tbuckley/cabot-search huggingface dataset:
Circulation of non-polio enteroviruses in 24 EU and EEA countries between 2015 and 2017: a retrospective surveillance study
Authors: Laura Bubba, Eeva K Broberg, Aftab Jasir, Peter Simmonds, Heli Harvala, Monika Redlberger-Fritz, Lubomira Nikolaeva-Glomb, Martina Havlíčková, Petra Rainetova, Thea K Fischer, Sofie E. Midgley, Jevgenia Epštein, Soile Blomqvist, Sindy Böttcher, Kathrin Keeren, Erika Bujaki, Ágnes Farkas, Guôrún Erna Baldvinsdóttir, Ursula Morley, Cillian De Gascun, Laura Pellegrinelli, Antonio Piralla, Oksana Martinuka, Natālija Zamjatina, Algirdas Griškevičius, Trung Nguyen, Susanne G. Dudman, Sanela Numanovic, Magdalena Wieczorek, Raquel Guiomar, Inês Costa, Tecu Cristina, Shubhada Bopegamage, Katarina Pastuchova, Nataša Berginc, María Cabrerizo, Rubén González-Sanz, Katherina Zakikhany, Elenor Hauzenberger, Kimberley Benschop, Erwin Duizer, Jake Dunning, Cristina Celma, James McKenna, Susan Feeney, Kate Templeton, Catherine Moore, Simon Cottrell
Journal: The Lancet Infectious Diseases (2019)
Xenobiotic receptors in mediating the effect of sepsis on drug metabolism
Authors: Chuanzhu Lv, Ling Huang
Journal: Acta Pharmaceutica Sinica B (2019)

Sepsis is an infection-induced systemic inflammatory syndrome. The immune response in sepsis is characterized by the activation of both proinflammatory and anti-inflammatory pathways. When sepsis occurs, the expression and activity of many inflammatory cytokines are markedly affected. Xenobiotic receptors are chemical-sensing transcription factors that play essential roles in the transcriptional regulation of drug-metabolizing enzymes (DMEs). Xenobiotic receptors mediate the functional crosstalk between sepsis and drug metabolism because the inflammatory cytokines released during sepsis can affect the expression and activity of xenobiotic receptors and thus impact the expression and activity of DMEs. Xenobiotic receptors in turn may affect the clinical outcomes of sepsis. This review focuses on the sepsis-induced inflammatory response and xenobiotic receptors such as pregnane X receptor (PXR), aryl hydrocarbon receptor (AHR), glucocorticoid receptor (GR), and constitutive androstane receptor (CAR), DMEs such as CYP1A, CYP2B6, CYP2C9, and CYP3A4, and drug transporters such as p-glycoprotein (P-gp), and multidrug resistance-associated protein (MRPs) that are affected by sepsis. Understanding the xenobiotic receptor-mediated effect of sepsis on drug metabolism will help to improve the safe use of drugs in sepsis patients and the development of new xenobiotic receptor-based therapeutic strategies for sepsis.
Abstract B25: Engrailed-1 promotes pancreatic cancer progression via antagonizing COMPASS activity
Authors: Chang-il Hwang, Jae-Seok Roe, Eun Jung Lee, Claudia Tonelli, Tim D.D. Somervile, Melissa Yao, Joseph P. Milazzo, Hervé Tiriac, Youngkyu Park, Christopher Vakoc, David Tuveson
Journal: Cancer Research (2019)

Abstract Pancreatic ductal adenocarcinoma (PDA) is the most deadly disease in human malignancies. Using pancreatic organoid models, we have shown that enhancer reprogramming allows pancreatic cancer cells to acquire aggressive characteristics during disease progression. Recently we found that organoid cultures (mM) derived from metastatic lesions of KPC mice (Kras+/LSL-G12D; Trp53+/LSL-R172H; Pdx1-Cre) can survive in the reduced condition, unlike the paired primary tumor-derived organoid cultures (mT). We implicate Engrailed-1 (EN1), a neurodevelopmental transcription factor (TF), in this process as a prosurvival factor. We show that EN1 is indispensable for organoid survival in the reduced condition, highly expressed in mM compared to mT organoid cultures, and associated with poor prognosis. Gain- and loss-of-function experiments further show that EN1 is responsible for the aggressiveness of pancreatic cancer cells in vitro (anchorage-independent growth, migration, and invasion) and in vivo. On the other hand, subcutaneous tumors derived from EN1 expressing mT organoids exhibit squamous-like differentiation compared to control. In line with this, squamous-type PDA patients tend to express EN1 compared to other subtypes of PDA. Furthermore, EN1 perturbation renders the changes of squamous-PDA identity and KDM6A deficiency signatures. Mechanistically, EN1 can physically interact with KDM6A and repress H3K4me3 occupancy in a subset of genes without affecting H3K27me3 and H3K27ac occupancies, suggesting that the regulation of COMPASS (Complex Proteins Associated with Set1) activity by EN1 might be critical in this process. Finally, by combining EN1 with FOXA1, previously shown to be responsible for enhancer activation in PDA organoids, we were able to fully reprogram pancreatic cancer cells into highly aggressive pancreatic cancer cells. In sum, we report that EN1 confers the aggressiveness of pancreatic cancer cells via regulation of COMPASS activity and contributes to squamous-type identity and PDA progression. Citation Format: Chang-il Hwang, Jae-Seok Roe, Eun Jung Lee, Claudia Tonelli, Tim D.D. Somervile, Melissa Yao, Joseph P. Milazzo, Hervé Tiriac, Youngkyu Park, Christopher Vakoc, David Tuveson. Engrailed-1 promotes pancreatic cancer progression via antagonizing COMPASS activity [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B25.
Abstract 12729: Ultrasound-Mediated Mir-495 Delivery Improves Cardiac Remodeling and Left Ventricular Function Post Myocardial Ischemia/Reperfusion Injury
Authors: Zaman Afrasiabi, Michael A Kuliszewski, Pratiek N Matkar, Hao H Chen, Howard Leong-Poi
Journal: Circulation (2018)

Introduction: MiRNAs play crucial regulatory roles in multiple pathways involved in cardiovascular diseases. RUNX3, a post-transcriptional factor, induces apoptosis in various cells. Hypothesis: We...
The effect of HIV-associated tuberculosis, tuberculosis-IRIS and prednisone on lung function
Authors: Cari Stek, Brian Allwood, Elsa Du Bruyn, Jozefien Buyze, Charlotte Schutz, Friedrich Thienemann, Adele Lombard, Robert J. Wilkinson, Graeme Meintjes, Lutgarde Lynen
Journal: European Respiratory Journal (2019)

Residual pulmonary impairment is common after treatment for tuberculosis (TB). Lung function data in patients with HIV-associated TB are scarce, especially in the context of paradoxical TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) and prophylactic prednisone. We aimed to determine the prevalence of lung function abnormalities in patients with HIV-associated TB and CD4 counts ≤100 cells·μL-1 and assess the effect of prophylactic prednisone and the development of paradoxical TB-IRIS on pulmonary impairment.We performed spirometry, 6-min walk test (6MWT) and chest radiography at baseline (week 0) and at weeks 4, 12 and 28 in participants of the PredART trial, which evaluated a 28-day course of prednisone to prevent TB-IRIS in patients with HIV-associated TB commencing antiretroviral therapy.153 participants underwent spirometry and/or 6MWT at one or more time points. Abnormal spirometry measurements were present in 66% of participants at week 0 and 50% at week 28; low forced vital capacity was the commonest abnormality. Chest radiographs showed little or no abnormalities in the majority of participants. Prednisone use resulted in a 42 m greater 6-min walk distance and a 4.9% higher percentage of predicted forced expiratory volume in 1 s at week 4; these differences were no longer significantly different from week 12 onwards. TB-IRIS did not significantly impair lung function outcome.Residual pulmonary impairment is common in HIV-associated TB. In patients with low CD4 counts, neither prophylactic prednisone as used in our study nor the development of TB-IRIS significantly affected week-28 pulmonary outcome.
High-dimensionality Data Analysis of Pharmacological Systems Associated with Complex Diseases
Authors: Jhana O. Hendrickx, Jaana van Gastel, Hanne Leysen, Bronwen Martin, Stuart Maudsley
Journal: Pharmacological Reviews (2019)

It is widely accepted that molecular reductionist views of highly complex human physiologic activity, e.g., the aging process, as well as therapeutic drug efficacy are largely oversimplifications. Currently some of the most effective appreciation of biologic disease and drug response complexity is achieved using high-dimensionality (H-D) data streams from transcriptomic, proteomic, metabolomics, or epigenomic pipelines. Multiple H-D data sets are now common and freely accessible for complex diseases such as metabolic syndrome, cardiovascular disease, and neurodegenerative conditions such as Alzheimer's disease. Over the last decade our ability to interrogate these high-dimensionality data streams has been profoundly enhanced through the development and implementation of highly effective bioinformatic platforms. Employing these computational approaches to understand the complexity of age-related diseases provides a facile mechanism to then synergize this pathologic appreciation with a similar level of understanding of therapeutic-mediated signaling. For informative pathology and drug-based analytics that are able to generate meaningful therapeutic insight across diverse data streams, novel informatics processes such as latent semantic indexing and topological data analyses will likely be important. Elucidation of H-D molecular disease signatures from diverse data streams will likely generate and refine new therapeutic strategies that will be designed with a cognizance of a realistic appreciation of the complexity of human age-related disease and drug effects. We contend that informatic platforms should be synergistic with more advanced chemical/drug and phenotypic cellular/tissue-based analytical predictive models to assist in either de novo drug prioritization or effective repurposing for the intervention of aging-related diseases. <h3>Significance Statement</h3> All diseases, as well as pharmacological mechanisms, are far more complex than previously thought a decade ago. With the advent of commonplace access to technologies that produce large volumes of high-dimensionality data (e.g., transcriptomics, proteomics, metabolomics), it is now imperative that effective tools to appreciate this highly nuanced data are developed. Being able to appreciate the subtleties of high-dimensionality data will allow molecular pharmacologists to develop the most effective multidimensional therapeutics with effectively engineered efficacy profiles.
Limitations of Hoerl and McCormack's dual systems model of temporal consciousness
Authors: Eve A Isham, Elijah M Ziskin, Mary A Peterson
Journal: Behavioral and Brain Sciences (2019)

Hoerl & McCormack's dual systems framework provides a new avenue toward the scientific investigation of temporal cognition. However, some shortcomings of the model should be considered. These issues include their reliance on a somewhat vague consideration of "systems" rather than specific computational processes. Moreover, the model does not consider the subjective nature of temporal experience or the role of consciousness in temporal cognition.
Preoperative <i>N</i>-Terminal Pro–B-Type Natriuretic Peptide and Cardiovascular Events After Noncardiac Surgery
Authors: Emmanuelle Duceppe, Ameen Patel, Matthew T.V. Chan, Otavio Berwanger, Gareth Ackland, Peter A. Kavsak, Reitze Rodseth, Bruce Biccard, Clara K. Chow, Flavia K. Borges, Gordon Guyatt, Rupert Pearse, Daniel I. Sessler, Diane Heels-Ansdell, Andrea Kurz, Chew Yin Wang, Wojciech Szczeklik, Sadeesh Srinathan, Amit X. Garg, Shirley Pettit, Erin N. Sloan, James L. Januzzi Jr., Matthew McQueen, Giovanna Lurati Buse, Nicholas L. Mills, Lin Zhang, Robert Sapsford, Guillaume Paré, Michael Walsh, Richard Whitlock, Andre Lamy, Stephen Hill, Lehana Thabane, Salim Yusuf, P.J. Devereaux
Journal: Annals of Internal Medicine (2019)

Background: Preliminary data suggest that preoperative N-terminal pro–B-type natriuretic peptide (NT-proBNP) may improve risk prediction in patients undergoing noncardiac surgery. Objective: To determine whether preoperative NT-proBNP has additional predictive value beyond a clinical risk score for the composite of vascular death and myocardial injury after noncardiac surgery (MINS) within 30 days after surgery. Design: Prospective cohort study. Setting: 16 hospitals in 9 countries. Patients: 10 402 patients aged 45 years or older having inpatient noncardiac surgery. Measurements: All patients had NT-proBNP levels measured before surgery and troponin T levels measured daily for up to 3 days after surgery. Results: In multivariable analyses, compared with preoperative NT-proBNP values less than 100 pg/mL (the reference group), those of 100 to less than 200 pg/mL, 200 to less than 1500 pg/mL, and 1500 pg/mL or greater were associated with adjusted hazard ratios of 2.27 (95% CI, 1.90 to 2.70), 3.63 (CI, 3.13 to 4.21), and 5.82 (CI, 4.81 to 7.05) and corresponding incidences of the primary outcome of 12.3% (226 of 1843), 20.8% (542 of 2608), and 37.5% (223 of 595), respectively. Adding NT-proBNP thresholds to clinical stratification (that is, the Revised Cardiac Risk Index [RCRI]) resulted in a net absolute reclassification improvement of 258 per 1000 patients. Preoperative NT-proBNP values were also statistically significantly associated with 30-day all-cause mortality (less than 100 pg/mL [incidence, 0.3%], 100 to less than 200 pg/mL [incidence, 0.7%], 200 to less than 1500 pg/mL [incidence, 1.4%], and 1500 pg/mL or greater [incidence, 4.0%]). Limitation: External validation of the identified NT-proBNP thresholds in other cohorts would reinforce our findings. Conclusion: Preoperative NT-proBNP is strongly associated with vascular death and MINS within 30 days after noncardiac surgery and improves cardiac risk prediction in addition to the RCRI. Primary Funding Source: Canadian Institutes of Health Research.
Role of Changes in Magnetic Resonance Imaging or Clinical Stage in Evaluation of Disease Progression for Men with Prostate Cancer on Active Surveillance
Authors: Gregory T. Chesnut, Emily A. Vertosick, Nicole Benfante, Daniel D. Sjoberg, Jonathan Fainberg, Taehyoung Lee, James Eastham, Vincent Laudone, Peter Scardino, Karim Touijer, Andrew Vickers, Behfar Ehdaie
Journal: European Urology (2019)
Does reducing the height of the tackle through law change in elite men’s rugby union (The Championship, England) reduce the incidence of concussion? A controlled study in 126 games
Authors: Keith A Stokes, Duncan Locke, Simon Roberts, Lewis Henderson, Ross Tucker, Dean Ryan, Simon Kemp
Journal: British Journal of Sports Medicine (2019)

Most concussions in rugby union occur during tackles. We investigated whether legislation to lower maximum tackle height would change tackle behaviour, and reduce concussion incidence rate.In an observational evaluation using a prospective cohort design, 12 elite men's teams played in two competitions during the 2018/2019 season. The Championship (90 games) retained standard Laws of Rugby for the tackle; the Championship Cup (36 games) used revised laws-the maximum tackle height was lowered from the line of the shoulders on the ball carrier to the line of the armpits. Videos of tackles were analysed for ball carrier and tackler behaviour. Injury data were collected using standardised methods.In the lowered tackle height setting, there was a significantly lower proportion of tackles; (1) in which ball carriers (rate ratio (RR) 0.83, 95% CI 0.79 to 0.86) and tacklers (RR 0.80, 95% CI 0.76 to 0.84) were upright, (2) in which the tackler's initial contact was to the ball carrier's head or neck (RR 0.70, 95% CI 0.58 to 0.84) and (3) in which initial contact was above the line of the ball carrier's armpit (RR 0.84, 95% CI 0.80 to 0.88). Concussion incidence rate did not differ between conditions (RR 1.31, 95% CI 0.85 to 2.01). Unexpectedly, compared with the standard tackle height setting, tacklers in the lowered tackle height setting were themselves concussed at a higher rate as measured by; (1) incidence (RR 1.90, 95% CI 1.05 to 3.45) and (2) concussions per 1000 tackles (2.09, 95% CI 1.15 to 3.80).Legislating to lower the height of the tackle meant that tacklers made contact with the ball carrier's head and neck 30% less often. This did not influence concussion incidence rates. Tacklers in the lowered tackle height setting suffered more concussions than did tacklers in the standard tackle height setting.
BAP1 mutations define a homogeneous subgroup of hepatocellular carcinoma with fibrolamellar-like features and activated PKA
Authors: Théo Z. Hirsch, Ana Negulescu, Barkha Gupta, Stefano Caruso, Bénédicte Noblet, Gabrielle Couchy, Quentin Bayard, Léa Meunier, Guillaume Morcrette, Jean-Yves Scoazec, Jean-Frédéric Blanc, Giuliana Amaddeo, Jean-Charles Nault, Paulette Bioulac-Sage, Marianne Ziol, Aurélie Beaufrère, Valérie Paradis, Julien Calderaro, Sandrine Imbeaud, Jessica Zucman-Rossi
Journal: Journal of Hepatology (2019)
TMPRSS4 Drives Angiogenesis in Hepatocellular Carcinoma by Promoting HB‐EGF Expression and Proteolytic Cleavage
Authors: Zhao‐Ru Dong, Dong Sun, Ya‐Fei Yang, Wei Zhou, Rui Wu, Xiao‐Wei Wang, Kai Shi, Yu‐Chuan Yan, Lun‐Jie Yan, Cheng‐Yu Yao, Zhi‐Qiang Chen, Xu‐Ting Zhi, Tao Li
Journal: Hepatology (2019)

Heparin-binding epidermal growth factor (HB-EGF), a member of the epidermal growth factor family, plays a pivotal role in the progression of several malignancies, but its role and regulatory mechanisms in hepatocellular carcinoma (HCC) remain obscure. Here, we report that transmembrane protease serine 4 (TMPRSS4) significantly enhanced the expression and proteolytic cleavage of HB-EGF to promote angiogenesis and HCC progression.A mechanistic analysis revealed that TMPRSS4 not only increased the transcriptional and translational levels of HB-EGF precursor, but also promoted its proteolytic cleavage by enhancing matrix metallopeptidase 9 expression through the EGF receptor/Akt/mammalian target of rapamycin/ hypoxia-inducible factor 1 α signaling pathway. In addition, HB-EGF promoted HCC proliferation and invasion by the EGF receptor/phosphoinositide 3-kinase/Akt signaling pathway. The level of HB-EGF in clinical samples of serum or HCC tissues from patients with HCC was positively correlated with the expression of TMPRSS4 and the microvessel density, and was identified as a prognostic factor for overall survival and recurrence-free survival, which suggests that HB-EGF can serve as a potential therapeutic target for HCC. More importantly, we provide a demonstration that treatment with the HB-EGF inhibitor cross-reacting material 197 alone or in combination with sorafenib can significantly suppress angiogenesis and HCC progression.HB-EGF can be regulated by TMPRSS4 to promote HCC proliferation, invasion, and angiogenesis, and the combination of the HB-EGF inhibitor cross-reacting material 197 with sorafenib might be used for individualized treatment of HCC.
Prospective of nanoscale metal organic frameworks [NMOFs] for cancer therapy
Authors: Mohammed Razeeth Shait Mohammed, Varish Ahmad, Abrar Ahmad, Shams Tabrez, Hani Choudhry, Mazin A. Zamzami, Muhammed A. Bakhrebah, Aftab Ahmad, Samina Wasi, Hasan Mukhtar, Mohammad Imran Khan
Journal: Seminars in Cancer Biology (2019)
Maximising and evaluating the uptake, use and impact of golf and health studies
Authors: Andrew Murray, Paul Kelly, Sarah Morton, Danny Glover, Jennifer Duncan, Roger Hawkes, Liz Grant, Nanette Mutrie
Journal: British Journal of Sports Medicine (2019)

Introduction The dissemination of research, and evaluation of its impact is an increasing priority for the scientific community and funders. We take the topic of golf and health and aim to outline processes that may contribute to improved research uptake, use and impact proposing a research impact (RI) tool. We then evaluate our published research using the Research Contributions Framework (RCF). Methods Building on existing research and frameworks we i) assessed the need for, ii) carried out and iii) published research, before iv) creating digital resources, v) sharing these resources widely and vi) evaluating our research. To evaluate uptake, use and impact of our three principal golf and health research outputs, we performed a contributions analysis, using the RCF first proposed by Morton. Results/Discussion We developed a specific six-step Research Impact tool. Having implemented this, research uptake and use included over 300 press articles, a dedicated website and social media channels. Golf’s global industry leadership dispersed information across &gt;150 countries, embedded golf and health into curricula for industry professionals and used leading tournaments to promote health. National policy makers hosted dedicated meetings regarding golf and health and began to implement policy change. Conclusion To date, strong uptake and use can be demonstrated for these studies, while a final contribution to impact requires further time to determine. Frameworks we used aiming to maximise impact (Research Impact tool) and evaluate its contribution to uptake, use and impact (Research Contribution Framework) could potentially add value to public health/sports medicine researchers.
Artificial Intelligence in Health Care
Authors: Michael E. Matheny, Danielle Whicher, Sonoo Thadaney Israni
Journal: JAMA (2019)

This Viewpoint summarizes the 2019 AI in Healthcare report from the National Academy of Medicine (NAM), which reviews best practices for AI development, adoption, and maintenance and urges prioritization of equity, inclusion, and human rights in AI health system implementation.
CD8+ T cells target cerebrovasculature in children with cerebral malaria
Authors: Brittany A. Riggle, Monica Manglani, Dragan Maric, Kory R. Johnson, Myoung-Hwa Lee, Osorio Lopes Abath Neto, Terrie E. Taylor, Karl B. Seydel, Avindra Nath, Louis H. Miller, Dorian B. McGavern, Susan K. Pierce
Journal: Journal of Clinical Investigation (2019)

BACKGROUND. Cerebral malaria (CM) accounts for nearly 400,000 deaths annually in African children. Current dogma suggests that CM results from infected RBC (iRBC) sequestration in the brain microvasculature and resulting sequelae. Therapies targeting these events have been unsuccessful; findings in experimental models suggest that CD8+ T cells drive disease pathogenesis. However, these data have largely been ignored because corroborating evidence in humans is lacking. This work fills a critical gap in our understanding of CM pathogenesis that is impeding development of therapeutics.
A Stimulus Package to Address the Pediatric Sleep Debt Crisis in the United States
Authors: Ariel A. Williamson, Lisa J. Meltzer, Alexander G. Fiks
Journal: JAMA Pediatrics (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal