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Brian Tsui, Michelle Dow, Dylan Skola, Hannah Carter
The Sequence Read Archive (SRA) contains over one million publicly available sequencing runs from various studies using a variety of sequencing library strategies. These data inherently contain information about underlying genomic sequence variants which we exploit to extract allelic read counts on an unprecedented scale. We reprocessed over 250,000 human sequencing runs (>1000 TB data worth of raw sequence data) into a single unified dataset of allelic read counts for nearly 300,000 variants of biomedical relevance curated by NCBI dbSNP, where germline variants were detected in a median of 912 sequencing runs, and somatic variants were detected in a median of 4,876 sequencing runs, suggesting that this dataset facilitates identification of sequencing runs that harbor variants of interest...
2019: Pacific Symposium on Biocomputing
Karoline Freeman, Brian H Willis, Hannah Fraser, Sian Taylor-Phillips, Aileen Clarke
OBJECTIVE: Test accuracy of faecal calprotectin (FC) testing in primary care is inconclusive. We aimed to assess the test accuracy of FC testing in primary care and compare it to secondary care estimates for the detection of inflammatory bowel disease (IBD). METHODS: Systematic review and meta-analysis of test accuracy using a bivariate random effects model. We searched MEDLINE, EMBASE, Cochrane Library and Web of Science until 31 May 2017 and included studies from auto alerts up until 31 January 2018...
March 8, 2019: BMJ Open
Huiying Liang, Brian Y Tsui, Hao Ni, Carolina C S Valentim, Sally L Baxter, Guangjian Liu, Wenjia Cai, Daniel S Kermany, Xin Sun, Jiancong Chen, Liya He, Jie Zhu, Pin Tian, Hua Shao, Lianghong Zheng, Rui Hou, Sierra Hewett, Gen Li, Ping Liang, Xuan Zang, Zhiqi Zhang, Liyan Pan, Huimin Cai, Rujuan Ling, Shuhua Li, Yongwang Cui, Shusheng Tang, Hong Ye, Xiaoyan Huang, Waner He, Wenqing Liang, Qing Zhang, Jianmin Jiang, Wei Yu, Jianqun Gao, Wanxing Ou, Yingmin Deng, Qiaozhen Hou, Bei Wang, Cuichan Yao, Yan Liang, Shu Zhang, Yaou Duan, Runze Zhang, Sarah Gibson, Charlotte L Zhang, Oulan Li, Edward D Zhang, Gabriel Karin, Nathan Nguyen, Xiaokang Wu, Cindy Wen, Jie Xu, Wenqin Xu, Bochu Wang, Winston Wang, Jing Li, Bianca Pizzato, Caroline Bao, Daoman Xiang, Wanting He, Suiqin He, Yugui Zhou, Weldon Haw, Michael Goldbaum, Adriana Tremoulet, Chun-Nan Hsu, Hannah Carter, Long Zhu, Kang Zhang, Huimin Xia
Artificial intelligence (AI)-based methods have emerged as powerful tools to transform medical care. Although machine learning classifiers (MLCs) have already demonstrated strong performance in image-based diagnoses, analysis of diverse and massive electronic health record (EHR) data remains challenging. Here, we show that MLCs can query EHRs in a manner similar to the hypothetico-deductive reasoning used by physicians and unearth associations that previous statistical methods have not found. Our model applies an automated natural language processing system using deep learning techniques to extract clinically relevant information from EHRs...
February 11, 2019: Nature Medicine
Etimbuk Umana, Josephine Hannah Kelliher, Christiaan Johannes Blom, Brian McNicholl
CLINICIAN'S CAPSULEWhat is known about the topic?Methoxyflurane is an inhalation analgesic with minimal sedative properties.What did this study ask?What is the success rate of methoxyflurane for acute anterior shoulder dislocation reduction and its impact on emergency department (ED) patient flow, as compared with propofol?What did this study find?Successful reduction was achieved in 80% of patients administered methoxyflurane; recovery time and ED length of stay was shorter, as compared with propofol sedation...
February 11, 2019: CJEM
Troy S Wildes, Angela M Mickle, Arbi Ben Abdallah, Hannah R Maybrier, Jordan Oberhaus, Thaddeus P Budelier, Alex Kronzer, Sherry L McKinnon, Daniel Park, Brian A Torres, Thomas J Graetz, Daniel A Emmert, Ben J Palanca, Shreya Goswami, Katherine Jordan, Nan Lin, Bradley A Fritz, Tracey W Stevens, Eric Jacobsohn, Eva M Schmitt, Sharon K Inouye, Susan Stark, Eric J Lenze, Michael S Avidan
Importance: Intraoperative electroencephalogram (EEG) waveform suppression, often suggesting excessive general anesthesia, has been associated with postoperative delirium. Objective: To assess whether EEG-guided anesthetic administration decreases the incidence of postoperative delirium. Design, Setting, and Participants: Randomized clinical trial of 1232 adults aged 60 years and older undergoing major surgery and receiving general anesthesia at Barnes-Jewish Hospital in St Louis...
February 5, 2019: JAMA: the Journal of the American Medical Association
Fresia Pareja, Felipe C Geyer, David N Brown, Ana P Martins Sebastião, Rodrigo Gularte-Mérida, Anqi Li, Marcia Edelweiss, Arnaud Da Cruz Paula, Pier Selenica, Hannah Y Wen, Achim A Jungbluth, Zsuzsanna Varga, Juan Palazzo, Brian P Rubin, Ian O Ellis, Edi Brogi, Emad A Rakha, Britta Weigelt, Jorge S Reis-Filho
Breast adenomyoepitheliomas (AMEs) are rare epithelial-myoepithelial neoplasms that may occasionally produce myxochondroid matrix, akin to pleomorphic adenomas (PAs). Regardless of their anatomic location, PAs often harbor rearrangements involving HMGA2 or PLAG1 . We have recently shown that the repertoire of somatic genetic alterations of AMEs varies according to their estrogen receptor (ER) status; whilst the majority of ER-positive AMEs display mutually exclusive PIK3CA or AKT1 hotspot mutations, up to 60% of ER-negative AMEs harbor concurrent HRAS Q61 hotspot mutations and mutations affecting either PIK3CA or PIK3R1 ...
2019: NPJ Breast Cancer
Meltem Lammertz, Hannah Kuhn, Sebastian Pfeilmeier, Jacob G Malone, C Zipfel, Mark Kwaaitaal, Nai-Chun Lin, Brian H Kvitko, Ralph Panstruga
Successful pathogens must efficiently defeat or delay host immune responses, including those triggered by release or exposure of microbe-associated molecular patterns (MAMPs). Knowledge on the molecular details leading to this phenomenon in plant-pathogen interactions is still scarce. We took advantage of the well-established Arabidopsis thaliana-Pseudomonas syringae pathovar tomato DC3000 (Pst DC3000) patho-system to explore the molecular prerequisites for the suppression of MAMP-triggered host defense by the bacterial invader...
January 21, 2019: Molecular Plant-microbe Interactions: MPMI
Hannah Wolfe, Virginia Mela Rivas, Aedin M Minogue, Anne-Marie Miller, Chris McGuigan, Laura Williams, Deirdre Lohan, Brian A Lawlor, Marina A Lynch
The search for a blood-based biomarker that identifies Alzheimer's disease (AD) and can replace current invasive and expensive diagnostic tests, continues. The most extensively-examined peripheral marker is β-amyloid (Aβ) but the results are inconsistent across studies and do not reflect the changes that take place in the brain. Several studies have assessed possible proteomic signatures but with inconsistent findings, although increases in circulating inflammatory molecules are generally observed. Here, rather than focus on identifying changes in the circulation, we evaluated the effect of plasma from patients with mild cognitive impairment (MCI) and AD on the human monocyte-like cell line, THP-1 cells, and plasma from an AD mouse model on a mouse monocyte-macrophage cell line, J774...
January 11, 2019: Neuroscience Research
Brian J Levandowski, Trevor A Hamlin, Hannah J Eckvahl, F Matthias Bickelhaupt, K N Houk
Quantum chemical calculations were used to investigate the Diels-Alder reactivities for a series of cycloalkenediones with tetrazine. We find that the reactivity trend of cycloalkenediones toward tetrazine is opposite to cycloalkenes. The electrostatic interactions between the cycloalkenediones and tetrazine become more stabilizing as the ring size of the cycloalkenediones increases, resulting in lower activation energies. The origin of the more favorable electrostatic interactions and the accelerated reactivities of larger cycloalkenediones result from a stabilizing CH/π interaction that is not present in the reaction of the 4-membered cycloalkenedione...
January 9, 2019: Journal of Molecular Modeling
Stephen J Aston, Antonia Ho, Hannah Jary, Jacqueline Huwa, Tamara Mitchell, Sarah Ibitoye, Simon Greenwood, Elizabeth Joekes, Arthur Daire, Jane Mallewa, Dean Everett, Mulinda Nyirenda, Brian Faragher, Henry C Mwandumba, Robert S Heyderman, Stephen B Gordon
RATIONALE: In the context of rapid antiretroviral therapy (ART) rollout and an increasing burden of non-communicable diseases, there are few contemporary data describing the aetiology and outcome of community-acquired pneumonia (CAP) in sub-Saharan Africa. OBJECTIVES: To describe the current aetiology of CAP in Malawi and identify risk factors for mortality. METHODS: We conducted a prospective observational study of adults hospitalised with CAP to a teaching hospital in Blantyre, Malawi...
January 9, 2019: American Journal of Respiratory and Critical Care Medicine
Hannah Ernst, Agnieszka Dzioba, Jordan Glicksman, Josee Paradis, Brian Rotenberg, Julie Strychowsky
OBJECTIVES/HYPOTHESIS: To evaluate the impact of adenotonsillectomy for pediatric sleep-disordered breathing (SDB) on parental sleep quality, daytime sleepiness, and child quality of life. STUDY DESIGN: Prospective cohort study. METHODS: Pediatric patients aged 2 to 10 years with SDB and suspected obstructive sleep apnea (OSA) requiring adenotonsillectomy were identified at a single tertiary-care pediatric otolaryngology hospital. Parental daytime sleepiness and quality of sleep were evaluated pre- and postoperatively using the Epworth Sleepiness Scale (ESS) and Pittsburg Sleep Quality Index (PSQI), respectively...
January 8, 2019: Laryngoscope
Caigang Zhu, Martin Li, Thomas Vincent, Hannah L Martin, Brian T Crouch, Amy F Martinez, Megan C Madonna, Gregory M Palmer, Mark W Dewhirst, Nimmi Ramanujam
Therapeutically exploiting vascular and metabolic endpoints becomes critical to translational cancer studies because altered vascularity and deregulated metabolism are two important cancer hallmarks. The metabolic and vascular phenotypes of three sibling breast tumor lines with different metastatic potential are investigated in vivo with a newly developed quantitative spectroscopy system. All tumor lines have different metabolic and vascular characteristics compared to normal tissues, and there are strong positive correlations between metabolic (glucose uptake and mitochondrial membrane potential) and vascular (oxygen saturations and hemoglobin concentrations) parameters for metastatic (4T1) tumors but not for micro-metastatic (4T07) and non-metastatic (67NR) tumors...
December 18, 2018: Journal of Biophotonics
Gonzalo Almanza, Jeffrey J Rodvold, Brian Tsui, Kristen Jepsen, Hannah Carter, Maurizio Zanetti
The successful implementation of miRNA (miR) therapies in humans will ultimately rely on the use of vehicles with improved cellular delivery capability. Here we tested a new system that leverages extracellular vesicles (EVs) laden with a tumor suppressor miRNA (miR-335) produced in B cells by plasmid DNA induction (iEVs). We demonstrate that iEVs-335 efficiently and durably restored the endogenous miR-335 pool in human triple negative breast cancer cells, downregulated the expression of the miR-335 target gene SOX4 transcription factor, and markedly inhibited tumor growth in vivo...
December 4, 2018: Scientific Reports
Brian G Vassallo, Hannah P Litwa, Mark F Haussmann, Ryan T Paitz
Vertebrates release glucocorticoids during stressful events. If stress occurs during reproduction, the resulting offspring can show altered phenotypes that are thought to arise from increased exposure to maternal glucocorticoids. Developing offspring can metabolize maternal glucocorticoids, which can alter the pattern of exposure they encounter. For egg laying vertebrates, we are just beginning to understand how embryonic steroid metabolism impacts embryonic exposure to maternal glucocorticoids. Here we injected three doses of radioactive corticosterone into Japanese quail (Coturnix japonica) eggs to determine the degree of embryonic exposure at days six and nine of development...
November 27, 2018: General and Comparative Endocrinology
So-Yoon Won, Kristin Hunt, Hannah Guak, Benedeta Hasaj, Nathalie Charland, Nathalie Landry, Brian J Ward, Connie M Krawczyk
Cell-mediated immunity is an important component of immediate and long-term anti-viral protection. Dendritic cells (DCs) are essential for the induction of cell-mediated immunity by instructing the activation and differentiation of antigen-specific T cell responses. Activated DCs that express co-stimulatory molecules and pro-inflammatory cytokines are necessary to promote the development of type 1 immune responses required for viral control. Here we report that plant-derived virus-like particles (VLPs) bearing influenza hemagglutinins (HA) directly stimulate mouse and human DCs...
November 14, 2018: Vaccine
Matthew A Jolley, Andras Lasso, Hannah H Nam, Patrick V Dinh, Adam B Scanlan, Alex V Nguyen, Anna Ilina, Brian Morray, Andrew C Glatz, Francis X McGowan, Kevin Whitehead, Yoav Dori, Joseph H Gorman, Robert C Gorman, Gabor Fichtinger, Matthew J Gillespie
BACKGROUND: Pulmonary insufficiency is a consequence of transannular patch repair in Tetralogy of Fallot (ToF) leading to late morbidity and mortality. Transcatheter native outflow tract pulmonary valve replacement has become a reality. However, predicting a secure, atraumatic implantation of a catheter-based device remains a significant challenge due to the complex and dynamic nature of the right ventricular outflow tract (RVOT). We sought to quantify the differences in compression and volume for actual implants, and those predicted by pre-implant modeling...
November 15, 2018: Catheterization and Cardiovascular Interventions
Hadj S Aoued, Soma Sannigrahi, Nandini Doshi, Filomene G Morrison, Hannah Linsenbaum, Sarah C Hunter, Hasse Walum, Justin Baman, Bing Yao, Peng Jin, Kerry J Ressler, Brian G Dias
BACKGROUND: Stressors affect populations exposed to them as well as offspring. Strategies preventing the intergenerational propagation of effects of stress would benefit public health. Olfactory cue-based fear conditioning provides a framework to address this issue. METHODS: We 1) exposed adult male mice to an odor, acetophenone (Ace) or Lyral (parental generation [F0]-Exposed), 2) trained mice to associate these odors with mild foot shocks (F0-Trained), and 3) trained mice to associate these odors with mild foot shocks and then extinguished their fear toward these odors with odor-only presentations (F0-Extinguished)...
August 27, 2018: Biological Psychiatry
Michelle Dow, Rachel M Pyke, Brian Y Tsui, Ludmil B Alexandrov, Hayato Nakagawa, Koji Taniguchi, Ekihiro Seki, Olivier Harismendy, Shabnam Shalapour, Michael Karin, Hannah Carter, Joan Font-Burgada
Cancer genomics has enabled the exhaustive molecular characterization of tumors and exposed hepatocellular carcinoma (HCC) as among the most complex cancers. This complexity is paralleled by dozens of mouse models that generate histologically similar tumors but have not been systematically validated at the molecular level. Accurate models of the molecular pathogenesis of HCC are essential for biomedical progress; therefore we compared genomic and transcriptomic profiles of four separate mouse models [MUP transgenic, TAK1-knockout, carcinogen-driven diethylnitrosamine (DEN), and Stelic Animal Model (STAM)] with those of 987 HCC patients with distinct etiologies...
October 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
Clare Brennan, Hannah Whillis, Choy Man, Brian Wynne, Vani Vannappagari
Objective : Increased rates of suicidal ideation/behavior have been reported in individuals with human immunodeficiency virus infection/acquired immunodeficiency syndrome. The electronic Columbia-Suicidality Severity Rating Scale (eC-SSRS™) is a validated tool for assessment of suicidal risk. The objective of this study was to assess the site perspectives on implementation of the eC-SSRS used in Phase IIIb studies of dolutegravir. Methods : We developed and validated the ViiV eC-SSRS Metrics and Perspectives Site Questionnaire (VEQ)...
July 2018: Innovations in Clinical Neuroscience
Luke C Dutton, Jayesh Dudhia, Brian Catchpole, Hannah Hodgkiss-Geere, Dirk Werling, David J Connolly
Cardiosphere-derived cells (CDCs) are a cardiac progenitor cell population, which have been shown to possess cardiac regenerative properties and can improve heart function in a variety of cardiac diseases. Studies in large animal models have predominantly focussed on using autologous cells for safety, however allogeneic cell banks would allow for a practical, cost-effective and efficient use in a clinical setting. The aim of this work was to determine the immunomodulatory status of these cells using CDCs and lymphocytes from 5 dogs...
September 6, 2018: Scientific Reports
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