tbuckley/cabot-search huggingface dataset:
Abstract 12448: AMPKα1 Knockout Mice Have Dysfunctional Perivascular Adipose Tissue (PVAT) and Impaired Vascular Function
Authors: Tarek A Almabrouk, Alex Riddell, Aziza B Ugusman, Ian P Salt, Simon Kennedy
Journal: Circulation (2016)

Introduction: Perivascular adipose tissue (PVAT) surrounds blood vessels and releases many mediators which regulate vascular tone. AMP-activated protein kinase (AMPK) is a critical regulator of cellular metabolism and although expressed throughout the vessel wall, its function in PVAT is unknown. Although aortic PVAT from mice with global AMPKα1 knockout releases significantly less adiponectin and does not augment vasodilator responses in isolated vessels, these mice remain normotensive. Hypothesis: Mice with global AMPKα1 deficiency will have inflamed PVAT and that high fat feeding will increase PVAT inflammation further and raise blood pressure. Methods: Unfixed samples of wild-type (WT) and KO aortic PVAT (n&gt;3 for each) were incubated with dihydroethidium (DHE) or 4,5 diaminofluorescein diacetate (DAF-2DA) to detect superoxide and NO respectively. Images were captured using a fluorescence microscope. Nitrotyrosine expression and macrophages in the PVAT were examined using immunohistochemistry and FACS respectively. Matched KO and WT littermates were fed either chow diet or hfd (21% lard, 0.15% chol.) for up to 12 weeks and BP measured by tail-cuff plethysmography every 4 weeks. Measurement of vascular function in aortic rings was via wire myography and adiponectin release was measured using ELISA assay. Results: In aortic PVAT, superoxide and NO production was unchanged in KO mice but nitrotyrosine expression and macrophage content was significantly higher. In WT mice, 12 weeks of hfd attenuated vasodilator responses of aortic rings containing PVAT (n=6; p&lt;0.05) and reduced adiponectin production by PVAT. In KO rings containing PVAT the vasodilator response was already suppressed and hfd did not lower it further or alter production of adiponectin. High fat diet increased PVAT macrophage content of both WT and KO but did not alter mean arterial BP after 8 weeks in either strain. Conclusions: AMPK in aortic PVAT regulates production of adiponectin and suppresses inflammation. Mice lacking AMPKα1 lose the beneficial effects of PVAT on vascular relaxation and while fat feeding increases inflammation of the PVAT, BP did not rise, perhaps through compensation effects in smooth muscle or endothelial function.
P3.04-013 Phase 1 Study of the Anti-HER3 Antibody Drug Conjugate U3-1402 in Metastatic or Unresectable EGFR-Mutant NSCLC
Authors: P. Jänne, H. Yu, M. Vigliotti, N. Shipitofsky, J. Singh, F. Guevara, C. Yu
Journal: Journal of Thoracic Oncology (2017)
La vigilancia de los resultados del tratamiento antituberculoso - ¿es momento de actualizar las recomendaciones europeas?
Authors: D Falzon, J Scholten, A Infuso
Journal: Eurosurveillance (2006)

En este trabajo son objeto de discusion los resultados de la vigilancia del tratamiento antituberculoso y la adherencia de los paises de la region Europea de la Organizacion Mundial de la Salud (OMS), a los cambios introducidos en 2001 para mejorar la comparabilidad entre los paises.
Se compararon los resultados de tratamiento de los casos de tuberculosis pulmonar confirmada, notificados en 2001 y 2000. Se consideraba completa la notificacion cuando se disponia del resultado para el 98% o mas de los casos notificados al origen. Para los dos anos el periodo maximo de observacion era de 12 meses desde el inicio del tratamiento. En 2000, los resultados estaban clasificados como curacion, tratamiento completo, muerte, fracaso terapeutico, abandono, traslado y otro, no evaluado para las cohortes de nuevos casos o casos tratados previamente. En 2001, tras nuevos cambios, se pidio a los paises que vigilaran tambien los casos sin antecedentes de tratamiento y fueron anadidas otras dos categorias de resultados: continua en tratamiento, y desconocido.
De los 42 paises que declararon datos en el periodo de observacion, el 74% (31/42) tenia datos nacionales completos, comparado con el 50% (19/38) en 2000. Doce paises de los 21 que habian declarado datos en este periodo siguieron las recomendaciones. Se utilizaron las categorias abandono y traslado en lugar de desconocido. Entre los nuevos casos, 15 de los 31 paises utilizaron la categoria continua en tratamiento (1% a 15%). El fracaso terapeutico es raramente recogido en los paises de Europa occidental (l1%). 
La vigilancia europea de los resultados del tratamiento antituberculoso deberia incluir todos los casos pulmonares confirmados, aplicar el periodo de observacion estandar y las categorias revisadas, asi como utilizar de forma preferente datos individuales.
Comparative Efficacy of Colonoscope Distal Attachment Devices in Increasing Rates of Adenoma Detection: A Network Meta-analysis
Authors: Antonio Facciorusso, Valentina Del Prete, Rosario Vincenzo Buccino, Nicola Della Valle, Maurizio Cosimo Nacchiero, Fabio Monica, Renato Cannizzaro, Nicola Muscatiello
Journal: Clinical Gastroenterology and Hepatology (2017)
P2.01-053 Outcome of Clinical Management of Elderly and Younger Patients with NSCLC Inside a Private Institution (Oncosalud-AUNA)
Authors: J.M. Gutierrez Castañeda, C. Flores, R. Ruiz Mendoza, L.A. Mas Lopez, A. Aguilar, C. Vallejos, L. Pinillos-Ashton
Journal: Journal of Thoracic Oncology (2017)
La vigilancia de la sífilis y la evolución de la epidemia en Alemania desde mediados de los años 90
Authors: U Marcus, V Bremer, O Hamouda
Journal: Eurosurveillance (2004)

Segun informes recientes de vigilancia en Europa y Estados Unidos, el numero de casos de sifilis esta en aumento. Para un funcionamiento adecuado de los Programas de deteccion y de intervencion se necesita disponer de datos epidemiologicos precisos sobre la distribucion de la sifilis. El sistema aleman de declaracion de la sifilis fue modificado en 2001, y se basa en la notificacion de los laboratorios en lugar de los medicos. Este cambio fue acompanado por un nuevo sistema centinela de vigilancia de las infecciones de transmision sexual (ITS). 
Despues de haber alcanzado la tasa de notificaciones mas baja en los anos 1990, las declaraciones de sifilis aumentaron de nuevo de manera significativa desde 2001, fecha que coincide con la introduccion del nuevo sistema de notificacion. Este aumento de la incidencia no se debe unicamente a una sub-notificacion del sistema precedente, sino que refleja un verdadero aumento en el numero de casos . Este incremento esta relacionado con la aparicion de brotes de sifilis en hombres que tienen relaciones sexuales con otros hombres (HRSH); el primero de estos brotes fue en Hamburgo en 1997. En 2003, la incidencia era 10 veces mayor en hombres que en mujeres. Se estima que el 75% de los casos de sifilis diagnosticados actualmente son HRSH. 
Una gran proporcion de estos pacientes (hasta el 50%, segun los datos del sistema centinela) son positivos para el VIH. El numero creciente de casos de sifilis en heterosexuales en Alemania en los ultimos anos, comparado con otros paises de Europa occidental, podria ser debido a movimientos de poblacion frecuentes entre Alemania y regiones del Este y Sureste de Europa con alta incidencia de sifilis.
MA 09.11 Isotoxic Intensity Modulated Radiotherapy (IMRT) in Stage III Non-Small Cell Lung Cancer (NSCLC) – a Feasibility Study
Authors: K. Haslett, N. Bayman, K. Franks, N. Groom, G. Hanna, S. Harden, C. Harris, S. Harrow, M. Hatton, P. Mccloskey, F. Mcdonald, L. Ashcroft, D. Ryder, C. Faivre-Finn
Journal: Journal of Thoracic Oncology (2017)
Notes from a Practitioner's Day Book
Authors: C. Arnecaple
Journal: BMJ (1847)

ACAI}EMIE DES-SCIRNESi +PARIS.1. Tu:terculization of the bronchial glands is not confined to infancy, as has been thought, but may likewise occur in the adult.2. The disease may be a cause of sudden death by compression of the trachea and bronchial tubes.3, Independently of this sudden destruction, death may be produced by gradual compression of the same parts.4. The serous infiltrations which are obsexved in tlAi, conplaint, in both children and adults, are caused by compression of the nervous trunks. SPARKLING SYNCHISIS.T-his ophthalmic affection has again occupied the attatrtiosn of nAetnbers.M. Bruissbn has addreised a 14ttr to the Academy, in which he endeaVours to shi*, -that the m"oTing and glittering particles which characterize the disease, are not portions of the hyaloid membtane, but are fragments of a crystalline; nature, floating in the vitreous humour; and as he has as6ertained that this humour contains fatty matters in a state of solution, he thinks It probable that the 6h6lsterine becomes separated in the crystalline form, Und gives' ise 'to the sparkling appearance.M. Alphonse Robert presented a patient, the subject of the above affection, a woman of 60 years of age.For the space of a year she had been gradually, and without apparent cause, losing her sight.The pupil was regular, sligbtly dilated, but the iris had an antero.posterior oscillation.The lens was displaced, and was 'ftxid at' the inferior part of the vitreous humour.But ^the most remarkable appearance was that of a great number of shining spangles floating in the vitreous humour, some of which were constantly changing their place, others remaining more fixed.M. Robert considers also that they are crystals of cholesterine, either attached to the fragments of the hyaloid mem- brane, or floating free in the vitreous humour.
NIMG-62. RADIOLOGIC RESPONSE RATE OF IDH MUTANT GLIOMA FOLLOWING RADIATION TREATMENT: A RETROSPECTIVE ANALYSIS
Authors: Julie Miller, Shilpa Tummala, Tristan Penson, Tareq Juratli, Franziska Loebel, Daniel Cahill
Journal: Neuro-Oncology (2017)

IDH mutant gliomas are typically slow-growing and non-contrast enhancing on MRI. Standard-of-care treatment of high risk IDH mutant tumors involves radiation followed by chemotherapy. At present, there are no large studies that have formally characterized the radiologic response of IDH mutant tumors to radiation treatment. We performed a retrospective review of 160 cases of IDH mutant glioma who received post-operative radiation treatment (RT) +/- chemotherapy and had follow-up MRI with T1, T1 post-contrast, T2 and FLAIR sequences available for review. We determined the mean tumor diameter, defined as the cubic root of the three largest tumor diameters, at post-surgical baseline and at 6, 12 and 24 months following RT completion. Radiologic response rate at each of these timepoints was determined using Radiologic Assessment in Neuro-Oncology-Low Grade Glioma criteria (RANO-LGG). Complete analysis has been performed on a subset of cases (N = 99) and suggests that during the follow-up period of up to 2 years post-RT, the vast majority of patients with IDH mutant gliomas experience a stable disease (SD) response as defined by RANO-LGG. No minor responses (MR), defined as a 25% or less decrease in tumor area, have been observed at 1 and 2 years. Further quantitative analyses are ongoing. These data indicate that RT +/- chemotherapy for IDH mutant glioma rarely results in tumor shrinkage, as measured by RANO-LGG criteria. Appropriate power for surrogate endpoints such as radiologic response rate will be critical in the design of future clinical trials examining novel therapies for newly diagnosed IDH mutant gliomas. This dataset provides a cohort that can serve as a historical comparator for future studies of novel therapeutic approaches.
MA 03.06 Effect of 2L Ramucirumab after Rapid Time to Progression on 1L Therapy: Subgroup Analysis of REVEL in Advanced NSCLC
Authors: M. Reck, F. Shepherd, M. Pérol, F. Cappuzzo, J. Shih, K. Park, K. Winfree, E. Alexandris, P. Lee, A. Sashegyi, E. Garon
Journal: Journal of Thoracic Oncology (2017)
Infecções humanas por H5N1 : tantos casos – porquê ainda se sabe tão poco ?
Authors: A Nicoll
Journal: Eurosurveillance (2006)

O numero deste mes contem um destaque sobre clusters de infeccoes por H5N1 humanas no Azerbaijan [1]. Este evento e raro por varias razoes. A fonte parece estar ligada com aves silvestres , o que esta relatado pela primeira vez. A leitura do que aconteceu tranquiliza no entanto, pois as pessoas infectadas provavelmente mataram e desplumaram cisnes infectados. Isso significa que nao e uma exposicao occasional a aves silvestres, mas pode se comparar com uma exposicao proxima a aves domesticas doentes, o que continua a ser o factor de risco mais potente (um estudio analitico recente revelou um odds ratio de 29 [2]).
Abstract 19704: Tribbles Homolog-1 (Trib1) Deficiency Promotes Hyperlipidemia, Inflammation and Atherosclerosis in Mice Lacking the LDL-Receptor
Authors: Lilli Arndt, Doreen Moos, Janine Dokas, Joachim Thiery, Jan L Breslow, Ralph Burkhardt
Journal: Circulation (2016)

TRIB1  was recently identified in genome-wide association studies as a novel candidate gene influencing the concentration of plasma lipids and the development of coronary artery disease. The aim of the present study was to analyze the consequences of  Trib1 -deficiency on lipid metabolism and atherosclerotic lesion formation in atherosclerosis-susceptible LDL-receptor knockout mice ( Ldlr -/-  ).   Trib1  -/-  mice were crossed onto the  Ldlr  -/-  background to generate double knockout mice ( Trib1 -/- Ldlr  -/- ) and fed a semisynthetic, modified AIN76 diet (0.02% cholesterol). At 20 weeks of age,  Trib1 -/- Ldlr  -/-  mice exhibited 7.4-fold larger (457763 vs. 62127 μm 2 , p Trib1 +/+ Ldlr  -/-  littermate controls. Further, we observed significantly elevated plasma total cholesterol (TC) and triglyceride (TG) levels in  Trib1 -/- Ldlr  -/-  mice (TC: 1024 vs. 609mg/dL, p Trib1 -/- Ldlr  -/-  mice. Hepatic inflammation was corroborated by histological analysis, revealing infiltration of inflammatory cell clusters and higher expression of macrophage marker CD68 in livers of  Trib1 -/- Ldlr  -/-  mice. Concomitantly, plasma levels of Interleukin-6 were 3.6-fold higher (9.9 vs. 2.7 pg/ml; p Trib1 -/- Ldlr  -/-  mice.  In conclusion, we provide experimental evidence for the first time that the novel lipid candidate gene  Trib1  modulates atherosclerotic lesion formation. In  Ldlr -/-   mice,  Trib1 –deficiency increases plasma VLDL-C and VLDL-TG levels and causes hepatic inflammation, which likely contributes to the exacerbation of atherosclerotic lesion formation. Additional functional studies are necessary to unravel the precise molecular mechanisms by which  Trib1  regulates lipoprotein metabolism and inflammation.
PATH-04. DISTINGUISHING PINEOBLASTOMA FROM MEDULLOBLASTOMAS USING TISSUE MASS SPECTROMETRY IMAGING
Authors: David Calligaris, Amanda Clark, Laura Kallay, Daniel Pomeranz Krummel, Jeffrey Agar, Matthew Schniederjan, Scott Pomeroy, Nathalie Y Agar, Soma Sengupta
Journal: Neuro-Oncology (2017)

Medulloblastoma (MB) is a common pediatric malignant primary brain tumor originating in the posterior fossa. There are four molecular subgroups of MB: Wnt, Shh, Group 3, and Group 4. Interestingly, MB was originally included in the primitive neuroectodermal tumor (PNET) class together with pineoblastoma. An approach that could accurately distinguish the MB tumors and pineoblastoma based on their molecular composition would bring additional information on these tumor types. MALDI mass spectrometry imaging (MALDI MSI) is a powerful technique to investigate the distribution of molecules within tissue sections. Studies have shown that MALDI MSI can be used to classify different tissue types by obtaining comprehensive lipid molecular signatures. We performed MALDI MSI analyses using a Fourier transform ion cyclotron resonance mass spectrometer on seven MB samples from the different MB subgroups and one pineoblastoma. The mass spectrometry analyses indicated that it is possible to distinguish the pineoblastoma and the medulloblastomas according to their lipid signatures. The proposed research has the potential to pave the way for more comprehensive diagnostic approaches of MB, other pediatric brain tumors and can be extended to other neurological disorders.
P2.03-007 Loxoprofen Prevents EGFR-TKI-Related Skin Rash in Non-Small Cell Lung Cancer Patients: A Single-Center Retrospective Study
Authors: Y. Iimura, H. Shimomura, K. Imanaka, G. Yamaguchi, N. Kawasaki, C. Konaka
Journal: Journal of Thoracic Oncology (2017)
P2.02-046 Assessment of PDL1 and Immunoprofiling Using Multiplex Quantitative Immunofluorescence in Lung Cancer: Clinical Implications
Authors: T. Prieto, C. Fahrat, T. Takagaki, J. Rodriguez-Canales, I. Wistuba, V. Capelozzi, E. Parra Cuentas
Journal: Journal of Thoracic Oncology (2017)
Targeting CTP synthetase in pediatric malignancies by the European consortium “Innovative Therapies for Children with Cancer”
Authors: Ac Verschuur, Ml Den Boer, G. Vassal, Abp Van Kuilenburg, R. Versteeg, M. Serra, C. Lanvers, O. Delattre, K. Pritchard Jones, J. Shipley, T. Pietsch, B. Geoerger, J. Boos, R. Pieters, H. N. Caron
Journal: Cancer Research (2006)

4324   On behalf of ITCC Biology and Preclinical Evaluation Committee Innovative Therapies for Children with Cancer (ITCC) is a European consortium of ± 30 pediatric oncology clinical centres in five European countries for early clinical trials, and a consortium of 9 laboratories for the preclinical evaluation of targeted anti-cancer compounds in childhood cancer models (ITCC Biology). This ITCC Biology Consortium evaluates novel targeted anti-cancer compounds. Six high risk childhood cancers have been selected representing over 50% of therapy failures in children: neuroblastoma, Ewing sarcoma, rhabdomyosarcoma, acute lymphoblastic leukemia (ALL), medulloblastoma, osteosarcoma. The preclinical evaluation strategy consists of: 1. Target presence screening (mRNA profiles of ± 100 tumour samples per tumour type and of 95 cell lines (CL) representing the 6 tumour types) 2. In vitro drug efficacy screening on cell lines 3. In vivo drug efficacy screening using mouse xenografts 4. Target validation by siRNA Recently we screened the mRNA expression of the enzyme cytidine triphosphate synthetase (CTPs) by real-time quantitative (RTQ) PCR on the 24 cell lines of the ITCC core panel. CTPs is a key-enzyme for the pyrimidine (deoxy)ribonucleotide synthesis and has a high activity in various malignancies. Moreover, we performed in vitro incubations with the CTPs inhibitor Cyclopentenyl cytosine (CPEC, kindly provided from CTEP/NCI). Cell lines were incubated under their respective culturing and seeding conditions for 72H with 5 concentrations of CPEC. The anti-proliferative effects were measured by MTT-assay. Results: CTPs was expressed in all tumour types with the highest expression in osteosarcoma (70-530 AU, cut-off value >5 AU), ALL (80-210 AU) and neuroblastoma (65-220 AU. In vitro drug sensitivity to CPEC proved to be high in 4 out of 4 CL of ALL (72H IC50 34-46 nM) and neuroblastoma (IC50 35-49 nM, 1 cell line not sensitive).Three out of 4 Ewing sarcoma CL (IC50 337-491 nM), 2 out of 4 osteosarcoma CL (216-487 nM) and 1 out of 4 rhabdomyosarcoma (331nM) were intermediate sensitive. The other CL were less sensitive (IC50 > 500 nM). Medulloblastoma CL were resistant. In all malignancies 72H LC50-values were > 1000 nM, being consistent with a cytostatic effect, and not a cytotoxic effect of CPEC. Conclusion: CTPs is an attractive target for hematological and solid pediatric malignancies. The ITCC-consortium is extending the in vitro testing of CPEC to more CL of the sensitive tumour types.
RBIO-06. NADPH OXIDASE (NOX) PROMOTES RADIATION RESISTANCE THROUGH OXIDATION OF PTEN IN GLIOBLASTOMA
Authors: Kirsten Ludwig, Janel Le Belle, Jantzen Sperry, Erina Vlashi, Frank Pajonk, Harley Kornblum
Journal: Neuro-Oncology (2017)

Radiation is a mainstay of treatment for glioblastoma (GBM). While all the effects of radiation are not known, it is thought to induce cell death by increasing the production of reactive oxygen species (ROS). High amounts of ROS are known to induce cell death, however recent data suggests that a moderate increase in ROS can promote proliferation, migration, tumorigenesis, and stem cell maintenance. We have found that in primary patient-derived gliomasphere lines both exogenous and endogenous ROS oxidizes PTEN, resulting in Akt activation and increased proliferation. Under hypoxic conditions, endogenous ROS is produced primarily by a complex called NADPH oxidase (NOX), whose formation results in PTEN oxidation and downstream activation of Akt and cell proliferation. Prior studies demonstrate that radiation itself can induce activation of Akt, however the mechanism is still unclear. In the present study, we tested the hypothesis that NOX-produced ROS plays a role in the response to radiation in GBM. We find that following radiation, NOX4 expression and activation increases, and chemical or genetic inhibition of this complex decreases radiation induced ROS, and rescues PTEN oxidation as well as Akt activation. Most importantly, NOX inhibition decreases cell viability and survival following radiation, suggesting that activation of this complex helps promote survival following radiation. While NOX inhibition did decrease ROS levels in PTEN null lines, no significant difference in survival or Akt activation was found, suggesting that NOX protection functions through the inactivation of PTEN. Finally, NOX-produced ROS occurs primarily in the cytosol, as no significant decrease in mitochondrial ROS levels were detected following NOX inhibition. Taken together, these data indicate that NOX may be a viable target to promote the sensitization of GBM to radiation, especially in PTEN-intact tumors.
Whole-exome sequencing analysis identifies recurrent mutation rate in BAP1 gene in intrahepatic cholangiocarcinoma patients exposed to asbestos
Authors: G. Brandi, M. Deserti, A. Astolfi, V. Indio, A. Farioli, S. Mattioli, A. Palloni, S. De Lorenzo, I. Garajova, F. Vasuri, A.D. Pinna, M. Cescon, S. Tavolari
Journal: Annals of Oncology (2017)
Reciprocal Nucleopeptides as the Ancestral Darwinian Self-Replicator
Authors: Eleanor F Banwell, Bernard M A G Piette, Anne Taormina, Jonathan G Heddle
Journal: Molecular Biology and Evolution (2017)

Even the simplest organisms are too complex to have spontaneously arisen fully-formed, yet precursors to first life must have emerged ab initio from their environment. A watershed event was the appearance of the first entity capable of evolution: the Initial Darwinian Ancestor. Here we suggest that nucleopeptide reciprocal replicators could have carried out this important role and contend that this is the simplest way to explain extant replication systems in a mathematically consistent way. We propose short nucleic-acid templates on which amino-acylated adapters assembled. Spatial localization drives peptide ligation from activated precursors to generate phosphodiester-bond-catalytic peptides. Comprising autocatalytic protein and nucleic acid sequences, this dynamical system links and unifies several previous hypotheses and provides a plausible model for the emergence of DNA and the operational code.
CabaCy—evaluating Cabazitaxel efficaCy by patterns of treatment and disease in metastatic castration resistant prostate cancer (mCRPC) patients: a 5 years, “Real Life”, mono-institutional experience
Authors: S. Rossetti, C. Cavaliere, F.J. Romano, M. Di Napoli, S.C. Cecere, G. Iovane, M.A. Porricelli, S. Pignata, G. Facchini
Journal: Annals of Oncology (2017)