation as viable tumor, necrosis or infiltration zone, and lipid/peptide imaging. Four main groups of tumors were identified after unsupervised lipid or peptide MALDI imaging. Regions of interest defined by these 2 imaging techniques correlated only partially. Ten patients have died. Actuarial median overall survival was 513,5 days (n=3), 638 days (n=6), 709 days (n=3) and 856 (n=2) in the lipid-defined –groups, and 312 days (n=4), 463 days (n=7), 674.5 days (n=10) and 813 days (n=5) in the peptide-defined groups. Microproteomic analyses showed that one pattern is associated with cell division processes and associated with a more aggressive phenotype. In conclusion, MALDI MSI combined with microproteomics may allow the identification of new subgroups of glioblastoma and may provide new information on glioblastoma heterogeneity.
CSIG-05. THE HISTONE CHAPERONE Spt6 IS REQUIRED FOR GENOMIC STABILITY OF GLIOBLASTOMA CANCER STEM-LIKE CELLS
Authors: Rikke Rasmussen, Elisabeth A Obara, Kristoffer Vitting-Serup, Kamilla E Jensen, Jane Skjøth-Rasmussen, Jannick Brennum, Jiri Bartek, Petra Hamerlik
Journal: Neuro-Oncology (2017)

Rampant genomic instability is a hallmark of glioblastoma (GBM). Despite recent advances in our understanding of this deadly disease, molecular mechanism contributing to treatment resistance are poorly understood. Histone chaperones regulate chromatin structure and gene expression through interaction with histones and RNA polymerase II. Spt6 is a highly conserved transcription elongation factor and histone chaperone. We have identified a novel role of Spt6 in glioblastoma-derived cancer stem-like cells (GSCs) using high-throughput siRNA microscopy-based screening. Our data show that the loss of Spt6 in GSCs, but not their differentiated counterparts (non-GSCs), results in decreased proliferation rates, cell cycle arrest and increased double-strand DNA breaks due to hyper-activation of error-prone non-homologous end-joining DNA repair (NHEJ). Importantly, shRNA-mediated knockdown significantly impairs tumor initiation capacity of GSCs and extends survival of tumor-bearing mice. Our findings indicate an important role of Spt6 in glioblastoma maintenance and resistance to DNA damaging therapies.
Méningites virales à Chypre et en Angleterre : été 1996
Authors: M E Ramsay, D W Brown, H Appleton, B Megson, A Polynikis, L Papantoniou, A Eleftheriou
Journal: Eurosurveillance (1996)

Une epidemie de meningite virale a debute a Chypre le 5 juillet 1996. Jusqu'au 28 aout, 316 cas au total ont ete hospitalises dont la plupart etaient des jeunes et tres jeunes enfants ; 55 (17%) avaient moins d'un an, 117 (37%) de 1 a 4 ans, 103 (33%) de 5 a 14 ans et 41 (13%) de 15 a 80 ans. La majeure partie des cas rapportes provenait de la region de Limassol (213/316 cas), mais des cas sont aussi apparus a Nicosie (43), Larnaca (39), Famagouste (13) et Paphos (7) ; pour un cas, la region n'etait pas precisee. Les cas etaient en general peu graves et l'hospitalisation ne durait que quelques jours ; on n'a pas note de deces ni de complications severes.
Temporally precise single-cell-resolution optogenetics
Authors: Or A. Shemesh, Dimitrii Tanese, Valeria Zampini, Changyang Linghu, Kiryl Piatkevich, Emiliano Ronzitti, Eirini Papagiakoumou, Edward S. Boyden, Valentina Emiliani
Journal: Nature Neuroscience (2017)
Mejora del valor predictivo de los frotis faríngeos en la vigilancia virológica de la gripe
Authors: K Leitmeyer, U Buchholz, M. Kramer, B Schweiger
Journal: Eurosurveillance (2002)

Segun un estudio nacional realizado en Alemania, la vigilancia virologica de la gripe puede mejorar cuando los medicos centinela obtienen muestras de frotis faringeos unicamente de pacientes que les consultan inmediatamente despues del inicio de los sintomas (dentro de las primeras 48 horas), y cuando se utiliza estrictamente la definicion de caso de sindrome gripal. Para la deteccion primaria de virus gripales se debe utilizar PCR.
Risk of developing chronic myeloid neoplasms in well-differentiated thyroid cancer patients treated with radioactive iodine
Authors: R J Molenaar, C Pleyer, T Radivoyevitch, S Sidana, A Godley, A S Advani, A T Gerds, H E Carraway, M Kalaycio, A Nazha, D J Adelstein, C Nasr, D Angelini, J P Maciejewski, N Majhail, M A Sekeres, S Mukherjee
Journal: Leukemia (2017)
MA 10.05 Improved Outcome for Immune Checkpoint Inhibitors (ICI) in Patients Previously Treated with Bavituximab in the SUNRISE Trial
Authors: M. Boyer, D. Spigel, P. Mainwaring, H. Lena, M. Mccleod, G. Losonczy, R. Sanborn, R. Natale, M. Tang, J. Lai, N. Kallinteris, J. Shan, D. Gerber
Journal: Journal of Thoracic Oncology (2017)
RBIO-04. ELUCIDATION OF PHOSPHOLIPID ALTERATION IN BRAIN AFTER IRRADIATION USING BRAIN RADIATION NECROSIS MOUSE MODEL
Authors: Natsuko Kondo, Kenji Nakayama, Yoshinori Sakurai, Takushi Takata, Kyo Kume, Shin-Ichi Miyatake, Osamu Ogawa, Minoru Suzuki
Journal: Neuro-Oncology (2017)

Brain radiation necrosis (RN) is chronic inflammation caused as a late side effect after radiation therapy for brain or head and neck tumors. Re-irradiation to the recurrent tumor increases the risk of RN which can be fatal depending on location in brain. To elucidate the mechanism of RN and develop its new treatment, we established mouse brain RN model that develops RN 6-8 months after proton beam irradiation where the histology of the necrosis recapitulates the human RN patients. Although various studies have been done on RN in terms of protein, such as vascular endothelial growth factor (VEGF) but there is no report related to lipid. In clinical setting, corticosteroids which block the release of arachnoid acid from phospholipid are effective to suppress acute inflammation after irradiation, but useless in chronic phase. More specific inhibitors to bock the lipid mediators involved in promoting RN should be developed. Because the lipid mediators are very small amount and difficult to detect, we investigated phospholipid alteration in mouse brain of RN model, 4 months after irradiation, using high-resolution matrix-assisted laser desorption /ionizing imaging mass spectrometry (HR-MALDI-IMS). Compared to non-irradiated area, increase of phosphatidylcholine (PC) (34:1, 36:4, 36:1, 38:6, 40:6) and decrease of phosphatidylinositol (PI) (36:4, 38:4) were detected. In addition, PC gradually increased from 2 days to 2 months after irradiation in the irradiated area of RN model. Further analysis elucidated that fatty acids, components of the PC, were arachidonic acid and polyunsaturated forms. The fatty acids are well known precursors of various lipid mediators involved in inflammation. Therefore, we will identify the alteration of phospholipids and lipid mediators by comprehensive analysis using LC-MS/MS and reveal the target of lipid mediators as specific to RN.
Abstract 21081: Coffee Intake Affects Heart Failure and Stroke Survival and is Significant in Predicting Heart Failure and Stroke Risk
Authors: Laura Stevens, Carsten Görg, David Kao
Journal: Circulation (2017)

Introduction: Heart Failure (HF) and stroke are complex diseases with multiple phenotypes. While many risk factors for these diseases are well known, it is likely that there are as-yet unidentified risk factors given the complex pathophysiology of each disease. We investigated the diet domain in the Framingham Heart Study (FHS), Cardiovascular Heart Study (CHS), and Atherosclerosis Risk In Communities (ARIC) study to identify potential diet factors associated with HF and stroke. Methods: We used random forest machine-learning methods to identify risk factors associated with cardiovascular diseases in the Framingham Heart Study. We used Cox proportional hazards analysis to investigate these findings further in the FHS and validated our findings using the CHS and ARIC datasets. Results: Random forest analysis identified known risk factors such as blood pressure, age, and cholesterol. In addition, coffee and red meat intake were also found to be important in predicting heart failure and stroke. Survival analysis confirmed these results suggesting coffee intake is significantly associated with HF and stroke. Coffee decreased risk with HF and stroke by 7% and 8% respectively with every increased cup consumed per week (p = .001 for both HF and Stroke). Validation of this trend was confirmed in the CHS and ARIC which resulted in similar outcomes. Furthermore, we built a risk model using known risks from the Framingham Risk Score guidelines and predicted CHF and stroke outcomes. By including coffee in the model, the prediction accuracy increased by 4%. Conclusion: Increased coffee intake is associated with reduced HF and stroke outcomes in FHS, CHS and ARIC.
TMOD-04. A COMPREHENSIVE GENOMIC LANDSCAPE OF GLIOMA SPHEROID CULTURES RECAPITULATES THE HETEROGENEITY OF GLIOBLASTOMA AND IDENTIFIES DNA METHYLATION PREDICTORS OF RADIOTHERAPY RESPONSE
Authors: Qianghu Wang, Ravesanker Ezhilarasan, Lindsey Goodman, Eskil Eskilsson, Jie Yang, Joy Gumin, Siyuan Zheng, Ming Tang, Mona Jaffari, Lihong Long, Kosuke Yoshihara, Peng Sun, Tim Heffernan, W K Alfred Yung, Giulio Draetta, Kenneth Aldape, Frederick F Lang, Roel Verhaak, Erik Sulman
Journal: Neuro-Oncology (2017)

Glioma sphere-forming cells (GSCs) are important in glioblastoma (GBM) initiation, maintenance, and treatment resistance. We performed whole exome and transcriptome sequencing, DNA methylation profiling, DNA copy number determination, and functional characterization of 43 GSCs and matching tumors. Comparative analyses revealed that GSCs recapitulate the molecular landscape of GBM and provide a unique means for discovering the inter- and intra-tumor heterogeneity of GBM. We performed clonogenic assays to explore the relationship between methylation status and radiation response in twelve IDH wild type GSCs irradiated with 2-, 4-, and 6-Gy ionizing radiation. The survival fraction at 4Gy and 6Gy (SF4 and SF6, respectively) were used to dichotomize GSCs as either radiation-sensitive or resistant. DNA CpG methylomes of the GSCs were profiled using Infinium 450K methylation beadchip arrays. We observed that 304,458 out of 465,844 methylation probes (65.4%) showed increased methylation in radiation-resistant relative to radiation-sensitive GSCs (Fisher’s Exact Test, p < 1e-15). Using GSEA, we observed that fifteen of sixteen oxidative stress genes were methylated in radiation-resistant GSCs (p-value=0.019), suggesting an association between radiation-resistance and reactive oxygen species metabolism (ROS). To validate our finding, we derived a methylation signature differentiating the two GSC radiation response groups and used this to classify TCGA cases that received radiotherapy into a responder and non-responder group. We found that survival was significantly different between the two groups (median survival 84 vs. 61 weeks; HR 1.64 adjusting for patient age, p-value<0.008), suggesting that the methylation signature predicts clinical response to radiation treatment. This study identified a novel predictor of radiation response and confirms that the genomic landscape of GSCs can be used to determine clinical and functional properties of GBM.
P2.07-060 Response Assessment and Subgroups Analysis According to the Lung Immune Prognostic Index (LIPI) for Immunotherapy in Advanced NSCLC Patients
Authors: L. Mezquita, E. Auclin, R. Ferrara, C. Caramella, M. Charrier, J. Remon, D. Planchard, S. Ponce, L. Paz-Ares, J. Lahmar, L. Leroy, C. Audigier-Valette, J. Zeron-Medina, P. Garrido, G. Zalcman, J. Mazieres, J. Adam, N. Chaput, J. Soria, B. Besse
Journal: Journal of Thoracic Oncology (2017)
Infections à SARM acquises dans la communauté chez des enfants en Grèce
Authors: S Vourli, D Perimeni, A Makri, M Polemis, A Voyiatzi, A Vatopoulos
Journal: Eurosurveillance (2005)

L’etude suivante presente les caracteristiques de 20 souches de Staphylococcus aureus resistant a la methicilline (SARM) acquis dans la communaute, isolees dans un hopital pour enfants d’Athenes. Dix-huit de ces souches, provenant toutes de prelevements de sites d’infections dermatologiques et de tissus mous, sont porteuses de genes codant pour la leucocidine Panton-Valentine (PVL). Ces 18 souches presentent une resistance a l’acide fusidique, a la tetracycline et a la kanamycine et leur profil d’electrophorese en champ pulse est identique a celui du clone de co-SARM ST80 en circulation dans plusieurs pays d’Europe deja decrit dans la litterature.
Truth in Advertising: Do Clinical Trial Publications Tell It All?
Authors: Mohammad K. Khan, Zachary S. Buchwald, Waleed F. Mourad
Journal: Journal of the National Comprehensive Cancer Network (2017)

He is also the coleader of the Immuno-Oncology program at Winship, and serves on the phase I clinical trials working group.Dr. Khan is a nationally and internationally renowned for his work with radiation abscopal effects and for the management of skin cancers, lymphoma, hematological malignancies, lung cancer, pediatrics, and prostate cancer.He leads several clinical trials as a PI, including 2 current trials focusing on a deeper understanding of interactions between radiation and immunotherapy to improve outcomes for patients with melanoma, NSCLC, and myeloma.Dr. Khan was one of the first physicians to adopt radiation and immunotherapy combinations in the management of patients with cancer.
QLIF-30. RISK FACTORS FOR BURNOUT AMONG NEURO-ONCOLOGY PROVIDERS: A PREDICTIVE MODEL
Authors: Barbara J O’Brien, Shlomit Yust-Katz, Elizabeth Vera, Alvina A Acquaye, Terri S Armstrong
Journal: Neuro-Oncology (2017)

Burnout is increasingly recognized as a common problem among physicians and other healthcare providers. The burnout incidence and associated risk factors among neuro-oncology providers has yet to be reported. The Neuro-Oncology Burnout and Career Satisfaction survey was offered to neuro-oncology professionals September-December 2016. The survey included the Maslach Burnout Inventory-Health Services (MBI-HS; 22-item questionnaire measuring 3 domains of professional burnout) and questions regarding demographic (including age, sex, marital status), lifestyles (including alcohol use, hobbies, sleep quantity), and practice characteristics (including practice setting, hours, responsibilities. Group differences between participants were evaluated by independent samples t-test and chi-square tests. Variables significant at univariate level p<0.10 were included in a multivariate logistic regression with backwards selection (p<0.05) to identify risk factors for high burnout. 427 participated, with 344 with complete data were included in the risk factor analysis. High burnout was present for 63% of participants. On univariate analysis, variables associated (p<0.10) with high burnout were income, lack of exercise, limited time spent with family or on hobbies, stress level, job satisfaction, subjective burnout, history of burnout, depression or anxiety, and lack of institutional mechanism for burnout support. On multivariate analysis, significant risk factors (p<0.05) for high burnout were identified as not spending regular time with family per week (OR=2.4), self-report of currently “feeling” burnout (OR=8.5), having a history of depression (OR=3.7) or anxiety (OR=2.9), and profession (basic science) (OR=8.4). Protective factors against high burnout were exercising >30 min/week (OR=0.13-0.26) and self-report of greater job satisfaction (OR=0.70). Together, these variables can correctly classify 83% of participants with high burnout. Burnout risk was associated with limited self-care, as well as social, professional and underlying psychologic factors. Identifying risk factors is imperative for implementation of preventative strategies to promote wellness and awareness to combat the effects of burnout.