tbuckley/cabot-search huggingface dataset:
GENE-11. CHROMATIN ACCESSIBILITY DEFINES TRANSCRIPTIONAL DRIVERS OF MIGRATION IN HUMAN GLIOBLASTOMA
Authors: Nadejda Tsankova, Parsa Erfani, Jessica Tome-Garcia, German Nudelman, Alexander Tsankov, Martin Walsh, Elena Zaslavsky
Journal: Neuro-Oncology (2017)

While glioblastoma (GBM) cells at the tumor core respond to surgery and chemoradiation, the more infiltrative tumor element evades therapy and has been implicated in tumor recurrence. As cell fate decisions converge on epigenetic control, one attractive strategy to study the intricate biology of migration is to define its transcription factor (TF) drivers in a system that recapitulates the cell’s native biological state. To this effect, our laboratory has developed novel epigenetic tools to characterize the transcriptional activity for proliferation and migration in GBM stem cell populations (GSC), prospectively isolated from fresh human GBM samples without pre-culturing (Tome_Garcia_et_al_2017). Here, we used chromatin accessibility analysis in freshly-sorted human GSCs and germinal matrix progenitors, to define two distinct open chromatin GBM signatures –developmentally shared one related to stem cell proliferation, and tumor-specific one related to migration. We inferred the most salient TF motifs within each, and discovered the TEAD family to be most selectively overrepresented at tumor-specific regulatory regions, which annotated to functional gene sets related to motility, mitochondrial metabolism, neuroinflammation, and WNT/Cadherin signaling. TEADs, along with their co-activators YAP/TAZ, are the downstream effectors of the Hippo pathway. While extensively studied in carcinomas for their role in growth, invasion, and chemoresistance, hippo-TEAD activity in GBM is still poorly understood. Through computational integration of ATACseq and RNAseq data, we inferred the top transcriptional TEAD-targets in uncultured GSCs, and confirmed their TEAD1 cis and trans occupancy via footprinting and immunoprecipitation. Next, we employed CRISPR/Cas9 to knockout TEAD1 in primary GSCs. Notably, eliminating TEAD1 reduced drastically cell invasion in transwell assays, caused subtle anti-proliferative effect, and showed repression of top TEAD1-GBM targets. Our data puts forward novel tools for dissecting the epigenetic plasticity of GSCs in the context of tumor migration and implicates TEAD1 as an important driver of infiltrative cell malignancy in GBM.
HPV vaccinated women need just three cervical screens in their lifetime
Authors: Anne Gulland
Journal: BMJ (2017)

A new study has found that women who have been given the human papillomavirus (HPV) vaccine may only need three cervical screens in their lifetime.1

The authors, writing in the International Journal of Cancer , used statistical modelling to show that women vaccinated under the current NHS vaccination programme would need screens at ages 30, 40, and 55, rather than the current 12 lifetime screens offered in England. The models were based on both vaccinated and unvaccinated …
P1.02-034 Non-Invasive Qualitative Diagnosis of Lung Cancer Enabled by Spectrum Analysis of Ultrasound
Authors: R. Ihara, T. Anayama, T. Aoki, E. Narukami, T. Nakajima, H. Wada, K. Hirohashi, R. Miyazaki, K. Yasufuku, K. Orihashi
Journal: Journal of Thoracic Oncology (2017)
P1.13-003 Recurrence Dynamics in Resected Pathological Stage I Lung Adenocarcinoma Depend on the IASLC/ATS/ERS Histological Subtype
Authors: Y. Takahashi, T. Eguchi, K.S. Tan, Z. Tano, W. Travis, D. Jones, P. Adusumilli
Journal: Journal of Thoracic Oncology (2017)
Staphylococcus aureus résistant à la méticilline : vers une réponse coordonnée à un défi persistant
Authors: M J Struelens, O Denis
Journal: Eurosurveillance (2000)

Staphylococcus aureus resistant a la meticilline (SARM) represente un defi majeur en sante publique dans de nombreux etablissements de soins a travers le monde. Les SARM sont une cause frequente d’epidemies par transmission inter-humaine et sont devenus endemiques dans beaucoup de regions ou ils alourdissent le bilan de la morbidite, de la mortalite et le cout des soins associes aux infections nosocomiales. Les donnees rapportees par le systeme europeen de surveillance de la resistance antimicrobienne (EARSS, European Antimicrobial Resistance Surveillance System), mis en place recemment, suggerent que la resistance des isolats de S. aureus a la meticilline est plus frequente dans les pays du sud de l’Europe que dans ceux du nord (1).
P3.02c-077 Cardiac Troponin-I Elevation in Patients with Non-Small Cell Lung Cancer during PD1/PDL1 Inhibition with Nivolumab
Authors: Erika Rijavec, Carlo Genova, Matteo Sarocchi, Simone Musu, Eleonora Arboscello, Andrea Bellodi, Giulia Barletta, Federica Biello, Giovanni Rossi, Claudia Maggioni, Maria Giovanna Dal Bello, Claudio Brunelli, Michele Mussap, Paolo Spallarossa, Francesco Grossi
Journal: Journal of Thoracic Oncology (2017)
TMIC-14. HYPOXIA INDUCIBLE OLIG2 MEDIATES GLIOMA STEM CELL MIGRATION
Authors: James Ross, Monica Chau, Brandon Miller, Subhas Mukherjee, Changming Zhang, Jun Kong, Emily Kaissi, Austin Newsam, Darius Mahboubi, Jameson Berry, Carol Tucker-Burden, Daniel Brat
Journal: Neuro-Oncology (2017)

Glioblastoma (GBM) is the most malignant primary brain tumor and GBM stem cells (GSCs) are thought to drive its behavior and resistance to therapy. GSCs are self-renewing and reside in supportive microenvironmental niches such as perinecrotic zones composed of pseudopalisades. Pseudopalisades are a wave of hypoxic tumor cells migrating away from central necrosis. The mechanisms of GSC accumulation within pseudopalisades are poorly understood but could be related to their enhanced survival, proliferation, or active migration. Interestingly, the majority of GBM tumor cells show a mass migration radially outward from the necrotic core away from hypoxia, yet GSCs within pseudopalisades are maintained centrally. We hypothesized that GSCs home towards hypoxic microenvironments to benefit from the hypoxia-induced factors that support stemness and survival. We treated human-derived GBM stem and non-stem cells with hypoxia in vitro and found that hypoxia enhanced the expression of stem cell, pro-survival and migratory factors and also accelerated their migration capacity. Of the four induced tumor propagating stem cell (iTPC) transcription factors (Sall2, Sox2, Pou3f2, Olig2), Olig2 was most upregulated by hypoxia and preferentially expressed in the severely hypoxic pseudopalisading cells in human GBM specimens. We found that the expression of Olig2 was associated with enhanced hypoxia-induced migration in an in vitro transwell migration assay and in an in vivo mouse model of hypoxia. Our data demonstrate that Olig2 expression is induced by hypoxia and that Olig2 knockdown correlates with reduced expression of iTPC markers Sall2, Sox2, Pou3f2, and migratory markers FAK, Rho-A, Rock1, and CXCR4. This data suggests that OLIG2 may be responsible for the homing of GSCs to the hypoxic-perinecrotic niche and represents a novel mechanism potentially responsible for glioma progression following the onset of necrosis.
Infecções gastrointestinais em turistas : de quem é a responsabilidade?
Authors: R Cartwright
Journal: Eurosurveillance (2004)

Os progressos em saude publica e no controlo das doencas transmissiveis na Europa foram possiveis devidos aos esforcos dos medicos de saude publica mas tambem devidos a uma visao multidisciplinaria. Os resultados da equipa espanhola [1] que investigou o surto de gastroenterite em turistas da Republica Dominicana sao um bom exemplo da necessidade de uma boa cooperacao entre disciplinas e entre paises. Ao nivel mundial, o turismo faz parte das tres forcas economicas mais importantes, dado que o numero de turistas aumenta cada ano. Estima-se a mais de 70 milhoes por ano o numero de viagens organisadas vendidas na Europa para todos os destinos. Os turistas estao expostos a uma grande variedade de ambientes e organismos patogenos.
Chlamydia trachomatis mutant au Danemark
Authors: S Hoffmann, J S Jensen
Journal: Eurosurveillance (2007)

Un variant de Chlamydia trachomatis mutant a ete detecte en Suede en 2006 et a, depuis, ete egalement diagnostique depuis en Norvege, mais pas en Irlande, ni aux Pays Bas. Cet article decrit une etude visant a evaluer la presence du nouveau variant au Danemark.
RET rearrangements define an uncommon molecular subtype of metastatic colorectal cancer (mCRC)
Authors: F. Pietrantonio, A.B. Schrock, J. Lee, A. Drilon, J. Christiansen, V.K. Chiu, A. Zaniboni, G. Fucà, F. Morano, B. Borelli, D. Rossini, M. Milione, S. Corallo, M. Prisciandaro, C. Cagnazzo, A. Bardelli, L. Trusolino, F. Di Nicolantonio, A. Falcone, F. de Braud, C. Cremolini
Journal: Annals of Oncology (2017)
P1.01-002 TP53 Mutations Predict for Poor Survival in ALK Rearrangement Lung Adenocarcinoma Patients Treated with Crizotinib
Authors: W. Wang, C. Xu, Y. Chen, W. Zhuang, G. Lin, X. Chen, B. Wu, Y. Huang, R. Chen, Y. Guan, X. Yi, M. Fang, T. Lv, G. Chen, Y. Song
Journal: Journal of Thoracic Oncology (2017)
La formación en Epidemiología de Campo en Europa ante un futuro prometedor
Authors: Arthur L. Reingold
Journal: Eurosurveillance (2001)

Resulta oportuno que el grupo de articulos aqui publicado en los que se describen algunos programas de formacion en epidemiologia de campo aparezca en 2001, ano en que se cumple el 50o aniversario de la creacion del Servicio de Investigacion Epidemica (Epidemic Intelligence Service; -EIS-) de los Centros para el Control y Prevencion de Enfermedades (Centers for Disease Control and Prevention; -CDC-). Si hoy estuviera entre nosotros Alex Langmuir, fundador de EIS, comprobaria encantado la consolidacion y el exito que han conseguido estos programas de formacion en Europa. En America Latina, Asia y Africa tambien estan surgiendo programas similares destinados a proporcionar a los profesionales sanitarios la practica y experiencia necesarias para realizar investigaciones epidemiologicas oportunas y pertinentes en el ‘mundo real’ de la salud publica. Algunos de estos programas de formacion han comenzado a desarrollarse y son ofertados por instituciones academicas locales, mientras que otros requieren un vinculo oficial con el propio CDC, y otros son esfuerzos independientes de organismos sanitarios locales.
Erratum: Corrigendum: The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue
Authors: Matthew D Lynes, Luiz O Leiria, Morten Lundh, Alexander Bartelt, Farnaz Shamsi, Tian Lian Huang, Hirokazu Takahashi, Michael F Hirshman, Christian Schlein, Alexandra Lee, Lisa A Baer, Francis J May, Fei Gao, Niven R Narain, Emily Y Chen, Michael A Kiebish, Aaron M Cypess, Matthias Blüher, Laurie J Goodyear, Gökhan S Hotamisligil, Kristin I Stanford, Yu-Hua Tseng
Journal: Nature Medicine (2017)
Vigilância da listeriose na Finlândia, 1995-2004
Authors: O Lyytikäinen, U M Nakari, S Lukinmaa, E Kela, N Nguyen Tran Minh, A Siitonen
Journal: Eurosurveillance (2006)

O artigo seguinte apresenta a analise dos dados de vigilância dos casos de listeriose declarados ao Registo Nacional Finlandez de Doencas Infecciosas entre 1995 e 2004 e a descricao das experiencias recentes de investigacoes de clusters de casos de listeriose neste pais. O numero annual de casos oscilou entre 18 e 53, mas foram identificadas tendencias na incidencia (incidencia annual media : 7 casos por milhao de habitantes). So um pequeno numero de casos ocurreram em mulheres gravidas ou em recem-nascidos. A maioria dos pacientes eram pessoas idosas com doencas benignas subjacentes ; 25% entre elas morreram por causa de essas infeccoes. Varios clusters foram detectados por meio de serotipagem e genotipagem dos isolamentos de listeria feitos em rotina. O vehiculo da infeccao so foi identificado em dois surtos. Pelo menos um quarto dos casos de listeriose (78/315) foram devidos a um sero-genotipo especifico ou a genotipos estreitamente ligados, tambem encontrados em produtos da pesca fumados ou salgados a frio e empaquetados em vacuo. Durante o periodo 2000-2003, os consumidores finlandeses foram informados varias vezes das recomendacoes sobre alimentacao nos grupos de risco. A mesma informacao tambem foi fornecida aos medicos e clinicas prenatales.
P1.01-021 FISH and IHC Discordance in ALK Rearranged Non-Small Cell Lung Cancer
Authors: A. Kapoor, V. Noronha, A. Joshi, V. Patil, R. Kaushal, A. Mahajan, A. Janu, K. Prabhash
Journal: Journal of Thoracic Oncology (2017)
Prognostic relevance of VEGF, VEGFR, IGF and IGFR immunohistochemical expression in gastroenteropancreatic neuroendocrine tumors
Authors: M. Torniai, A. Savini, F. Morgese, S. Rinaldi, C. Rubini, M. Santoni, S. Onorati, S. Pompili, A. Onofri, M. Scarpelli, R. Berardi
Journal: Annals of Oncology (2017)
UK-trained junior doctors' intentions to work in UK medicine: questionnaire surveys, three years after graduation
Authors: Geraldine Surman, Michael J Goldacre, Trevor W Lambert
Journal: Journal of the Royal Society of Medicine (2017)

Objective To report on the career intentions, three years after qualification, of 12 national cohorts of UK-trained doctors who qualified between 1974 and 2012, and, specifically, to compare recent UK medical graduates' intentions to work in medicine in the UK with earlier graduates. Design Questionnaire surveys of cohorts of UK medical graduates defined by year of graduation. Setting UK. Participants 30,272 UK medical graduates. Main outcome measures Stated level of intention to pursue a long-term career in medicine in the UK. Results The response rate was 62% (30,272/48,927). We examined responses to the question ' Apart from temporary visits abroad, do you intend to practise medicine in the United Kingdom for the foreseeable future?' Of doctors from UK homes, 90% had specified that they would 'definitely or probably' practise medicine in the UK in the surveys of 1977-1986, 81% in 1996-2011 and 64% in 2015. Those who said that they would probably or definitely not practise medicine in the UK comprised 5% in 1977-1986, 8% in 1996-2011 and 15% in 2015. Most who were not definite about a future career in UK medicine indicated that they would wish to practise medicine outside the UK rather than to leave medicine. Conclusions The wish to remain in UK medical practice in the 2015 survey was unprecedentedly low in this unique series of 40 years of surveys.
DDIS-09. IDH1 MUTATION-INSPIRED Α-KETOGLUTARIC ACID MIMICS FOR EPIGENETIC THERAPY OF HIGHER GRADE GLIOMAS
Authors: Hanumantha Rao Madala, Surendra Reddy Punganuru, Kalkunte Srivenugopal
Journal: Neuro-Oncology (2017)

Mutations at the active site of isocitrate dehydrogenase 1 gene (IDH1; R132H) occur at a high frequency (>70%) early in the oncogenesis of lower grade malignant gliomas, and result in a dramatic accumulation of the oncometabolite D-2 hydroxyglutarate (D-2HG), that effectively replaces the normal metabolite α-ketoglutarate (α-KG) in cell physiology. Surprisingly, IDH1 mutations bestow superior therapeutic responses to alkylating agents and better patient survival. D-2HG, effectively competes with α-KG and potently inhibits various dioxygenase reactions, including the TET1&2 DNA -demethylases and histone demethylases thereby, re-shaping and reprogramming the epigenetic landscape, and consequent transcriptional silencing; the DNA repair protein O6-lguanine DNA methyltransferase (MGMT), which confers drug resistance is one major target for such repression. As a novel and innovative strategy of turning the tide against GBMs by exploiting the mechanistic aspects of the oncometabolite, we hypothesized that D-2HG and α-KG derivatives that can replace the natural metabolite in epigenomic dioxygenase reactions will serve as potent anti-glioma drugs either by themselves or in combination with the alkylating agents. To this end, we synthesized a 2,4-dimethyleneglutaric acid (DMG), an α-KG mimic with methylene groups inserted at the C2 and C4 positions. The hydrophobic DMG ester, by itself, was cytotoxic with IC50 values up to 300 µM against brain tumor cell lines, however, when combined at 100 µM with TMZ resulted in >20-fold increased synergistic cell killing. DMG induced oxidative stress inhibited α-KG dehydrogenase, MGMT and TET1&2. We also observed a marked reduction in ATP levels and rapid metabolic flux changes indicating an altered cellular metabolism. Collectively, these data reveal that acute treatments of α-KG analogs can alter the cellular metabolic and epigenetic makeup in a manner ascribed to D-2HG, and open up much-needed novel and exciting avenues of oncometabolite-based therapies for brain tumors (supported by CPRIT grant RP170693 to KSS)
EXTH-76. OPTIMIZING TRANSDUCER ARRAY CONFIGURATION FOR TREATING TUMORS IN THE INFRATENTORIAL AND SUPRATENTORIAL BRAIN USING TUMOR TREATING FIELDS (TTFIELDS)
Authors: Shay Levi, Ariel Naveh, Ze’ev Bomzon, Eilon D Kirson, Uri Weinberg
Journal: Neuro-Oncology (2017)

TTFields is an antimitotic cancer treatment that utilizes low intensity (1–3 V/cm) alternating electric fields in the intermediate frequency (100–300 kHz). TTFields are delivered in two orthogonal directions using 2 pairs of transducer arrays placed on the patient’s scalp. TTFields are approved for Glioblastoma Multiforme (GBM) located in the supratentorial regions of the brain. Infratentorial location of the tumor is rare in adult patients but common in the pediatric population. Infratentorial GBM presents with limited surgical treatment options and a poorer prognosis. Computational studies have shown a strong connection between the array layout and the field distribution within the supratentorial region. Here we present a computer simulations-based study designed to identify new array layouts that could deliver high field intensities concurrently to the supratentorial and infratentorial regions of the brain. To simulate delivery of TTFields to the brain, we used realistic computerized models of an adult human female and an adult male. We simulated various layouts involving placement of the arrays on the scalp and upper neck of the model. All tested layouts delivered field intensities with median intensities above the therapeutic threshold of 1 V/cm to both the infratentorial and supra-tentorial brain. The highest field intensities were delivered to the infratentorial region by a layout, in which each array of one pair was laterally placed superficially to the lower region of the occipital lobe, and the two arrays of the second pair were placed on the calvarium and the superior aspect of the neck. This work shows the feasibility of TTFields in treating tumors in the cerebellum, brain stem and surrounding regions which are located inferior to the tentorium. Careful selection of layouts should enable an effective treatment of multi-focal disease with tumors located in both supratentorial and infratentorial regions simultaneously.
OA 12.07 LOXO-292, a Potent, Highly Selective RET Inhibitor, in MKI-Resistant RET Fusion-Positive Lung Cancer Patients with and without Brain Metastases
Authors: V. Velcheti, T. Bauer, V. Subbiah, M. Cabanillas, N. Lakhani, L. Wirth, G. Oxnard, M. Shah, E. Sherman, S. Smith, T. Eary, S. Cruickshank, B. Tuch, K. Ebata, M. Nguyen, S. Corsi-Travali, S. Rothenberg, A. Drilon
Journal: Journal of Thoracic Oncology (2017)
Un brote de Campylobacter jejuni asociado al consumo de pollo, Copenhague, 2005
Authors: A Mazick, S Ethelberg, E Møller Nielsen, K Mølbak, M Lisby
Journal: Eurosurveillance (2006)

En Mayo-Junio de 2005, se declaro en Copenhague un brote de infecciones intestinales en empleados de varias companias. Los casos procedian de siete de las ocho firmas que recibian su comida del mismo centro de elaboracion. Las muestras de heces de tres pacientes de dos companias daban positivo para Campylobacter jejuni. Se llevo a cabo un estudio de cohorte retrospectivo entre los empleados que frecuentaban el comedor en las tres companias mas importantes, con el objetivo de identificar la fuente del brote y prevenir su diseminacion. Se recogieron las informaciones sobre la enfermedad, los dias de asistencia al comedor y los alimentos consumidos usando un cuestionario auto-administrado. Fue investigada la cocina del establecimiento de elaboracion y se tomaron muestras de alimentos. De los 348 empleados entrevistados, 295 (85%) rellenaron el cuestionario. Entre las 247 personas que comian en el comedor, fueron identificados 79 casos, lo que equivale a una tasa de ataque (TA) del 32%. Comer en el comedor el 25 de Mayo fue asociado con la enfermedad (TA 75/204, RR=3,2 ; 1,3-8,2). Solo el consumo de ensalada de pollo, en ese mismo dia, se asocio con la infeccion (TA=43/97, RR=2,3 ; IC 95% 1,3-4,1). Los empleados de la cocina indicaron la posibilidad de una contaminacion cruzada entre el pollo crudo y la ensalada de pollo durante el almacenamiento. 
Describimos aqui el primer brote de Campylobacter conocido asociado a pollo contaminado en Dinamarca. Es probable que el manejo de los alimentos haya contribuido a la transmision de la infeccion. Tras ese brote, los empleados de la cocina fueron sensibilizados hacia unas buenas practicas de manejo y de conservacion de los alimentos. El escaso numero de muestras positivas en ese brote sugiere una sub-estimacion general (por un factor 20) de los casos adultos por el sistema de notificacion de laboratorio.
P1.02-043 A Comparison of Consistency of Detecting BRAF Gene Mutations in Peripheral Blood and Tumor Tissue of Non-Small-Cell Lung Cancer Patients
Authors: M. Fang, W. Wang, C. Xu, X. Liao, Y. Zhu, K. Du, W. Zhuang, Y. Chen, G. Chen, T. Lv, Y. Song
Journal: Journal of Thoracic Oncology (2017)
Utility of Growth Differentiation Factor-15, A Marker of Oxidative Stress and Inflammation, in Chronic Heart Failure
Authors: Abhinav Sharma, Susanna R. Stevens, Joseph Lucas, Mona Fiuzat, Kirkwood F. Adams, David J. Whellan, Mark P. Donahue, Dalane W. Kitzman, Ileana L. Piña, Faiez Zannad, William E. Kraus, Christopher M. O’Connor, G. Michael Felker
Journal: JACC Heart Failure (2017)
P3.10-002 Implementing an Innovative Distress/Supportive Care Screening Tool in a Lung Cancer Clinic
Authors: M. Pasquinelli, Z. Deliu, D. Rosenberg, C. Weldon, S. Obilade, A. Shah, A. Gordon, M. Carpinelli, E. Knightly, L. Feldman
Journal: Journal of Thoracic Oncology (2017)
Reasons to Amplify the Role of Parental Permission in Pediatric Treatment
Authors: Mark Christopher Navin, Jason Adam Wasserman
Journal: The American Journal of Bioethics (2017)

Two new documents from the Committee on Bioethics of the American Academy of Pediatrics (AAP) expand the terrain for parental decision making, suggesting that pediatricians may override only those parental requests that cross a harm threshold. These new documents introduce a broader set of considerations in favor of parental authority in pediatric care than previous AAP documents have embraced. While we find this to be a positive move, we argue that the 2016 AAP positions actually understate the importance of informed and voluntary parental involvement in pediatric decision making. This article provides a more expansive account of the value of parental permission. In particular, we suggest that an expansive role for parental permission may (1) reveal facts and values relevant to their child's treatment, (2) encourage resistance to suboptimal default practices, (3) improve adherence to treatment, (4) nurture children's autonomy, and (5) promote the interests of other family members.