tbuckley/cabot-search huggingface dataset:
Abstract 404: FK506-binding Protein 38 Protects the Heart From Pressure Overload-induced Cardiac Dysfunction via Endoplasmic Reticulum-associated Apoptosis
Authors: Tomofumi Misaka, Tomokazu Murakawa, Kazuhiko Nishida, Kinya Otsu
Journal: Circulation Research (2016)

Backgrounds: FK506-binding protein 38 (FKBP38) is a membrane chaperone with its peptidyl-prolyl cis-trans isomerase activity, localized to mitochondria and endoplasmic reticulum. It has been reported that chaperone systems in the heart play a protective role against the toxicity of misfolded proteins during the development of heart failure, but the pathophysiological effect of FKBP38 in the heart has not been investigated. Methods and Results: To study the role of FKBP38 in the heart, we have generated cardiac-specific FKBP38 knockout (KO) mice. KO mice had no effect on cardiac function compared to wild type (WT) littermates under unstressed conditions at 8 to 10 weeks old. The mice were subjected to transverse aortic constriction (TAC) or Sham surgeries. Echocardiography demonstrated that KO mice showed significantly decreased fractional shortening and increased end-diastolic left ventricular dimension compared to WT mice 1 week after TAC (20.7 + 2.6 vs 39.3 + 2.4%, 3.92 + 0.4 vs 3.32 + 0.4 mm, P&lt;0.01, respectively). TAC-operated KO mice exhibited similar heart weight/tibial length (11.1 + 0.2 vs 11.8 + 0.3 mg/mm, P=NS) but significantly higher lung weight/tibial length (13.7 + 1.0 vs 9.4 + 0.3 mg/mm, P&lt;0.01) compared to TAC-operated WT, indicating that KO mice had more progressive left ventricular dysfunction with pulmonary congestion in response to pressure overload. TUNEL staining revealed that the numbers of TUNEL positive nuclei of cardiomyocytes were dramatically increased in KO mice compared to WT mice after TAC (140 + 13 vs 25 + 9 per 10 5 nuclei, P&lt;0.01). To understand further mechanisms of apoptosis, we estimated the activation of caspase 12, which is responsible for ER stress-induced apoptosis. The expression levels of cleaved caspase 12 were significantly elevated in KO mice compared to WT mice after TAC. Moreover, the expression levels of ER stress markers such as 94 kDa glucose-regulated protein, 78 kDa glucose-regulated protein and protein disulfide-isomerase were significantly upregulated in KO mice compared to WT mice after TAC. Conclusion: Our findings demonstrate for the first time that FKBP38 plays protective effects in the heart against pressure overload-induced cardiac dysfunction via endoplasmic reticulum-associated apoptosis.
P3.14-004 Pathological Study on the Clinical Target Volume (CTV) in Limited-Stage SCLC for CT-Simulation Based Thoracic Radiotherapy Planning
Authors: X. Hu, H. Zhu, J. Liu, C. Yu, L. Zhu, Y. Tong, W. Sun, W. Mao, M. Chen
Journal: Journal of Thoracic Oncology (2017)
Clinical and Translational Implications of RET Rearrangements in Non–Small Cell Lung Cancer
Authors: Roberto Ferrara, Nathalie Auger, Edouard Auclin, Benjamin Besse
Journal: Journal of Thoracic Oncology (2017)

Since the discovery in 2012 of rearranged during transfection proto-oncogene gene (RET) rearrangements in NSCLC, at least 12 different fusion variants have been identified, with kinesin family member 5B gene (KIF5B)-RET being the most frequent and the best characterized. Unlike ALK receptor tyrosine kinase gene (ALK) and ROS1 rearrangements, RET fusion genes cannot be adequately detected by immunohistochemistry (IHC), although fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction are fully complementary diagnostic tools. In large retrospective studies, RET rearrangements correlate with adenocarcinoma histologic subtype, never-smoking status, younger age, more advanced disease stage, potentially higher chemosensitivity (in particular, to pemetrexed-based regimens), and coexistence of other genomic alterations. To date, several preclinical models, clinical trials, and retrospective studies have investigated multitarget inhibitors with anti–rearranged during transfection proto-oncogene (RET) activity in patients with RET-rearranged lung cancer. In the clinical setting, the benefit in terms of response (16%–47%) and progression-free survival (2–7 months) is clearly not comparable to that seen with other targeted agents in oncogene-addicted NSCLC. Furthermore, multikinase agents showed high rates of severe toxicities, leading to frequent dose reduction and drug discontinuation. To date, no definitive conclusions about a potentially different impact of anti-RET therapies according to RET fusion variants have been drawn on account of discordant data coming mostly from small subgroup analyses. Importantly, the absence of a striking clinical benefit in RET oncogene–addicted NSCLC underscores the clear need for development of more selective and potent RET inhibitors and for better characterization of concomitant genomic alterations and mechanisms of resistance to RET inhibition in patients with lung cancer.
L'indagine EUVAC-NET: i sistemi nazionali di sorveglianza della pertosse nell'Unione Europea, e in Svizzera, Norvegia e Islanda
Authors: J E Schmidt, A E Tozzi, L Rava, S Glismann
Journal: Eurosurveillance (2001)

Attraverso un questionario inviato agli stati membri dell'Unione Europea, e di Svizzera, Norvegia e Islanda, e stata condotta un'inchiesta sul tipo di informazioni registrate routinariamente nei sistemi nazionali di sorveglianza della pertosse. Le informazioni richieste riguardavano i metodi di sorveglianza, il tipo di dati registrati sui casi, il calendario vaccinale, il tipo di vaccino usato, i metodi per la stima della copertura vaccinale. Esiste una grande variabilita tra i paesi partecipanti per quanto riguarda metodi locali di sorveglianza, strategie vaccinali e metodi di stima della copertura, ma i risultati dell'inchiesta mostrano l'esistenza di sottogruppi di variabili comuni a molti paesi. Le future attivita del progetto EUVAC-NET includono la definizione di elementi omogenei nei sistemi nazionali e il raggruppamento di paesi con aspetti comuni di sorveglianza.
ACTR-43. TUMOR TREATING FIELD COMPLIANCE AND OVERALL SURVIVAL IN PATIENTS WITH PRIMARY GBM
Authors: Manjari Pandey, Kaitlin Qualls, Madison Michael, Jeffrey Sorenson, Brandon Baughman, Enrique Izaguirre, Matthew Ballo
Journal: Neuro-Oncology (2017)

Determine the significance of tumor treating field (TTF) compliance in patients with primary GBM. In 2015, we adopted a current practice protocol of treating all primary GBM patients with TTFs during the adjuvant TMZ component of their therapy. We used support groups and consistent messaging across specialties to encourage all patients to initiate TTFs. Thirty-four patients underwent maximal surgical debulking, completed radiotherapy with concurrent TMZ, and initiated adjuvant TMZ. We performed this univariate and multivariate analysis of patient, tumor, and treatment related factors to assess their association with overall survival. Of the 34 patients, 20 were male and the median age was 62 years (range, 26 to 79). ECOG performance status was 0 in 20 patients, 1 in 10, 2 in 3, and 4 in 1. Seventeen patients underwent GTR, while 11 had STR and six had biopsy only. We divided TTF compliance into 3 subgroups: 9 patients that refused to start TTFs, 15 patients with monthly compliance of 1 to 75%, and 10 patients with compliance greater than 75%. With a median follow up of 9.7 months, the median overall survival for all patients was 19 months and the 1-year survival was 59%. Univariate analysis of factors associated with 1-year survival revealed TTF compliance (refused, 0% vs. compliance 1–75%, 65% vs. compliance >75%, 83%, p=0.04), ECOG performance status (ECOG 2–4, 0% vs. ECOG 0/1, 63%, p<0.001), extent of resection (biopsy only, 0% vs. STR, 67% vs. GTR 79%, p<0.001) and age (>65, 36% vs. ≤65, 65%, p=0.06) as significant. On multivariate analysis TTF compliance (p=0.001), ECOG performance status (p=0.02), and extent of surgical resection (p=0.01) remained significant. TTF compliance is associated with improved OS and is independent of performance and resection status. The neuro-oncology community should focus on barriers to TTF use.
Sexual and Gender Minority Issues Across NCCN Guidelines: Results From a National Survey
Authors: Janella Hudson, Matthew B. Schabath, Julian Sanchez, Steven Sutton, Vani N. Simmons, Susan T. Vadaparampil, Peter A. Kanetsky, Gwendolyn P. Quinn
Journal: Journal of the National Comprehensive Cancer Network (2017)

Background: The lesbian, gay, bisexual, transgender, queer/questioning (LGBTQ) population is at higher risk for multiple types of cancers compared with the heterosexual population. Expert NCCN panels lead the nation in establishing clinical practice guidelines addressing cancer prevention, early detection, and treatment of cancer sites and populations. Given the emergence of new data identifying cancer disparities in the LGBTQ population, this study examined the inclusion of medical and/or psychosocial criteria unique to LGBTQ within NCCN Guidelines. Methods: Data were collected for 32 of the 50 NCCN Guidelines. Results: NCCN panel members reported that neither sexual orientation (84%) nor gender identity (94%) were relevant to the focus of their guidelines; 77% responded that their panels currently do not address LGBTQ issues, with no plans to address them in the future. Conclusions: Greater consideration should be given to the needs of LGBTQ patients across the cancer care continuum. Given that research concerning LGBTQ and cancer is in its infancy, additional empirical and evidence-based data are needed to bolster further integration of LGBTQ-specific criteria into clinical care guidelines.
Meningitis vírica en Chipre e Inglaterra: verano de 1996
Authors: M E Ramsay, D W Brown, H Appleton, B Megson, A Polynikis, L Papantoniou, A Eleftheriou
Journal: Eurosurveillance (1996)

El 5 de julio de 1996 se inicio un brote de meningitis virica en Chipre. A 28 de agosto habian ingresado en el hospital un total de 316 casos, la mayoria de los cuales eran bebes y ninos pequenos; 55 (17%) eran menores de 1 ano de edad, 117 (37%) tenian entre 1 y 4 anos, 103 (33%) entre 5 y 14 anos, y 41 (13%) entre 15 y 80 anos. Los casos notificados procedian principalmente del distrito de Limassol (213/316 casos), pero tambien de Nicosia (43), Larnaca (39), Famagusta (13), Paphos (7), y en uno de los casos no se notifico el distrito. La mayoria de los casos fueron leves y en pocos dias recibieron el alta del hospital; no hubo muertes ni complicaciones graves.
Formación en epidemiología de las enfermedades transmisibles en el Norte de Europa
Authors: P Aavitsland, S Andresen
Journal: Eurosurveillance (2001)

Los cinco paises nordicos (Dinamarca, Finlandia, Islandia, Noruega y Suecia) disfrutan de una larga tradicion de colaboracion en el campo de la epidemiologia y control de las enfermedades transmisibles. Los epidemiologos publicos y los gestores de programas de inmunizacion se reunen periodicamente para estudiar los retos en comun e intercambiar experiencias en materia de vigilancia y control de enfermedades transmisibles.
SCDT-34. TIME-DEPENDENT ACTIVATION OF ADENOSINE A2A RECEPTOR DISRUPTS CYTOSKELETON AND TIGHT JUNCTIONS IN BRAIN MICROVASCULAR CELLS TO ENHANCE PARACELLULAR PERMEABILITY
Authors: Amelie Vezina, Matt McCord, Mark Gilbert, Sadhana Jackson
Journal: Neuro-Oncology (2017)

The blood-brain barrier (BBB) is a highly regulated and poorly permeable blockade against effective drug delivery. The BBB regulates drug entry by tight and adherens junctions and multidrug resistance proteins. Activation of adenosine A2A receptor (A2AR) by regadenoson, an FDA approved A2AR agonist, in non-tumor bearing rodents demonstrated transiently increased BBB permeability. Here, we studied the time dependent impact of regadenoson on brain endothelial cell junctional disruption, and ABC transporter expression to understand the causative effect of increased BBB permeability. Mouse brain endothelial cells (bEnd.3), were treated with 10μM regadenoson on a time-course of 0-24hrs. Claudin-5, Occludin, ZO-1, and VE-Cadherin expression studies were assessed by western blotting of subcellular fractions, immunofluorescence and qRT-PCR. Expression of ABCG2 was reported by western blotting and qRT-PCR. Time-dependent dynamic cell impedance of endothelial cell monolayers was monitored with and without regadenoson to further describe barrier function changes. Calcium influx was assayed with fluo-8 AM dye while morphological changes were monitored by F-actin cytoskeleton staining. Regadenoson decreased electrical endothelial barrier impedance by 40% while altering expression of Claudin-5, Occludin, ZO-1, and VE-Cadherin approximately 30min to 4hrs after treatment. Expression of the tight and adherens junction proteins returned to basal levels after 8hrs. Short-term desensitization of the A2AR allowed for transient modulation of endothelial cell-cell junctional interaction and decreased expression of the F-actin cytoskeleton. Also, eight hours after treatment, expression of ABCG2 was decreased by 50%. Our results demonstrate A2AR agonism causes transient changes in junctional cell-cell interaction, leading to increased paracellular permeability. Decreased expression of ABC transporters may lead to further chemotherapy delivery to the brain suggested by the use of regadenoson concomitant therapy. The short-term regadenoson effects on BBB function may serve important clinical applications to enhance drug delivery of varied CNS diseases.
P1.02-036 Fine Needle Aspiration as a Diagnostic Tool in Lung Cancer: Worth Pursuing?
Authors: E. Cunha, A. Sousa, H. Paiva, F. Rodrigues, M.T. Accioly, L. Bastos, C. Silva, N. Carvalho, C.A. Sousa, I. Small, C.G. Ferreira, L.H. Araujo
Journal: Journal of Thoracic Oncology (2017)
SCDT-07. BORDER LINE SIZED NANO DRUGS FOR EFFICIENT TARGETING AND DELIVERY THROUGH MULTI BIO BARRIERS
Authors: Eggehard Holler, Hui Ding, Liron Israeli, Keith Black, Julia Ljubimova
Journal: Neuro-Oncology (2017)

Most conventional nano drugs are drug encapsulating particles of unfavorable hydrodynamic diameters in the range 30-300 nm. Encapsulation and size are promiscuous to toxic side effects through spontaneous drug escape by diffusion and dissolution of particles. Mini nanodrugs of hydrodynamic diameter 5-8 nm, elongated shape and chemical attachment of drug and operational groups to a polymer platform is the solution of the future. The platform is ideally biodegradable and made of multiple polymerized units with chemical anchorage for multiple drugs and operational groups which serve receptor targeting, endosome disruption, MRI and fluorescence imaging or protection. Cleavable linkers enable activation in response to chemistry in the targeted compartment. Several targeting molecules can be designed for programmed delivery through multiple bio barriers. We have developed a mini nano drug for highly efficient treatment of preclinical HER2-positive human breast cancer by replacement of targeting antibodies with a HER2-affine peptide. The mini nano drug delivered multiple copies of antisense oligonucleotide or docetaxel to the cytoplasm of tumor cells and arrested tumor growth. In another example, we have achieved delivery of imaging agents across the blood-brain barrier (BBB) with peptides targeting different delivery routes and which can be attached separately or combination. In another case, we designed a targeted mini nano device carrying a fluorescent dye that brightens glioblastoma in mice for guided tumor resection. In all the cases, mini nano devices cleared with short half-lives and several times longer residing times resulting in efficacious delivery to targeted tissue and cells. - Supported by Martz discovery funds, NIH R01 CA188743, R01CA209921 and Neurosurgey Department funds. Keith L. Black, Julia Y. Liubimova and Eggehard Holler disclose affiliations with Arrogene Inc. USA.
La région Europe de l’OMS indemne de poliomyélite
Authors: M. S. Vilayleck
Journal: Eurosurveillance (2002)

La Region europeenne* de l’OMS est declaree  indemne de poliomyelite , a-t-il ete annonce lors d’une reunion de la Commission regionale europeenne de certification de l’eradication de la poliomyelite, qui s’est tenue a Copenhague le 21 juin dernier.
Microbiologic and clinical characteristics of biofilm-forming Candida parapsilosis isolates associated with fungaemia and their impact on mortality
Authors: S. Soldini, B. Posteraro, A. Vella, E. De Carolis, E. Borghi, M. Falleni, A.R. Losito, G. Maiuro, E.M. Trecarichi, M. Sanguinetti, M. Tumbarello
Journal: Clinical Microbiology and Infection (2017)
ACTR-28. FINAL RESULTS FROM THE DOSE-ESCALATION STAGE OF A PHASE 1/2 TRIAL OF TPI 287, A BRAIN PENETRABLE MICROTUBULE INHIBITOR, PLUS BEVACIZUMAB IN PATIENTS WITH RECURRENT GLIOBLASTOMA
Authors: Samuel Goldlust, Louis Nabors, Nimesh Mohile, Tara Benkers, Sigmund Hsu, Sandra Silberman, Samuel Singer, Mayank Rao, Lori Cappello, George Farmer
Journal: Neuro-Oncology (2017)

Microtubule inhibitors are active in preclinical models of glioblastoma (GBM), however, clinical benefit is hampered by poor CNS accumulation. TPI 287, a taxane designed to evade P-glycoprotein mediated efflux, readily penetrates the blood brain barrier and overcomes this limitation. CB-017 is a multi-center phase 1/2 trial designed to determine the optimal dose of TPI 287 and potential efficacy in combination with bevacizumab (BEV) for treatment of recurrent GBM. Final results of the dose escalation Phase 1 stage of this trial are reported. GBM patients at first or second relapse after standard therapy and without prior exposure to anti-angiogenic agents were eligible for enrollment. BEV was administered at 10 mg/kg every 2 weeks and TPI 287 every 3 weeks IV. RANO response was assessed every 6 weeks. Twenty-four patients were enrolled in seven TPI 287 dose-escalation cohorts (140–220 mg/m2) from 6 U.S. centers. Twenty and 23 patients were evaluable for response and survival, respectively. 12/20 (60%) achieved an objective response (3 CR, 9 PR) and 10/23 patients had stable disease. Two of the patients achieving CR had converted from PR after subsequent treatment cycles. Median and 6-month PFS was 5.5 months and 40%, respectively. Median and 12-month overall survival was 13.4 months and 64%, respectively. Fifteen- and 18-month overall survival was 45% and 27%, respectively. Of the 9 patients from which tumor data was available, eight (89%) harbored an unmethylated MGMT promoter at diagnosis. No DLTs were reported and myelosuppression (n=3) was the only drug-related grade 3/4 adverse event. TPI 287 in combination with BEV is safe and well tolerated at doses up to 220 mg/m2. Final survival results from the Phase 1 portion of this study compare favorably with historical controls and support further investigation of TPI 287 plus BEV for treatment of recurrent GBM.
MA 20.13 etDNA: Tumor-Derived DNA from Pleural Effusion Supernatant as a Promising Source for NGS-Based Mutation Profiling in Lung Cancer
Authors: L. Tong, N. Ding, J. Li, X. Wang, Y. Zhang, X. Xu, M. Ye, C. Li, H. Zhang, X. Zhu, Z. Zhu, J. Zhou, J. She, J. Zhou, Y.W. Shao, X. Zhang, H. Bao, S. Xu, X. Zhang, Q. Hong, C. Bai, J. Hu
Journal: Journal of Thoracic Oncology (2017)
Estudio caso-control de los factores de riesgo para la Fiebre Q en el suroeste de Inglaterra y Irlanda del Norte
Authors: H J Orr, H Christensen, B Smyth, D Ab Dance, D Carrington, I Paul, J M Stuart
Journal: Eurosurveillance (2006)

La fiebre Q (Coxiella burnetti), representa el 1% (700 casos) de neumonias adquiridas en la comunidad en el Reino Unido cada ano y puede producir complicaciones serias como las endocarditis. Aunque se produzcan brotes con relativa frecuencia en el mundo, las causas se identifican en raras ocasiones, y tambien son escasos los estudios sobre los factores de riesgo de los casos esporadicos. 
Llevamos a cabo un estudio caso-control apareado. Se identificaron casos agudos de fiebre Q en personas de mas de 15 anos en el suroeste de Inglaterra y en Irlanda del Norte entre enero de 2002 y diciembre de 2004. Se aparearon los controles por edad, sexo, y segun el medico al que acudian. Se enviaron por correo cuestionarios a los casos y los controles, para recoger informacion acerca del contacto con animales, y las actividades de tiempo libre y profesionales. 
Fueron rellenados los cuestionarios por 39/50 casos (78%) y 90/180 (50%) controles. Segun el analisis univariado, la exposicion profesional a animales o productos animales era el unico factor de riesgo asociado a los casos (P=0,05, odds ratio (OR) 3,4). Una enfermedad larga podria tener un efecto protector significativo (P=0.03, OR 0.3). En el analisis multivariado, la asociacion entre exposicion profesional y la enfermedad seguia siendo elevada (OR 3.6, 95% intervalo de confianza (IC) 0.9 a 14.8) y el hecho de fumar aparecia como un posible factor de riesgo. 
Este estudio caso-control es el primero que identifica la exposicion profesional a animales o productos animales como ruta de infeccion mas probable en los casos esporadicos de fiebre Q, contrariamente a los casos epidemicos.
Number of UK patients with metastatic breast cancer isn’t known
Authors: Jane Feinmann
Journal: BMJ (2017)

Two thirds of NHS hospitals in England don’t accurately record the number of patients who receive a diagnosis of metastatic breast cancer, despite the fact that trusts were told to collect the data as far back as 2012.

In December 2012 the then National Cancer Intelligence Network, now merged into Public Health England’s National Cancer Registration and Analysis Service, wrote to hospital trusts requiring them to “ensure that data are collected on breast cancer recurrences and metastases at the time of patient contact.”1

“The policy was unfortunately introduced with no support plan in place to help hospitals implement the change,” said Gunes Kalkan, head of policy at the UK breast cancer charity Breast Cancer Care, at the Advanced Breast Cancer (ABC4) International …