tbuckley/cabot-search huggingface dataset:
Carta à redacção : Surtos de parvovirus B19
Authors: B J Cohen
Journal: Eurosurveillance (2005)

In response to the recent report of school outbreaks of parvovirus B19 infection in Portugal [1], Heath Kelly and Jennie Leydon of the Western Pacific Regional Measles Laboratory, have echoed the call for parvovirus B19 tests to be included in measles and rubella surveillance.
GENE-24. ATRX DEFICIENCY IN GLIOMA CELLS OF ORIGIN PROMOTES DISEASE-DEFINING PHENOTYPES BY WAY OF GLOBAL EPIGENOMIC REMODELING
Authors: Carla Danussi, Promita Bose, Prasanna Parthasarathy, Pedro Silberman, John S Van Arnam, Mark Vitucci, Oliver Tang, Adriana Heguy, Timothy Chan, Erik Sulman, Fred Lang, Chad J Creighton, Benjamin Deneen, C Ryan Miller, David Picketts, Kasthuri Kannan, Jason Huse
Journal: Neuro-Oncology (2017)

Epigenomic abnormalities are increasingly recognized as driver mechanisms in cancer, and somatic mutations in genes encoding epigenetic regulators have now been widely reported across a number of cancer types. Diffusely infiltrating gliomas, feature loss-of function mutations in the SWI/SNF chromatin remodeler gene ATRX as defining molecular alterations delineating major adult and pediatric disease subtypes. Within this disease context, ATRX deficiency invariably co-occurs with mutations in TP53 and in genes encoding either IDH1/2 in adults or H3.3 histone in children. So far, ATRX deficiency has been linked to a wide spectrum of physiological dysfunction, including aberrant gene regulation, abnormal telomere maintenance, genomic instability, and aneuploidy, but the molecular mechanism(s) by which ATRX deficiency promotes oncogenesis are still largely unknown, particularly those involving epigenomic dysregulation. To model these events in putative glioma cells of origin, we inactivated Atrx in primary murine neuroepithelial progenitors (mNPCs). Interestingly, Atrx loss induced NPCs to stop growing as neurospheres and adopt an adherent phenotype, while also exhibiting significantly increased motility. Moreover, when cultured in differentiation conditions, Atrx deficient cells displayed upregulation of astrocyte markers and downregulation of neuronal and oligodendrocyte markers, suggesting that Atrx directly regulates NPCs differentiation state and potential. Notably, the observed phenotypes correlated with altered gene expression profiles involving molecular networks implicated in development, regulation of signal transduction and cellular motility and invasion. Integrating these transcriptional changes with shifts in chromatin accessibility occurring with Atrx deficiency and genome-wide Atrx distribution, as determined by ChIP-seq, revealed highly significant spatial correlations between differentially expressed genes, regions of altered chromatin compaction, histone composition and genomic sites normally occupied by Atrx. Taken together, these findings demonstrate that Atrx deficiency induces widespread disruptions in chromatin organization, which in turn lead to dramatic shifts in gene expression and acquisition of disease-relevant phenotypes in putative glioma cells of origin.
OA 08.06 Exploratory Analysis for Predictors of Benefit of PARP Inhibitor Therapy in Extensive Stage Small Cell Lung Cancer: ECOG-ACRIN 2511 Study
Authors: T. Owonikoko, S. Dahlberg, J. Poirier, G. Sica, C. Rudin, S. Ramalingam
Journal: Journal of Thoracic Oncology (2017)
IMMU-59. ALTERNATING ELECTRIC FIELDS (TTFIELDs) INDUCE IMMUNOGENIC CELL DEATH RESULTING IN ENHANCED ANTITUMOR EFFICACY WHEN COMBINED WITH ANTI-PD-1 THERAPY
Authors: Tali Voloshin, Orna Tal Yitzhaki, Noa Kaynan, Moshe Giladi, Anna Shteingauz, Mijal Munster, Yaara Porat, Rosa Schneiderman, Shay Cahal, Aviran Itzhaki, Eilon D Kirson, Uri Weinberg, Yoram Palti
Journal: Neuro-Oncology (2017)

Tumor Treating Fields (TTFields) are an effective anti-neoplastic treatment modality delivered via noninvasive application of low intensity, intermediate frequency, alternating electric fields. TTFields are employed as a local treatment modality with the intent to kill tumor cells and reduce local recurrence. This therapy is approved for the treatment of patients with glioblastoma. Previous investigations have shown that TTFields disrupt formation of the mitotic spindle, leading to abnormal chromosome segregation and various modes of cell death. In this study we evaluated whether TTFields-induced cell death can be perceived as immunogenic by the immune system. We demonstrate that cancer cells that die under TTFields application exhibit release of the chromatin-binding protein high mobility group B1(HMGB-1), endoplasmic reticulum (ER) stress leading to Calreticulin translocation to the cell surface, and autophagy leading to decreased intracellular levels of adenosine triphosphate (ATP), all of which are cardinal signs of immunogenic cell death. In vivo, the combined treatment of lung tumor-bearing mice with TTFields plus the immune checkpoint inhibitor anti-programmed death 1 (PD-1) led to a significant decrease in tumor volume compared to anti-PD-1 alone or to the control group. Significant increases in CD45+ tumor infiltrating cells were observed in the TTFields plus anti-PD-1 group. These infiltrating cells, specifically macrophages (F4/80+CD11b+) and dendritic (CD11c+) cells, demonstrated a significant upregulation of surface PD-L1 expression as compared to infiltrating immune cells in the control group. Our results demonstrate the potential of TTFields therapy to induce immunogenic cell death in vitro which may lead enhanced immune response against cancer cells. We also demonstrate significant efficacy of concurrent application of TTFields and anti PD-1 therapy in vivo. These data suggest that combining TTFields with anti-PD-1 might achieve tumor control by further enhancing antitumor immunity.
High cumulative anthracycline dose without cardiac toxicity: a study on outlier patients
Authors: M.L. Canale, A. Camerini, M. Magnacca, J. Del Meglio, A. Lilli, S. Donati, L. Belli, S. Lencioni, D. Amoroso, G. Casolo
Journal: Annals of Oncology (2017)
P2.01-038 Determinants of Frailty and Treatment Toxicity in Non-Small Cell Lung Cancer Patient
Authors: M. Boucher, L. Mezquita, E. Auclin, M. Mons, J. Marghadi, M. Charrier, R. Ferrara, D. Planchard, G. Anas, C. Le Pechoux, A. Botticella, C. Caramella, J. Adam, J. Soria, B. Besse
Journal: Journal of Thoracic Oncology (2017)
Final analysis of the phase III multicentric Italian study Short-HER: 9 weeks vs 1 year adjuvant trastuzumab for HER2+ early breast cancer
Authors: P. Conte, P. Conte, G. Bisagni, A. Frassoldati, A. Brandes, L. Cavanna, F. Giotta, M. Aieta, V. Gebbia, A. Musolino, O. Garrone, M. Donadio, G. Cavazzini, A. Turletti, C. Zamagni, S. Danese, A. Ferro, F. Piacentini, S. Balduzzi, R. D'Amico, V. Guarneri
Journal: Annals of Oncology (2017)
Randomized phase 1b/3 study of erlotinib plus ramucirumab in first-line EGFR mut + stage IV NSCLC: phase 1b safety results
Authors: K. Nakagawa, E.B. Garon, L. Paz-Ares, S. Ponce, J. Corral Jaime, O. Juan Vidal, E. Nadal, K. Kiura, S. He, J. Treat, R. Dalal, P. Lee, M. Reck, S. Novello
Journal: Annals of Oncology (2017)
P1.01-056 Quality of Life and Clinical Outcomes of Nivolumab as 2+ Line Treatment in Advanced Refractory NSCLC Pts: Interim Analysis
Authors: T. Ionova, A. Arzumanyan, L. Bolotina, V. Breder, N. Buevich, A. Danilova, E. Filippova, A. Kornietskaya, M. Kramchaninov, E. Kushniruk, D. Latipova, D. Lipatova, O. Malova, F. Moiseenko, T. Nikitina, S. Orlov, R. Orlova, S. Protsenko, K. Sarantseva, D. Stroyakovsky, A. Zinkovskaya, K. Laktionov
Journal: Journal of Thoracic Oncology (2017)
P1.01-074 Exosomal RNA-Profiling of Lung Pleural Effusions Identifies Adenocarcinoma Patients through Elevated miR-200 Expression
Authors: P. Hydbring, L. De Petris, E. Branden, H. Koyi, M. Novak, L. Kanter, P. Hååg, J. Hurley, V. Tadigotla, J. Skog, K. Viktorsson, S. Ekman, R. Lewensohn
Journal: Journal of Thoracic Oncology (2017)
Activity of Entrectinib in a Patient With the First Reported <i>NTRK</i> Fusion in Neuroendocrine Cancer
Authors: Darren Sigal, Marie Tartar, Marin Xavier, Fei Bao, Patrick Foley, David Luo, Jason Christiansen, Zachary Hornby, Edna Chow Maneval, Pratik Multani
Journal: Journal of the National Comprehensive Cancer Network (2017)

Despite advances in genomic analysis, the molecular origin of neuroendocrine tumors (NETs) is complex and poorly explained by described oncogenes. The neurotrophic TRK family, including NTRK1, 2, and 3, encode the proteins TRKA, TRKB, TRKC, respectively, involved in normal nerve development. Because NETs develop from the diffuse neuroendocrine system, we sought to determine whether NTRK alterations occur in NETs and whether TRK-targeted therapy would be effective. A patient with metastatic well-differentiated NET, likely of the small intestine, was enrolled on the STARTRK2 trial (ClinicalTrials.gov identifier: NCT02568267) and tissue samples were analyzed using an RNA-Seq next-generation sequencing platform. An ETV6:NTRK3 fusion was identified and therapy was initiated with the investigational agent entrectinib, a potent oral tyrosine kinase inhibitor of TRKA, TRKB, and TRKC. Upon treatment with entrectinib, the patient experienced rapid clinical improvement; his tumor response was characterized by initial tumor growth and necrosis. This is the first report of an NTRK fusion in NETs. Our patient's response to entrectinib suggests that NTRK fusions can be important in the pathogenesis of NETs. Recent DNA-based genomic analyses of NETs may have missed NTRK fusions due its large gene rearrangement size and multiple fusion partners. The tumor's initial pseudoprogression may represent a unique response pattern for TRK-targeted therapies. An effort to characterize the prevalence of NTRK fusions in NETs using optimal sequencing technology is important.
HELICS : projet européen pour standardiser la surveillance des infections hospitalières, 1994-1995
Authors: R Mertens, J. M.J van den Berg, J Fabry, O. B Jepsen
Journal: Eurosurveillance (1996)

Durant les annees 1990, plusieurs pays europeens ont commence a mettre en place des reseaux regionaux ou nationaux de surveillance des infections acquises a l'hopital. La plupart de ces reseaux etait basee sur le modele du Systeme National de Surveillance des Infections Nosocomiales (NNIS) des Centers for Disease Control and Prevention (CDC) americains, le projet EURONIS soutenu par l'UE (Surveillance des Infections Nosocomiales dans les Unites de Soins Intensifs en Europe) ou l'initiative DANOP/WHOCARE coordonnee par le Bureau Europe de l'OMS et le Statens Seruminstitut a Copenhague.
P2.02-040 Cytology Cell Block Is Suitable for Immunohistochemical Testing for PD-L1 in Lung Cancer
Authors: H. Wang, J. Agulnik, G. Kasymjanova, A. Wang, V. Cohen, C. Pepe, D. Small, L. Sakr, P. Fiset, M. Auger, S. Camilleri-Broet, M. Alam Ei Din, A. Spatz
Journal: Journal of Thoracic Oncology (2017)
Abstract 20955: Synergistic Effects of Rivaroxaban With Direct-Acting Anti-Platelet Agents on Platelet Reactivity and Thrombin Generation
Authors: Jayaprakash Kotha, Juan M Cardenas, Matthew T Roe, Erik M Ohman, Charles M Gibson, Lisa K Jennings
Journal: Circulation (2017)

Introduction: Direct-acting oral anticoagulants (DOACs) are increasingly evaluated for the secondary prevention of thrombosis-related events; however, DOAC dose-related effects on platelet function, particularly with anti-platelet agents, are unknown. Hypothesis: Factor Xa inhibitors do not have direct anti-platelet activity; however, by their capacity to inhibit thrombin generation (TG), they indirectly regulate thrombin-dependent platelet activation. This indirect mode of action may have additive effects with anti-platelet agents such as aspirin or P2Y12 antagonists. Methods: Platelet-rich plasma (PRP) from healthy individuals (n=6) was incubated with increasing amounts, and combinations of rivaroxaban (Riva), aspirin (ASA) and/or ticagrelor(T). The impact on platelet function was studied using light transmission aggregometry (LTA) and fluorogenic TG assays (TGA). For LTA, maximal aggregation (MA) was measured after initiation of tissue factor (TF)-induced TG. Similarly, for TG assays in platelet-poor plasma (PPP) and PRP low TF concentrations were used to initiate TG. Results and Conclusions: Riva treatment alone decreased % MA by TF-generated thrombin by 24% (15 ng/ml; akin to 2.5 mg bid dosing) and 71% (120 ng/ml; akin to 10 - 20 mg bid dosing). Riva, in combination with both anti-platelet agents, decreased MA substantially by 69% at 15 ng/ml and significantly by 89% at 120 ng/ml (p&lt;0.05). However, when PRP is treated only with ASA or T (sans Riva), thrombin-mediated MA decreased by 12% and 25%, respectively. In TGA, Riva alone in PPP caused significant inhibition of TG (p &lt;0.05). At 15 ng/ml, ~40% inhibition of peak TG was noted in PPP, though in PRP, inhibition was only 22% with donor variability observed. At 120 ng/ml Riva, peak TG inhibition was 90% and 64% for PPP or PRP, respectively. Though evident at higher Riva doses, the 15 ng/ml dose showed no synergy with ASA or T or the ASA/T combination in inhibiting TG in PRP. These results demonstrate that Riva provides an additive effect in reducing platelet reactivity, and its impact is highly dose-dependent and influenced by anti-platelet therapies. Such findings should be taken into consideration for anti-FXa dosing, either when anti-platelet therapies are or are not part of a treatment regimen.
EPID-05. AUTOLOGOUS STEM CELL TRANSPLANT FOR PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA IN IMMUNOCOMPETENT PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Iyad Alnahhas, Mohammad Jawish, Mouaz Alsawas, Hassan Murad, Alicia Zukas, Mark Malkin
Journal: Neuro-Oncology (2017)

Primary central nervous system lymphoma (PCNSL) is a rare aggressive variant of extranodal non-Hodgkin lymphoma (NHL) that involves the brain, leptomeninges, eyes, or spinal cord. First-line therapy includes methotrexate-based chemotherapy. New treatment modalities have been sought to avoid WBRT and related neurotoxicity. Autologous stem cell transplant (ASCT) is increasingly used in the management of PCNSL. A systematic search of several databases was conducted up until October 11th, 2016. Two investigators independently assessed the articles for eligibility and extracted the data. Studies that reported survival outcomes in patients with PCNSL treated with ASCT as 1st line therapy or at relapse were included in the analysis. 1274 studies were screened and subsequently 62 full articles were assessed for inclusion. 41 and 35 studies (totaling 717 patients) were finally included in the systematic review and meta-analysis, respectively. The vast majority of pathology was DLBCL. BEAM, TBC and CCNU/ thiotepa were commonly used conditioning regimens. Collectively, 91% of patients achieved or maintained a complete or partial response after ASCT and 75% had an improved response after ASCT. Our analysis further concludes that there is a 90%, 84%, 79% and 66% chance of overall survival (OS) after 1, 2, 3 and 5 years of ASCT, respectively. Odds of progression-free survival (PFS) at the same intervals were 81%, 69%, 68% and 59%, respectively. Among the studies that included direct comparison between ASCT vs. non-ASCT groups, HR was 0.37 (0.22, 0.63) for OS and 0.22 (0.12, 0.39) for PFS. Risk of relapse at 5 years after ASCT was 23% and treatment related mortality (TRM) was 2%. Our meta-analysis provides pooled response and survival data and confirms the efficacy of ASCT in the management of PCNSL.
Female Mimicry by Sneaker Males Has a Transcriptomic Signature in Both the Brain and the Gonad in a Sex-Changing Fish
Authors: Erica V Todd, Hui Liu, Melissa S Lamm, Jodi T Thomas, Kim Rutherford, Kelly C Thompson, John R Godwin, Neil J Gemmell
Journal: Molecular Biology and Evolution (2017)

Phenotypic plasticity represents an elegant adaptive response of individuals to a change in their environment. Bluehead wrasses (Thalassoma bifasciatum) exhibit astonishing sexual plasticity, including female-to-male sex change and discrete male morphs that differ strikingly in behavior, morphology, and gonadal investment. Using RNA-seq transcriptome profiling, we examined the genes and physiological pathways underlying flexible behavioral and gonadal differences among female, dominant (bourgeois) male, and female-mimic (sneaker) male blueheads. For the first time in any organism, we find that female mimicry by sneaker males has a transcriptional signature in both the brain and the gonad. Sneaker males shared striking similarity in neural gene expression with females, supporting the idea that males with alternative reproductive phenotypes have "female-like brains." Sneaker males also overexpressed neuroplasticity genes, suggesting that their opportunistic reproductive strategy requires a heightened capacity for neuroplasticity. Bourgeois males overexpressed genes associated with socio-sexual behaviors (e.g., isotocin), but also neuroprotective genes and biomarkers of oxidative stress and aging, indicating a hitherto unexplored cost to these males of attaining the reproductively privileged position at the top of the social hierarchy. Our novel comparison of testicular transcriptomes in a fish with male sexual polymorphism associates greater gonadal investment by sneaker males with overexpression of genes involved in cell proliferation and sperm quality control. We propose that morphological female-mimicry by sneaker male teleosts entails pervasive downregulation of androgenesis genes, consistent with low androgen production in males lacking well-developed secondary sexual characters.
DNA amount comparison between cytologic and histologic samples for epithelial growth factor receptor (EGFR) testing in non-small-cell lung cancer (NSCLC) patients: a single institution experience
Authors: E. Gobbini, M.L. Reale, E. De Luca, L. Righi, M. Gianetta, E. Capelletto, L. Buffoni, M. Giaj Levra, S. Novello
Journal: Annals of Oncology (2017)
Abstract 24077: Differential, Sex Related, Response To High-fat Diet In Mice Impairs Cardiac Autophagy And Mitophagy
Authors: Amandine Thomas, Stefanie Marek, Kyle C Tucker, Allen M Andres, Roberta A Gottlieb
Journal: Circulation (2017)

Introduction: Premenopausal women, as well as females in animal studies, have a reduced risk of cardiovascular diseases and a reduced myocardial susceptibility to ischemia/reperfusion (I/R) injury. However, with constantly increasing prevalence of obesity, the impact of diet-induced obesity on females remains unclear. Mechanisms of autophagy and mitophagy, differentially regulated between males and females, have been shown to be cardioprotective and impacted under nutritional overload. Hypothesis: Autophagy and mitophagy pathways can be involved in both female cardio protection and deleterious effect of obesity. Methods: Male and female C57Bl/6J mice (n =20 per group) of 8 weeks old were fed a low-fat (LFD, 10% fat) or high-fat (HFD, 60% fat) diet for 12 weeks. At 12 weeks, hearts from mice were studied under basal conditions and after global no-flow ischemia and reperfusion on a Langendorff perfusion system. Results: In both males and females, HFD significantly increases body weight (31.4g vs 48.3g and 22.1g vs 39.9g respectively), fat mass (+200% in males and +300% in females) and blood glucose (+79mg/dl and + 54mg/dl, respectively) (all p&lt;0.01). HFD tends to decrease flow reperfusion after global no-flow ischemia and to increase infarct size (p=0.08 in female and p=0.1 in male, n=5) in both sexes. In males and females, HFD increases pSer757-Ulk1 and decreases Parkin levels under basal conditions (all p&lt;0.006). Moreover, HFD tends to decrease pThr172-AMPK only in females. After I/R, Parkin levels remain lower in HFD groups without sex-difference (p&lt;0.004) but a drastic increase of LC3-II occurs only in females under HFD (p=0.047). Conclusion: All together, these results suggest an impairment of autophagy and mitophagy pathways under HFD. A more drastic change occurs in female mice and may imply a more important response of female mice to HFD, although further studies are needed. However, this result suggests that cardiovascular disease may be more deleterious in women despite their lower cardiovascular risk; additional studies examining sex differences in the response to metabolic syndrome and ischemic heart disease are warranted.
CMET-17. A NEW PREDICTIVE INDEX FOR SURVIVAL IN SYMPTOMATIC SPINAL METASTASES
Authors: Arthur Jenkins
Journal: Neuro-Oncology (2017)

Spinal metastases are associated with high variability in morbidity and mortality. Existing prognostic scoring systems, including the Tomita and Tokuhashi scores, are over a decade old and have limited predictive value. Our aim is to improve upon the accuracy of the Tomita and Tokuhasi score given recent advances in surgical care for spinal metastases, and to develop a new survival index with superior prognostic value. We completed a retrospective analysis on 77 patients who received surgery for metastatic tumors to the spine. After analysis of more than 20 different patient factors, the JSI (Jenkins Survival Index) was derived from the two patient factors (pre-operative Hauser ambulation index and degree of metastatic or primary tumor burden in the lung) that best predicted survival. We then compared the predictive value of JSI with the Tomita and Tokuhashi scales. Lung tumor burden and Hauser ambulation index (HAI) were found to be individually significant in survival. The JSI (0–21 scale) consists of the sum of the HAI (0–9 scale) and the lung tumor burden score (0–3 scale) with a four times multiplier. JSI score was significantly associated with survival time (Rho=-0.588, P<0.0001) and had a positive predictive value of 92.0% compared to 54.1% and 56.9% for Tokuhashi and Tomita scales respectively. The JSI predicts in a meaningful way survival outcomes for patients suffering from spinal metastases. The development of the JSI will be of value to oncologists and physicians treating patients with metastatic disease.
P1.13-004 The Role of Lymph Node Staging by EBUS-TBNA in Stereotactic Body Radiation Therapy for patients with Non-Small Cell Lung Cancer.
Authors: K. Hashimoto, N. Daddi, M. Giuliani, A. Hope, L. Le, K. Czarnecka, M. Cypel, A. Pierre, M. De Perrot, G. Darling, T. Waddell, S. Keshavjee, K. Yasufuku
Journal: Journal of Thoracic Oncology (2017)
P3.03-060 Characteristics and Long Term Outcomes of Advanced Pleural Mesothelioma in Latin America (MeSO-CLICaP)
Authors: Oscar Arrieta, Andrés Cardona, Luis Corrales, George Oblitas, Leonardo Rojas, Ludwing Bacon, Claudio Martin, Mauricio Cuello, Luis Mas, Beatriz Wills, Carlos Vargas, Hernan Carranza, Jorge Otero, Maria Perez, Lisde González, Luis Chirinos, Rafael Rosell
Journal: Journal of Thoracic Oncology (2017)