tbuckley/cabot-search huggingface dataset:
Current Tobacco Smoking and Desire to Quit Smoking Among Students Aged 13–15 Years — Global Youth Tobacco Survey, 61 Countries, 2012–2015
Authors: René A. Arrazola, Indu B. Ahluwalia, Eugene Pun, Isabel Garcia de Quevedo, Stephen Babb, Brian S. Armour
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Tobacco use is the world's leading cause of preventable morbidity and mortality, resulting in nearly 6 million deaths each year (1). Smoked tobacco products, such as cigarettes and cigars, are the most common form of tobacco consumed worldwide (2), and most tobacco smokers begin smoking during adolescence (3). The health benefits of quitting are greater for persons who stop smoking at earlier ages; however, quitting smoking at any age has health benefits (4). CDC used the Global Youth Tobacco Survey (GYTS) data from 61 countries across the six World Health Organization (WHO) regions from 2012 to 2015 to examine the prevalence of current tobacco smoking and desire to quit smoking among students aged 13-15 years. Across all 61 countries, the median current tobacco smoking prevalence among students aged 13-15 years was 10.7% (range = 1.7%, Sri Lanka to 35.0%, Timor-Leste). By sex, the median current tobacco smoking prevalence was 14.6% among males (range = 2.9%, Tajikistan to 61.4%, Timor-Leste) and 7.5% among females (range = 1.6%, Tajikistan to 29.0%, Bulgaria). In the majority of countries assessed, the proportion of current tobacco smokers who desired to quit smoking exceeded 50%. These findings could be used by country level tobacco control programs to inform strategies to prevent and reduce youth tobacco use (1,4).
GENE-11. LSD1/KDM1A MODULATES AN ONCO-IMMUNOGENIC GENE SIGNATURE IN ADULT GBM AND EPIGENOME-MUTATED PEDIATRIC DIPG
Authors: Cavan Bailey, Melissa Singh, Joya Chandra
Journal: Neuro-Oncology (2017)

Diffuse intrinsic pontine glioma (DIPG) patients often possess a lysine-to-methionine mutation in histone H3 (H3.1/.3-K27M) that renders them sensitive to perturbations in histone methylation. However, the demethylase KDM1A/LSD1 has not yet been investigated as a therapeutic target in DIPG. Our lab has studied LSD1 in adult GBM, generating RNA-Seq data from LSD1 knockdown cells, for which DAVID pathway analysis was performed with a 1.5-fold change filter. Significantly changed was a set of immune response genes (18 upregulated, 6 downregulated) including stimulatory ligands, antigen presentation and cell motility genes. To validate, LSD1 was knocked down via shRNA in LN18 cells and RT-qPCR performed using unique primers for 13 of the most upregulated immunomodulatory genes. T-tests were significant (p<0.05) for 5/13 of these genes, and one-way ANOVA analysis of all genes was highly significant (p<0.0001) versus scramble control. We further hypothesized that LSD1 chemical inhibitors (LSD1i) could replicate these immunomodulatory gene changes in LN18 cells, as well as in DIPG cells bearing K27M mutations. SLAMF7, 4-1BB, and LCP1 were most significantly changed in LN18 cells across LSD1i treatments via T-test (p<0.05). DIPG cells showed significant data via T-test (p<0.05) for SLAMF7, RAET1E, and MICB. Importantly, ANOVA comparison of data between TCP-treated LN18 and DIPG cells, as well as LN18 LSD1i and LSD1-KD, was not significant (q>0.9999), indicating their induced immunomodulatory gene expression profiles are similar. Interestingly, cytotoxicity of tranylcypromine (TCP), GSK LSD1, and RN-1 was tested, with LN18 significantly more resistant to LSD1i cytotoxicity than DIPG cells, indicating LSD1 may play a key role in DIPG survival. TCP is FDA-approved and the only LSD1 inhibitor known to pass through the blood-brain barrier, which is critical for its use as a potential glioma therapeutic. Ongoing studies are examining if LSD1i can enhance immunotherapeutic efficacy against target cells via our documented gene changes.
EPIDEMIOLOGY OF INJURIES IN POLE SPORTS: EMERGING CHALLENGES IN A NEW TREND
Authors: Vasileios Mitrousias, Georgios Halatsis, Ioannis Bampis, Antonios Koutalos, Georgios Psareas, Athanasios Sakkas
Journal: British Journal of Sports Medicine (2017)

Background Pole sports, such as pole dancing, are recently gaining popularity as a form of fitness, combining dance and acrobatics. Many new, recreational athletes are joining pole sports every year. According to the international pole sports federation, this emerging new sport is so popular that it could be a future olympic sport. Objective The aim of this study is to describe the epidemiology of injuries in recreational athletes of pole sports, who were referred to the emergency demartment of our hospital. Design This a retrospective, case-series study based on hospital records, collected between December 2015 and July 2016. Setting The study took place in the department of orthopaedic surgery, of the general hospital of karditsa, a provincial hospital in central Greece. Patients (or Participants) The study included all recreational athletes who were presented to our emergency department, due to injuries occured while performing pole dancing. 34 patients were finally included. Main Outcome Measurements The primary study outcome is the epidemiology of injuries in pole sports. Results Overall, 29.4% of patients suffered from low back and hip, strains and contusions, 20.6% suffered from knee sprains and contusions, 17.7% suffered from wrist sprains, 14.7% suffered from ankle sprains, 5.9% suffered from neck (cervical spine) strains, 5.9% suffered from concussion, 1 patient (2.9%) presented with a sizable disc herniation and 1 patient (2.9%) presented with a fracture of the fifth metatarsal bone. Conclusions As pole sposts become more and more popular every year, injuries occuring during performance of this demanding activity are increasing. Sprains, strains, and contusions are the most frequent but more severe injuries such as concussions and fractures are also present due to falls from the pole. Studies with bigger samples are required in order to define the epidemiology of injuries in this new, emerging sport.
Epidemiology and one‐year outcomes in patients with chronic heart failure and preserved, mid‐range and reduced ejection fraction: an analysis of the ESC Heart Failure Long‐Term Registry
Authors: Ovidiu Chioncel, Mitja Lainscak, Petar M. Seferovic, Stefan D. Anker, Maria G. Crespo‐Leiro, Veli‐Pekka Harjola, John Parissis, Cecile Laroche, Massimo Francesco Piepoli, Candida Fonseca, Alexandre Mebazaa, Lars Lund, Giuseppe A. Ambrosio, Andrew J. Coats, Roberto Ferrari, Frank Ruschitzka, Aldo P. Maggioni, Gerasimos Filippatos
Journal: European Journal of Heart Failure (2017)
Pathogenesis of Peripheral T Cell Lymphoma
Authors: Marco Pizzi, Elizabeth Margolskee, Giorgio Inghirami
Journal: Annual Review of Pathology Mechanisms of Disease (2018)

Peripheral T cell lymphomas (PTCLs) are highly heterogeneous tumors, displaying distinct clinical and biological features. The pathogenesis and normal counterpart of such entities have been elusive for decades. Recent studies have, however, disclosed key mechanisms of peripheral T cell transformation, including (a) the deregulation of signaling pathways controlling T cell development, differentiation, and maturation; (b) the remodeling of the peritumor microenvironment; and (c) the virus-mediated rewiring of T cell biology. Uncovering the molecular mechanisms of T cell transformation will help elucidate the peculiar clinical and pathological features of each PTCL entity and will lead to the characterization of novel antitumor therapies. These therapies will combine conventional and new-generation compounds with immune-modulating agents to ablate both the neoplastic cells and the tumor-supporting microenvironment. This review addresses the pathogenic mechanisms of PTCLs, with special attention paid to novel therapeutic strategies for the clinical management of such aggressive tumors.
La vidéocapsule oesophagienne: une méthode non invasive et fiable pour le diagnostic et la surveillance des varices oesophagiennes chez l'enfant
Authors: J Cardey, C Le Gall, L Michaud, A Dabadie, C Talbotec, M Bellaiche, T Lamireau, E Mas, A Lachaux
Journal: Endoscopy (2016)

La fibroscopie oesogastroduodénale (FOGD) est l'examen de référence pour rechercher des varices oesophagiennes (VO). Nous rapportons la première étude pédiatrique permettant de valider la vidéocapsule oesophagienne (VCO) pour cette complication survenant au cours de l'hypertension portale (HTP).
Annual trends in follow-up visits for paediatricpediatric concussion in emergency departments and doctors’ offices in ontario, canada between 2003–2013
Authors: Liraz Fridman, Michal Scolnik, Alison Macpherson, Linda Rothman, Astrid Guttmann, Anne Grool, Daniel Rodriguez Duque, Roger L Zemek
Journal: British Journal of Sports Medicine (2017)

Background Over the past ten years, ED and physician office visits for paediatric concussion have more than quadrupled. Current concussion management guidelines recommend follow-upand clearance by a physician prior to resumption of contact activities. However, compliance with recommended follow-up is not well documented in the literature. Objective To examine trends in follow-up visits in accordance with current recommended guidelines for children with concussion. Design Retrospective population-based study. Setting Children and youth presenting to emergency departments (EDs) and doctors’ offices with concussion over a 10-year time period (2003–2013) in Ontario, Canada. Outcome measures We examined the percentage of children and youth who were seen for follow-up visit post-concussion. Trends in the percent of children with a follow-up visit following an index visit to either a doctor’s office or an ED were reported. Main results The proportion of children and youth assessed for concussion follow-up (N=45,150) has increased significantly (p&lt;0.0001). In 2003, only 1010 of 7170 (14.2%) patients with an index visit for concussion had follow-up assessment; in 2009, 2733 of 10,134 (27.0%) had a follow-up visit, and by 2013, 11,806 of 21,681 (54.5%) received follow-up care. Conclusions Despite increasing trends in the proportion of children being examined for concussion follow-up over a 10-year period, nearly half of all children with an index visit for concussion still do not receive follow-up assessment. This suggests that ongoing efforts to improve compliance with recommended guidelines will be important. Competing interests None.
INRを除いた末期肝臓病のモデル(MELD‐XI)スコアリングシステムは急性非代償性心不全患者の死亡様式を予測する
Authors: Yamada Takahisa, Morita Takashi, Furukawa Yoshio, Tamaki Shunsuke, Iwasaki Yusuke, Kawasaki Masato, Kikuchi Atsushi, Kondou Takumi, Kawai Tsutomu, Takahashi Satoshi, Ishimi Masashi, Hakui Hideyuki, Ozaki Tatsuhisa, Sato Yoshihiro, Seo Masahiro, Fukunami Masatake
Journal: Circulation (2015)
The association between<i>catechol o-methyltransferase (comt) rs4680 polymorphism, harm avoidance scores, and concussion history in rugby union players</i>
Authors: Sarah MC Fie, Shameemah Abrahams, Jon Patricios, Jason Suter, Michael Posthumus, Alison V September
Journal: British Journal of Sports Medicine (2017)

Objective To investigate the relationship between personality traits and Catechol O-methyltransferase (COMT) rs4680 genotypewith concussion history in rugby players. Design Case-control study. Setting High school, amateur, and professional rugby teams in South Africa. Participants Participants were excluded if they reported a previous brain-related medical condition or a non rugby-related concussion, or were not of European ancestry. Three hundred and one participants were included in the study. Based on self-reported concussion history (30 suspected concussion cases were excluded), participants were grouped into the control (non-concussed, n=140) or case group (one or more diagnosed concussions, n=131). Assessment of risk factors Participants completed a concussion history questionnaire, Cloninger’s Tridimensional Personality Questionnaire (TPQ) and all DNA samples were genotyped for COMT rs4680. Logistic regression, co-varying for age, was used to determine differences in genotype frequencies. A one-way analysis of variance was used to compare TPQ dimension (novelty seeking, harm avoidance, and reward dependence) scores. Outcome measures COMT rs4680 genotype frequencies and TPQ scores. Main results The COMT rs4680 VV genotype was overrepresented in the controlgroup when all participants were combined (p=0.030, OR: 1.89, 95% CI: 1.05 – 3.45; control: 31%, cases: 18%) and whenonly school participants were analysed (p=0.009, OR: 3.23, 95% CI: 1.27 – 8.33; control:37%, cases:15%). Furthermore, the schoolcontrol group had higher harm avoidance scores compared to cases (p=0.004), andthe VV genotype was associated with increased harm avoidance subscale 1 scores (p=0.023). Conclusions This study provides preliminary indication that personality traits, and associated genetic variants, can influence concussion in rugby. Competing interests None.
Assessment of herpes virus occurrence frequency in lymphoma patients.
Authors: Tatyana A. Zykova, Irina B. Lysenko, Olga A. Bogomolova, Viktoriya V. Dmitrieva, Nadezhda V. Nikolaeva, Elena A. Kapuza, Olga N. Shatokhina, Tatiana F. Pushkareva, Elena E. Pak, Olga V. Kozyuk, Kristina A. Novoselova
Journal: Journal of Clinical Oncology (2014)

e19530 Background: Herpesvirus infections are still a serious problem for patients with immunosuppression. The purpose of the study was to assess frequency of occurrence of herpes group viruses in patients of Hematology Department of Rostov Scientific Research Institute of Oncology. Methods: DNA of herpes simplex virus type 1 and type 2, cytomegalovirus (CMV), Epstein-Barr virus (EBV) and herpes virus type 6 were extracted from samples of whole peripheral blood in MagNa Pure Compact apparatus and manually on silica gel particles. DNA amplification and detection were performed by PCR method in real time with Rotor-Gene 6000 thermocycler with the use of reagent kits by InterLabService. 115 pts with lymphoma were examined, 31 (27%) of them were children aged 3-18 years and 84 (73%) adults aged 19-78 years. Results: DNA of herpes simplex virus type 1,2 was found in 1 adult pt. CMV DNA was found in adult pts in 3 cases, EBV DNA in 23 cases , herpes virus type 6 DNA in 3. DNA of CBV, EBV and herpes virus type 6 in the children amounted for 2, 13 и 9 cases respectively. EBV was the most frequent in all pts (27,3% adults, 41,9% children), CMV and herpes virus type 6 were similar by their occurrence frequency - 3,6% cases. Herpes virus type 6 was found in children in about 1/3 cases (29%). Several simultaneous DNA pathogens were detected in 6 (19,4%) children (EBV and herpes virus type 6) and only in 1 (1,2%) adult pt (CMV and EBV). General frequency of herpesvirus DNA detection in blood samples of children was 51,6%, of adults - 37,2%. Conclusions: Considering high occurrence frequency of herpes group viruses in peripheral blood leucocytes of immunocompromised patients, diagnostic on time is necessary for prevention of latent virus carrying reactivation.
Gene silencing and a novel monoallelic expression pattern in distinct CD177 neutrophil subsets
Authors: Claudia Eulenberg-Gustavus, Sylvia Bähring, Philipp G. Maass, Friedrich C. Luft, Ralph Kettritz
Journal: The Journal of Experimental Medicine (2017)

CD177 presents antigens in allo- and autoimmune diseases on the neutrophil surface. Individuals can be either CD177-deficient or harbor distinct CD177neg and CD177pos neutrophil subsets. We studied mechanisms controlling subset-restricted CD177 expression in bimodal individuals. CD177pos, but not CD177neg neutrophils, produced CD177 protein and mRNA. Haplotype analysis indicated a unique monoallelic CD177 expression pattern, where the offspring stably transcribed either the maternal or paternal allele. Hematopoietic stem cells expressed both CD177 alleles and silenced one copy during neutrophil differentiation. ChIP and reporter assays in HeLa cells with monoallelic CD177 expression showed that methylation reduced reporter activity, whereas demethylation caused biallelic CD177 expression. HeLa cell transfection with c-Jun and c-Fos increased CD177 mRNA. Importantly, CD177pos human neutrophils, but not CD177neg neutrophils, showed a euchromatic CD177 promoter, unmethylated CpGs, and c-Jun and c-Fos binding. We describe epigenetic mechanisms explaining the two distinct CD177 neutrophil subsets and a novel monoallelic CD177 expression pattern that does not follow classical random monoallelic expression or imprinting.
Occupational health should be part of the NHS
Authors: Ian Torrance, Richard Heron
Journal: BMJ (2017)

Integration would benefit people in and out of work, and the UK economy

Occupational health was not included in the NHS when it was formed in 1948, and this has not changed despite successive reports arguing that work is important for overall wellbeing.12 The growing shortage of occupational health doctors adds urgency to calls for the specialty to be integrated fully within the NHS.

In 1948, funding for occupational health and the development of the specialty were driven principally by health and safety legislation. Workplaces were more physically hazardous than they are now. Many workers developed diseases caused by exposure to agents such as asbestos and coal dust, prompting targeted, specialist health surveillance of those at risk. The duty to manage work place hazards, including provision of health surveillance, rested then, as now, with the employer.

In the past 70 years work has been made safer and the prevalence of occupational illnesses caused by exposure to specific workplace hazards has fallen. At the same time, emphasis …
Abstract P020: A Bioengineered Neonatal Cardiomyocyte Scaffold Promotes Cell Survival and Improves Left Ventricular Function in Rats with Heart Failure
Authors: Jordan Lancaster, Elizabeth Juneman, Nicholle Johnson, Joseph Bahl, Steven Goldman
Journal: Circulation Research (2011)

Background: Cell-based regenerative therapies hold promise as a new treatment for heart failure. Tissue engineered scaffolds used for cell delivery enhance potential improvements in cardiac function by providing the structural and nutrient support for transplanted cell survival, integration, and re-population of injured tissues. Previously, our laboratory reported improvements in left ventricular (LV) function in rats with chronic heart failure (CHF) after placement of a neonatal cardiomyocyte (NCM) seeded 3-dimensional fibroblast construct (3DFC). In brief, 3 weeks after implantation of the NCM-3DFC, LV function improves by increasing (p&lt;0.05) ejection fraction 26% and cardiac index 33%, while decreasing (p&lt;0.05) LV end diastolic pressure 38%. The current report focuses on NCM survival and LV improvements out to 7 weeks post NCM-3DFC implantation. Methods and Results: Cardiomyocytes were isolated from neonatal rat hearts and seeded onto a 3DFC. We evaluated NCM-3DFC in vitro for cellular organization and the presence of functional gap junctions, which demonstrated extensive cell-to-cell connectivity. At 5 days in culture, the seeded patch contracted spontaneously in a rhythmic and directional fashion, beating at 43±3 beats/min with a mean displacement of 1.3±0.3 mm and contraction velocity of 0.8±0.2 mm/sec. The seeded patch could be electrically paced at near physiological rates (270±30 beats/min) while maintaining coordinated, directional contractions. For in vivo evaluation, rats underwent coronary artery ligation and allowed to recover for 3 weeks to establish CHF. NCM-3DFC were implanted 3 weeks after ligation and evaluated 3 and 7 weeks later (6 and 10 weeks after ligation respectively). Live cell tracking of implanted NCM using Q-Dots revealed ∼9% survival of transplanted cells 3 weeks after implantation. In addition, improvements in LV function continued at 7 weeks after implantation of the NCM-3DFC by increasing (p&lt;0.05) ejection fraction 37%. Conclusion: A multicellular, electromechanically organized, cardiomyocyte scaffold, engineered in vitro can improve LV function when implanted directly on the hearts of rats with CHF; the transplanted cells survive and improve LV function chronically.
LGG-09. PEDIATRIC LOW-GRADE GLIOMAS WITH CRAF GENE FUSIONS ARE THERAPEUTICALLY DISTINCT FROM BRAF-FUSIONS BASED ON DIMERIZATION MEDIATED BY N-TERMINAL FUSION PARTNER
Authors: Payal Jain, Tamara M. Fierst, Harry Han, Tiffany Smith, Phillip J. Storm, Angela J. Waanders, Adam C. Resnick
Journal: Neuro-Oncology (2017)

Pediatric low-grade gliomas (PLGGs) are the most common brain tumors in children mainly defined by activating gene fusions that dysregulate the mitogen-associated protein kinase (MAPK) pathway. Our lab has characterized the molecular mechanism of PLGG-associated KIAA1549-BRAF gene fusion and response to targeted MAPK pathway inhibitors. We have since gone on to explore non-BRAF gene fusions, specifically CRAF (or RAF1) fusions, QKI-RAF1 and SRGAP3-RAF1, as potential PLGG driver mutations. As CRAF and BRAF are shared targets of MAPK therapeutics, we sought to investigate the mechanistic and response of CRAF-fusions to clinically relevant RAF inhibitors (RAFi) and downstream pathway inhibitors. We focused on the role of N-terminal fusion partners and RAF dimerization for successful targeting. Using heterologous model systems, we found that CRAF-fusions do not respond to RAFi, show partial response to single-agent MEKi, but robustly respond to combinatorial targeting of both MAPK and PI3K pathways and novel RAF dimer inhibitors. Upon comparing the homo- and hetero-dimerization profiles of QKI-RAF1and BRAF-fusions in the presence of RAFi, we found that QKI-RAF1 retains robust homo- and hetero-dimerization that, in contrast, are disrupted in BRAF fusions that respond to RAFi. Interestingly, we found that CRAF-fusions’ dimerization is unaffected primarily due to robust protein-protein interactions mediated by the non-kinase N-terminal fusion partner, such as QKI. This suggests that dimerization is essential for MAPK pathway activation and determines responsiveness to RAFi. Furthermore, we found that the novel RAF dimer inhibitor, LY3009120, stabilized CRAF-fusions in an inactive dimer conformation and suppressed oncogenic potential. Overall, CRAF-fusions are distinct from BRAF-fusions in responsiveness to targeted therapies, especially due to effect of N-terminal fusion partner in mediating stable dimerization. Our study suggests that molecular classification of PLGGs should inform therapeutic intervention of RAF-altered PLGGs even within RAF-mutant subtypes.
The Next Generation of Episode-Based Payments
Authors: Amol S. Navathe, Zirui Song, Ezekiel J. Emanuel
Journal: JAMA (2017)

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