tbuckley/cabot-search huggingface dataset:
Vigilância das salmoneloses humanas na Bulgaria, 1999-2004 : evolução, mudanças e resistência aos antibióticos
Authors: G Asseva, P Petrov, I Ivanov, T Kantardjiev
Journal: Eurosurveillance (2006)

Este artigo estuda a distribuicao de salmonelas resistentes e dos mecanismos de resistencia entre os serotipos mais frequentes na Bulgaria. A identificacao foi realizada por cultivos, testes bioquimicos e serotipagem: teste de diffusao em disco Bauer-Kirby para o estudo da resistencia a 14 antibioticos ; test de sinergia em duplo disco para buscar estirpes productoras de β-lactamases de espectro amplo (extended–spectrum β-lactamases, ESBL) e transferencia dos genes codificadores para ESBL por conjugacao experimental. Para a deteccao por reacao em cadeia da polimerase (PCR) utilisou-se bla-CTX-M, bla-SHV e bla–TEM. Duzentos quarenta e cinco estirpes de salmonelas resistentes foram identificadas dessa maneira. A maioria delas provinham de casos humanos esporadicos ou de infeccoes asintomaticas. So 23 estirpes tinham sido isoladas de surtos. Foram detectadas 79 estirpes productoras de ESBL: cinco S. Enteritidis, uma S. Typhimurium, nove S. Isangi e 62 S. Corvallis produzendo os enzimas CTX-M3, TEM e SHV. Os genes codificadores para ESBL foram transferidos com sucesso a uma estirpe de E. coli C1A com os genes codificadores para a resistencia aos aminoglucosidos e ao cloranfenicol (para bla-SHV e bla-TEM). A amplificacao por PCR revelou a presenca de genes bla-CTX- M3 na estirpe S. Enteritidis, e de genes bla-SHV e bla-TEM em S. Corvallis. A Bulgaria e o primeiro pais no mundo aonde foram detectadas estirpes de S. Corvallis BLSE. Uma grande variedade de genes de resistencia foi identificada entre os serotipos de salmonella mais frequentemente associados com doencas humanas na Bulgaria.
Abstract PR04: HER3 crosstalk with HPV16-E6E7 is a feedback resistance mechanism to PI3K-targeted therapies in head and neck cancer
Authors: Toni M. Brand, Stefan Hartmann, Neil E. Bhola, Hua Li, Yan Zeng, Rachel O'Keefe, Max V. Ranall, Sourav Bandyopadhyay, Margaret Soucheray, Danielle L. Swaney, Nevan Krogan, Carolyn Kemp, Umamaheswar Duvvuri, Daniel E. Johnson, Michelle A. Ozbun, Julie E. Bauman, Jennifer R. Grandis
Journal: Clinical Cancer Research (2017)

Abstract Human papillomavirus (HPV) 16 plays an etiologic role in a growing subset of head and neck squamous cell carcinoma (HNSCC), where viral expression of the E6 and E7 oncoproteins is necessary for tumor growth and maintenance. Although patients with HPV(+) tumors have a more favorable prognosis, there are currently no HPV-selective therapies. Accumulating evidence indicates that HPV oncoproteins can activate the Phosphoinositol-3-Kinase (PI3K) pathway, which contributes to transformation. Furthermore, PI3K is genomically activated by PIK3CA mutation or amplification in a disproportionately high number of HPV(+) tumors as compared to HPV(-) tumors. Based on this knowledge, we investigated the efficacy of PI3K-targeted therapies in preclinical models of HPV(+) HNSCC. Our results indicate that HPV(+) preclinical models were less sensitive to the PI3K inhibitors BYL719, BKM120, and BEZ235 as compared with HPV(-) models. Sensitivity of HPV(+) cell lines to PI3K inhibitors was increased upon knockdown of the E6 and E7 oncoproteins. Reciprocally, overexpression of E6 and E7 in HPV(-) cells rendered them resistant to PI3K-targeted therapies. Proteomic analyses indicated that treatment of HPV(+) cell lines and patient-derived xenografts (PDXs) with the PI3Kα inhibitor BYL719 induced expression of the receptor tyrosine kinase HER3, as well as E6 and E7. HER3 was found to regulate the abundance of E6 and E7 in the HPV(+) models. Targeting HER3 with siRNAs or the monoclonal antibody, KTN3379, blocked the increase in E6 and E7 protein levels following BYL719 treatment, and enhanced the efficacy of PI3K inhibitors in HPV(+) cell line and PDX models. Taken together, these results suggest that crosstalk between HER3 and HPV16-E6E7 can limit the efficacy of PI3K inhibitors, and that co-targeting HER3 and PI3K may be an effective therapeutic strategy in HPV(+) tumors. This abstract is also being presented as Poster 67. Citation Format: Toni M. Brand, Stefan Hartmann, Neil E. Bhola, Hua Li, Yan Zeng, Rachel O'Keefe, Max V. Ranall, Sourav Bandyopadhyay, Margaret Soucheray, Danielle L. Swaney, Nevan Krogan, Carolyn Kemp, Umamaheswar Duvvuri, Daniel E. Johnson, Michelle A. Ozbun, Julie E. Bauman, Jennifer R. Grandis. HER3 crosstalk with HPV16-E6E7 is a feedback resistance mechanism to PI3K-targeted therapies in head and neck cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr PR04.
Normal LDL-Cholesterol Levels Are Associated With Subclinical Atherosclerosis in the Absence of Risk Factors
Authors: Leticia Fernández-Friera, Valentín Fuster, Beatriz López-Melgar, Belén Oliva, José M. García-Ruiz, José Mendiguren, Héctor Bueno, Stuart Pocock, Borja Ibáñez, Antonio Fernández-Ortiz, Javier Sanz
Journal: Journal of the American College of Cardiology (2017)

Absence of cardiovascular risk factors (CVRFs) is traditionally considered low risk for atherosclerosis; however, individuals without CVRFs, as currently defined, still have events.This study sought to identify predictors of subclinical atherosclerosis in CVRF-free individuals.Participants from the PESA (Progression of Early Subclinical Atherosclerosis) study (n = 4,184) without conventional CVRFs were evaluated (n = 1,779; 45.0 ± 4.1 years, 50.3% women). CVRF freedom was defined as no current smoking and untreated blood pressure <140/90 mm Hg, fasting glucose <126 mg/dl, total cholesterol <240 mg/dl, low-density lipoprotein cholesterol (LDL-C) <160 mg/dl, and high-density lipoprotein cholesterol ≥40 mg/dl. A subgroup with optimal CVRFs (n = 740) was also defined as having blood pressure <120/80 mm Hg, fasting glucose <100 mg/dl, glycosylated hemoglobin <5.7%, and total cholesterol <200 mg/dl. We evaluated ultrasound-detected carotid, iliofemoral, and abdominal aortic plaques; coronary artery calcification; serum biomarkers; and lifestyle. Adjusted odds ratios (with 95% confidence interval) and ordinal logistic regression models were used.Subclinical atherosclerosis (plaque or coronary artery calcification) was present in 49.7% of CVRF-free participants. Together with male sex and age, LDL-C was independently associated with atherosclerosis presence and extent, in both the CVRF-free and CVRF-optimal groups (odds ratio [×10 mg/dl]: 1.14 to 1.18; p < 0.01 for all). Atherosclerosis presence and extent was also associated in the CVRF-free group with glycosylated hemoglobin levels.Many CVRF-free middle-aged individuals have atherosclerosis. LDL-C, even at levels currently considered normal, is independently associated with the presence and extent of early systemic atherosclerosis in the absence of major CVRFs. These findings support more effective LDL-C lowering for primordial prevention, even in individuals conventionally considered at optimal risk. (Progression of Early Subclinical Atherosclerosis [PESA] Study; NCT01410318).
MST4 Phosphorylation of ATG4B Regulates Autophagic Activity, Tumorigenicity, and Radioresistance in Glioblastoma
Authors: Tianzhi Huang, Chung Kwon Kim, Angel A. Alvarez, Rajendra P. Pangeni, Xuechao Wan, Xiao Song, Taiping Shi, Yongyong Yang, Namratha Sastry, Craig M. Horbinski, Songjian Lu, Roger Stupp, John A. Kessler, Ryo Nishikawa, Ichiro Nakano, Erik P. Sulman, Xinghua Lu, Charles David James, Xiao-Ming Yin, Bo Hu, Shi-Yuan Cheng
Journal: Cancer Cell (2017)

ATG4B stimulates autophagy by promoting autophagosome formation through reversible modification of ATG8. We identify ATG4B as a substrate of mammalian sterile20-like kinase (STK) 26/MST4. MST4 phosphorylates ATG4B at serine residue 383, which stimulates ATG4B activity and increases autophagic flux. Inhibition of MST4 or ATG4B activities using genetic approaches or an inhibitor of ATG4B suppresses autophagy and the tumorigenicity of glioblastoma (GBM) cells. Furthermore, radiation induces MST4 expression, ATG4B phosphorylation, and autophagy. Inhibiting ATG4B in combination with radiotherapy in treating mice with intracranial GBM xenograft markedly slows tumor growth and provides a significant survival benefit. Our work describes an MST4-ATG4B signaling axis that influences GBM autophagy and malignancy, and whose therapeutic targeting enhances the anti-tumor effects of radiotherapy.
Preventing fractures in the masters athlete: we can do better
Authors: Amy P Powell, Lauren Borowski, Andrea Kussman, Aurelia Nattiv
Journal: British Journal of Sports Medicine (2017)

Our population is ageing. By 2030, the number of Americans over age 65 years is expected to reach 74.1 million.1 Maintaining physical activity levels will become increasingly important to mitigate the effects of chronic disease in our ageing patient population.

The American College of Sports Medicine recommends 150 min per week of moderate intensity exercise.2 A subset of ageing athletes are meeting and exceeding recommended physical activity levels, with an increasing number of athletes ages 40 years and older participating in Ironman competitions, ultracycling events, ultramarathons and long-distance inline skating.

Exercise can reduce many of the negative effects of ageing, and weight-bearing exercise is one of the mainstays of osteoporosis management. However, exercise alone cannot overcome physiological age-related declines in bone density. Bone density peaks in the third decade of life, and then steadily declines,3 4 placing older athletes at risk for …
Does ‘proximal control’ need a new definition or a paradigm shift in exercise prescription? A clinical commentary
Authors: Steven L Dischiavi, Alexis A Wright, Eric J Hegedus, Kevin R Ford, Chris Bleakley
Journal: British Journal of Sports Medicine (2017)

There is level 1 evidence that ‘proximal control’ exercises are effective in the management of common musculoskeletal injuries of the lower extremity.1 2 However, there is little agreement on what ‘proximal control’ entails. A meta-analysis by Sugimoto et al 2 examined neuromuscular training for ACL injury prevention and found that exercises incorporating a ‘proximal control’ component (OR 0.33, 95% CI 0.23 to 0.47) were comparable to strength-based exercise or ‘multiple exercise’ interventions. Sugimoto et al 2 chose a global definition of proximal control (any exercise involving segments proximal to the knee joint) which included full-body dynamic warm-up programmes with plyometrics, jumps/hops, bounding, and various running and agility movements. One might argue that while these full-body interventions represent an integrated holistic approach, calling them ‘proximal control’ is inaccurate, as they fail to incorporate hip-specific exercises as the next ‘proximal’ link in the kinetic chain.

In comparison, a review by Lack et al 1 reported on the benefits of proximal control interventions for patellofemoral pain syndrome defining ‘proximal control’ as ‘exercises directed at the hip or lumbopelvic musculature or both.’ Consequently, Lack  et al ’s review1 was limited to more traditional static, …
Effects of International Electrocardiographic Interpretation Recommendations on African American Athletes
Authors: Sanjay Sharma
Journal: JAMA Cardiology (2017)

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High-Dimensional Phenotypic Mapping of Human Dendritic Cells Reveals Interindividual Variation and Tissue Specialization
Authors: Marcela Alcántara-Hernández, Rebecca Leylek, Lisa E. Wagar, Edgar G. Engleman, Tibor Keler, M. Peter Marinkovich, Mark M. Davis, Garry P. Nolan, Juliana Idoyaga
Journal: Immunity (2017)
Ambient Ozone Pollution and Daily Mortality: A Nationwide Study in 272 Chinese Cities
Authors: Peng Yin, Renjie Chen, Lijun Wang, Xia Meng, Cong Liu, Yue Niu, Zhijing Lin, Yunning Liu, Jiangmei Liu, Jinlei Qi, Jinling You, Maigeng Zhou, Haidong Kan
Journal: Environmental Health Perspectives (2017)

Background: Few large multicity studies have been conducted in developing countries to address the acute health effects of atmospheric ozone pollution. Objective: We explored the associations between ozone and daily cause-specific mortality in China. Methods: We performed a nationwide time-series analysis in 272 representative Chinese cities between 2013 and 2015. We used distributed lag models and over-dispersed generalized linear models to estimate the cumulative effects of ozone (lagged over 0–3 d) on mortality in each city, and we used hierarchical Bayesian models to combine the city-specific estimates. Regional, seasonal, and demographic heterogeneity were evaluated by meta-regression. Results: At the national-average level, a 10-μg/m3 increase in 8-h maximum ozone concentration was associated with 0.24% [95% posterior interval (PI): 0.13%, 0.35%], 0.27% (95% PI: 0.10%, 0.44%), 0.60% (95% PI: 0.08%, 1.11%), 0.24% (95% PI: 0.02%, 0.46%), and 0.29% (95% PI: 0.07%, 0.50%) higher daily mortality from all nonaccidental causes, cardiovascular diseases, hypertension, coronary diseases, and stroke, respectively. Associations between ozone and daily mortality due to respiratory and chronic obstructive pulmonary disease specifically were positive but imprecise and nonsignificant. There were no statistically significant differences in associations between ozone and nonaccidental mortality according to region, season, age, sex, or educational attainment. Conclusions: Our findings provide robust evidence of higher nonaccidental and cardiovascular mortality in association with short-term exposure to ambient ozone in China. https://doi.org/10.1289/EHP1849
HIV antibody screening. An ethical framework for evaluating proposed programs
Authors: R. Bayer
Journal: JAMA (1986)

We believe that the greatest hope for stopping the spread of HIV infection lies in the voluntary cooperation of those at higher risk--their willingness to undergo testing and to alter their personal behavior and goals in the interests of the community. But we can expect this voluntary cooperation--in some cases, sacrifice--only if the legitimate interests of these groups and individuals in being protected from discrimination are heeded by legislators, professionals, and the public. Yet voluntary testing is not enough. We must proceed with vigorous research and educational efforts to eliminate both the scourge of AIDS and the social havoc that has accompanied it.The use of blood tests to identify individuals who have been infected with the human immunodeficiency virus (HIV) challenges us to protect the community from the spread of a fatal disease while preserving the values of individual liberty and equal rights. Acquired immunodeficiency syndrome (AIDS) has prompted calls for mandatory screening of various segments of society--food handlers, military personnel, health workers, prostitutes, and so on. The authors recommend a set of principles and prerequisites for evaluating the ethical acceptability of proposed screening programs. They contend that the voluntary cooperation of those at higher risk is the ideal, and that screening programs must be based on the principles of respect for persons, minimal harm, beneficence, and justice. Health insurance must be available to those who test positive for HIV, confidentiality must be preserved, counseling should be provided, and voluntary testing should be publicly funded.
Not all HPV nucleic acid tests are equal: only those calibrated to detect high grade lesions matter for cervical screening: Response to ‘Concordant testing results between various human papillomavirus assays in primary cervical cancer screening: systematic review’ by de Thurah, Bonde, Uyen, Lam and Rebolj. Published 27 May, 2017
Authors: L. de Thurah, J. Bonde, J.U.H. Lam, M. Rebolj
Journal: Clinical Microbiology and Infection (2017)
Vigilancia serológica de la rubéola en Europa: Red Europea de Seroepidemiología (European Sero-Epidemiology Network; ESEN2)
Authors: A Nardone, E Miller
Journal: Eurosurveillance (2004)

La vigilancia serologica es un recurso importante para evaluar los programas de vacunacion, especialmente de enfermedades como la rubeola, donde un programa que no sea optimo puede dar lugar a un aumento de la morbilidad. En Europa hace falta una politica de vacunacion coordinada y el objetivo de ESEN2 es estandarizar la vigilancia serologica de ocho enfermedades en 22 paises, incluyendo la rubeola.
S1PR5 is essential for human natural killer cell migration toward sphingosine-1 phosphate
Authors: Annabelle Drouillard, Anne-Laure Mathieu, Antoine Marçais, Alexandre Belot, Sébastien Viel, Michaël Mingueneau, Kevin Guckian, Thierry Walzer
Journal: Journal of Allergy and Clinical Immunology (2017)
An interactive framework for whole-brain maps at cellular resolution
Authors: Daniel Fürth, Thomas Vaissière, Ourania Tzortzi, Yang Xuan, Antje Märtin, Iakovos Lazaridis, Giada Spigolon, Gilberto Fisone, Raju Tomer, Karl Deisseroth, Marie Carlén, Courtney A. Miller, Gavin Rumbaugh, Konstantinos Meletis
Journal: Nature Neuroscience (2017)
Polyunsaturated fatty acids in plasma at 8 years and subsequent allergic disease
Authors: Jessica Magnusson, Sandra Ekström, Inger Kull, Niclas Håkansson, Sara Nilsson, Magnus Wickman, Erik Melén, Ulf Risérus, Anna Bergström
Journal: Journal of Allergy and Clinical Immunology (2017)

Polyunsaturated fatty acids (PUFAs) are hypothesized to modulate the risk of allergic disease. However, evidence from previous studies is inconclusive, and limited longitudinal data exist using circulating biomarkers of PUFA intake and metabolism.We aimed to investigate associations between n-3 and n-6 PUFAs at age 8 years and asthma, rhinitis, and aeroallergen sensitization at age 16 years.Proportions of n-3 PUFAs (very long-chain n-3 [VLC n-3; sum of eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid] and α-linolenic acid) and n-6 PUFAs (linoleic acid and arachidonic acid [AA]) in blood samples at age 8 years were measured for 940 children from the prospective Swedish birth cohort BAMSE (Children, Allergy, Milieu, Stockholm, Epidemiology). Allergic disease phenotypes were defined by using questionnaires and IgE measures at the ages of 8 and 16 years. Logistic regression was used to examine potential associations.A higher proportion of total VLC n-3 PUFAs in plasma at age 8 years was associated with a reduced risk of prevalent asthma, rhinitis, and aeroallergen sensitization at age 16 years and with incidence of asthma between 8 and 16 years (adjusted odds ratio, 0.67; 95% CI, 0.47-0.94). AA was associated with a reduced risk of asthma, aeroallergen sensitization, and allergic rhinitis. The findings were most evident for allergic phenotypes of asthma and rhinitis. Additionally, AA was associated with an increased probability of asthma and rhinitis remission between 8 and 16 years of age.Higher proportions of certain VLC n-3 and very long-chain n-6 PUFAs in plasma phospholipids at age 8 years were associated with a reduced risk of allergic disease at age 16 years.
Avaliação epidemiológica e virológica da actividade gripal na Europa, inverno 2004-2005
Authors: A Meijer, W J Paget, T J Meerhoff, C S Brown, L. E. Meuwissen, J Van Der Velden
Journal: Eurosurveillance (2006)

A temporada gripal 2004-2005 comecou no final de dezembro de 2004, manifestando-se primeiro no sul e oeste da Europa (Espanha, Reino-Unido e Irlanda). A actividade gripal foi movendo-se pouco a pouco em direccao do leste atravessando a Europa em janeiro e em principio de fevereiro de 2005, e ao final principalmente do sul ao norte entre o fim de janeiro e principio de fevereiro de 2005. Em 10 dos 23 paises, a actividade gripal foi mais intensa que na temporada 2003-2004, e presentou uma intensidade iegual ou inferior nos outros 13. As taxas mais altas de consultas foram observadas geralmente em criancas de 0 a 14 anos. Nao se notaram aumentos nos picos de consultas para sindromes gripais ou infeccoes respiratorias agudas, comparados com datos historicos. Predominava a estirpe viral A (83% das deteccoes totais), com um sub-tipo H3 (85% dos virus A sub-tipos H), seguida pela estirpe B (17% das deteccoes) ou A(H1) (15% dos virus A sub-tipos H). A maior parte dos virus A(H3) eram similares as estirpes de referencia A/Wellington/1/2004 (H3N2) e consequentemente as estirpes A/California/7/2004 (H3N2), que sao variantes muito proximas da estirpe A/Fujian/411/2002 (H3N2) da vacina prototipo. Os virus A e B co-circularam durante toda a temporada em 11 dos 24 paises. 
Sete deles estao situados no nordeste da Europa, e nos tais, a a proporcao de virus B foi mais alta (31 a 60%) do que no resto do continent (6 a 26%). Em 13 dos 24 paises, os virus B circularam relativamente tarde na temporada. Ums 43% de todos os virus B com antigeno caracterizado eram do tipo B/Hong Kong/330/2001 (linha dos B/Victoria/2/87), uma estirpe distinta da estirpe vacinal anti-grippal B, ou seja um virus de tipo B/Yamagata/16/88. Basandose nos virus detectados pelo mundo ate fevereiro de 2005, a Organizacao Mundial da Saude mudou a composicao da vacina anti-grippal 2005-2006, incluindo um novo componente : uma estirpe similar ao virus A/California/7/2004 (H3N2).
Hemophilia B Gene Therapy with a High-Specific-Activity Factor IX Variant
Authors: Lindsey A. George, Spencer K. Sullivan, Adam Giermasz, John E.J. Rasko, Benjamin J. Samelson-Jones, Jonathan Ducore, Adam Cuker, Lisa M. Sullivan, Suvankar Majumdar, Jerome Teitel, Catherine E. McGuinn, Margaret V. Ragni, Alvin Y. Luk, Daniel Hui, J. Fraser Wright, Yifeng Chen, Yun Liu, Katie Wachtel, Angela Winters, Stefan Tiefenbacher, Valder R. Arruda, Johannes C.M. van der Loo, Olga Zelenaia, Daniel Takefman, Marcus E. Carr, Linda B. Couto, Xavier M. Anguela, Katherine A. High
Journal: New England Journal of Medicine (2017)

The prevention of bleeding with adequately sustained levels of clotting factor, after a single therapeutic intervention and without the need for further medical intervention, represents an important goal in the treatment of hemophilia.