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James K Kirklin, Rongbing Xie, Jennifer Cowger, Theo M M H de By, Takeshi Nakatani, Stephan Schueler, Rhiannon Taylor, Jenny Lannon, Paul Mohacsi, Jan Gummert, Daniel Goldstein, Kadir Caliskan, Margaret M Hannan
The second annual IMACS registry report includes over 14, 000 patients from 35 countries. Survival, adverse events, and an updated risk model is presented. Continuous flow pumps continue to dominate the world's experience. One and Two-year survival remains at 80% and 70%. Congenital heart disease and biventricular support are the most dominant risk factors. The database is poised for major novel analyses.
January 31, 2018: Journal of Heart and Lung Transplantation
Wen Jin, Yinglu Deng, Hai Jiang, Qianyan Xie, Wei Shen, Weijian Han
Car insurance is quickly becoming a big data industry, with usage-based insurance (UBI) poised to potentially change the business of insurance. Telematics data, which are transmitted from wireless devices in car, are widely used in UBI to obtain individual-level travel and driving characteristics. While most existing studies have introduced telematics data into car insurance pricing, the telematics-related characteristics are directly obtained from the raw data. In this study, we propose to quantify drivers' familiarity with their driving routes and develop models to quantify drivers' accident risks using the telematics data...
March 14, 2018: Accident; Analysis and Prevention
Amelia Weber Hall, Anna M Battenhouse, Haridha Shivram, Adam R Morris, Matthew C Cowperthwaite, Max Shpak, Vishwanath R Iyer
Glioblastoma multiforme (GBM) can be clustered by gene expression into four main subtypes associated with prognosis and survival, but enhancers and other gene regulatory elements have not yet been identified in primary tumors. Here, we profiled six histone modifications and CTCF binding as well as gene expression in primary gliomas, and identified chromatin states that define distinct regulatory elements across the tumor genome. Enhancers in mesenchymal and classical tumor subtypes drove gene expression associated with cell migration and invasion, while enhancers in proneural tumors controlled genes associated with a less aggressive phenotype in GBM...
March 16, 2018: Cancer Research
M Martínez-García, J Vargas-Barrón, F Bañuelos-Téllez, H González-Pacheco, C Fresno, E Hernández-Lemus, M A Martínez-Ríos, M Vallejo
OBJECTIVE: ST-segment elevation myocardial infarction (STEMI) has an important economic burden that poised the urgent need to evaluate its catastrophic medical expense. This study evaluates the first 5 years of the national health initiative called Popular Insurance (PI) at the National Institute of Cardiology in Mexico. STUDY DESIGN: Retrospective data analysis. METHODS: STEMI patients with (n=317) and without (n=260) PI were selected. Analysed variables included socio-economical context, management care, cost evaluation and three outcomes (mortality, hospital readmission and therapeutic adherence)...
March 13, 2018: Public Health
Verity A Jackson, Dimphna H Meijer, Maria Carrasquero, Laura S van Bezouwen, Edward D Lowe, Colin Kleanthous, Bert J C Janssen, Elena Seiradake
Teneurins are ancient cell-cell adhesion receptors that are vital for brain development and synapse organisation. They originated in early metazoan evolution through a horizontal gene transfer event when a bacterial YD-repeat toxin fused to a eukaryotic receptor. We present X-ray crystallography and cryo-EM structures of two Teneurins, revealing a ~200 kDa extracellular super-fold in which eight sub-domains form an intricate structure centred on a spiralling YD-repeat shell. An alternatively spliced loop, which is implicated in homophilic Teneurin interaction and specificity, is exposed and thus poised for interaction...
March 14, 2018: Nature Communications
Takudzwa J Mtisi, Charles Maponga, Tsitsi G Monera-Penduka, Tinashe Mudzviti, Dexter Chagwena, Faithful Makita-Chingombe, Robin DiFranchesco, Gene D Morse
Background: A growing number of drug development studies that include pharmacokinetic evaluations are conducted in regions lacking a specialised pharmacology laboratory. This necessitated the development of an International Pharmacology Specialty Laboratory (IPSL) in Zimbabwe. Objectives: The aim of this article is to describe the development of an IPSL in Zimbabwe. Methods: The IPSL was developed collaboratively by the University of Zimbabwe and the University at Buffalo Center for Integrated Global Biomedical Sciences...
2018: African Journal of Laboratory Medicine
Stephen M King, Winfield S Sale
Motility of cilia (also known as flagella in some eukaryotes) is based on axonemal doublet microtubule sliding that is driven by the dynein molecular motors. Dyneins are organized into intricately patterned inner and outer rows of arms, whose collective activity is to produce inter-microtubule movement. However, to generate a ciliary bend, not all dyneins can be active simultaneously. The switch point model accounts, in part, for how dynein motors are regulated during ciliary movement. On the basis of this model, supported by key direct experimental observations as well as more recent theoretical and structural studies, we are now poised to understand the mechanics of how ciliary dynein coordination controls axonemal bend formation and propagation...
March 15, 2018: Molecular Biology of the Cell
Michelle G Craske
The theme of the Association for Behavioral and Cognitive Therapies (ABCT) 50th Anniversary was to honor the past and envision the future. From the wisdom, foresight, and determination of the pioneers of our organization, and the continuous upholding of the scientific method over the last 50 years, cognitive behavioral therapy (CBT) has become the most empirically supported psychological treatment for a wide array of mental health problems. Yet, we still have a long way to go. This address outlines a vision for the future of CBT, which involves greater collaborative science, with all minds working together on the same problem, and greater attention to the risk factors and critical processes that underlie psychopathology and explain treatment change...
March 2018: Behavior Therapy
Joseph Acquaye, Michael S Borofsky
PURPOSE OF REVIEW: As benign prostatic hypertrophy (BPH) becomes a more common disease, there has been a dramatic rise in the number of investigational procedures being developed to manage it. We seek to present an overview of the most recently developed treatments and present clinical data related to application wherever available. RECENT FINDINGS: As a greater number of treatments become available for BPH, improved diagnostic testing could prove beneficial in helping guide patient selection...
March 9, 2018: Current Opinion in Urology
Younguk Sun, Bo-Rui Chen, Aniruddha Deshpande
The importance of epigenetic dysregulation to acute myeloid leukemia (AML) pathophysiology has become increasingly apparent in recent years. Epigenetic regulators, including readers, writers, and erasers, are recurrently dysregulated by way of chromosomal translocations, somatic mutations, or genomic amplification in AML and many of these alterations are directly implicated in AML pathogenesis. Mutations in epigenetic regulators are often discovered in founder clones and persist after therapy, indicating that they may contribute to a premalignant state poised for the acquisition of cooperating mutations and frank malignancy...
2018: Frontiers in Oncology
David Castel, Meryem B Baghdadi, Sébastien Mella, Barbara Gayraud-Morel, Virginie Marty, Jérôme Cavaillé, Christophe Antoniewski, Shahragim Tajbakhsh
Skeletal muscle satellite cells are quiescent adult resident stem cells that activate, proliferate and differentiate to generate myofibres following injury. They harbour a robust proliferation potential and self-renewing capacity enabling lifelong muscle regeneration. Although several classes of microRNAs were shown to regulate adult myogenesis, systematic examination of stage-specific microRNAs during lineage progression from the quiescent state is lacking. Here we provide a genome-wide assessment of the expression of small RNAs during the quiescence/activation transition and differentiation by RNA-sequencing...
March 9, 2018: Scientific Reports
Alex Root, Peter Allen, Paul Tempst, Kenneth Yu
Approximately 75% of patients with pancreatic ductal adenocarcinoma are diagnosed with advanced cancer, which cannot be safely resected. The most commonly used biomarker CA19-9 has inadequate sensitivity and specificity for early detection, which we define as Stage I/II cancers. Therefore, progress in next-generation biomarkers is greatly needed. Recent reports have validated a number of biomarkers, including combination assays of proteins and DNA mutations; however, the history of translating promising biomarkers to clinical utility suggests that several major hurdles require careful consideration by the medical community...
March 7, 2018: Cancers
Jessica Snowden, Paul Darden, Paul Palumbo, Phil Saul, Jeannette Lee
PURPOSE OF REVIEW: The institutional development award (IDeA) program was created to increase the competitiveness of investigators in states with historically low success rates for National Institutes of Health (NIH) research funding applications. IDeA states have high numbers of rural and medically underserved residents with disproportionately high rates of infant mortality, obesity, and poverty. This program supports the development and expansion of research infrastructure and research activities in these states...
April 2018: Current Opinion in Pediatrics
Angelo A Manfredi, Giuseppe A Ramirez, Patrizia Rovere-Querini, Norma Maugeri
Neutrophils recognize particulate substrates of microbial or endogenous origin and react by sequestering the cargo via phagocytosis or by releasing neutrophil extracellular traps (NETs) outside the cell, thus modifying and alerting the environment and bystander leukocytes. The signals that determine the choice between phagocytosis and the generation of NETs are still poorly characterized. Neutrophils that had phagocytosed bulky particulate substrates, such as apoptotic cells and activated platelets, appear to be "poised" in an unresponsive state...
2018: Frontiers in Immunology
Julia Krasensky-Wrzaczek, Jaakko Kangasjärvi
The remarkable plasticity of the biochemical machinery in plants allows the integration of a multitude of stimuli, enabling acclimation to a wide range of growth conditions. The integration of information on light and temperature enables plants to sense seasons and time growth, defense, and transition to flowering according to the prevailing conditions. By now, the role of reactive oxygen species (ROS) as important signaling molecules has been established. Here we review recent data on ROS as important components in the integration of light and temperature signaling by crosstalk with the circadian clock and calcium signaling...
March 5, 2018: Journal of Experimental Botany
Melanie Trobe, Martin D Burke
Today we are poised for a transition from the highly customized crafting of specific molecular targets by hand to the increasingly general and automated assembly of different types of molecules with the push of a button. Creating machines that are capable of making many different types of small molecules on demand, akin to that which has been achieved on the macroscale with 3D printers, is challenging. Yet important progress is being made toward this objective with two complementary approaches: 1) Automation of customized synthesis routes to different targets by machines that enable the use of many reactions and starting materials, and 2) automation of generalized platforms that make many different targets using common coupling chemistry and building blocks...
March 7, 2018: Angewandte Chemie
Aviv Paz, Derek P Claxton, Jay Prakash Kumar, Kelli Kazmier, Paola Bisignano, Shruti Sharma, Shannon A Nolte, Terrin M Liwag, Vinod Nayak, Ernest M Wright, Michael Grabe, Hassane S Mchaourab, Jeff Abramson
Sodium-dependent transporters couple the flow of Na+ ions down their electrochemical potential gradient to the uphill transport of various ligands. Many of these transporters share a common core structure composed of a five-helix inverted repeat and deliver their cargo utilizing an alternating-access mechanism. A detailed characterization of inward-facing conformations of the Na+ -dependent sugar transporter from Vibrio parahaemolyticus (vSGLT) has previously been reported, but structural details on additional conformations and on how Na+ and ligand influence the equilibrium between other states remains unknown...
March 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Heath E Johnson, Jared E Toettcher
In developmental biology, localization is everything. The same stimulus-cell signaling event or expression of a gene-can have dramatically different effects depending on the time, spatial position, and cell types in which it is applied. Yet the field has long lacked the ability to deliver localized perturbations with high specificity in vivo. The advent of optogenetic tools, capable of delivering highly localized stimuli, is thus poised to profoundly expand our understanding of development. We describe the current state-of-the-art in cellular optogenetic tools, review the first wave of major studies showcasing their application in vivo, and discuss major obstacles that must be overcome if the promise of developmental optogenetics is to be fully realized...
March 2, 2018: Current Opinion in Biotechnology
Alexandra Whicher, Eloi Camprubi, Silvana Pinna, Barry Herschy, Nick Lane
Metabolism is primed through the formation of thioesters via acetyl CoA and the phosphorylation of substrates by ATP. Prebiotic equivalents such as methyl thioacetate and acetyl phosphate have been proposed to catalyse analogous reactions at the origin of life, but their propensity to hydrolyse challenges this view. Here we show that acetyl phosphate (AcP) can be synthesised in water within minutes from thioacetate (but not methyl thioacetate) under ambient conditions. AcP is stable over hours, depending on temperature, pH and cation content, giving it an ideal poise between stability and reactivity...
March 3, 2018: Origins of Life and Evolution of the Biosphere
Ross D Markello, R Nathan Spreng, Wen-Ming Luh, Adam K Anderson, Eve De Rosa
The basal forebrain (BF) is poised to play an important neuromodulatory role in brain regions important to cognition due to its broad projections and complex neurochemistry. While significant in vivo work has been done to elaborate BF function in nonhuman rodents and primates, comparatively limited work has examined the in vivo function of the human BF. In the current study we used multi-echo resting state functional magnetic resonance imaging (rs-fMRI) from 100 young adults (18-34 years) to assess the potential segregation of human BF nuclei as well as their associated projections...
February 26, 2018: NeuroImage
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