tbuckley/cabot-search huggingface dataset:
Papel y funciones que desempeña en la Unión Europea un Centro de Salud Pública para las Enfermedades Transmisibles y otras amenazas para la salud
Authors: F Van Loock, N Gill, S Wallyn, A Nicoll, J C Desenclos, P Leinikki
Journal: Eurosurveillance (2002)

Se ha llegado a un consenso internacional en cuanto a la necesidad de crear una Estructura de Coordinacion Tecnica (ECT) para las enfermedades transmisibles en el ambito de la Union Europea (EU) destinada a mejorar la futura respuesta europea a las amenazas internacionales de enfermedades transmisibles, dentro y fuera de sus fronteras. Tras los eventos ocurridos en Norteamerica el 11 de septiembre 2001 y las emisiones intencionadas de carbunco, la UE creo un Comite de Seguridad Sanitaria, adopto una normativa en materia de proteccion civil y, durante 18 meses, destino un equipo a la tarea de desarrollar una respuesta a las emisiones intencionadas de agentes biologicos y quimicos. Estas dos iniciativas, es decir el enfoque de red y el trabajo en torno a la seguridad sanitaria, deben converger en una fuerza unica que se ocupe de proteger la salud de las personas en Europa. Ambas se podrian llegar a combinar y, con ello, dar lugar a la creacion de un Centro Europeo para las Enfermedades Transmisibles, cuya puesta en marcha esta prevista para el ano 2005.
QLIF-03. UNUSUAL ADVERSE DRUG REACTIONS IN HIGH GRADE GLIOMA PATIENTS TREATED WITH TEMOZOLOMIDE
Authors: Boris Lisa, Elizabeth Vera, Jing Wu, Deric M Park, Christine Bryla, Sonja Crandon, Nancy Garren, Ann McCoy, Christine Siegel, Brett J Theeler, Joo-Hee Sul, Mark Gilbert, Terri Armstrong
Journal: Neuro-Oncology (2017)

Temozolomide (TMZ) is an oral alkylating agent which is the most common chemotherapy used in neuro-oncology and is typically well tolerated. The most common adverse events include fatigue, nausea, vomiting, headache, and constipation and most serious being myelosuppression. Review of the literature uncovered rare reports of acute reactions to TMZ, typically limited to skin rashes and eruptions. The Neuro-Oncology Branch has initiated a natural history study in which clinical course and current status are interrogated. A retrospective analysis of this protocol was performed, and cases of unusual reactions to TMZ were identified. This study included 144 patients, with the majority being males (65%) with glioblastoma (31%) and a mean age of 47. Ninety (62%) received TMZ with concurrent radiation or in the adjuvant setting, of which 3 patients (4%) developed unusual symptoms within hours of taking TMZ. A 70-year-old male developed severe rigors, joint pains, and fever within 1 hour of ingesting TMZ, prescribed in the adjuvant setting. Infectious work-up was negative and re-challenge with TMZ produced the same syndrome. A 47-year-old female on C2D2 of TMZ with nivolumab in the adjuvant setting, developed chills, joint pain, and a fever that resolved with drug cessation. A re-challenge with TMZ resulted in the same symptoms within two hours of ingestion. A 24-year-old female developed severe burning paresthesias on C4D2 of TMZ with nivolumab which resolved with lorazepam and cessation of TMZ. Re-challenge with TMZ resulted in recurrence of burning paresthesias within 1-2 hours of ingestion. In all 3 cases, symptoms resolved with stopping TMZ, and alternative therapeutic strategies were initiated. Awareness of these unusual reactions to TMZ is important in clinical practice as the prompt recognition and discontinuation of the drug improves patient safety and may avoid the use of unnecessary diagnostic procedures.
Restricting the use of antibiotics in food-producing animals and its associations with antibiotic resistance in food-producing animals and human beings: a systematic review and meta-analysis
Authors: Karen L Tang, Niamh P Caffrey, Diego B Nóbrega, Susan C Cork, Paul E Ronksley, Herman W Barkema, Alicia J Polachek, Heather Ganshorn, Nishan Sharma, James D Kellner, William A Ghali
Journal: The Lancet Planetary Health (2017)

Antibiotic use in human medicine, veterinary medicine, and agriculture has been linked to the rise of antibiotic resistance globally. We did a systematic review and meta-analysis to summarise the effect that interventions to reduce antibiotic use in food-producing animals have on the presence of antibiotic-resistant bacteria in animals and in humans.On July 14, 2016, we searched electronic databases (Agricola, AGRIS, BIOSIS Previews, CAB Abstracts, MEDLINE, Embase, Global Index Medicus, ProQuest Dissertations, Science Citation Index) and the grey literature. The search was updated on Jan 27, 2017. Inclusion criteria were original studies that reported on interventions to reduce antibiotic use in food-producing animals and compared presence of antibiotic-resistant bacteria between intervention and comparator groups in animals or in human beings. We extracted data from included studies and did meta-analyses using random effects models. The main outcome assessed was the risk difference in the proportion of antibiotic-resistant bacteria.A total of 181 studies met inclusion criteria. Of these, 179 (99%) described antibiotic resistance outcomes in animals, and 81 (45%) of these studies were included in the meta-analysis. 21 studies described antibiotic resistance outcomes in humans, and 13 (62%) of these studies were included in the meta-analysis. The pooled absolute risk reduction of the prevalence of antibiotic resistance in animals with interventions that restricted antibiotic use commonly ranged between 10 and 15% (total range 0-39), depending on the antibiotic class, sample type, and bacteria under assessment. Similarly, in the human studies, the pooled prevalence of antibiotic resistance reported was 24% lower in the intervention groups compared with control groups, with a stronger association seen for humans with direct contact with food-producing animals.Interventions that restrict antibiotic use in food-producing animals are associated with a reduction in the presence of antibiotic-resistant bacteria in these animals. A smaller body of evidence suggests a similar association in the studied human populations, particularly those with direct exposure to food-producing animals. The implications for the general human population are less clear, given the low number of studies. The overall findings have directly informed the development of WHO guidelines on the use of antibiotics in food-producing animals.World Health Organization.
PATH-09. MOLECULAR CHARACTERIZATION OF CHORDOMAS INCLUDING TUMOR MUTATIONAL LOAD AND OTHER IMMUNE BIOMARKERS
Authors: William Kelly, Amjad Anaizi, Joanne Xiu, Deepa S Subramaniam
Journal: Neuro-Oncology (2017)

Chordomas, rare tumors of the bone that frequently involve the skull base, spine and sacrum, can be aggressive and locally invasive. The gold standard is en-bloc surgical resection, and adjuvant radiation. Incompletely resected or recurrent chordomas are difficult to treat systemically as they are not responsive to cytotoxic therapies. Sigari et al (2013) noted over expression of PDGFR, MET, and EGFR suggesting oncogene addiction. We hypothesize that molecular characterization of chordomas will help to identify therapeutic targets to treat refractory chordomas. The study cohort consisted of 68 chordoma cases consecutively submitted to Caris Life Science for molecular profiling using Next Gen Sequencing (NGS), immunohistochemistry (IHC) and in situ hybridization (ISH). Mutation, IHC-positive and ISH-positive frequencies were compared using Fisher’s exact test (p-value < 0.05 considered significant). NGS showed mutations in ARID1A (10%), TP53 (9.1%), PBRM1 (5%), TSC1 (5%), PIK3CA (4.5%), HNF1A (2.4%) and IDH1 (2.3%). By IHC, tumors were found to frequently express EGFR (75%), PTEN (58%), PDGFR (14%) and c-MET (8%) in keeping with prior literature. Average tumor mutational load (TML) was low at 4.3 per megabase, all were microsatellite stable, and PD-L1 expression was noted in 35% of tumors. A number of potentially druggable oncogenic drivers were identified in this study. Small molecular inhibitors could be tested in EGFR, PDGFR and MET overexpressing tumors. Vaccines and small molecular inhibitors are being developed to target mutant IDH. TSC mutations are associated with downstream mTOR activation and may be amenable to treatment with mTOR inhibitors like everolimus. Mutations in ARID1A and TP53 suggest defective DNA repair and drugs such as PARP inhibitors or checkpoint kinase inhibitors may induce synthetic lethality. Although TML was low and microsatellite stable, there may be a role for checkpoint inhibition as more than a third of tumors expressed PD-L1.
GENE-42. MOLECULAR AND HISTOLOGIC FEATURES OF A SERIES OF SPORADIC AND FAMILIAL SCHWANNOMAS
Authors: Erik Williams, James Kim, Alona Muzikansky, McKenzie Shaw, A John Iafrate, Scott Plotkin, Mario Suva, Anat Stemmer-Rachamimov
Journal: Neuro-Oncology (2017)

Schwannomas are found either sporadically or as part of a syndrome. Genetic alterations found in schwannomas include those in NF2 and SMARCB1 (implicated in schwannomatosis), and BRAF V600E. Reduced copy number of chromosome 22q can be the mechanism for loss of the unaltered allele ofNF2 and/orSMARCB1in some schwannomas. We analyzed a cohort of 57 vestibular and non-vestibular schwannomas from three clinical subtypes (Neurofibromatosis 2, schwannomatosis, and sporadic) for reduced copy number (NF2 and SMARCB1), and mutations (NF2, SMARCB1, LZTR1, NF1 and BRAF). Tumors were histologically classified as conventional/classic, or hybrid. Genomic DNA was extracted from FFPE biopsies. Full coding regions of genes NF1, NF2, LZTR1, SMARCB1 and BRAF were enriched by anchored multiplex-PCR (AMP). Resulting libraries were quantitated and sequenced on the Illumina MiSeq System. Bioinformatics analyses were performed using custom scripts. Copy number alteration was detected using a read depth approach after consolidation of single molecule derived reads. INI1 immunohistochemistry was performed. RNA ISH for SMARCB1 was performed. Five tumors were of hybrid histology, and all five were syndromic. Reduced copy number for NF2 was identified in 33% of vestibular schwannomas and 18% of non-vestibular schwannomas. There was no significant difference in reduced copy number of NF2 between sporadic and syndromic forms. BRAF V600E and NF1 mutations were not identified in any case. For most INI1 mosaics, there was no molecular event explaining the partial loss of INI1 IHC. This study confirms the association of hybrid histology with syndromic schwannomas. NF1 mutations did not explain hybrid histology. We did not find BRAF V600E mutations in this series. INI1 mosaic pattern was not explained by reduced copy number or mutation of SMARCB1 as this was found in only a small number of the cases. These results suggest that loss of INI1 expression could be the result of epigenetic alterations.
PDTM-10. SYSTEMIC AND CONVECTION-ENHANCED DELIVERY OF DASATINIB EXTENDS SURVIVAL IN MURINE HISTONE H3.3K27M MUTANT BRAINSTEM GLIOMA
Authors: Vadim Tsvankin, Christopher Lascola, T N Venkatraman, Brainard Burrus, Oren Becher, Eric Thompson
Journal: Neuro-Oncology (2017)

Diffuse intrinsic pontine glioma (DIPG) is the leading cause of brain tumor-related death in children, with a median survival of nine months. The efficacy of in vitro preclinical models contrasted to poor outcomes in clinical trials suggests the possibility of inadequate drug delivery to the tumor; this has been attributed to a combination of poor penetration beyond the blood-brain barrier (BBB) and rapid drug efflux via ATP-binding cassette (ABC) transporters. Convection-enhanced delivery (CED) mechanically circumvents the BBB; however, the mechanism underlying infusate clearance is poorly understood, and may include passive diffusion through a leaky BBB or active efflux via ABC transporters. The multi-kinase inhibitor dasatinib was administered systemically or via CED in transgenic mice harboring histone H3.3K27M mutant DIPG. Concurrently, infusate retention behind the BBB was augmented by blocking ABC transporters with tariquidar and reducing BBB permeability with dexamethasone. Real-time MRI was used to evaluate the rate of CED infusate clearance and distribution volume. Systemic and CED administration routes both extended survival over vehicle (median 37.5 and 36 days, respectively, compared to 28.5 days; P=0.01) Notably, no survival benefit was found in CED-treated animals (5µL at 2µM) over intraperitoneal injection (25mg/kg; p=0.36). Systemic pretreatment with dexamethasone (0.5mg/kg) and tariquidar (5µg/kg) in CED-treated animals did not result in increased survival (p=0.66). Real-time MRI of animals infused with dasatinib-gadolinium did not reveal significant differences in distribution volume or clearance rate in animals pretreated with tariquidar and dexamethasone (p>0.05). Dasatinib delivered either systemically or via CED significantly improves survival in histone H3.3K27M mutant DIPG. Histologic mechanistic data regarding cellular apoptosis and proliferation are forthcoming. ABC transporter inhibition and BBB permeability reduction do not appear to improve the efficacy of dasatinib delivered by CED; it is therefore unlikely that these are significant mechanisms of CED infusate clearance.
Abstract 21319: Racial Differences in the Prevalence of Atrial Fibrillation in Patients With Dual-Chamber Pacemakers
Authors: Eisha Wali, Amrish Deshmukh, Abdallah Bukari, Cevher Ozcan
Journal: Circulation (2017)

Introduction: Several cohort studies have reported racial differences in prevalence of atrial fibrillation (AF). This may be due to ascertainment bias. Thus, we aimed to determine incidence of AF with respect to race in patients with sinus node dysfunction and conduction disease. Hypothesis: Ethnicity may have significant impact on development of AF in patients with sinus node dysfunction and conduction disease requiring pacemaker. Methods: All patients followed at the University of Chicago with a dual-chamber pacemaker implanted between January 2005 to December 2011 and sinus node dysfunction (SND) or high-degree atrio-ventricular block (HGAVB) requiring dual chamber pacemaker were included. Patients were identified retrospectively. Electronic medical records, ECGs, device interrogation data, and procedure notes were examined. Logistic regression analysis was used to evaluate the association of race and device-detected AF incidence, controlling for clinical characteristics and medical comorbidities, including age, gender, HTN, diabetes, chronic obstructive pulmonary disease, obstructive sleep apnea, coronary artery disease (CAD), chronic kidney disease (CKD), and valvular heart disease. Results: Three-hundred and twenty-four patients met criteria, including 125 (38%) Caucasians, 173 (53%) African Americans, 7 (2.2%) Hispanics, and 10 (3.1%) Asian-Americans. Average age was 68.9 +/- 14.8, 185 (57%) were female. Chi-squared analysis revealed no significant relationship between race and diabetes, CAD, or valvular disease in this population. Hypertension (p&lt;0.01) and CKD (p=0.02) were associated with race; both were more common in African Americans and Hispanics. In a multivariate analysis, younger age (p=0.01; OR=1.02 (1.005-1.04)), African American race (p=0.03; OR=0.6 (0.3-0.9)), and Asian American race (p=0.04; OR=0.2 (0.03-0.8)) were associated with a decreased risk of device-detected AF. Conclusions: African American race was associated with a decreased incidence of AF in patients with continuous monitoring, despite a relatively increased rate of CKD and hypertension in this population. This suggests that racial differences in AF cannot be fully explained by ascertainment bias.
P3.13-012 Fast Fourier Transform Analysis for the Outline of Pulmonary Nodules on Computed Tomography Images
Authors: T. Yoshimasu, M. Kawago, Y. Hirai, T. Ohashi, Y. Yata, A. Fusamoto, S. Oura, M. Miyasaka, H. Nishiguchi, Y. Aoishi, Y. Nishimura
Journal: Journal of Thoracic Oncology (2017)
P1.01-064 Efficacy and Tolerability of Nivolumab in Elderly Patients with Advanced Non-Small Cell Lung Cancer
Authors: K. Yamane, K. Takeda, M. Yanai, N. Tanaka, H. Izumi, T. Sakamoto, K. Yamaguchi, A. Yamasaki, T. Igishi, S. Eiji
Journal: Journal of Thoracic Oncology (2017)
Long-term results of a low-dose cytarabine-based regimen for the treatment of acute megakaryoblastic leukemia and myelodysplastic syndrome in children with Down syndrome
Authors: Johann K. Hitzler, Ali Al-Ahmari, Niketa Shah, Lillian Sung, Alvin Zipursky
Journal: Cancer Research (2006)

4325   Children with Down syndrome (DS) have an estimated 500-fold increased risk of acute megakaryoblastic leukemia (DS-AMKL), which is frequently preceded by a myelodysplastic syndrome. The leukemic blasts of DS-AMKL uniquely harbor somatic mutations of the hematopoietic transcription factor  GATA1  and are highly sensitive to cytarabine  in vitro . Highly dose-intensive chemotherapy regimens developed for the general pediatric population result in excessive treatment-related mortality in children with DS. Thus, a low dose chemotherapy approach has been developed, in which cytarabine (10 mg/m2/dose) is administered subcutaneously to out-patients over a prolonged period of time. We report the outcomes of 18 children with DS and AMKL (or MDS) treated with a low dose regimen and 16 patients treated with standard dose chemotherapy at The Hospital for Sick Children and collaborating centers between 1990 and 2003. In the low dose group, 15 of 18 patients (83.3 %) achieved a complete remission. Of three patients with refractory leukemia, one achieved a long term remission after subsequent treatment with standard therapy. Twelve of the 15 responders remain in continuous remission (median duration 93 months; range 4 to156 months). All five deaths (27%) in the low dose group were due to refractory or relapsed disease (in three cases no second chemotherapy regimen was used). In the standard dose group, 15 of 16 patients (93.7%) achieved a complete remission lasting for a median duration of 57 months (range 5 to 152 months). One patient, who showed no response, was subsequently treated with intensive AML chemotherapy (UKMRCAML 10) and remains in remission. Three of the 15 responding patients relapsed: one patient received a stem cell transplant and died in remission from pulmonary hypertension; two patients were refractory to further therapy and died. In a  intention-to-treat  analysis, the event-free and overall survival were not significantly different in the low dose and standard dose group (EFS 66.7 and 75.0%, p=0.5; OS 76.5% and 80.4 %, p=0.6, respectively). In the entire cohort age, gender and cytogenetic abnormalities in addition to constitutional trisomy 21 were not associated with significant differences in survival. Two patients with monosomy 7 in the low dose group died compared to a EFS of 66.7% of 3 patients with monosomy 7 in the standard dose group. Based on the largest experience reported to date on the use of low-dose cytarabine for the treatment of AMKL in children with DS, we conclude that this therapeutic option merits prospective evaluation.
HOUT-22. PATTERN OF BEVACIZUMAB USE IN PATIENTS WITH GLIOBLASTOMA AT NATIONAL CANCER INSTITUTE-DESIGNATED CANCER CENTERS IN 2017
Authors: Surabhi Ranjan, Nebojsa Skorupan, Xiaobu Ye, Olga Yankulina, Stuart A Grossman, Matthias Holdhoff
Journal: Neuro-Oncology (2017)

Bevacizumab (BEV) received accelerated FDA approval in 2009 for the treatment of recurrent glioblastoma (rGBM). Three prospective randomized controlled phase III studies (2 in newly-diagnosed, one in rGBM) failed to show an overall survival benefit of BEV in the treatment of GBM. We aimed to capture current use patterns and perceived value of BEV in the treatment of GBM among experts in the field. An online questionnaire comprised of 14 questions was sent to 207 oncologists/neuro-oncologists at all National Cancer Institute-designated cancer centers in the United States. Sixty of 207 (29%) invitees responded (by training, 70% neuro-oncologists, 20% medical oncologists, 10% pediatric oncologists or neuro-oncologists). Participants reported use of BEV in the following clinical settings (multiple answers allowed): rGBM for the control of edema (84% participants), when no other treatment options are available (69%), in newly diagnosed GBM for control of edema (60% respondents), but rarely as a standard of care (3%). In newly diagnosed GBM, most (78%) of respondents use BEV in <5% of patients. In rGBM, 84% of participants stated that they use BEV in >25% of patients at some point during the disease course. Twenty-six percent of participants consider the role of BEV only as a steroid-sparing agent, 2% only as an antineoplastic agent, and 72% as both. Sixty-six percent of participants felt that BEV improves symptoms, 30% that it improves symptoms and survival, 4% that it has no benefit. No respondents reported that BEV has no value at all, the others that it was either very valuable (50%) or somewhat valuable (50%). Based on survey responses, BEV is only rarely used in select patients with newly-diagnosed GBM, and that it is primarily used in select patients with rGBM.
RTHP-06. END-TO-END WORKFLOW FOR FINITE ELEMENT ANALYSIS OF TUMOR TREATING FIELDS IN GLIOBLASTOMAS
Authors: Joshua Timmons, Edwin Lok, Pyay San, Kevin Bui, Eric Wong
Journal: Neuro-Oncology (2017)

Tumor Treating Fields (TTFields) therapy is an approved modality of treatment for glioblastoma. Patient anatomy-based finite element analysis (FEA) has the potential to reveal not only how these fields affect tumor control but also how to improve efficacy. While the automated tools for segmentation speed up the generation of FEA models, multi-step manual corrections are required, including removal of disconnected voxels, incorporation of unsegmented structures, and addition of 36 electrodes plus gel layers matching the TTFields transducers. Existing approaches are also not scalable for the high throughput analysis of large patient volumes. A semi-automated workflow was developed to prepare FEA models for TTFields mapping in the human brain. Magnetic resonance imaging (MRI) pre-processing, segmentation, electrode and gel placement, and post-processing were all automated. The material properties of each tissue were applied to their corresponding mask in silico using COMSOL Multiphysics (COMSOL, Burlington, MA). The fidelity of the segmentations with and without post-processing was compared against the full semi-automated segmentation workflow approach using Dice coefficient analysis. The average relative differences for the electric fields generated by COMSOL were calculated in addition to observed differences in electric field-volume histograms. Furthermore, the mesh file formats in MPHTXT and NASTRAN were also compared using the differences in electric field-volume histogram. The Dice coefficient was less for auto-segmentation without versus auto-segmentation with post-processing, indicating convergence on a manually corrected model. An existent but marginal relative difference of electric field maps from models with manual correction versus those without was identified, and a clear advantage of using the NASTRAN mesh file format was found. The software and workflow outlined here may be used to accelerate the investigation of TTFields in glioblastoma patients by facilitating the creation of FEA models derived from patient MRI datasets. Supported by A Reason To Ride research fund.
EPIDEMIC CEREBRO-SPINAL FEVER: THE PLACE OF THE MENINGOCOCCUS IN ITS ETIOLOGY: A Bacteriological Study. (Interim Report.)
Authors: E. C. Hort, C. E. Lakin, T. H. C. Benians
Journal: BMJ (1915)

t activity is no doubt the presence of bodies which we call metabolic, which are'shed into the tI'subspates' by the active cells; the cause of the similar phenomena in the case of inflammation is the presence of bodies which we call toxic in these sameI spaces.Whether a scientific truth underlies the apparent similarity depends upon the, as yet unascertained, relation of these two classes of bodies..In the meantime so long as we have anything to learn from such comparisons they are worth drawing, and I h1ope in my next lecture to deal writh a comparison which is at least something more than a coincidence.REFERENCES.