tbuckley/cabot-search huggingface dataset:
Epidemiologia descritiva dos exantemas na região de Roterdão, Janeiro de 1997 a Junho de 1998
Authors: O Ronveaux, A Bosman, R Reintjes, M A E Conyn-Van Spaendonck
Journal: Eurosurveillance (1998)

O Grupo de Aconselhamento Europeu sobre a Imunizacao recomendou que o sarampo deve ser eliminado da Europa no ano 2007 (1), um objectivo aceite pelos Responsaveis do Programa de Imunizacao Nacional da Organizacao Mundial de Saude (OMS) para os paises da Regiao Europeia. Na corrida para a eliminacao do sarampo e importante estudar a epidemiologia dos exantemas (rashes associados a doenca febril). No passado, o sarampo era a doenca exantematica mais comum na Europa, mas cada vez tem sido menos observada, a medida que a cobertura da vacina aumenta.
Amphiphysin (BIN1) negatively regulates dynamin 2 for normal muscle maturation
Authors: Belinda S. Cowling, Ivana Prokic, Hichem Tasfaout, Aymen Rabai, Frédéric Humbert, Bruno Rinaldi, Anne-Sophie Nicot, Christine Kretz, Sylvie Friant, Aurélien Roux, Jocelyn Laporte
Journal: Journal of Clinical Investigation (2017)

Regulation of skeletal muscle development and organization is a complex process that is not fully understood. Here, we focused on amphiphysin 2 (BIN1, also known as bridging integrator-1) and dynamin 2 (DNM2), two ubiquitous proteins implicated in membrane remodeling and mutated in centronuclear myopathies (CNMs). We generated Bin1–/– Dnm2+/– mice to decipher the physiological interplay between BIN1 and DNM2. While Bin1–/– mice die perinatally from a skeletal muscle defect, Bin1–/– Dnm2+/– mice survived at least 18 months, and had normal muscle force and intracellular organization of muscle fibers, supporting BIN1 as a negative regulator of DNM2. We next characterized muscle-specific isoforms of BIN1 and DNM2. While BIN1 colocalized with and partially inhibited DNM2 activity during muscle maturation, BIN1 had no effect on the isoform of DNM2 found in adult muscle. Together, these results indicate that BIN1 and DNM2 regulate muscle development and organization, function through a common pathway, and define BIN1 as a negative regulator of DNM2 in vitro and in vivo during muscle maturation. Our data suggest that DNM2 modulation has potential as a therapeutic approach for patients with CNM and BIN1 defects. As BIN1 is implicated in cancers, arrhythmia, and late-onset Alzheimer disease, these findings may trigger research directions and therapeutic development for these common diseases.
RTHP-19. DIFFUSE INTRINSIC PONTINE GLIOMA AS A LATE COMPLICATION OF MEDULLOBLASTOMA THERAPY
Authors: Hunter Gits, Maia Anderson, Becky Zon, Christopher Howell, Katayoon Kasaian, Daniel Polan, Martha Matuszak, Marcia Leonard, Daniel Spratt, Sriram Vennneti, Rajen Mody, James Leach, Blaise Jones, Sarah Leary, Ute Bartels, Torunn Yock, Patricia Robertson, Maryam Fouladi, Nick Gottardo, Carl Koschmann
Journal: Neuro-Oncology (2017)

Radiation therapy has been associated with increased risk of secondary gliomas in survivors of childhood medulloblastoma. Despite this clear association, no studies have specifically addressed the risk of diffuse intrinsic pontine glioma (DIPG) after craniospinal irradiation in medulloblastoma survivors. We performed a systematic review of patients enrolled in the DIPG Registry and Repository as well as a literature review of studies reporting recent cooperative group medulloblastoma trials in order to identify cases of DIPG occurring after radiation therapy for pediatric medulloblastoma. Eleven cases of secondary DIPG in patients with primary medulloblastoma were identified from the DIPG Registry (n=5) and literature review (n=6). Patients were diagnosed with primary medulloblastoma between the ages of 2-9 years. All patients underwent surgical resection followed by craniospinal photon irradiation (range 18-36 Gy) and posterior fossa boost (range 19.8-36 Gy). For cases with dosimetric information available, mean brainstem exposure was 50.1-54.0 Gy. Median time to diagnosis of secondary DIPG was 7.4 years (range 2-11 years). Patients died of secondary DIPG a median of 8 months after diagnosis (range 4-17 months). We performed germline and tumor DNA and RNA sequencing of secondary DIPGs at autopsy, when available, which revealed no germline cancer predisposition syndromes and mutations associated with DIPG and non-brainstem high-grade glioma (TP53 loss, PTEN loss, and NRAS mutation). The incidence of DIPG as a secondary malignancy after medulloblastoma ranged from 0.3-2.6% between the involved institutions and reported studies. In conclusion, we report that survivors of pediatric medulloblastoma are at increased risk for the development of secondary DIPG. While treatment varied for the patients in our cohort, all cases resulted in death within 2 years of diagnosis. This risk highlights the importance of radiation field and modality in the treatment of children with medulloblastoma, and provides a compelling argument for efforts to reduce brainstem exposure.
Cessation of nucleos(t)ide analogue treatment after HBeAg seroconversion is associated with a 4-fold increased risk of relapse in cirrhotic compared to non-cirrhotic patients
Authors: S Van Hees, S Bourgeois, H Van Vlierberghe, T Sersté, S Francque, P Michielsen, D Sprengers, H Reynaert, J Henrion, S Negrin Dastis, Jean Delwaide, L Lasser, J Decaestecker, H Orlent, F Janssens, G Robaeys, I Colle, P Starkel, C Moreno, F Nevens, T Vanwolleghem
Journal: Hepatology (2017)

Isabelle Colle - Consulting: Promethera; Grant/Research Support: abbvie; Patent Held/Filed: Trombogenics; Speaking and Teaching: BMS
Christophe Moreno - Consulting: Abbvie, Janssen, Gilead, BMS, MSD; Grant/Research Support: Janssen, Gilead, Roche, Astellas, Abbvie
Frederik Nevens - Consulting: MSD, CAF, Intercept, Gore, BMS, Abbvie, Novartis, Durect, Janssens-Cilag, Ono Pharma, Promethera Biosciences, Gilead; Grant/Research Support: Ferring, Roche, Astellas, Novartis, Janssen-Cilag, Abbvie, Gilead
NIMG-75. NECROSIS DURING TREATMENT IS ASSOCIATED WITH WORSE SURVIVAL IN RECURRENT GLIOBLASTOMA PATIENTS – POST HOC IMAGE ANALYSIS OF EORTC 26101
Authors: Martha Nowosielski, Thierry Gorlia, Jacolien Bromberg, Felix Sahm, Inga Harting, Philipp Kickingereder, Alba Brandes, Martin J B Taphoorn, Walter Taal, Julien Domont, Ahmed Idbaih, Mario Campone, Paul Clement, Michael Weller, Michel Fabbro, Francois Dubois, Michael Platten, Vassilis Golfinopoulos, Martin Bendszus, Martin van den Bent, Wolfgang Wick
Journal: Neuro-Oncology (2017)

In this exploratory analysis of EORTC 26101, a randomized phase III clinical study comparing single-agent lomustine with lomustine plus bevacizumab in patients with progressive glioblastoma, development of necrosis on treatment was radiographically assessed and compared to outcome. Sufficient imaging data for this post hoc analysis were available for 373 patients (lomustine = 129, lomustine + bevacizumab = 244). MRI scans from baseline until tumor progression were reviewed and presence of necrosis (>10x10mm) was noted if 1) necrosis developed during treatment, 2) occurred at progression or 3) was present at baseline and increased >25% in two perpendicular diameters during follow-up. Frequencies were compared by Wilcoxon rank test, univariate associations of necrosis with overall survival (OS) were tested by log-rank test, hazard ratios (HR) with 95% Confidence interval were calculated by Cox model. Necrosis was more commonly detected in the lomustine group (lomustine 30/99 (23.3%) versus combination 34/210 (13.9%), p=0.023). Looking at the two treatment groups independently, necrosis was associated with worse OS in both treatment arms (lomustine HR=1.76 [1.09;2.82], combination HR=1.79 [1.21;2.66]), unrelated to the treatment received. Importantly, increase of necrosis preceded progression according the RANO criteria in 20% of cases, was detected at progression in 16% and was already present at baseline (with a subsequent increase) in 64% of patients. When monitoring treatment response in patients with progressive glioblastoma, presence and increase of necrosis is associated with worse outcome. The correlation with worse outcome is independent of the type of treatment delivered.
Abstract 20492: Cumulative Negative Traumatic Life Events and Obesity in Women
Authors: Fumika Matsushita, Eva M Durazo, Tiffany Powell-Wiley, Alan M Zaslavsky, Natalie Slopen, Julie E Buring, Michelle A Albert
Journal: Circulation (2017)

Background:  Both psychosocial stress and obesity are risk factors for cardiovascular disease (CVD). Although women are disproportionately affected by obesity and live longer than men conferring heightened risk for CVD, little is known about the relationship between stress as measured by major life events and obesity in women.   Methods and Results:  We evaluated the cross-sectional relationship between major life events (traumatic and negative) and obesity (body mass index (BMI) ≥ 30 kg/m 2 ) in the Women’s Health Study (WHS) 2012-2013 follow-up cohort of 21,904 middle-aged and older women (excluding women with cancer or missing life event or BMI data). Mean age was 72.0 ± 6.0 years and 23.3% of women reported BMI ≥ 30 kg/m 2 . Participants reported experiencing traumatic life events (death of a child, being victim of serious physical attack/assault, life-threatening illness or accident to spouse/child) on 3 survey questions. Negative life events in the past 5 years were scored as the count of positive reports out of 12 questions (e.g. death of someone close, being unemployed for 3+ months, robbed or burglarized). Logistic regression models adjusted for age, race/ethnicity, socioeconomic status, marital status, diabetes, smoking, physical activity, caloric intake, and depression/anxiety symptoms revealed that women with ≥ 1 traumatic life events had higher odds of obesity than those without any (Odds Ratio (95% Confidence Interval): 1.11 (1.03-1.20)). Increasing reports of negative life events were associated with higher odds of obesity; adjusted odds ratios relative to those with no events were 1.17 (1.03-1.33) (1 event); 1.11 (0.98-1.25) (2 events); 1.17 (1.02-1.33) (3 events); 1.36 (1.20-1.55) (4+ events)). These relationships may be moderated by physical activity with little association of negative events to obesity apparent among those with low levels of physical activity.   Conclusion:  Women who reported ≥ 1 traumatic event in their lifetime or who reported 4+ negative life events in the past 5 years had increased odds of being obese. This association appeared to be strongest among women who reported moderate or high physical activity. These findings suggest addressing psychosocial stress related to major life events as part of obesity interventions.
P1.02-022 Spontaneous Regression of Primary Pulmonary Synovial Sarcoma; A Case Report
Authors: N. Miyata, H. Tsunezuka, N. Ishikawa, T. Furuya, C. Nakazono, S. Ishihara, S. Okada, D. Kato, J. Shimada, E. Konishi, M. Inoue
Journal: Journal of Thoracic Oncology (2017)
Mode and Rate of Evolution of Haemosporidian Mitochondrial Genomes: Timing the Radiation of Avian Parasites
Authors: M Andreína Pacheco, Nubia E Matta, Gediminas Valkiūnas, Patricia G Parker, Beatriz Mello, Craig E Stanley, Miguel Lentino, Maria Alexandra Garcia-Amado, Michael Cranfield, Sergei L Kosakovsky Pond, Ananias A Escalante
Journal: Molecular Biology and Evolution (2017)

Haemosporidians are a diverse group of vector-borne parasitic protozoa that includes the agents of human malaria; however, most of the described species are found in birds and reptiles. Although our understanding of these parasites' diversity has expanded by analyses of their mitochondrial genes, there is limited information on these genes' evolutionary rates. Here, 114 mitochondrial genomes (mtDNA) were studied from species belonging to four genera: Leucocytozoon, Haemoproteus, Hepatocystis, and Plasmodium. Contrary to previous assertions, the mtDNA is phylogenetically informative. The inferred phylogeny showed that, like the genus Plasmodium, the Leucocytozoon and Haemoproteus genera are not monophyletic groups. Although sensitive to the assumptions of the molecular dating method used, the estimated times indicate that the diversification of the avian haemosporidian subgenera/genera took place after the Cretaceous-Paleogene boundary following the radiation of modern birds. Furthermore, parasite clade differences in mtDNA substitution rates and strength of negative selection were detected. These differences may affect the biological interpretation of mtDNA gene lineages used as a proxy to species in ecological and parasitological investigations. Given that the mitochondria are critically important in the parasite life cycle stages that take place in the vector and that the transmission of parasites belonging to particular clades has been linked to specific insect families/subfamilies, this study suggests that differences in vectors have affected the mode of evolution of haemosporidian mtDNA genes. The observed patterns also suggest that the radiation of haemosporidian parasites may be the result of community-level evolutionary processes between their vertebrate and invertebrate hosts.
Infección por VIH en Europa: gran disparidad entre este y oeste
Authors: C Semaille, J Alix, A M Downs, F F Hamers
Journal: Eurosurveillance (2003)

En 2001, Europa occidental se enfrenta a una situacion endemica de sida (22,8 casos por millon de personas) e infeccion por VIH (54,9 casos por millon de personas), y los grupos mas afectados siguen siendo los usuarios de drogas por via parenteral y los varones homo/bisexuales. Sin embargo, las cifras correspondientes a nuevos diagnosticos de VIH en personas infectadas por contacto heterosexual van en aumento. Europa Central se ha librado relativamente, con una incidencia de sida inferior a seis casos por millon de habitantes y ano, y entre 7 y 10 casos por millon para nuevos diagnosticos de VIH. Por otro lado, Europa del este registra un aumento epidemico en el numero de infecciones por VIH de diagnostico reciente (233 casos en 1994, alrededor de 100.000 casos declarados en 2001, es decir, 349 casos por millon de habitantes) que afecta a todos los paises.
PDCT-12. TRACKING T-CELL IMMUNE RECONSTITUTION AFTER ADOPTIVE CELLULAR THERAPY TARGETING RECURRENT MEDULLOBLASTOMA AND PNETS USING DEEP T-CELL RECEPTOR (TCR) REPERTOIRE SEQUENCING
Authors: Oleg Yegorov, Yanina Yegorova, Anjelika Dechkovskaia, Jianping Huang, Sridharan Gururangan, Duane Mitchell
Journal: Neuro-Oncology (2017)

Adoptive cellular therapy (ACT) using transfer of tumor-specific lymphocytes has demonstrated significant clinical activity in different cancers. T-cells represent a crucial component of the adaptive immune system and are able to mediate antitumor immunity. We have employed deep TCR repertoire sequencing approach to explore dynamics of T-cell immunity in patients with recurrent medulloblastoma and PNETs undergoing adoptive cellular therapy (Re-MATCH protocol, FDA IND BB-14058). Total RNA was isolated from patient PBMC samples collected prior to adoptive cellular therapy and weekly for one month and then monthly following immunotherapy treatment. cDNA was generated with addition of a common adapter at 5’ end using RACE technology. Raw sequencing data were preprocessed using MiXCR software. Further TCR repertoire analysis was performed using tcR R-package and VDJtools software. We observed remarkable dynamic changes in the TCR repertoire in peripheral blood following ACT in all patients. We found that after lymphodepletive therapy, immune system regeneration at early time points following ACT comes from ex vivo antigen-driven expansion of T lymphocytes and subsequently from de novo expansion of host reconstituting T-cells. The blood samples collected after adoptive cellular therapy revealed that certain T-cells were clonally expanded after ACT, with an increasing number of “hyper-expanded” TCR clones (comprising >1% of all TCR beta or alpha sequences). These TCR clones established a new balance in the peripheral blood. Hyper-expanded TCR clones and increased TCR diversity following ACT was associated with radiographic response to ACT and prolonged progression-free and overall survival. Limited TCR expansion and diversity following ACT was observed in patients with short overall and progression-free survival. These findings support further study of the use of TCR sequencing to monitor responses to adoptive cellular therapy and suggest that TCR clonal expansion and increasing TCR diversity following treatment may be associated with positive clinical responses.
Portraits in Health Policy
Authors: Theresa BrownGold
Journal: JAMA (2017)

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CSIG-12. EXPLORING THE FUNCTIONAL RELATIONSHIP BETWEEN CAPICUA (CIC) AND ATAXIN-1-LIKE (ATXN1L) IN GLIOMA
Authors: Derek Wong, Kohl Lounsbury, Veronique LeBlanc, Suganthi Chittaranjan, Marco Marra, Stephen Yip
Journal: Neuro-Oncology (2017)

Oligodendroglioma (ODG), a molecularly defined subtype of glioma, is a treatment responsive, slow growing tumour strongly associated with IDH mutation and 1p19q co-deletion. Mutations in CIC, located on chromosome 19q, have been found in up to 70% of IDH mutated, 1p19q co-deleted ODGs; suggesting that loss or altered function of CIC may be crucially associated with ODG’s unique biology. CIC and ATXN1L have previously been implicated in neurodegeneration, however, this interaction has not been studied in cancer. CIC and ATXN1L interaction was confirmed using immunoprecipitation and immunofluorescence in multiple cell lines. CIC and ATXN1L knockout (KO) cell lines were generated using CRISPR/Cas9 followed by gene expression profiling using Affymetrix microarray. Differential gene expression analysis was also performed on patient lower grade glioma (LGG) RNAseq data publicly available through TCGA. Functional biology experiments to further characterize CIC-ATXN1L interaction were also performed using KO cell systems. Immunoprecipitation and immunofluorescence confirmed CIC and ATXN1L interaction within the cell nucleus of multiple cell lines. Differential expression (DE) analysis of CIC KO, ATXN1L KO and TCGA LGG cohort converged on activation of the MAPK pathway and dysregulation of central nervous system development; with significant overlap in differentially expressed genes (n=110). Furthermore, experiments using our KO cell systems suggest a functionally reciprocal relationship between CIC and ATXN1L and regulation of their respective pathways. CIC and ATXN1L form a functionally reciprocal relationship where loss of one partner leads to dysregulation of both partners. Although CIC mutations are predominant in ODGs, the CIC-ATXN1L axis may be exploited in other gliomas and cancers which rely on maintaining MAPK signaling such as EGFR amplified glioblastoma and may be a target for future prognostics and therapeutics.
Abstract 20861: Depletion of BM Progenitor Cell Reserve, Rather Than Progenitor Cell Mobilization is Associated With Major Events in Severe Limb Ischemia
Authors: Hendrik Gremmels, Martin Teraa, Femke C van Rhijn-Brouwer, Diana A Papazova, Joost O Fledderus, Marianne C Verhaar
Journal: Circulation (2016)

Introduction: Lower numbers of progenitor cells (PCs) in peripheral blood (PB) have been associated with cardiovascular events in high-risk populations. It is currently unknown what causes the redu...
QLIF-31. SYMPTOM BURDEN AND HEALTH STATUS OF PATIENTS WITH RARE VERSUS COMMON BRAIN TUMORS
Authors: Elizabeth Vera, Tito Mendoza, Sonja Crandon, Boris Lisa, Nancy Garren, Christine Siegel, Deric M Park, Joo-Hee Sul, Brett Theeler, Jing Wu, Mark R Gilbert, Terri Armstrong
Journal: Neuro-Oncology (2017)

There are over 130 types of primary central nervous system neoplasms, many with annual incidences of less than 2,000 patients. Their rarity present challenges in generating sufficient patient accrual to understand the disease trajectory and impact on patients. Patients enrolled in the Neuro-Oncology Branch Natural History Study (NOB-NHS) were categorized as having rare brain tumors (ependymoma, glioneuronal tumor, gliomatosis cerebri, medulloblastoma) and compared to a random sample of patients with common CNS tumors matched on age, recurrence, treatment phase, and time from diagnosis to study entry. Group differences in symptoms (MD Anderson Symptom Inventory-Brain Tumor), depression (PHQ-9), anxiety (GAD-7), and health status (EQ-5D) were compared using effect sizes with 95% confidence interval via bootstrapping technique. The sample included 15 rare tumor patients and 15 matched controls. The average patient was a white (83%) male (63%) aged 44 (SD=16). Most patients had received treatment (87%), had not experienced a recurrence (53%), and had a KPS≥90 (74%). A pattern emerged of fewer symptoms among rare tumor patients, but no difference in the percent with moderate-to-severe symptoms compared to more common tumors. Moderate effect sizes were found; patients with rare tumors had less sleep and mood disturbance (r=0.6, 95%CI: 0.3-0.8; r=0.5, 95%CI: 0.1-0.7, respectively) unrelated to steroid use or therapies received. Both groups had similar health states, and levels of anxiety and depression. Rare tumor patients are not dissimilar from those with more common brain tumors in terms of symptoms reported and measures of health status. Sleep and disturbed mood were less common in patients with rare tumors but their effect were moderate. The NOB-NHS is a mechanism for inclusion of rare CNS tumor patients, allowing longitudinal assessment and comparison with other CNS cancers. Future studies will explore biologic correlates and trajectory of symptoms in these rare tumor patients.