tbuckley/cabot-search huggingface dataset:
GENE-49. ABERRANT SUPER-ENHANCERS ASSOCIATED WITH DOWNREGULATION OF RET FINGER PROTEIN OVERCOMES CHEMORESISTANCE IN GLIOBLASTOMA
Authors: Masaki Hirano, Melissa Ranjit, Akane Yamamichi, Kosuke Aoki, Fumiharu Ohka, Takuya Kato, Atsushi Enomoto, Masahide Takahashi, Toshihiko Wakabayashi, Atsushi Natsume
Journal: Neuro-Oncology (2017)

RET finger protein (RFP, aka TRIM27) plays pivotal roles in acquirement of chemoresistance, via the formation of the complex with nuclear transcription factor Y (NF-Y) and histone deacetylase1 (HDAC1), which are associated with deacetylation of histone H3K27 and specific enhancer activity. Although the chemoresistance driven by RFP may result from aberrant deacetylation of histone H3K27 and dysregulation of enhancers, the details of the mechanism has not been studied so far. The aim of this study was to comprehensively investigate the effects of RFP on super-enhancers and gene expression. We also evaluated the effects of RFP knock-down (KD) on growth of GBM treated with temozolomide (TMZ) both in vitro and vivo. We found that the combination of RFP-KD and TMZ markedly suppressed growth of GBM cells and extended the survival time of mice bearing intracranial GBM compared to TMZ alone. Chromatin immunoprecipitation sequencing (ChIP-seq) using anti-H3K27ac antibody revealed that RFP-KD GBM cells aberrantly acquired several super-enhancers that were different from ones in RFP normal GBM cells. Whole-transcriptome sequencing (RNA-seq) confirmed overexpression of the corresponding genes in RFP-KD GBM cells. This study suggests that RFP contributes to chemoresistance via aberrant deacetylation of histone H3K27 and dysregulation of RFP-associated super-enhancers in GBM and that the combination of targeting RFP and TMZ might become an effective novel treatment strategy for lethal GBM.
Staged development of long-lived T-cell receptor αβ T H 17 resident memory T-cell population to Candida albicans after skin infection
Authors: Chang Ook Park, Xiujun Fu, Xiaodong Jiang, Youdong Pan, Jessica E. Teague, Nicholas Collins, Tian Tian, John T. O'Malley, Ryan O. Emerson, Ji Hye Kim, Yookyung Jung, Rei Watanabe, Robert C. Fuhlbrigge, Francis R. Carbone, Thomas Gebhardt, Rachael A. Clark, Charles P. Lin, Thomas S. Kupper
Journal: Journal of Allergy and Clinical Immunology (2017)
Agrupación de casos de leptospirosis en Rochefort, Francia, junio de 2001
Authors: A Perra, V Servas, G Terrier, D Postic, G Baranton, G André-Fontaine, V Vaillant, I Capek
Journal: Eurosurveillance (2002)

En la region de Rochefort, Francia, se diagnosticaron cinco casos agrupados de leptospirosis en junio de 2001, todos ellos adolescentes que se habian banado en el canal Genouille. Los sintomas incluyeron fiebre, cefalea, dolor abdominal y vomitos, temblores y mialgia. Tres casos se confirmaron por reaccion en cadena de la polimerasa (polymerase chain reaction; PCR) y serologia. La duracion media acumulada del bano fue significativamente mas alta en los casos (23,8 horas) que en los controles (14,4 horas). No se observaron otros factores de riesgo especificos. La investigacion ambiental revelo la presencia de roedores excretores de leptospiras junto a la zona de bano. En todos los antigenos estudiados, la frecuencia de roedores seropositivos fue del 30,8%, siendo L. icterohaemorrhagiae el serogrupo predominante (23,1%).
ANGI-06. CHARACTERISATION OF INVASION OF HUMAN BRAIN TUMOUR INITIATING CELLS IN HUMAN GLIOBLASTOMA
Authors: Verena Leidgens, Maria Alieva, Xin Lu, Nina Patwary, Eugen Kerkhoff, Martin Proescholdt, Arabel Vollmann-Zwerenz, Jacco van Rheenen, Christoph Klein, Peter Hau
Journal: Neuro-Oncology (2017)

A main pathophysiological feature of glioblastoma (GBM) is widespread invasion of the brain parenchyma, rendering localized therapies ineffective. In addition, brain tumour initiating cells (BTIC) may repopulate the tumour site after initially effective treatments. Thus, the invasive tumour cell fraction is a strategic prime target for early anti-invasion therapies. With organotypic brain slice cultures (OBSC) and single cell RNA expression analysis, we established a novel integrated approach to investigate the expression profile of invasion leading cells. In comparison, we used long-term intravital imaging through a cranial window to analyse the interaction of invasive with non-invasive cells and the microenvironment in vivo. The in situ OBSC model allowed us to monitor human BTIC cell invasion in real time. Invasive cells (that we determined leader cells) emerge from the initial cell population and drive invasion into the surrounding tissue. Those cells differ in morphology and behaviour from stationary cells, which remain at the implantation site. Leader cells have a markedly distinct gene expression pattern in comparison to stationary cells. The leader cell-specific expression signature is currently verified in patient tumour biopsies and in the cranial window model. Updated results will be presented at the SNO meeting. We show that invasive leader cells in GBM have a specific functional and molecular profile. We hypothesize that a deep characterization of these cells in respect to their interaction with and response to the microenvironment will shed light on the chronology of one of the gliomagenesis milestones, namely invasion.
PATH-45. INTEGRATION OF MULTI-REGION (EPI)GENOMICS WITH MULTIMODALITY ADVANCED IMAGING HIGHLIGHTS GLIOMA INTRATUMORAL HETEROGENEITY
Authors: Niels Verburg, Kevin C Johnson, Floris P Barthel, Michael Taylor, Joseph Costello, Philip C de Witt Hamer, Pieter Wesseling, Roel Verhaak
Journal: Neuro-Oncology (2017)

Intratumoral (epi)genetic heterogeneity is recognized to be an important driver in glioma therapy resistance. A single biopsy is unlikely to represent the true spatial and temporal heterogeneity. Therefore, multiple sampling schemes guided by imaging are needed. We obtained 74 stereotactic image-guided biopsies preceding craniotomy in eight patients with glioma. Imaging included standard MRI, diffusion and perfusion weighted MRI, MR spectroscopy and PET FET and CHO. We performed multi-region genome-wide methylation profiling of all samples with DNA copy number profiles inferred from methylation array data. To assess variability in methylation profiles from Ceccarelli et al, Cell, 2016, we conducted supervised classification of each sample biopsy. Phylo(epi)genetic trees were constructed to investigate tumor evolutionary paths. Multimodality imaging data was used to predict (epi)genetic characteristics. Data was validated in two independent populations of respectively 32 multi-region samples in 5 patients and 80 single and multi-region initial and patient-matched recurrence samples in 19 patients. Six out of eight gliomas demonstrated spatial heterogeneity of epigenetic classification. In three IDH mutant gliomas of the G-CIMP high subtype (LGm2) regions were classified as G-CIMP low (LGm1) or Codel subtype (LGm3). In three IDH wild type gliomas of the Mesenchymal subtype (LGm5) regions were classified as Classic subtype (LGm4). This was validated in the second dataset in which one of six gliomas showed spatial and three of twenty gliomas showed temporal heterogeneity. Phyloepigenetic and phylogenetic trees showed high concordance. IDH status of the samples could be predicted using multimodality imaging. These findings provide valuable information concerning intratumoral heterogeneity in gliomas. Moreover, imaging was able to predict molecular characteristics, which could lead to multi-region sampling schemes that direct future therapy development.
Stereotactic Body Radiotherapy for Early-Stage Non–Small-Cell Lung Cancer: American Society of Clinical Oncology Endorsement of the American Society for Radiation Oncology Evidence-Based Guideline
Authors: Bryan J. Schneider, Megan E. Daly, Erin B. Kennedy, Mara B. Antonoff, Stephen Broderick, Jill Feldman, Shruti Jolly, Bryan Meyers, Gaetano Rocco, Chad Rusthoven, Ben J. Slotman, Daniel H. Sterman, Brendon M. Stiles
Journal: Journal of Clinical Oncology (2017)

Purpose The American Society for Radiation Oncology (ASTRO) produced an evidence-based guideline on treatment with stereotactic body radiotherapy (SBRT) for patients with early-stage non-small-cell lung cancer. ASCO has a policy and set of procedures for endorsing and/or adapting clinical practice guidelines that have been developed by other professional organizations. Methods The ASTRO Evidence-Based Guideline for Stereotactic Body Radiotherapy for Early-Stage Non-Small-Cell Lung Cancer was reviewed for developmental rigor by methodologists. An ASCO Expert Panel updated the literature search and reviewed the guideline content and recommendations. Results The ASCO Expert Panel determined that the recommendations from the ASTRO guideline, published in 2017, are clear, thorough, and based on the most relevant scientific evidence. ASCO statements and minor modifications were added to enhance the applicability of the ASTRO guideline for the broader ASCO audience. Recommendations For standard operative risk patients with stage I NSCLC, SBRT is not recommended outside of a clinical trial. Lobectomy with systematic lymph node evaluation remains the recommended treatment, although a sublobar resection may be considered in select clinical scenarios. Recommendations are provided regarding the use of SBRT in high operative risk patients and for inoperative patients, including in challenging scenarios where tumors are: centrally located, > 5 cm in diameter, lacking tissue diagnosis, synchronous primary or multifocal, second primary after pneumonectomy, proximal to or involved with mediastinal structures, abutting the chest wall, or recurring after previous treatment. Qualifying statements are included to provide further guidance for implementation, and the importance of a discussion of treatment options among members of the multidisciplinary cancer care team is emphasized. Additional information is available at: www.asco.org/thoracic-cancer-guidelines and www.asco.org/guidelineswiki .
CBIO-10. GLIOBLASTOMA RECURRENCE CORRELATES WITH INCREASED APE1 AND AN IMMUNE-SUPPRESSION MICROENVIRONMENT
Authors: Amanda Hudson, Nicole Parker, Peter Khong, Jonathon Parkinson, Rowan Ikin, Ying Zhu, Helen Wheeler, Viive Howell
Journal: Neuro-Oncology (2017)

Glioblastoma, the most common and aggressive brain cancer in adults, has a very grim prognosis and a 5 year survival rate of less than 10%. While treatment with surgery, radiotherapy and/or chemotherapy may prolong life, progression is inevitable. What is still unknown however, is how much these treatments and progression of disease affect the molecular profiles of these tumours and how these tumours adapt to withstand these treatment pressures. Understanding such changes will uncover pathways used by the tumour to evade destruction and will elucidate new targets for treatment development. Nineteen matched pre-treatment and post-treatment glioblastoma tumours were subjected to gene expression profiling (Fluidigm, TaqMan assays), MGMT promoter methylation analysis (pyrosequencing) and protein expression analysis of the DNA repair pathways, known to be involved in treatment resistance (immunohistochemistry). Gene expression profiling used to molecularly subtype tumours revealed that 26% of recurrent post-treatment specimens did not match their primary diagnostic specimen. Post-treatment specimens had molecular changes which correlated with known resistance mechanisms including increased expression of APEX1 (p<0.05) and altered MGMT methylation status. Increased expression of GPNMB, CCL5 and KLRC1 (associated with immune suppression, invasion and aggression) and polarisation towards an M2 phenotype (anti-inflammatory and immune suppressive) in post-treatment tumours demonstrated an overall change in the tumour microenvironment favouring aggressive tumour growth and disease progression. These findings highlight the ability of glioblastomas to evade not only the toxic onslaught of therapy but also to evade the immune system suggesting that immune-altering therapies may be of value in treating this terrible disease.
CMET-45. USING CUMULATIVE INTRACRANIAL TUMOR VOLUME AS A PROGNOSTIC FACTOR IN THE GI-SPECIFIC GRADED PROGNOSTIC ASSESSMENT (GPA) MODEL
Authors: Rushikesh Joshi, Brian Hirshman, Mir Amaan Ali, Kate Carroll, Bayard Wilson, James Proudfoot, Toru Serizawa, Masaaki Yamamoto, Osamu Nagano, Hitoshi Aiyama, Bob Carter, Clark Chen
Journal: Neuro-Oncology (2017)

The incidence of brain metastases (BM) originating from cancers of the gastrointestinal tract (GI) has been on a steady increase. Based on the disease-specific graded prognostic assessment (ds-GPA) scale, Karnofsky Performance Score (KPS) is the only clinical variable that prognosticates overall survival for patients undergoing stereotactic radiosurgery (SRS) for GI BM. Here we test whether cumulative intracranial tumor volume (CITV) augments the prognostic utility of KPS. Univariate and multivariate logistic regression models were used to determine the prognostic value of CITV in a cohort of 328 SRS-treated patients with GI BM. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to assess whether CITV improved the prognostic utility of GI ds-GPA. In univariate logistic regression models CITV and KPS independently associated with patient survival. While CITV correlated with KPS (R2=0.069, p<0.001), the association between CITV and survival remained robust after controlling for KPS (p<0.001) in a multivariable Cox proportional hazard model. Addition of CITV into the GI ds-GPA model (consisting of KPS) improved prognostic accuracy for one year survival with NRI>0 of 0.397 (95% CI=0.165–0.630, p<0.001) and integrated discrimination improvement of 0.021 (95% CI=0.0057–0.0369, p=0.008). CITV is an important prognostic variable in SRS-treated GI patients with BM. Improvement in prognostic accuracy was achieved by incorporation of CITV into the GI ds-GPA scale.
P3.03-019 Activity of PARP Inhibitor in NSCLC with Germline and Somatic Mutation and in Silico Chemotherapy Lethality
Authors: C. Barreto, P. Aguiar, F. Silverio, M. Yaksic, M.F. Manfrivato, L. Naraki, E. Souza, P. Tamura, K. Kobayashi, L. Zapata, T. Padua, F. Silva, M. Spada, R. Parmigiani, N. Yamaguchi
Journal: Journal of Thoracic Oncology (2017)
Abstract 17504: Compensatory Alterations in Cardiomyocyte Ca2+ Homeostasis During Aortic Stenosis
Authors: åsmund T Røe, Jan Magnus Aronsen, Michael Frisk, Ida G Lunde, Jon Riise, Ole M Sejersted, Geir Christensen, Theis Tønnessen, Ivar Sjaastad, William E Louch
Journal: Circulation (2013)

Concentric left ventricular hypertrophy is commonly associated with impaired myocardial relaxation, leading to reduced end diastolic volume and lower cardiac output. Indeed, diastolic dysfunction underlies approximately 50% of heart failure cases. Stiffening of the myocardium may be caused by active and/or passive mechanisms, which are respectively determined by Ca 2+  homeostasis or properties of the cytoskeleton/extracellular matrix. In aortic stenosis patients with diastolic dysfunction we observed marked SERCA and NCX upregulation in ventricular biopsies, suggesting that cardiomyocyte Ca 2+  homeostasis may be enhanced. To investigate this hypothesis, we examined the contribution of active and passive mechanisms to myocardial stiffness in a rat model of hypertrophy following aortic banding (AB). Experiments were performed six weeks after AB, and sham-operated animals served as controls. AB rats with detectable systolic heart failure were excluded. Hypertrophy and diastolic dysfunction in AB were confirmed in vivo by echocardiography, indicated by thickening of the posterior wall and reduced peak early diastolic tissue velocities. When stimulated to develop isometric force across a range of pacing frequencies (0.5 - 6 Hz), excised left ventricular muscle strips also exhibited slower relaxation kinetics in AB. Interestingly, isolated cardiomyocytes stimulated at the same frequencies exhibited opposite characteristics, as time to 50% relaxation was faster in AB (78±4% of SHAM at 1 Hz, P 2+  transients in single cardiomyocytes (whole-cell fluo-4 AM fluorescence) were faster to 50% decay in AB (63±2% of SHAM at 1 Hz, P 2+  removal, we measured significantly increased rates of both sarcoplasmic reticulum Ca 2+  reuptake and sarcolemmal Ca 2+  extrusion in AB, suggesting increased SERCA and NCX activity. In conclusion, there is a discrepancy between the phenotype of single cardiomyocytes and intact myocardial tissue in AB. We propose that enhanced Ca 2+  homeostasis in aortic banding / aortic stenosis compensates for increased passive stiffness and that the primary determinants of diastolic dysfunction in this condition are alterations in the extracellular matrix or ventricular geometry.
Issues of Awareness Related to Human Papillomavirus Infection Positivity Among US Adult Men—Reply
Authors: Jasmine J. Han, Thomas Beltran, John Song
Journal: JAMA Oncology (2017)

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Abstract 20670: Epidemiological Trends in Atrial Fibrillation in Europe: The EURObservational Research Programme in Atrial Fibrillation Pilot and Long-Term Registries and Euro Heart Survey on Atrial Fibrillation
Authors: Marco Proietti, Cécile Laroche, Robby Nieuwlaat, Harry J Crijns, Aldo Maggioni, Deirdre A Lane, Giuseppe Boriani, Gregory Y Lip
Journal: Circulation (2017)

Introduction:  In 2003, European Society of Cardiology conducted the Euro Heart Survey (EHS) on AF to describe AF management in Europe. With similar aims the EURObservational Research Programme in AF Pilot and Long-Term (LT) registries were conducted in 2012 and 2015.   Hypothesis:  We hypothesised temporal changes across the three cohorts in baseline characteristics, thromboembolic/bleeding risks and use of antithrombotic drugs.   Methods:  Direct comparison of the three cohorts after datasets merging.   Results:  The three cohorts comprised 19,549 patients; AF patients were progressively older in the EHS, EORP-AF Pilot and LT cohorts [mean (SD) age 66.6 (12.8) vs. 68.8 (11.5) vs. 69.2 (11.4) years; p 2 DS 2 -VASc was significantly higher in EORP-AF Pilot and LT compared to EHS [3.2 (1.8) and 3.1 (1.8) vs. 2.8 (1.7); p 2 DS 2 -VASc ≥2) was higher in EORP-AF Pilot (81.7%) and LT (80.8%) vs. EHS (74.8%) (p   Conclusions:  Significant temporal changes in baseline characteristics of AF patients and changes in thromboembolic and bleeding risk have been demonstrated in the last 13 years, with increased uptake of OAC over time, and increased growth in NOACs use recently.
Une épidémie régionale de S. Typhimurium au Danemark : identification de la source par typage MLVA
Authors: M Torpdahl, G Sørensen, S Ethelberg, G Sandø, K Kammelgard, L Jannok Porsbo
Journal: Eurosurveillance (2006)

Au Danemark, dans le cadre du systeme national de surveillance microbiologique des infections enteriques, le sous-typage de tous les isolats de S. Typhimurium est en cours par lysotypage, typage par antibiogramme et electrophorese en champ pulse (PFGE). Cependant, pour certain lysotypes, la capacite discriminatoire du PFGE est insuffisante, et il n’est pas toujours possible de separer les isolats associes des isolats non associes. C’est pourquoi, depuis 2004, nous avons applique la methode de sous-typage MLVA (multiple locus variable number of tandem repeats analysis) pour la surveillance des isolats de S. Typhimurium. Une epidemie de 26 cas de S. Typhimurium a ainsi ete identifiee par cette methode en mai et juin 2005. Les isolats correspondant a l’un des lysotypes (DT12) et de meme profil PFGE les plus frequents au Danemark, etaient sensibles a tous les antibiotiques. Les souches de S. Typhimurium DT12 obtenues dans le cadre de la surveillance en routine chez les animaux et dans les aliments ont ete analysees par MLVA et PFGE afin de les comparer aux isolats humains. Les resultats du typage ont mis en evidence une parfaite similitude (meme PFGE et meme type MLVA) entre les isolats humains et un isolat provenant d’un elevage porcin et de l’abattoir correspondant, situe dans la region ou a eu lieu l’epidemie. En revanche, les autres isolats DT12 analyses qui partageaient le meme profil en PFGE, differaient lors de l’analyse MLVA. L’hypothese que l’elevage porcin etait la source des infections humaines, a ete etayee par les informations sur les patients. La viande de cet elevage a ete interdite a la vente le 29 juin. L’analyse par MLVA peut donc contribuer efficacement a la surveillance aussi bien qu’aux investigations d’epidemies de S. Typhimurium. En effet, sans cette methode de typage, l’epidemie n’aurait pu etre ni detectee, ni sa source identifiee.
Abstract 9373: Strict Rate Control Induced Sympathetic Augmentation in Patients with Atrial Fibrillation.
Authors: Tatsunori Ikeda, Masayuki Takamura, Daisuke Kobayashi, Keiko Ikeda, Hisayoshi Murai, Jyunichirou Inomata, Souichirou Usui, Shuichi Kaneko
Journal: Circulation (2010)

Prognosis of rate-control therapy in atrial fibrillation (AF) has been shown to be similar to that of rhythm-control therapy. However, the degree of optimal heart rate control in AF patient remains...