tbuckley/cabot-search huggingface dataset:
SCDT-30. SURGICAL IMPLANTATION OF AN OSMOTIC PUMP FOR CONVECTION ENHANCED DELIVERY INTO DIPG XENOGRAFT MURINE MODELS
Authors: Kathleen Knudson, Sridevi Yadavilli, Roger Packer, Javad Nazarian
Journal: Neuro-Oncology (2017)

Diffuse intrinsic pontine gliomas (DIPG) are fatal, high-grade tumors arising in the pons of children. Convection-enhanced delivery (CED) is a method for directly delivering agents into the tumor, bypassing the blood brain barrier. CED can achieve effective long-term continuous administration when connected to an osmotic pump filled with chemotherapeutic agents. Our objective is to optimize the technique for placement of the CED cannula carrying an osmotic pump into the tumor of preclinical DIPG mouse models. Using agarose gel, Evans blue dye (EBD) was injected at various rates to determine area of distribution. Then, an osmotic pump with a capacity to infuse 100ml over 28 days was used in two cohorts of mice. A cannula was stereotactically implanted into the pons in both cohorts and connected to a subcutaneously placed osmotic pump loaded with EBD or DII. The first cohort assessed the feasibility of implantation into the pons. The second cohort was transplanted with murine DIPG cells and allowed to develop pontine tumors before cannula implantation. The EBD/DII signal was evaluated and compared to tumor cell location to assess delivery to targeted site and distribution. We have established a methodology for surgical implantation of a cannula attached to an osmotic pump into mouse pons, and assessed the distribution of EBD/DII in healthy as well as tumor bearing murine models of DIPG. We also show that CED cannula installation does not affect the overall survival of the mouse. We show that precise pontine delivery of cargo (dye) has optimal distribution within the pons, tissue integrity is not compromised, and more importantly, does not alter overall survival. This technique will serve as a platform for rapid assessment of tumor response to therapeutic agents. An effective agent can then be translated in clinical setting through upcoming clinical trials.
Estrogen receptor mutation: a new strategy to overcome endocrine resistance
Authors: A. Moretti, L. Lupini, I. Carandina, C. Bassi, L.R. Martella, F. Lancia, F. Daniel, L. Belluomini, I. Toma, E. Bannò, C. Nisi, L. Da Ros, P. Querzoli, M. Negrini, A. Frassoldati
Journal: Annals of Oncology (2017)
ACTR-48. AN APPRAISAL OF THE IMPACT ON SURVIVAL OF NEOADJUVANT TREATMENTS DELAYING RADIOTHERAPY IN ‘ONLY-BIOPSIED GLIOBLASTOMA’ TRIALS CONDUCTED BY THE GEINO GROUP COMPARED TO PATIENTS TREATED WITH THE STUPP’S REGIME. EXPERIENCE OF THE GEINO AND THE GLIOCAT GROUP
Authors: Carme Balana, Iris Teruel, Anna Estival, Eugenia Verger, Juan Sepulveda, Estela Pineda, Maria Martinez Garcia, Oscar Gallego, Raquel Luque, Miquel Gil Gil, Carlos Mesia, Sonia Del Barco, Jose Maria Velarde, Juan Jose Garcia Mosquera, Ana Herrero, Salvador Villa, Ramon de las Penas
Journal: Neuro-Oncology (2017)

We aimed to study differences in outcome and the effect on overall survival (OS) of radiotherapy delays in glioblastoma (GB) patients included in three NeoAdjuvant trials (NAT) conducted by the Spanish Group for Research in Neurooncology (GEINO) compared to similar patients treated with the Stupp’s treatment (SR) from the data base of the GLIOCAT project. Three neo-adjuvant (NAT) trials including ‘only biopsy GB patients were conducted by the Group between 2003–2015: GBM99 (3 cycles of TMZ and Cisplatin before RT: 30 patients; J.Neurooncol 70; 2004), GENOM 008 (2 months of sunitinib before RT with TMZ or sunitinib: 12 patients; Target Oncol 9; 2014) and the GENOM 009 (Randomized phase II between TMZ (35 patients) or TMZ and BEV (42 patients) for 2 cycles; J Neurooncol 127, 2016). Patients (p): NAT: 119, SR: 96. mOS: NAT: 8.8m, SR: 8.3m; p=0.77. Median time to start RT was 3 months for NAT p and 1 month in SR p. Age (≤65), PS (≤1) and MMSE (≥27) conferred better OS, MGMT status was NS at the univariate analyses. NAT p had better PS than SR p (35% vs 65%; P=0.018). At the multivariate analyses (PS, MMSE, Age, NAT or SR) only methylated MGMT was positively associated with a better OS. Worse OS was found for patients that started RT within 4 weeks. A multivariate analyses including MGMT status, NAT or SR, Age, PS, RT start within 4weeks, 4-8weeks, 8-12weeks o > 12weeks, disclosed that only starting radiotherapy within 4 weeks was a significant factor for worse OS. NAT patients lived similar than ST patients. Delays of RT treatment after 4, 8, or 12 weeks did not impact OS as independent variables in NAT.
P3.13-030 Metabolic Parameters of FDG PET at Early Evaluation of NSCLC Differ with Histological Subtypes
Authors: Y. Landman, M. Nidam, L. Domachevsky, E. Dudnik, N. Peled, D. Groshar, H. Bernstein, A. Zer
Journal: Journal of Thoracic Oncology (2017)
Posology for Regenerative Therapy
Authors: Andre Terzic, Atta Behfar
Journal: Circulation Research (2017)

Sola dosis facit venenum (The dosage makes it either a poison or a remedy) -Paracelsus (1493-1541)T he science of dosage or posology (from Greek posos, how much, and logos, study) is a branch of pharmacology and therapeutics concerned with treatment dosage and dosage regimen.Establishing optimum dosage underpins every clinical development plan for novel therapeutic candidates.Failure to select the adequate drug dose is a leading culprit for regulatory delays or denial of initial applications for new drugs and, more generally, inadequate dose selection contributes to the high attrition rate of pivotal clinical trials.
Case 34-2017
Authors: Jennifer L. Lyons, Pamela W. Schaefer, Tracey A. Cho, Marwan M. Azar
Journal: New England Journal of Medicine (2017)

A 76-year-old man was admitted to the hospital because of weakness and fever. Seventeen days earlier, he had presented with fatigue, weight loss, and guaiac-positive stool. Within 12 hours after admission, altered mental status developed. A diagnostic test was performed.
P3.04-010 Validation of a ctDNA Methylation Assay to Differentiate Benign and Malignant Pulmonary Nodules: A Chinese Nationwide Multi-Center Study
Authors: W. Liang, J. He, X. Zhi, F. Yu, C. Cheng, Z. Wang, K. Cai, G. Jiang, C. Chen, Q. Luo, L. Chen, J. Hu, L. Liu, X. Li, Q. Wu, S. Xu, J. Liu, Y. Yang, H. Tian, X. Cai, J. Fan
Journal: Journal of Thoracic Oncology (2017)
El Centro europeo para la prevención y el control de las enfermedades
Authors: G Gouvras
Journal: Eurosurveillance (2004)

La ceremonia inaugural del Centro europeo para la prevencion y el control de las enfermedades tuvo lugar en Estocolmo el 27 de septiembre de 2004*. Esto marco el inicio de una nueva epoca para la vigilancia y el control de las enfermedades transmisibles.
El desafio mundial que representan las enfermedades transmisibles emergentes y reemergentes y, particularmente, las recientes amenazas de emision intencionada de agentes patogenos pusieron de manifiesto las inadecuaciones y los puntos debiles de los sistemas y planes de defensa nacionales e internacionales. Jamas se habia percibido de forma tan evidente y unanime la necesidad de una cooperacion mas estrecha entre organizaciones globales, como la Organizacion Mundial de la Salud (OMS) o la Union Europea (UE) y los paises individuales. La lucha frente a las amenazas para la salud que exige una respuesta rapida permitio reforzar la colaboracion entre los Estados miembros y las instituciones centrales de una Union Europea sin fronteras, donde cada dia millones de personas se mueven libremente y donde mercancias de toda clase son transportadas rapidamente a grandes distancias. Esta estructura europea supone que los riesgos de transmision de agentes patogenos son mayores si no se toman medidas para eliminar el problema en el origen. 
*Nota de la redaccion : los miembros del Comite de Direccion del Centro
TMOD-48. SNAIL1 REGULATES GLIOMAGENESIS INDEPENDENT OF ITS MESENCHYMAL TRANSFORM FUNCTION
Authors: Dongjiang Chen, Nagheme Thomas, Mohamed Kabbout, Diem-Hang Nguyen-Tran, Changwang Deng, Son Le, David Tran
Journal: Neuro-Oncology (2017)

Master mesenchymal factors such as Snail1 have long been implicated in local invasion and metastasis of various cancers including malignant brain tumors such as glioblastoma (GBM). However, mesenchymal factors are expressed early in tumorigenesis, well before first evidence of metastatic cells, suggesting that these factors have other critical functions independent of their mesenchymal regulation. We used a highly penetrant, retrovirally-delivered, PDGFB-induced mouse model of gliomagenesis in a conditional PTEN and/or P53 knockout background to produce GBM tumors of the proneural subtype, in which Snail1 expression is much lower compared to the mesenchymal subtype. We then examined the effect of conditional KO of Snail1 in glial cells when PDGFB overexpression occurred, using in vitro and in vivo loss-of-function experiments augmented by RNAseq expression profiling and computational network analysis. Snail1 expression peaked early in gliomagenesis although its expression is downregulated once PDGFB-induced proneural tumors are formed. In an immune intact background, Snail1-null GBM developed at a much slower pace. Snail1 cooperated with oncogene activity to promote higher transformative capacity and to influence the cancer stem cell compartment. Our data confirms a dual role for Snail1 in GBM progression, in which it cooperates with oncogenes to promote early transformation while independently also regulating mesenchymal changes at later stages of tumor development. Our platform combining RNAseq expression profiling and computational network analysis with biological validation provides a potentially powerful tool to study mechanistic events as gliomagenesis and proneural subtype GBM transformed into mesenchymal subtype GBM.
RARE-12. MINIMIZING FALLOUT WHILE MAXIMIZING EFFICACY IN TREATING EBV POSITIVE PRIMARY CNS POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE (PCNS-PTLD): RECOGNIZING THE ENTITY IN RENAL TRANSPLANT PATIENTS
Authors: Na Tosha Gatson, Jeffrey Summers, Maria Bermudez, Leonard Gitter, Omotayo Fasan
Journal: Neuro-Oncology (2017)

PCNS-PTLD is a rare complication following solid organ transplantation (SOT) and is a distinct entity from primary CNS lymphoma (PCNSL). With fewer than 100 cases reported since 1970, there is no standard of care for PCNS-PTLD. Existing data supports combining reduction of immunosuppression (RI), whole-brain radiotherapy, monoclonal antibody therapy, and systemic/IT chemotherapy. Treating kidney SOT (kSOT) PTLD is complicated by reduced renal clearance, contrast-dye restrictions, and nephrotoxicity. Treatment complications and allograft rejection cause early morbidity and mortality. Rapid identification of serum/CSF supporting diagnostic markers such as active EBV replication, elevated CSF protein, and positive cytology and flow cytometry is critical. We report two cases of mixed B/T-cell PTLD in kSOT patients >10 years on immunosuppression (steroids, mycophenolate, tacrolimus/sirolimus) who presented with focal and cognitive neurologic deficits. Brain MRI revealed multiple supra- and infratentorial lesions. Patients with confirmed CNS-isolated disease were treated with partial-RI (off mycophenolate) and dexamethasone prior to initiation of rituximab (375mg/m2) x4 weekly cycles. With objective response, patients underwent consolidative rituximab therapy q21-days x4 cycles and restaged. Residual enhancing lesions were treated by stereotactic radiosurgery along with 2-4 cycles of temozolomide chemotherapy (150mg/m2) days 1-5 on a 28-day cycle. With this strategy, both patients achieved a complete response. PCNS-PTLD long-term survival is one distinguishing feature from PCNSL. With multiple treatment obstacles in kSOT PTLD, maximized targeting and step-wise addition of minimally toxic regimens can improve patient outcomes. This data challenges traditional paradigms about diagnosis and treatment of PTLD, specifically EBV+ disease occurring >6 years post SOT. We propose that the brain’s specialized immune microenvironment permits EBV driving of neoplastic progression and that this process is particularly sensitive to B-cell targeting concurrent with partial restoration of host immunity achieved by minimal RI. Subsequent SRS, temozolomide therapy, and partial immunosuppression helps maintain patient quality-of-life and reduce risk for allograft rejection.
SRAS: Estudio de cohorte retrospectivo en huéspedes alemanes del Hotel 'M', Hong Kong
Authors: D Radun, M Niedrig, A Ammon, K Stark
Journal: Eurosurveillance (2003)

Hong Kong desempeno un papel fundamental en la diseminacion internacional del Sindrome Respiratorio Agudo Severo (SRAS): un medico alojado en el Hotel 'M' en la noche del 21-22 de febrero de 2003 fue identificado como el caso indice de cuatro agrupaciones nacionales e internacionales de SRAS. Simultaneamente con el estudio de colaboracion internacional dirigido por la OMS y los Estados Unidos, se realizo un estudio retrospectivo de la cohorte de personas alemanas hospedadas en el Hotel 'M'. Los criterios de inclusion abarcaron el periodo comprendido entre el 21 de febrero al 3 de marzo de 2003 para permitir la deteccion de casos posiblemente debidos a una contaminacion ambiental. En los veintiun huespedes alemanes de los que se supo que permanecieron en el Hotel M durante este periodo, se encontro un caso de SRAS con confirmacion microbiologica. Los antecedentes del caso sugieren que en la transmision puede haber intervenido una proximidad al paciente indice. En linea con los hallazgos de las investigaciones ambientales llevadas a cabo en el hotel, la contaminacion ambiental debe considerarse un origen posible de la infeccion.
Elevated lung clearance index in infants with cystic fibrosis shortly after birth
Authors: Elisabeth Kieninger, Sophie Yammine, Insa Korten, Pinelopi Anagnostopoulou, Florian Singer, Urs Frey, Anne Mornand, Maura Zanolari, Isabelle Rochat, Daniel Trachsel, Dominik Mueller-Suter, Alexander Moeller, Carmen Casaulta, Philipp Latzin
Journal: European Respiratory Journal (2017)

It is not known at what age lung function impairment may arise in children with cystic fibrosis (CF). We assessed lung function shortly after birth in infants with CF diagnosed by newborn screening. We performed infant lung function measurements in a prospective cohort of infants with CF and healthy controls. We assessed lung clearance index (LCI), functional residual capacity (FRC) and tidal breathing parameters. The primary outcome was prevalence and severity of abnormal lung function (±1.64 z-scores) in CF. We enrolled 53 infants with CF (mean age 7.8 weeks) and 57 controls (mean age 5.2 weeks). Compared to controls, LCI and FRC were elevated (mean difference 0.30, 95% CI 0.02–0.60; p=0.034 and 14.5 mL, 95% CI 7.7–21.3 mL; p&lt;0.001, respectively), while ratio of time to peak tidal expiratory flow to expiratory time was decreased in infants with CF. In 22 (41.5%) infants with CF, either LCI or FRC exceeded 1.64 z-scores; three infants had both elevated LCI and FRC. Shortly after birth, abnormal lung function is prevalent in CF infants. Ventilation inhomogeneity or hyperinflation may serve as noninvasive markers to monitor CF lung disease and specific treatment effects, and could thus be used as outcome parameters for future intervention studies in this age group.
Une importante épidémie d’ E. coli O157 en 2005 en Irlande
Authors: M Mannix, D Whyte, E McNamara, N O’Connell, R FitzGerald, M Mahony, T Prendiville, T Norris, A Curtin, A Carroll, E Whelan, J Buckley, J McCarthy, M Murphy, T Greally
Journal: Eurosurveillance (2007)

En octobre-novembre 2005, a eu lieu l’epidemie d’infections a Escherichia coli produisant des verocytotoxines (VTEC) la plus importante jamais enregistree en Irlande. Dix-huit cas avec des cultures positives pour E. coli O157, lysotype 32, positifs aux verocytotoxines 2, ont ete identifies dans une zone rurale restreinte au centre-ouest de l’Irlande. La moitie des patients etaient asymptomatiques. Deux enfants ont ete hospitalises avec un syndrome hemolytique uremique, dont l’un a necessite une dialyse peritoneale. Tous deux se sont retablis. Les 18 profils d’electrophorese en gel pulse (PFGE) etaient indiscernables ou tres proches. Neuf patients avec VTEC O157 etaient des enfants d’âge pre-scolaire qui frequentaient deux creches locales. Plusieurs des patients etaient apparemment exposes a un systeme prive de distribution d’eau (GWS) peu fiable dans une zone agricole. Les analyses microbiologiques n’ont pas permis de detecter de VTEC dans les aliments ou l’eau. Un echantillon veterinaire (un prelevement rectal animal) s’est revele positif pour E. coli O157 et le profil PFGE de cette souche etait indiscernable de celui de la souche epidemique. Une etude cas-temoin a mis en evidence l’existence d’un risque lie a une exposition potentielle au systeme de distribution d’eau GWS sans que ce risque ne soit associe a une consommation rapportee de cette eau. La selection des cas et des temoins a ete difficile. La transmission a d’abord eu lieu dans des environnements dedies aux enfants et a l’interieur des familles, avec une dissemination significative de personne a personne. Les mesures de controle ont consiste en une fermeture volontaire des creches, une exclusion des personnes appartenant aux groupes a risque et dont les cultures etaient positives jusqu’a confirmation des analyses microbiologiques. De plus, il a ete recommande de bouillir l’eau avant de la consommer en attendant la desinfection des installations.
Injuries in female and male elite taekwondo athletes: a 10-year prospective, epidemiological study of 1466 injuries sustained during 250 000 training hours
Authors: Ki Jun Park, Brian Byung Song
Journal: British Journal of Sports Medicine (2017)

We aimed to determine the injury patterns associated with training activities in elite South Korean taekwondo athletes training for the Olympic Games.We collected data prospectively from 2007 to 2016 at the Korea National Training Center in Seoul, South Korea. A sports injury was defined as acute or chronic musculoskeletal signs and symptoms due to taekwondo activities during training sessions. Athletes were assessed by an on-site sports medicine specialist. The elite taekwondo athletes were stratified according to sex, weight class (flyweight, featherweight, welterweight and heavyweight), injury location (body region and site) and injury severity (mild or level I, requiring treatment for 1-3 days; moderate or level II, requiring treatment for 4-7 days; or severe or level III, requiring treatment for ≥8 days).Athlete exposure was 56 160 training sessions that took 249 600 hours. 1466 injuries were recorded in 283 athletes, with an average of 4.6 injuries per athlete annually. Of these, more than half (56%) were mild injuries, with most injuries occurring in the lower extremities (65.5%), followed by injuries to the trunk (16%), upper extremities (14%) and head and neck area (4%). Among these athletes, women had higher injury rates in the featherweight and welterweight categories (P≤0.0001), but there were no sex differences in other weight categories. In general, female athletes and male athletes experienced a comparable risk of injury (relative ratio: 1.55; 95% CI 0.89 to 2.68).In elite South Korean taekwondo athletes, most injuries occur in the lower extremities and were graded as minor. Injury severity depended on weight class.
Infecções por virus coxsackie em 2002 na Grecia : verdadeira epidemia ou efeito mediático?
Authors: M Exindari, G Gioula, D Raptis, V Mavroidi, E Bouzia, V Kyriazopoulou
Journal: Eurosurveillance (2005)

O objetivo de nosso estudo era fornecer provas da existencia de um surto de virus coxsackie B em 2002 na Grecia. Os dados sobre infeccoes recentes confirmados por laboratorio entre 1998 e 2001 foram comparados com os dados de 2002. 
As infeccoes foram confirmadas serologicamente por deteccao de anticorpos IgM para o virus coxsackie B1-B6 por meio da immunofluorescencia indirecta. Foram analisados os soros de 2 701 pacientes residentes no norte da Grecia e suspeitos de sofrer de infeccoes por este virus: 2.056 pacientes entre 1998 e 2001, e 645 em 2002. 
A comparacao entre os resultados confirmados por laboratorio e os datos disponiveis entre os dois periodos mostrou que : 
-	O numero total de pacientes examinados por ano foi superior em 2002 (645 comparado com a media anual de 541 em 1998-2001). 
-	A proporcao de infeccoes recentes confirmadas por laboratorio foi inferior em 2002 (27,8% comparado com 32,7%) e a incidencia estimada foi de 0,66/10 000 em 2002 e de 0,32-0,84/10.000 para 1998-2001.
-	A distribucao por idade era differente : a proporcao de casos em criancas frente a casos em adultos estava invertida em 2002 comparada com 1998-2001, com uma maior proporcao de casos nas criancas em 2002. A differenca entre os dois periodos foi estatisticamente significativa. O grupo etario mais afectado em 2002 foram as criancas entre 3 e 5 anos. 
-	A distribuicao por estacao foi a mesma nos dois periodos (com picos em primavera e em outono). Em 2002, ocorreram tres obitos em Abril, mas nenhum em 1998-2001. 
-	Os sindromes clinicos implicados tambem eram differentes : os casos de infeccoes respiratorias, principalmente pneumonia, subiram de 5,75% a 24,3% em criancas em 2002, e os casos de miopericarditis subiram em adultos de 13% em 1998-2001 a 29,5% em 2002. 
Este ultimo resultado, combinado com a implicacao das medias (devido aos tres casos fatais), e o panico gerado em seguida na populacao, sugeriram a existencia de um surto, embora os dados obtidos em nosso estudo nao permitam de confirmar essa hipotese.
Glioblastoma and chemoresistance to alkylating agents: Involvement of apoptosis, autophagy, and unfolded protein response
Authors: Sabine Hombach-Klonisch, Maryam Mehrpour, Shahla Shojaei, Craig Harlos, Marshall Pitz, Ahmed Hamai, Krzysztof Siemianowicz, Wirginia Likus, Emilia Wiechec, Brian D. Toyota, Reyhane Hoshyar, Amir Seyfoori, Zahra Sepehri, Sudharsana R. Ande, Forough Khadem, Mohsen Akbari, Adrienne M. Gorman, Afshin Samali, Thomas Klonisch, Saeid Ghavami
Journal: Pharmacology & Therapeutics (2017)
Abstract 15110: Identification of the Characteristic Collateral Source in Patients With Arteriosclerosis Obliterans
Authors: Yuichiro Arima, Seiji Hokimoto, Noriaki Tabata, Osamu Nakagawa, Asahi Oshima, Yosuke Matsumoto, Takahiro Sato, Toshifumi Mukunoki, Jun Otani, Michie Uchikawa, Eiichiro Yamamoto, Yasuhiro Izumiya, Koichi Kaikita, Hisao Ogawa, Koichi Nishiyama, Kenichi Tsujita
Journal: Circulation (2017)

Introduction: Arteriosclerosis obliterans is a type of representative peripheral artery disease. Insufficient blood supply to the lower limb causes intermittent claudication, with severe ischemia, ...