tbuckley/cabot-search huggingface dataset:
Case report: West-Nile virus infection in two Dutch travellers returning from Israel
Authors: N Aboutaleb, M F Beersma, H F Wunderink, A CTM Vossen, L G Visser
Journal: Eurosurveillance (2010)

We report about West Nile virus (WNV) infections in a symptomatic traveller returning from Israel and in her asymptomatic travel companion. Knowledge of the current epidemiological situation in Israel from where WNV cases were reported recently enabled a rapid diagnosis. The described cases serve as a reminder for physicians to consider WNV in the diagnosis of patients returning from areas with potential circulation of the virus.
Yeast Bre1 and Dot1 histone modification enzymes are necessary for efficient homologous recombination repair
Authors: Kelly McCann, Tatiana Spicakova, Marsha Williamson, John Game, J. Martin Brown
Journal: Cancer Research (2007)

LB-234  Efficient DNA double-strand break (DSB) repair is essential for maintaining the stability of the genome. A single long-lived DSB, whether exogenously induced by a DNA damaging agent or purposefully induced endogenously during replication or DNA repair processes, can cause cell lethality. Humans with defects in DSB repair are sensitive to DNA damaging agents and are predisposed to developing cancers, as exemplified by such diseases as Nijmegan Breakage Syndrome, Ataxia Telangiectasia, and breast cancer susceptibility in women with mutations in the BRCA1 and BRCA2 genes.  Repair of DNA damage requires activation of cell cycle checkpoint controls, recruitment of repair proteins to DNA lesions, and transcriptional activation of relevant genes. As shown by our data, deletion of genes for proteins involved in histone modification produces sensitivity to ionizing radiation in Saccharomyces cerevisiae, suggesting a role for chromatin modification enzymes in the repair process as well. We are specifically interested in the roles of Bre1p, a ubiquitin ligase responsible for ubiquitination of H2B on lysine 123 (H2B-K123) and Dot1p, a methylase specific for lysine 79 on histone H3 (H3-K79).  We have confirmed that bre1Δ and dot1Δ are sensitive to IR and have placed bre1Δ and dot1Δ into the Rad6 post replication repair and Rad51 homologous recombination repair pathways via epistasis analysis. We have shown that bre1Δ and dot1Δ strains have a G1 checkpoint defect, but an intact G2 checkpoint. Because a G1 checkpoint defect alone is insufficient to cause the radiation sensitivity we observe, we have focused on determining other causes for IR sensitivity in bre1Δ and dot1Δmutants. We hypothesize that Bre1p and Dot1p are necessary for repair of the DNA break itself rather than as accessory proteins in the cell cycle checkpoint response. By monitoring phosphorylation of H2A over time, we have determined that the repair of DSB after IR in bre1Δ and dot1Δmutants is defective as compared to wild-type yeast.  Our current studies are focused on quantifying the frequency and repair of DSB after IR in bre1 and dot1 null mutants compared to WT by analyzing the chromosomes of our strains by pulsed field gel electrophoresis (PFGE), analyzing the genome-wide expression patterns in WT, bre1, dot1, and bre1 dot1 deletion mutants to determine if Bre1p and Dot1p have roles in upregulation of DNA repair genes, examining the relationship between Bre1p and Dot1p by exploring their potential interactions, and searching for protein candidates for binding to methylated H3 K79.
MEDU-16. TIME, PATTERN AND OUTCOME OF MEDULLOBLASTOMA RELAPSE IS BIOLOGY AND THERAPY-DEPENDENT
Authors: Rebecca Hill, Stacey Richardson, Janet Lindsey, Stephen Crosier, Ed Schwalbe, Debbie Hicks, Gholamreza Rafiee, Amanda Smithh, Abhijit Joshi, Keith Robson, Stephen Wharton, Tom Jacques, Simon Bailey, Steve Clifford
Journal: Neuro-Oncology (2017)
Survey of educators regarding the return to learn after a sport-related concussion
Authors: James D Carson, Alisha Garel, Alexandra Rendely, Christopher Meaney, Stefanie E Moser, Sarah T Rabinovitch, Sari A Kraft, Pierre Fremont
Journal: British Journal of Sports Medicine (2017)

Objective To evaluate the impact of an educational intervention upon educators’ knowledge of sport-related concussion (SRC) management strategies and their understanding of academic accommodations as part of the return to learn (RTL) strategy after an SRC. Design A pre- and post-intervention study. Setting A sport-focused Ontario (Canada) secondary school. Participants 94 educational staff, including teachers, administrators and school psychologists. Interventions Three ten-minute didactic lectures were followed by ninety minute facilitated focus groups during an educators’ professional development workshop. Participants learned about the nature and management of SRC with an emphasis upon RTL. Participants also had to reflect on their own experiences with some of the 63 students who had RTL at that school, after an SRC during the prior 3.5 years. Outcome measures Participants answered pre and post intervention surveys directed toward knowledge of SRC management principles and acknowledgement of accommodations. Main results 81 of the 94 participants submitted two matched pre and post surveys. Educators indicated significantly increased understanding of SRC management and showed a significantly increased support of accommodations after the intervention (p&lt;0.05). Conclusions Educators’ understanding of SRC management strategies is essential to facilitate a successful RTL. This study suggests that a brief educational intervention can improve the support of educators for academic accommodations as part of the RTL phase of SRC management. Competing interests None.
The interplay between metabolic remodeling and immune regulation in glioblastoma
Authors: Pravin Kesarwani, Shiva Kant, Antony Prabhu, Prakash Chinnaiyan
Journal: Neuro-Oncology (2017)

The fields of tumor metabolism and immune oncology have both independently received considerable attention over the last several years. The majority of research in tumor metabolism has largely focused on the Warburg effect and its resulting biologic consequences, including energy and macromolecule production. However, recent investigations have identified elegant, multifaceted strategies by which alterations in tumor metabolism can also contribute to a potent tolerogenic immune environment. One of the most notable is increased tryptophan metabolism through activation of indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO). However, this pathway represents one of numerous metabolic pathways that may modulate the immune system. For example, metabolites associated with aerobic glycolysis, adenosine, arginine, and prostaglandin metabolism have all been implicated in cancer-mediated immune tolerance and represent attractive therapeutic targets. In this review, we will provide an overview of the emerging interface between these 2 timely areas of cancer research and provide an overview of strategies currently being tested to target these next-generation metabolic immune checkpoints.
Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study
Authors: Stephen Zewinger, Marcus E Kleber, Vinicius Tragante, Raymond O McCubrey, Amand F Schmidt, Kenan Direk, Ulrich Laufs, Christian Werner, Wolfgang Koenig, Dietrich Rothenbacher, Ute Mons, Lutz P Breitling, Herrmann Brenner, Richard T Jennings, Ioannis Petrakis, Sarah Triem, Mira Klug, Alexandra Filips, Stefan Blankenberg, Christoph Waldeyer, Christoph Sinning, Renate B Schnabel, Karl J Lackner, Efthymia Vlachopoulou, Ottar Nygård, Gard Frodahl Tveitevåg Svingen, Eva Ringdal Pedersen, Grethe S Tell, Juha Sinisalo, Markku S Nieminen, Reijo Laaksonen, Stella Trompet, Roelof A J Smit, Naveed Sattar, J Wouter Jukema, Heinrich V Groesdonk, Graciela Delgado, Tatjana Stojakovic, Anna P Pilbrow, Vicky A Cameron, A Mark Richards, Robert N Doughty, Yan Gong, Rhonda Cooper-DeHoff, Julie Johnson, Markus Scholz, Frank Beutner, Joachim Thiery, J Gustav Smith, Ragnar O Vilmundarson, Ruth McPherson, Alexandre F R Stewart, Sharon Cresci, Petra A Lenzini, John A Spertus, Oliviero Olivieri, Domenico Girelli, Nicola I Martinelli, Andreas Leiherer, Christoph H Saely, Heinz Drexel, Axel Mündlein, Peter S Braund, Christopher P Nelson, Nilesh J Samani, Daniel Kofink, Imo E Hoefer, Gerard Pasterkamp, Arshed A Quyyumi, Yi-An Ko, Jaana A Hartiala, Hooman Allayee, W H Wilson Tang, Stanley L Hazen, Niclas Eriksson, Claes Held, Emil Hagström, Lars Wallentin, Axel Åkerblom, Agneta Siegbahn, Igor Karp, Christopher Labos, Louise Pilote, James C Engert, James M Brophy, George Thanassoulis, Peter Bogaty, Wojciech Szczeklik, Marcin Kaczor, Marek Sanak, Salim S Virani, Christie M Ballantyne, Vei-Vei Lee, Eric Boerwinkle, Michael V Holmes, Benjamin D Horne, Aroon Hingorani, Folkert W Asselbergs, Riyaz S Patel, Bernhard K Krämer, Hubert Scharnagl, Danilo Fliser, Winfried März, Thimoteus Speer
Journal: The Lancet Diabetes & Endocrinology (2017)
Elbasvir plus grazoprevir in patients with hepatitis C virus infection and stage 4–5 chronic kidney disease: clinical, virological, and health-related quality-of-life outcomes from a phase 3, multicentre, randomised, double-blind, placebo-controlled trial
Authors: Annette Bruchfeld, David Roth, Paul Martin, David R Nelson, Stanislas Pol, Maria-Carlota Londoño, Howard Monsour, Marcelo Silva, Peggy Hwang, Jean-Marie Arduino, Michael Robertson, Bach-Yen Nguyen, Janice Wahl, Eliav Barr, Wayne Greaves
Journal: The Lancet. Gastroenterology & hepatology (2017)
Disentangling Timing of Admixture, Patterns of Introgression, and Phenotypic Indicators in a Hybridizing Wolf Population
Authors: Marco Galaverni, Romolo Caniglia, Luca Pagani, Elena Fabbri, Alessio Boattini, Ettore Randi
Journal: Molecular Biology and Evolution (2017)

Hybridization is a natural or anthropogenic process that can deeply affect the genetic make-up of populations, possibly decreasing individual fitness but sometimes favoring local adaptations. The population of Italian wolves (Canis lupus), after protracted demographic declines and isolation, is currently expanding in anthropic areas, with documented cases of hybridization with stray domestic dogs. However, identifying admixture patterns in deeply introgressed populations is far from trivial. In this study, we used a panel of 170,000 SNPs analyzed with multivariate, Bayesian and local ancestry reconstruction methods to identify hybrids, estimate their ancestry proportions and timing since admixture. Moreover, we carried out preliminary genotype-phenotype association analyses to identify the genetic bases of three phenotypic traits (black coat, white claws, and spur on the hind legs) putative indicators of hybridization. Results showed no sharp subdivisions between nonadmixed wolves and hybrids, indicating that recurrent hybridization and deep introgression might have started mostly at the beginning of the population reexpansion. In hybrids, we identified a number of genomic regions with excess of ancestry in one of the parental populations, and regions with excess or resistance to introgression compared with neutral expectations. The three morphological traits showed significant genotype-phenotype associations, with a single genomic region for black coats and white claws, and with multiple genomic regions for the spur. In all cases the associated haplotypes were likely derived from dogs. In conclusion, we show that the use of multiple genome-wide ancestry reconstructions allows clarifying the admixture dynamics even in highly introgressed populations, and supports their conservation management.
The effect of a national body checking policy change on concussion risk in youth ice hockey players
Authors: Amanda Black, Luz Palacios-Derflingher, Kathryn J Schneider, Brent E Hagel, Carolyn A Emery
Journal: British Journal of Sports Medicine (2017)

Objective To determine if the risk of game-related concussion differs for Pee Wee (11–12 years) ice hockey players in the season following a national policy change disallowing body checking (2013/2014) when compared to a season (2011/2012) when body checking was allowed. Design Historical cohort study. Setting Community ice hockey rinks. Participants Pee Wee players were recruited from 59 teams in all divisions of play in Alberta (n=883) in 2011/12 prior to the rule change and from 73 teams in 2013/14 following the rule change (n=617). Assessment of risk factors Pee Wee ice hockey players before and after a national body checking policy change. Outcome measures Suspected concussions were identified by a team therapist/safety designate and referred to a sport medicine physician. Concussions were included if they met the Zurich 2013 Consensus definition of concussion. Main results There were 104 game-related concussions (IR=2.79/1000 game-hours) in Alberta prior to the rule change and 24 concussions (IR=1.08/1000 game-hours) after. Based on a multivariable Poisson regression model adjusting for player size, age, body checking attitudes, previous injury, level of play, and position, accounting for clustering by team, the rate of concussion declined following the policy change [IRR=0.34 (95% CI; 0.21 – 0.56)]. Overall, a physician diagnosed 67.3% and 79.1% of suspected game concussions in 2011/2012 and 2013/2014, respectively. Conclusions Introduction of the national policy change disallowing body checking in Pee Wee resulted in a 66% reduction in the Alberta Pee Wee ice hockey concussion rate. These findings have important implications for youth ice hockey policy. Competing interests None.
Endoscopic submucosal dissection for early gastric cancer: are expanded resection criteria safe for Western patients?
Authors: Andreas Probst, Annette Schneider, Tina Schaller, Matthias Anthuber, Alanna Ebigbo, Helmut Messmann
Journal: Endoscopy (2017)

Background and study aims Endoscopic submucosal dissection (ESD) is the standard treatment for early gastric cancer (EGC) fulfilling guideline resection criteria or the expanded resection criteria in Asia. It is unclear whether the expanded criteria can be transferred to European patients, and long-term follow-up data are lacking. The aim of this study was to evaluate long-term follow-up data after ESD of EGCs in Europe. Patients and methods Patients with EGC who underwent ESD were included in this single-center study at a German referral center. Patient and lesion characteristics, procedure characteristics, and follow-up data were recorded prospectively. Results A total of 179 patients with 191 EGCs were included over a period of 141 months, with 29.6 % of lesions meeting guideline criteria and 48.6 % meeting expanded criteria. The en bloc resection rate was 98.4 % for guideline criteria and 89.0 % for expanded criteria lesions (P = 0.09), and the R0 resection rate was 90.2 % and 73.6 %, respectively (P = 0.02). The main reason for the expanded criteria was a lesion diameter > 20 mm (81.6 %).perforation 1 %, delayed bleeding 6.3 %, stricture 2.1 %, procedure-related mortality 1.1 %. Local recurrence rate was 0 % for guideline criteria and 4.8 % for expanded criteria lesions (P = 0.06), and the rate of metachronous neoplasia was 15.1 % and 7.1 %, respectively (median follow-up 51 and 56 months, respectively); 92.9 % of metachronous neoplasia were treated curatively with repeat ESD. One patient developed lymph node metastasis after ESD of a submucosal invasive expanded criteria lesion. Long-term-survival was comparable between the two criteria (P = 0.58). No gastric cancer-related death was observed in either group. Conclusions ESD can achieve high rates of long-term curative treatment using the expanded criteria in EGCs in Western countries. We recommend ESD as treatment of choice not only for guideline criteria EGCs but also for intramucosal nonulcerated EGCs regardless of their diameter.
INJURY RISK DURING DUTCH PHYSICAL EDUCATION TEACHER EDUCATION: A PROSPECTIVE COHORT STUDY OVER THE PERIOD 2000–2014
Authors: Maarten Barendrecht, Carl Barten, Bouwien Smits-Engelsman, Evert Verhagen
Journal: British Journal of Sports Medicine (2017)

Background Injury risk is high during 4-year PE teacher education (PETE). However, recent studies have focussed on injury risk during the first year only. Objective To compare the overall, intra- and extracurricular injury risk per sex and curriculum year, and trends over time in Dutch PETE. Design Prospective cohort study. Setting A Dutch polytechnic for PETE. Patients (or Participants) PE students (male n=635, female n=448), who completed their full curriculum between 2000 and 2014. Assessment of Risk Factors Sport setting (intra- versus extracurricular), sex, curriculum year and (consecutive) cohorts. Main Outcome Measurements Any musculoskeletal complaint related to sports participation for which medical advice was sought. Intracurricular iincidence rates (injuries/1000 hours) were calculated using the scheduled time table. Overall/extracurricular exposure time was calculated in months from the start of the curriculum until injury or graduation date of individual students. Clinical incidence (CI; injuries/student) was calculated as well. Risk was compared using Cox regression analysis or Relative Risk (RR) and their 95% Confidence Intervals (95%CI). Results Overall 599 (55.3%, 95% CI 51.1–59.9%) students sustained at least one injury. Female students had a significantly higher risk for overall (RR 1.34, 95% CI 1.23–1.47) and for intracurricular injuries (RR 1.60, 95% CI 1.43–1.79). CI for intracurricular injuries was significantly higher than for extracurricular injuries (RR 2.27, 95% CI 1.98–2.61), specifically in female students during their first year (RR 4.29, 95% CI 3.13–5.88). Compared to the first year, overall CI dropped significantly during the 2nd (RR 0.62, 95% CI 0.54–0.71) and consecutive years. Injury risk increased over the period from 2000 to 2014 (RR 1.59, 95% CI 1.36–1.86). Conclusions Injury risk in Dutch PETE is increasing. Risk factors for the relatively high intracurricular injury risk found for the first year and for female students, should be investigated in prospective multi-center research.
ATRT-05. PRECLINICAL EFFICACY OF RADIATION-FREE TREATMENT OF ATYPICAL TERATOID/RHABDOID TUMORS BY COMBINED MEK AND MELK INHIBITION
Authors: Michaël H Meel, Miriam Guillén-Navarro, Mark C de Gooijer, Piotr Waranecki, Marcel P de Winter, Dannis G van Vuurden, Gertjan JL Kaspers, Esther Hulleman
Journal: Neuro-Oncology (2017)

Atypical teratoid/rhabdoid tumors (AT/RT) are highly malignant tumors that occur both in- and outside the central nervous system, predominantly in young children. Although therapeutic interventions, combining surgery with intensive chemotherapy and conformal radiotherapy, have shown curative potential, the long-term consequences of these treatment modalities in young children are often severe. Therefore, there is a dire need for novel, targeted therapeutic strategies that potentially reduce or eliminate chemo- and radiotherapy, especially for children under three years of age. Genetically, AT/RT is characterized by a biallelic inactivation of SMARCB1 or SMARCA4, causing aberrant chromatin remodeling and thereby expression of a variety of oncogenes. Recently, the importance of the mitogen-activated protein kinase (MAPK) pathway in the pathogenesis of AT/RT has been demonstrated, with preclinical efficacy of MEK inhibition in AT/RT cells. Preclinical patient-derived AT/RT models are largely lacking. We developed a patient-derived primary cell line and xenograft model, VUMC-AT/RT-01, from a surgical specimen of an AT/RT patient that had not received prior therapy. Immunohistochemistry was performed on xenograft tumors, revealing typical loss of SMARCB1 expression as well as heterogeneous expression of glial, epithelial, mesenchymal and neuronal differentiation markers. In silico analysis of gene expression revealed strong upregulation of MELK in AT/RT tumors compared to normal brain tissues. These high levels of MELK were subsequently confirmed in our xenograft model. Inhibition of MELK with the small molecule OTSSP167 effectively reduced proliferation and induced cell death in primary AT/RT neurospheres. Combined treatment of primary AT/RT cells with OTSSP167 and the MEK inhibitor Trametinib showed strongly synergistic cytotoxicity at low nanomolar concentrations. Treatment of mice carrying VUMC-AT/RT-01-Fluc xenografts with OTSSP167 and Trametinib confirmed this synergy in vivo. We conclude that combined MEK and MELK inhibition represents a promising targeted therapy strategy for AT/RT that might ultimately reduce or eliminate the need for radiation and intensive chemotherapy.
Global, Prospective, Non-Interventional, Observational Study of Presentation, Treatment Patterns, and Outcomes in Multiple Myeloma Patients: The Insight-MM Study
Authors: Robert M Rifkin, Faith E Davies, Antonio Palumbo, Jeffrey Zonder, Saulius K Girnius, Caitlin L Costello, Saad Z Usmani, Jesus G. Berdeja, Jim Omel, Michael A Thompson, Jatin Shah, J Sanford Schwartz, Roman Hajek, Evangelos Terpos, Vânia Hungria, Maria-Victoria Mateos, Gordon Cook, Xavier Leleu, Andrew Spencer, Hartmut Goldschmidt, Brian Seal, Chris L Pashos, Dawn Marie Stull, Dorothy Romanus, Roxanne Cacioppo, Jill A Bell, Shawn Yu, Katarina Luptakova, Liviu Niculescu, Stephen J Noga, Tomas Skacel, Ajai Chari
Journal: Blood (2016)