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National preparedness survey of pediatric intensive care units with simulation centers during the coronavirus pandemic

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World Journal of Critical Care Medicine 2020年第5期9卷 74-87页

作者： Kamal Abulebda Rami A Ahmed Marc A Auerbach Anna M Bona Lauren E Falvo patrick g hughes Isabel T gross Elisa J Sarmiento Paul R Barach Department of Pediatrics Division of Critical CareIndiana University School of MedicineRiley Hospital for Children at Indiana University HealthIndianapolisIN 46202United States Department of Emergency Medicine School of MedicineIndiana UniversityIndianapolisIN 46202United States Department of Pediatrics Division of Pediatrics Emergency MedicineYale University School of MedicineNew HavenCT 06504United States Department of Integrated Medical Science Florida Atlantic UniversityBoca RatonFL 33431United States Department of Emergency Medicine Yale University School of MedicineNew HavenCT 06504United States Department of Pediatrics Wayne State University School of MedicineDetroitMI 48202Jefferson College of Population HealthPhiladelphiaPA19107United States

The coronavirus disease pandemic caught many pediatric hospitals unpreparedand has forced pediatric healthcare systems to scramble as they examine and planfor the optimal allocation of medical resources for the highest priority *** is limited data describing pediatric intensive care unit (PICU) preparednessand their health worker *** describe the current coronavirus disease 2019 (COVID-19) preparedness effortsamong a set of PICUs within a simulation-based network *** A cross-sectional multi-center national survey of PICU medical director(s) fromchildren’s hospitals across the United States. The questionnaire was developedand reviewed by physicians with expertise in pediatric critical care, disasterreadiness, human factors, and survey development. Thirty-five children’shospitals were identified for recruitment through a long-established nationalresearch network. The questions focused on six themes: (1) PICU and medicaldirector demographics;(2) Pediatric patient flow during the pandemic;(3)Changes to the staffing models related to the pandemic;(4) Use of personalprotective equipment (PPE);(5) Changes in clinical practice and innovations;and(6) Current modalities of training including *** report on survey responses from 22 of 35 PICUs (63%). The majority of PICUswere located within children’s hospitals (87%). All PICUs cared for pediatricpatients with COVID-19 at the time of the survey. The majority of PICUs (83.4%)witnessed decreases in non-COVID-19 patients, 43% had COVID-19 dedicatedunits, and 74.6% pivoted to accept adult COVID-19 patients. All PICUsimplemented changes to their staffing models with the most common changesbeing changes in COVID-19 patient room assignment in 50% of surveyed PICUsand introducing remote patient monitoring in 36% of the PICU units. Ninety-fivepercent of PICUs conducted training for donning and doffing of enhanced *** 6 months into the pandemic, one-third of PICUs across the U

关键词： COVID-19 Pediatric intensive care unit Simulation Practice innovations Training Preparedness

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Refractory very early-onset inflammatory bowel disease associated with cytosolic isoleucyl-tRNA synthetase deficiency:A case report

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World Journal of gastroenterology 2020年第15期26卷 1841-1846页

作者： Andrew Fagbemi William g Newman Stuart g Tangye Stephen M hughes Edmund Cheesman Peter D Arkwright Department of Paediatric gastroenterology Royal Manchester Children’s HospitalManchester M199WLUnited Kingdom Department of Medical genetics Manchester University NHS Foundation TrustManchester M139WLUnited Kingdom Evolution and genomic Sciences University of ManchesterManchester M139WLUnited Kingdom garvan Institute of Medical Research DarlinghurstNSW 2010Australia St Vincent’s Clinical School Faculty of MedicineUNSW AustraliaSydneyNSW 2010Australia Department of Paediatric Allergy and Immunology Royal Manchester Children’s HospitalManchester M139WLUnited Kingdom Department of Paediatric Histopathology St Mary’s HospitalManchester M139WLUnited Kingdom Lydia Becker Institute of Immunology and Inflammation University of ManchesterManchester M139WLUnited Kingdom

BACKgROUND Aminoacyl tRNA synthetases/ligases(ARSs)are highly conserved enzymes involved in attaching amino acids to tRNA promoting protein *** deficiencies of ARSs localized to the mitochondria classically present with neuropathology,the clinical features of cytosolic ARS deficiencies are more *** have previously been associated with neonatal hepatitis,but never with early-onset inflammatory bowel *** SUMMARY A nine-year-old Bangladeshi boy presented with neonatal liver failure and deranged clotting,transaminitis and *** parents were first *** older brothers and a sister were *** patient suffered from loose stools from early infancy which became more troublesome and persistent from five years old with ten bloody motions a *** endoscopies showed persistent pancolitis,which was refractory to mesalazine,corticosteroids,azathioprine,sirolimus and anti-TNF(adalimumab)therapy,but has improved recently with subcutaneous *** genome Sequencing revealed a novel pathogenic missense variant(c.290A>g)in the cytosolic isoleucyl-tRNA synthetase gene,leading to an amino acid substitution(***97gly).Pathogenic variants in other genes associated with inflammatory bowel disease(IBD)(ADAM17,EgFR,FOXP3,IL10RA,IL10RB,IL21R,NCF4,STAT3)were *** assays demonstrated markedly elevated IL-2,IL-5,IL-13,IL-9 and IL-10 by the patient’s CD4+T-cells,while IL-17A,IL-17F,IFNβwere lower,and TNFαnot significantly different when compared to healthy *** This case report provides evidence that recessive mutations in cytosolic isoleucyltRNA synthetase are a novel monogenic cause of IBD,which should be considered,particularly in infants and children with a history of neonatal hepatitis and very early-onset IBD poorly responsive to treatment.

关键词： Inflammatory bowel disease Hepatitis gene Cytosolic isoleucine tRNA synthase

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Poly(ADP-ribose),adherens junctions,vinculin and the actin cytoskeleton:Current evidence,future perspectives and implications

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BIOCELL 2022年第12期46卷 2531-2535页

作者： LAURA LAFON-hughes Instituto de Investigaciones Biológicas Clemente Estable Ministerio de Educación y CulturaMontevideo11600Uruguay Centro Universitario Regional Litoral Norte Universidad de la RepúblicaSalto50000Uruguay

Poly(ADP-ribose)(PAR)is a highly negatively charged *** is synthesized by poly(ADP-ribose)polymerases(PARPs)and is involved in the assembly and stabilization of macromolecular ***,the presence and putative roles of poly(ADP-ribosyl)ation(PARylation)associated to adherens junctions(AJ)and the actin cytoskeleton in epithelial and Schwann cells,is *** hypothesis generated by analogy,stating that PAR is associated to AJ in other cell types,is *** to this hypothesis,PAR associated to puncta adherentia in chemical synapses would participate in plasticity,learning and *** turn,PAR associated to fascia adherens in cardiomyocytes,would affect heart *** inhibitors are currently under development and clinical *** research in different tissues will probably influence their clinical uses.

关键词： PARP Tankyrase Epithelia Neuron Schwann cell Cardiomyocyte Vinculin

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Use of stimulatory responsive soft nanoparticles for intracellular drug delivery

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Nano Research 2023年第5期16卷 6974-6990页

作者： Krystal A hughes Bishal Misra Maryam Maghareh Sharan Bobbala Department of Pharmaceutical Sciences West Virginia University School of PharmacyMorgantownWV 26505USA Department of Clinical Pharmacy West Virginia University School of PharmacyMorgantownWV 26505USA

Drug delivery has made tremendous advances in the last *** therapies are increasingly common,with intracellular delivery highly impactful and sought *** drug delivery systems have limitations due to imprecise and non-targeted release *** way this can be addressed is through using stimuli-responsive soft nanoparticles,which contain materials with an organic backbone such as lipids and *** choice of biomaterial is essential for soft nanoparticles to be responsive to internal or external *** nanoparticle must retain its integrity and payload in non-targeted physiological conditions while responding to particular intracellular environments where payload release is *** internal and external factors could stimulate the intracellular release of drugs from *** stimuli include pH,oxidation,enzymes,while external stimuli include ultrasound,light,electricity,magnetic *** responsive soft nanoparticulate systems specifically utilized to modulate intracellular delivery of drugs are explored in this review.

关键词： nanoparticles biomaterials stimuli-responsive targeted delivery intracellular drug delivery

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c-Met signaling in the development of tumorigenesis and chemoresistance: Potential applications in pancreatic cancer

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World Journal of gastroenterology 2014年第26期20卷 8458-8470页

作者： Daniel Delitto Eva Vertes-george Steven J hughes Kevin E Behrns Jose g Trevino Department of Surgery University of Florida-Gainesville Department of Pathology University of Florida-Gainesville

Pancreatic ductal adenocarcinoma is the 4th leading cause of cancer deaths in the United States. The majority of patients are candidates only for palliative chemotherapy, which has proven largely ineffective in halting tumor progression. One proposed mechanism of chemoresistance involves signaling via the mesenchymal-epithelial transition factor protein (MET), a previously established pathway critical to cell proliferation and migration. Here, we review the literature to characterize the role of MET in the development of tumorigenesis, metastasis and chemoresistance, highlighting the potential of MET as a therapeutic target in pancreatic cancer. In this review, we characterize the role of c-Met in the development of tumorigenesis, metastasis and chemoresistance, highlighting the potential of c-Met as a therapeutic target in pancreatic cancer.

关键词： Pancreatic adenocarcinoma c-Met Chemoresistance Receptor tyrosine kinase

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How functional programming mattered

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National Science Review 2015年第3期2卷 349-370页

作者： Zhenjiang Hu John hughes Meng Wang National Institute of Informatics Department of Computer Science and Engineering Chalmers University of Technology School of Computing University of Kent Department of Informatics SOKENDAI(Graduate University for Advanced Studies)

In 1989 when functional programming was still considered a niche topic, hughes wrote a visionary paper arguing convincingly ‘why functional programming maters’. More than two decades have passed. Has functional programming really matered? Our answer is a resounding ‘Yes!’. Functional programming is now at the forefront of a new generation of programming technologies, and enjoying increasing popularity and inluence. In this paper, we review the impact of functional programming, focusing on how it has changed the way we may construct programs, the way we may verify programs, and fundamentally the way we may think about programs.

关键词： functional programming functional languages equational reasoning monad high order function

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genomic resources for the brown planthopper, Nilaparvata lugens： Transcriptome pyrosequencing and microarray design

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Insect Science 2012年第1期19卷 1-12页

作者： Chris Bass Martin Bay Hebsgaard Joseph hughes Centre for Sustainable Pest and Disease Management Rothamsted Research Harpenden University of Edinburgh Institute of Evolutionary Biology Kings Buildings Edinburgh Institute of Biodiversity Animal Health and Comparative Medicine College of Medical Veterinary and Life Sciences University of Glasgow Glasgow United Kingdom

The brown planthopper, Nilaparvata lugens is a pest of cultivated rice through- out Asia and is controlled using insecticides and/or resistant rice varieties. This species has developed resistance to many classes of insecticide and biotypes have developed that are vir- ulent against formerly resistant rice cultivars. Insects use a suite of detoxification enzymes, including cytochrome P450s, glutathione S-transferases and carboxyl/cholinesterases to defend themselves against plant secondary metabolites and pesticides. Pyrosequencing on the Roche 454-FLX platform was used to produce a substantial expressed sequence tag （EST） dataset to complement the existing Sanger sequenced ESTs in genBank. A total of 78 959 reads were combined with the 37 392 publically available Sanger ESTs; these assembled into 8 911 contigs and 10 620 singletons. Analysis of the distribution of tenta- tive unique genes （TUgs） with the gene ontology for biological processes and molecular functions suggests that the 454 and Sanger EST assembly is broadly representative of the N. lugens transcriptome. The brown planthopper transcriptome was found to contain 31 TUgs encoding P450s, nine encoding glutathione S-transferases and 26 encoding car- boxyl/cholinesterases and many of these are putatively involved in the detoxification of xenobiotics. The Agilent eArray platform was used to construct an oligonucleotide mi- croarray populated with probes for ~ 19 000 unigene sequences, including all those known to encode detoxification enzymes. The genomic resources developed in this study will be useful to the community studying this crop pest and will help elucidate the molecular mechanism underlying insecticide resistance and planthopper adaptation to resistant rice cultivars.

关键词： brown planthopper detoxification enzymes insecticide resistance Nilaparvata lugens transcriptome sequencing

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Epitaxially aligned single-crystal gold nanoplates formed in large-area arrays at high yield

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Nano Research 2022年第1期15卷 296-303页

作者： Trevor B.Demille Robert D.Neal Arin S.Preston Zijuan Liang Allen g.Oliver Robert A.hughes Svetlana Neretina College of Engineering University of Notre DameNotre DameIndiana 46556USA Department of Chemistry and Biochemistry University of Notre DameNotre DameIndiana 46556USA

Well-tailored nanomaterials with a single-crystal character provide ideal building blocks for on-chip plasmonic *** colloidal methods have demonstrated mastery over the synthesis of such structures,it has proven quite difficult to deploy these same nanomaterials on substrate surfaces in a highly deterministic manner where precise control over position and orientation is ***,we demonstrate a room-temperature two-reagent liquid-phase seed-mediated synthesis of gold nanoplates directly on substrate surfaces in arrays over a square-centimeter *** synthesis is reliant on benchtop lithographic and directed-assembly processes that give rise to single-crystal seeds of gold that express both an epitaxial relationship with the underlying substrate and the internal defect structure required to promote a two-dimensional growth *** resulting structures are highly faceted and,because seed-substrate epitaxy is imposed upon the growing nanoplates,are identically aligned on the substrate *** yields are increased to values as high as 95%using a post-processing sonication procedure that selectively removes a small population of irregularly shaped nanostructures from the substrate surface,and in doing so,gives rise to an uncompromised plasmonic *** work,therefore,advances the techniques needed to integrate single-crystal nanomaterials with wafer-based technologies and provides leading-edge capabilities in terms of defining large-area arrays of plasmonic structures with the nanoplate geometry.

关键词： nanoplates epitaxial array plasmon Brij-700 block copolymer substrate

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A Study of Fluid Flow in Sediments and the Effect of Tidal Pumping

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Journal of Earth Science 2017年第5期28卷 842-847页

作者： Paulo Waltrich John Whitehead Richard hughes Karsten Thompson Department of Petroleum Engineering Louisiana State University

Offshore drilling and production operations can result in spills or leaks of hydrocarbons into seabed sediments, which can potentially contaminate these sediments with oil. If this oil later mi- grates to the water surface it has the potential for negative environmental impacts. For proper contin- gency planning and to avoid larger consequences in the environment, it is essential to understand me- chanisms and rates for hydrocarbon migration from oil containing sediments to the water surface as well as how much will remain trapped in the sediments. It is believed that the amount of oil transported out of the sediment can be affected by tidal pumping, a common form of subterranean groundwater dis- charge （SgD）. However, we could find no study experimentally investigating the phenomenon of fluid flow in subsea sediments containing oil and the effects of tidal pumping. This study presents an experi- mental investigation of tidal pumping to determine if it is a possible mechanism that may contribute to the appearance of an oil sheen on the ocean surface above a sediment bed containing oil. An experimen- tal apparatus was constructed of clear PVC pipe allowing for oil migration to be monitored as it flowed out of a sand pack containing oil, while tidal pressure oscillations were applied in three different man- ners. The effect of tidal pumping was simulated via compression of air above the water （which simulated the increasing static head from tidal exchange）. Experimental results show that sustained oil release oc- curred from all tests, and tests with oscillating pressure produced for longer periods of time. Further- more, the experimental results showed that the oil migration rate was affected by grain size, oil satura- tion, and oscillation wave type. In all oscillating experiments the rate and ultimate recovery was less than the comparable static experiments. For the conditions studied, the experimental results indicate that with an oscillating pressure on top of a

关键词： tidal pumping oil migration sediments oil release rate.

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Cheap and secure metatransactions on the blockchain using hash-based authorisation and preferred batchers

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Blockchain(Research and Applications) 2023年第2期4卷 41-66页

作者： William hughes Tobias Magnusson Alejandro Russo gerardo Schneider Dept.of Computer Science and Engineering University of Gothenburg41296GothenburgSweden Dept.of Computer Science and Engineering Chalmers University41296GothenburgSweden

Smart contracts are self-executing programs running in the blockchain allowing for decentralised storage and execution without a ***-chain execution is expensive,with miners charging fees for distributed execution according to a cost model defined in the *** particular,transactions have a high fixed *** present MultiCall,a transaction-batching interpreter for Ethereum that reduces the cost of smart contract executions by gathering multiple users’transactions into a *** current implementation of MultiCall includes the following features:the ability to emulate Ethereum calls and create transactions,both from MultiCall itself and using an identity unique to the user;the ability to cheaply pay Ether to other MultiCall users;and the ability to authorise emulated transactions on behalf of multiple users in a single transaction using hash-based authorisation rather than more expensive *** improves upon a previous version of *** experiments show that MultiCall provides a saving between 57%and 99%of the fixed transaction cost compared with the standard approach of sending Ethereum transactions directly.

关键词： Ethereum Domain-specific language Interpreter gas optimisation

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