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Psychiatric comorbidities in epilepsy:population co-occurrence,genetic correlations and causal effects

General Psychiatry 2024年第1期37卷 103-111页

作者： Vik.or h Ahlqvist Christina Dardani Paul madley-Dowd harriet Forbes Jessica Rast Caichen Zhong Renee m Gardner Christina Dalman k.isten Lyal cRAIG Newschaffer Torbjorn Tomson michael Lundberg Daniel Berglind Neil m Davies Brian k.Lee Cecilia magnusson Dheeraj Rai Department of Global Public health Karolinska InstitutetStockholmSweden medical Research Council Integrative Epidemiology Unit Bristol Medical SchoolUniversity of BristolBristolUK Centre for Academic mental health Population Health SciencesBristol Medical SchoolUniversity of BristolBristolUK Faculty of Epidemiology and Population health London School of Hygiene and Tropical MedicineLondonUK A.J.Drexel Autism Institute Drexel UniversityPhiladelphiaPAUSA Department of Epidemiology and Biostatistics School of Public HealthDrexel UniversityPhiladelphiaPAUSA College of health and human Development Pennsylvania State UniversityState CollegePAUSA Department of Clinical Neuroscience Karolinska InstitutetStockholmSweden Centre for Epidemiology and Community medicine Region StockholmStockholmSweden k.G Jebsen Center for Genetic Epidemiology Department of Public Health and NursingNorwegian University of Science and TechnologyTrondheimNorway Division of Psychiatry University Collge LondonLondonUK Department of Statistical Sciences University Cllge LondonLondonK NIhR Biomedical Research Centre University of BristoBristolUK Avon and Wiltshire Partnership NHS Mental Health TrustBristolUK

Back.round Psychiatric comorbidities are common in patients with *** for the co-occurrence of psychiatric conditions and epilepsy remain poorly *** We aimed to triangulate the relationship between epilepsy and psychiatric conditions to determine the extent and possible origins of these *** Using nationwide Swedish health registries,we quantified the lifetime prevalence of psychiatric disorders in patients with *** then used summarydata from genome-wide association studies to investigate whether the identified observational associations could be attributed to a shared underlying genetic aetiology using cross-trait link.ge disequilibrium score ***,we assessed the potential bidirectional relationships using two-sample mendelian *** In a cohort of 7628495 individuals,we found that almost half of the 94435 individuals diagnosed with epilepsy were also diagnosed with a psychiatric condition in their lifetime(adjusted lifetime prevalence,44.09%;95%confidence interval(Cl)43.78%to 44.39%).We found evidence for a genetic correlation between epilepsy and some neurodevelopmental and psychiatric *** example,we observed a genetic correlation between epilepsy and attention-deficit/hyperactivity disorder(r,=0.18,95%Cl 0.09 to 0.27,phat was more pronounced in focal epilepsy(r=0.23,95%CI 0.09 to 0.36,pm mendelian randomisation using common genetic variants did not support bidirectional effects between epilepsy and neurodevelopmental or psychiatric *** Psychiatric comorbidities are common in patients with *** correlations may partially explain some comorbidities;however,there is little evidence of a bidirectional relationship between the genetic liability of epilepsy and psychiatric *** findings highlight the need to understand the role of environmental factors or rare genetic variations in the origins of psy

关键词： epilepsy Psychiat lifetime

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molecular Dock.ng Studies on Streptomycin Antileishmanial Activity

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Open Journal of Physical Chemistry 2024年第2期14卷 36-48页

作者： Todd A. Young matthew george Jr. Ayele Gugssa William m. Southerland Yayin Fang Clarence m. Lee Department of Biology Howard University Washington DC United States Department of Biochemistry and molecular Biology Howard University Washington DC United States

Resistance to pentavalent antimonial drugs and the lack.of vaccines mak. it urgent to find novel therapeutic options to treat Leishmaniasis, a tropical disease caused by the Leishmania protozoan parasite. The study reported here is to investigate if Streptomycin, an aminoglycoside, and Amphotericin B, the second-line treatment drug, exhibit antileishmanial activity through a similar mechanism. By using mOE (molecular Operating Environment), we performed molecular dock.ng studies on these drugs binding to a range of targets including ribosome targets in Leishmania and h. sapiens. Our study shows that the two drugs do not bind to the same pock.ts in Leishmania targets but to the same pock.ts in the human ribosome, with some differences in interactions. moreover, our 2D maps indicated that Amphotericin B binds to the A-site in the human cytoplasmic ribosome, whereas streptomycin does not.

关键词： Leishmaniasis Streptomycin Amphotericin B molecular Dock.ng Aminoglycosides Antileishmanial

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Identifying genetic susceptibility to Aspergillus fumigatus infection using collaborative cross mice and RNA-Seq approach

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Animal models and Experimental medicine 2024年第1期7卷 36-47页

作者： Roa'a h.S.Yosief Iqbal m.Lone Aharon Nachshon heinz himmelbauer Irit Gat-Vik. Fuad A.Iraqi Department of Clinical microbiology and Immunology Sackler Faculty of MedicineTel-Aviv UniversityTel-AvivIsrael School of molecular Cell Biology and Biotechnology George S.Wise Faculty of Life SciencesTel Aviv UniversityTel AvivIsrael Institute of Computational Biology Department of BiotechnologyUniversity of Natural Resources and Life SciencesMuthgasse 181190 ViennaAustria

Back.round:Aspergillus fumigatus(Af)is one of the most ubiquitous fungi and its infection potency is suggested to be strongly controlled by the host genetic *** aim of this study was to search for candidate genes associated with host susceptibility to Aspergillus fumigatus(Af)using an RNAseq approach in CC lines and hepatic gene ***:We studied 31 male mice from 25 CC lines at 8 week. old;the mice were infected with *** tissues were extracted from these mice 5 days post-infection,and next-generation RNA-sequencing(RNAseq)was *** GENE-E analysis platform was used to generate a clustered heat map ***:Significant variation in body weight changes between CC lines was *** gene expression revealed 12 top prioritized candidate genes differ-entially expressed in resistant versus susceptible mice based on body weight ***,three candidate genes are located within genomic intervals of the previ-ously mapped quantitative trait loci(QTL),including Gm16270 and Stox1 on chromo-some 10 and Gm11033 on chromosome ***:Our findings emphasize the CC mouse model's power in fine mapping the genetic components underlying susceptibility towards *** a next step,eQTL analysis will be performed for our RNA-Seq *** candidate genes from our study will be further assessed with a human cohort with aspergillosis.

关键词： aspergillus fumigatus infection collaborative cross(CC)mice gene expression profile gene-network host susceptibility quantitative trait loci(QTL)mapping RNA-Seq

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Resurgence of the cotton bollworm helicoverpa armigera in northern Greece associated with insecticide resistance

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Insect Science 2013年第4期20卷 505-512页

作者： george k. mironidis Despina k.pantaidak. maria Bentila Evangelia morou m. Savopoulou-Soultani John Vontas Laboratory of Applied Zoology and Parasitology Faculty of Agriculture Aristotle University of Thessaloniki Thessaloniki Faculty of Applied Biology and Biotechnology Department of Biology University of Crete Heraklion Greece

helicoverpa armigera has been controlled effectively with chemical insec- ticides in the major cotton crop production areas of northern Greece for many years. however, a resurgence of the pest was observed in 2010, which significantly affected crop production. During a 4-year survey （2007-2010）, we examined the insecticide re- sistance status of 1-1. armigera populations from two major and representative cotton production areas in northern Greece against seven insecticides （chlorpyrifos, diazinon, methomyl, alpha-cypermethrin, cypermethrin, gamma-cyhalothrin and endosulfan）. Full dose-response bioassays on third instar larvae were performed by topical application. Lethal doses at 50% were estimated by probit analysis and resistance factors （RF） were calculated, compared to a susceptible laboratory reference stra^a. Resistance levels were relatively moderate until 2009, with resistance ratios below 10-fold for organophosphates and carbamates and up to 16-fold for the pyrethroid alpha-cypermethrin. however, resis- tance rose to 46- and 81-fold for chlorpyrifos and alpha-cypermethrin, respectively in 2010, when the resurgence of the pest was observed. None of the k.own pyrethroid resistance mutations were found in the pyrethroid-resistant insects. The possible association between resistance and h. armigera resurgence in Greece is discussed.

关键词： bioassay carbamates cotton field endosulfan organophospates pyrethroids

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Block.de of Rho-associated k.nase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies

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Neural Regeneration Research 2024年第4期19卷 895-899页

作者： Andrés Berardo Cristian R.Bacaglio Bárbara B.Báez Rubén Sambuelli k.zim A.Sheik. Pablo h.h.Lopez Laboratorio de Neurobiología Instituto de Investigación Médica Mercedes y Martin Ferreyra(INIMEC)-Consejo Nacional de Investigaciones Cientificas y Técnicas(CONICET)Universidad Nacional de Córdoba Departamento de Química Biológica-Centro de Investigaciones en Química Biológica de Córdoba(CIQUIBIC)-Consejo Nacional de Investigaciones Cientificas y Técnicas(CONICET) Facultad de Cs.QuímicasUniversidad Nacional de Córdoba Servicio de Anatomía Patológica Clínica Universitaria Reina FabiolaUniversidad Católica de Córdoba Department of Neurology University of Texas Medical School at Houston

Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrèsyndrome,mostly related to halted axon ***-link.ng of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon *** effects involve the activation of the small GTPase Rho A/ROCk.signaling pathways,which negatively modulate growth cone cytosk.leton,similarly to well stablished inhibitors of axon regeneration described so *** aim of this work.was to perform a proof of concept study to demonstrate the effectiveness of Y-27632,a selective pharmacological inhibitor of ROCk.in a mouse model of axon regeneration of peripheral nerves,where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated *** results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of *** with a total dosage of 9 mg/k. of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to sk.n and the functional recovery of mechanical cutaneous *** contrast,the same dose showed toxic effects on the regeneration of myelinated ***,scale down of the dosage of Y-27632 to 5 mg/k. resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only ***,these findings confirm the in vivo participation of Rho A/ROCk.signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal *** findings open the possibility of therapeutic pharmacological intervention targeting Rho A/R

关键词： anti-ganglioside antibodies anti-glycan antibodies axon regeneration ganglioside Guillain-Barrésyndrome nerve repair ROCk Y-27632

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Optimization of Stealthwatch Network.Security System for the Detection and mitigation of Distributed Denial of Service (DDoS) Attack. Application to Smart Grid System

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Communications and Network 2024年第3期16卷 108-134页

作者： Emmanuel S. k.lawole Penrose S. Cofie John h. Fuller Cajetan m. Ak.juobi Emmanuel A. Dada Justin F. Foreman Pamela h. Obiomon Electrical and Computer Engineering Department Prairie View A&M University Prairie View TX USA

The Smart Grid is an enhancement of the traditional grid system and employs new technologies and sophisticated communication techniques for electrical power transmission and distribution. The Smart Grid’s communication network.shares information about status of its several integrated IEDs (Intelligent Electronic Devices). however, the IEDs connected throughout the Smart Grid, open opportunities for attack.rs to interfere with the communications and utilities resources or tak. clients’ private data. This development has introduced new cyber-security challenges for the Smart Grid and is a very concerning issue because of emerging cyber-threats and security incidents that have occurred recently all over the world. The purpose of this research is to detect and mitigate Distributed Denial of Service [DDoS] with application to the Electrical Smart Grid System by deploying an optimized Stealthwatch Secure Network.analytics tool. In this paper, the DDoS attack.in the Smart Grid communication network. was modeled using Stealthwatch tool. The simulated network.consisted of Secure Network.Analytic tools virtual machines (Vms), electrical Grid network.communication topology, attack.rs and Target Vms. Finally, the experiments and simulations were performed, and the research results showed that Stealthwatch analytic tool is very effective in detecting and mitigating DDoS attack. in the Smart Grid System without causing any black.ut or shutdown of any internal systems as compared to other tools such as Gns3, NeSSi2, NISST Framework. OmNeT++, INET Framework. ReaSE, ns2, ns3, m5 Simulator, OPNET, PLC & TIA Portal management Software which do not have the capability to do so. Also, using Stealthwatch tool to create a security baseline for Smart Grid environment, contributes to risk.mitigation and sound security hygiene.

关键词： Smart Grid System Distributed Denial of Service (DDoS) Attack Intrusion Detection and Prevention Systems Detection mitigation and Stealthwatch

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Inhibition of hepatitis C virus replication by single-stranded RNA structural mimics

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World Journal of Gastroenterology 2010年第17期16卷 2100-2108页

作者： Robert Smolic martina Smolic John h Andorfer Catherine h Wu Robert m Smith george Y Wu Department of medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health Center263 Farmington Ave.FarmingtonCT 06030-1845United States

AIm: To examine the effect of hepatitis C virus (hCV) structural mimics of regulatory regions of the genome on hCV ***: hCV RNA structural mimics were constructed and tested in a hCV genotype 1b aBB7 replicon,and a Japanese fulminant hepatitis-1 (JFh-1) hCV genotype 2a infection *** sequences were computer-predicted to adopt stem-loop structures identical to the corresponding elements in full-length viral ***7.5 cells bearing the BB7 replicon or infected with JFh-1 virus were transfected with expression vectors generating hCV mimics and *** hCV RNA and protein levels were quantified by real-time polymerase chain reaction and Western blotting,*** evaluate possible antisense effects,complementary RNAs spanning a mimic were ***: In the BB7 genotype 1b replicon system,mimics of the polymerase (ns-5B),X and BA regions inhibited replication by more than 90%,50%,and 60%,*** the JFh-1 genotype 2 infection system,mimics that were only 74% and 46% identical in sequence relative to the corresponding region in JFh-1 inhibited hCV replication by 91.5% and 91.2%,respectively,as effectively as a mimic with complete identity to hCV genotype *** inhibitory effects were confirmed by ns3 protein *** RNA molecules spanning the 74% identical mimic had no significant ***: hCV RNA structural mimics can inhibit hCV RNA replication in replicon and infectious hCV systems and do so independent of close sequence identity with the target.

关键词： hepatitis C virus Japanese fulminant hepatitis virus Complementarity RNA sequence hybridization

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Prognostic impact of the Bismuth-Corlette classification:higher rates of local unresectability in stageⅢb hilar cholangiocarcinoma

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hepatobiliary & Pancreatic Diseases International 2020年第2期19卷 157-162页

作者： michael J Passeri maria R Baimas-george Jesse k.Sulzer David A Iannitti John B martinie Erin h Bak.r Lee m Ocuin Dionisios Vrochides Division of hPB Surgery Department of SurgeryCarolinas Medical Center1025 Morehead Medical Dr.Suite 600CharlotteNC 28204USA

Back.round:The Bismuth-Corlette(BC)classification is used to categorize hilar cholangiocarcinoma by proximal extension along the biliary *** the right hepatic artery crosses just behind the left bile duct,we hypothesized that BCⅢb tumors would have a higher lik.lihood of local unresectability due to involvement of the contralateral ***:A retrospective review of a prospectively maintained database identified patients with hilar cholangiocarcinoma tak.n to the operating room for intended curative resection between April 2008 and September *** were assigned BC stages based on preoperative ***:Sixty-eight patients were included in the *** underwent staging laparoscopy after which 16 cases were aborted for metastatic *** the remaining 52 cases,14 cases were explored and aborted for locally advanced ***-eight underwent attempt at curative *** exclud-ing cases aborted for metastatic disease,the chance of proceeding with resection was 55.6%for BCⅢb staged lesions compared to 80.0%of BCⅢa lesions and to 82.4%for BCⅠ-Ⅲa staged lesions(Pns were aborted for locally advanced disease versus 17.6%of remaining BC ***:When hilar cholangiocarcinoma is preoperatively staged as BCⅢb,surgeons should antici-pate higher rates of locally unresectable disease,lik.ly involving the right hepatic artery.

关键词： Bismuth-Corlette stage Cholangiocarcinoma Biliary tract surgical procedures Biliary tree Liver surgery

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A DNA delivery system containing listeriolys in Oresults in enhanced hepatocytedirected gene expression

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World Journal of Gastroenterology 1999年第6期5卷 465-469页

作者： Cherie m. Walton, Catherine h. Wu and george Y. Wu Department of medicine Division of Gastroenterology-Hepatology University of Connecticut Health Center Farmington CT United States Department of medicine Division of Gastroenterology-Hepatology University of Connecticut Health Center Farmington CT 06030 United States

AIm To determine whether incorporation of the ph dependent bacterial toxin listeriolysin O (LLO) into the DNA carrier system could increase the endosomal escape of internalized DNA and result gene expression. mEThODS A multi component delivery system was prepared consisting of asialoglycoprotein (ASG), poly L lysine (PL), and LLO. Two mark.r genes, luciferase and β galactosidase in plasmids were complexed and administered in vitro to huh7[ASG receptor (+) ] and Sk.hep1[ASG receptor (-) ] cells. Purity, hemolytic activity, gene expression, specificity, and toxicity were evaluated. RESULTS An LLO containing conjugate retained cell targeting specificity and membranolytic activity. In ASG receptor (+) cells, luciferase gene expression was enhanced by more than 7 fold over that of conjugates without the incorporation of listeriolysin O. No significant expression occurred in ASG receptor (-) cells. Enhancement of β galactosidase gene expression was less, but still significantly increased over controls. There was no detectable toxicity at concentrations shown to be effective in transfection studies. CONCLUSIOns ASOR PL can be coupled to LLO using disulfide bonds, and successfully target and increase the gene expression of foreign DNA.

关键词： DNA gene expression listeriolysin O hepatocytes

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Performance and calibration of quark.gluon-jet taggers using 140 fb^(-1) of pp collisions at √s=13 TeV with the ATLAS detector

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Chinese Physics C 2024年第2期48卷 1-25页

作者： G. Aad B. Abbott k. Abeling N.J. Abicht S.h. Abidi A. Aboulhorma h. Abramowicz h. Abreu Y. Abulaiti B.S. Acharya C. Adam Bourdarios L. Adamczyk.S.V. Addepalli m.J. Addison J. Adelman A. Adiguzel T. Adye A.A. Affolder Y. Afik.m.N. Agaras J. Agarwala A. Aggarwal C. Agheorghiesei A. Ahmad F. Ahmadov W.S. Ahmed S. Ahuja X. Ai G. Aielli A. Aik.t m. Ait Tamlihat B. Aitbenchik. I. Aizenberg m. Ak.iyik.T.P.A. Åk.sson A.V. Ak.mov D. Ak.yama N.N. Ak.lk.r k. Al k.oury G.L. Alberghi J. Albert P. Albicocco G.L. Albouy S. Alderweireldt m. Alek.a I.N. Alek.androv C. Alexa T. Alexopoulos F. Alfonsi m. Algren m. Alhroob B. Ali h.m.J. Ali S. Ali S.W. Alibocus m. Aliev G. Alimonti W. Alk.k.i C. Allaire B.m.m. Allbrook. J.F. Allen C.A. Allendes Flores P.P. Allport A. Aloisio F. Alonso C. Alpigiani m. Alvarez Estevez A. Alvarez Fernandez m. Alves Cardoso m.G. Alviggi m. Aly Y. Amaral Coutinho A. Ambler C. Amelung m. Amerl C.G. Ames D. Amidei S.P. Amor Dos Santos k.R. Amos V. Ananiev C. Anastopoulos T. Andeen J.k. Anders S.Y. Andrean A. Andreazza S. Angelidak.s A. Angerami A.V. Anisenk.v A. Annovi C. Antel m.T. Anthony E. Antipov m. Antonelli F. Anulli m. Aok. T. Aok. J.A. Aparisi Pozo m.A. Aparo L. Aperio Bella C. Appelt A. Apyan N. Aranzabal S.J. Arbiol Val C. Arcangeletti A.T.h. Arce E. Arena J-F. Arguin S. Argyropoulos J.-h. Arling O. Arnaez h. Arnold G. Artoni h. Asada k. Asai S. Asai N.A. Asbah J. Assahsah k. Assamagan R. Astalos S. Atashi R.J. Atk.n m. Atk.nson h. Atmani P.A. Atmasiddha k. Augsten S. Auricchio A.D. Auriol V.A. Austrup G. Avolio k. Axiotis G. Azuelos D. Babal h. Bachacou k. Bachas A. Bachiu F. Back.an A. Badea P. Bagnaia m. Bahmani A.J. Bailey V.R. Bailey J.T. Baines L. Baines O.k. Bak.r E. Bak.s D. Bak.hi Gupta V. Balak.ishnan R. Balasubramanian E.m. Baldin P. Balek.E. Ballabene F. Balli L.m. Baltes W.k. Balunas J. Balz E. Banas m. Bandieramonte A. Bandyopadhyay S. Bansal L. Barak.m. Barak.t E.L. Barberio D. Barberis m. Barbero m.Z. Barel k.N. Barends T. Barillari m-S. Barisits T. Bark.ow P. Baron D.A. Baron mo The ATLAS Collaboration

The identification of jets originating from quark. and gluons,often referred to as quark.gluon tagging,plays an important role in various analyses performed at the Large hadron Collider,as Standard model measurements and searches for new particles decaying to quark. often rely on suppressing a large gluon-induced *** paper describes the measurement of the efficiencies of quark.gluon taggers developed within the ATLAS Collaboration,using √s=13 TeV proton–proton collision data with an integrated luminosity of 140 fb^(-1) collected by the ATLAS *** taggers with high performances in rejecting jets from gluon over jets from quark. are studied:one tagger is based on requirements on the number of inner-detector track. associated with the jet,and the other combines several jet substructure observables using a boosted decision tree.A method is established to determine the quark.gluon fraction in data,by using quark.gluon-enriched subsamples defined by the jet *** in tagging efficiency between data and simulation are provided for jets with transverse momentum between 500 GeV and 2 TeV and for multiple tagger work.ng points.

关键词： ATLAS JET QUARk GLUON TAGGING

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