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Sequencing of high-efficacy disease-modifying therapies in multiple sclerosis： perspectives and approaches

Neural Regeneration Research 2018年第11期13卷 1871-1874页

作者： Francois Grand'Maison Michael Yeung Sarah A. Morrow Liesly Lee Francois Emond brian j. ward Pierre Laneuville Robyn Schecter Neuro Rive-Sud Hospital Charles LeMoyne Greenfield Park Quebec Canada Clinical Neurosciences Foothills Medical Centre Calgary Alberta Canada London Health Sciences Center (LHSC) Western University London Ontario Canada Department of Neurology Sunnybrook Health Sciences Centre Toronto Ontario Canada Centre Hospitalier Universitaire de Quebec - hospital de l'Enfant-j.sus Quebec City Quebec Canada Research Institute of the McGill University Health Centre Montreal Quebec Canada Department of Medicine McGill University Montreal Quebec Canada Novartis Pharmaceuticals Canada Inc. Dotal Quebec Canada

Multiple sclerosis（MS） is characterized by chronic inflammation in conj.nction with neurodegeneration within the central nervous system. Most individuals with MS begin with a relapsing remitting course that later transitions to secondary progressive MS. Currently available disease-modifying therapies（DMTs） for relapsing MS have been demonstrated to reduce disease activity, however most patients require a change in therapy over the course of their disease. Treatment goals include the prevention of relapses and disability accumulation and to achieve this obj.ctive requires careful planning. Sequencing of DMTs for individual patients should be designed in such a way to maximize disease control and minimize risk based on the mechanism of action, pharmacokinetic and pharmacodynamic properties of each therapy. This includes the DMT patients are being switched from to those they are being switched to. The reversibility of immune system effects should be a key consideration for DMT sequence selection. This feature varies across DMTs and should factor more prominently in decision making as newer treatments become available for the prevention of disability accumulation in patients with progressive MS. In this short review, we discuss the landscape of existing therapies with an eye to the future when planning for optimal DMT sequencing. While no cure exists for MS, efforts are being directed toward research in neuroregeneration with the hope for positive outcomes.

关键词： relapsing multiple sclerosis high efficacy disease-modifying therapies treatment optimization treatment sequencing therapeutic inertia sub-optimal treatment progressive disease immune effects

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Fetal Head Compression: Its Possible Role in Neurologic Inj.ry

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Open j.urnal of Obstetrics and Gynecology 2024年第1期14卷 124-143页

作者： Barry S. Schifrin brian j. Koos Wayne R. Cohen Department of Obstetrics and Gynecology The Western University of Health Sciences Pomona USA The David Geffen School of Medicine at UCLA Los Angeles USA The University of Arizona College of Medicine Tucson USA

It is widely assumed that fetal ischemic brain inj.ry during labor derives almost exclusively from severe, systemic hypoxemia with marked neonatal depression and acidemia. Severe asphyxia, however, is one of several causes of perinatal neurological inj.ry and may not be the most common;most neonates diagnosed with hypoxic-ischemic encephalopathy do not have evidence of severe asphyxia. Sepsis, direct brain trauma, and drug or toxin exposure account for some cases, while mechanical forces of labor and delivery that increase fetal intracranial pressure sufficiently to impair brain perfusion may also contribute. Because of bony compliance and mobile suture lines, the fetal skull changes shape and redistributes cerebrospinal fluid during labor according to constraints imposed by contractions, and bony and soft tissue elements of the birth canal as the head descends. These accommodations, including the increase in intracranial pressure, are adaptive and necessary for efficient descent of the head while safeguarding cerebral blood flow. Autonomic reflexes mediated through central receptors normally provide ample protection of the brain from the considerable pressure exerted on the skull. On occasion, those forces, which are transmitted intracranially, may overcome the various adaptive anatomical, cardiovascular, metabolic, and neurological mechanisms that maintain cerebral perfusion and oxygen availability, resulting in ischemic brain inj.ry. Accepting the notion of a potentially adverse impact of fetal head compression suggests that avoidance of excessive uterine activity and of relentless pushing without steady progress in descent may offer protection for the fetal brain during parturition. Excessive head compression should be considered in the differential diagnosis of ischemic encephalopathy.

关键词： Fetal Brain Inj.ry Fetal Head Compression Ischemic Encephalopathy Neonatal Encephalopathy

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液体硅橡胶垫片材料

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橡胶参考资料 1993年第3期23卷 42-46页

作者： brian j. ward Edward M. j.ram 黄祖长

1 前言从70年代初以来,液体硅橡胶已用于注模工艺,最早的应用主要有宇航连接件、O形圈、机械密封件及电子元件的密封套。在70年代和80年代期间,由于液体硅橡胶注模产品具有加工成本低、产品质量高等优点导致许多工业部门对液体硅橡胶的... 详细信息

1 前言从70年代初以来,液体硅橡胶已用于注模工艺,最早的应用主要有宇航连接件、O形圈、机械密封件及电子元件的密封套。在70年代和80年代期间,由于液体硅橡胶注模产品具有加工成本低、产品质量高等优点导致许多工业部门对液体硅橡胶的需求量剧增。本文将介绍两种新型的液体硅橡胶垫片材料,这些材料以低的成本获得模压速度快、耐燃油性得到改善、压缩永久变形低和耐油等优点。 Silicone表示一种通式为(RnSiO_4-n/2)_m的合成聚合物,其中n=1～3,m≥2。

关键词：硅橡胶垫片液体

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Metabolic reprogramming by Syntenin-1 directs RA FLS and endothelial cell-mediated inflammation and angiogenesis

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Cellular & Molecular Immunology 2024年第1期21卷 33-46页

作者： Anj. Meyer Stephanie R.Zack Wes Nij.m Adel Burgos Vishwa Patel brian Zanotti Michael V.Volin M.Asif Amin Myles j.Lewis Costantino Pitzalis Shiva Arami j.seph A.Karam Nadera j.Sweiss Shiva Shahrara j.sse Brown VA Medical Center ChicagoILUSA Department of Medicine Division of RheumatologyThe University of Illinois at ChicagoChicagoILUSA Department of Microbiology and Immunology Midwestern UniversityDowners GroveILUSA Division of Rheumatology and Clinical Autoimmunity Center of Excellence University of MichiganAnn ArborMIUSA Centre for Experimental Medicine and Rheumatology William Harvey Research InstituteBarts and The London School of Medicine and DentistryQueen Mary University of LondonLondonUnited Kingdom Centre for Experimental Medicine&Rheumatology William Harvey Research InstituteQueen Mary University of London and Barts NIHR BRC&NHS TrustLondonUK Department of Biomedical Sciences Humanitas Universityand Humanitas Research HospitalMilanItaly Department of Orthopedic Surgery the University of Illinois at ChicagoChicagoILUSA

A novel rheumatoid arthritis(RA)synovial fluid protein,Syntenin-1,and its receptor,Syndecan-1(SDC-1),are colocalized on RA synovial tissue endothelial cells and fibroblast-like synoviocytes(FLS).Syntenin-1 exacerbates the inflammatory landscape of endothelial cells and RA FLS by upregulating transcription of IRF1/5/7/9,IL-1β,IL-6,and CCL2 through SDC-1 ligation and HIF1α,or mTOR ***,Syntenin-1 orchestrates RA FLS and endothelial cell invasion via SDC-1 and/or mTOR *** Syntenin-1 reprogrammed endothelial cells,the dynamic expression of metabolic intermediates coincides with escalated glycolysis along with unchanged oxidative factors,AMPK,PGC-1α,citrate,and inactive oxidative ***,RA FLS rewired by Syntenin-1 displayed a modest glycolytic-ATP accompanied by a robust mitochondrial-ATP *** enriched mitochondrial-ATP detected in Syntenin-1 reprogrammed RA FLS was coupled with mitochondrial fusion and fission recapitulated by escalated Mitofusin-2 and DRP1 *** found that VEGFR1/2 and Notch1 networks are responsible for the crosstalk between Syntenin-1 rewired endothelial cells and RA FLS,which are also represented in RA *** to RA explants,morphological and transcriptome studies authenticated the importance of VEGFR1/2,Notch1,RAPTOR,and HIF1αpathways in Syntenin-1 arthritic mice and their obstruction in SDC-1 deficient ***,dysregulation of SDC-1,mTOR,and HIF1αnegated Syntenin-1 inflammatory phenotype in RA explants,while inhibition of HIF1αimpaired synovial angiogenic imprint amplified by *** conclusion,since the current therapies are ineffective on Syntenin-1 and SDC-1 expression in RA synovial tissue and blood,targeting this pathway and its interconnected metabolic intermediates may provide a novel therapeutic strategy.

关键词： Syntenin-1 Syndecan-1 RA FLS RA explants immunometabolism

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Towards an actionable One Health approach

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贫困所致传染病(英文) 2024年第2期13卷 1-6页

作者： Zhang Xiao-Xi Lederman Zohar Han Le-Fei Schurer j.nna M. Xiao Li-Hua Zhang Zhi-Bing Chen Qiu-Lan Pfeiffer Dirk ward Michael P. Sripa Banchob Gabri?l Sarah Dhama Kuldeep Acharya Krishna Prasad Robertson Lucy j. Deem Sharon L. Aenishaenslin Cécile Dantas-Torres Filipe Otranto Domenico Grace Delia Wang Yang Li Peng Fu Chao Poeta Patrícia Rahman Md. Tanvir Kassegne Kokouvi Zhu Yong-Zhang Yin Kun Liu j.ming Wang Zhao-j.n Guo Xiao-Kui Gong Wen-Feng Schwartl?nder Bernhard Ren Ming-Hui Zhou Xiao-Nong School of Global Health Chinese Center for Tropical Diseases Research Shanghai Jiao Tong University School of Medicine Shanghai People’s Republic of China Institute of One Health Shanghai Jiao Tong University Shanghai People’s Republic of China Medical Ethics and Humanities Unit Hong Kong University Hong Kong People’s Republic of China Center for One Health University of Global Health Equity Butaro Rwanda College of Veterinary Medicine South China Agricultural University Guangzhou People’s Republic of China School of Ecology and Environment Hainan University Haikou Hainan People’s Republic of China Branch of animal and vector-borne diseases Division of Infectious Disease Control Chinese Center for Disease Control and Prevention Beijing People’s Republic of China Centre for Applied One Health Research and Policy Advice Department of Infectious Diseases and Public Health Jockey Club College of Veterinary Medicine and Life Sciences City University of Hong Kong Hong Kong SAR People’s Republic of China Department of Pathobiology and Population Sciences Royal Veterinary College London United Kingdom Sydney School of Veterinary Science The University of Sydney Camden Australia Tropical Disease Research Center Department of Tropical Medicine Faculty of Medicine Khon Kaen University Khon Kaen Thailand Laboratory of foodborne parasitic zoonoses Department of translational physiology infectiology and public health Chair Faculty Committee on Internationalisation Faculty of Veterinary Medicine Ghent University Merelbeke Belgium Division of Pathology ICAR-Indian Veterinary Research Institute (IVRI) Bareilly Uttar Pradesh India Department of Livestock Services Animal Quarantine Office-Kathmandu Budhanilkantha Kathmandu Nepal Parasitology Department of Paraclinical Sciences Faculty of Veterinary Medicine Norwegian University of Life Sciences ?s Norway One Government Drive Saint Louis Zoo Institute for Conservation Medicine St. Louis USA Groupe de Recherche en épidémi

Background Despite the increasing focus on strengthening One Health capacity building on global level, challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region. Recognizing these gaps, the One Health Action Commission (OHAC) was established as an academic community for One Health action with an emphasis on research agenda setting to identify actions for highest *** text This viewpoint describes the agenda of, and motivation for, the recently formed OHAC. Recognizing the urgent need for evidence to support the formulation of necessary action plans, OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses, antimicrobial resistance, addressing food safety, and to enhance capacity building for context-sensitive One Health *** By promoting broader engagement and connection of multidisciplinary stakeholders, OHAC envisions a collaborative global platform for the generation of innovative One Health knowledge, distilled practical experience and actionable policy advice, guided by strong ethical principles of One Health.

关键词： One Health Global Health One Health Action Commission Research agenda

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Aerosol j.t printing of surface acoustic wave microfluidic devices

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Microsystems & Nanoengineering 2024年第1期10卷 231-242页

作者： j.seph Rich brian Cole Teng Li Brandon Lu Hanyu Fu Brittany N.Smith j.anping Xia Shuj.e Yang Ruoyu Zhong j.mes L.Doherty Kanj. Kaneko Hiroaki Suzuki Zhenhua Tian Aaron D.Franklin Tony j.n Huang Department of Biomedical Engineering Duke UniversityDurhamNC 27708USA Department of Electrical and Computer Engineering Duke UniversityDurhamNC 27708USA Department of Mechanical Engineering Virginia Polytechnic Institute and State UniversityBlacksburgVA 24061USA Thomas Lord Department of Mechanical Engineering and Materials Science Duke UniversityDurhamNC 27708USA Deptartment of Precision Mechanics Faculty of Science and EngineeringChuo UniversityTokyo 112-8551Japan Department of Chemistry Duke UniversityDurhamNC 27708USA

The addition of surface acoustic wave(SAW)technologies to microfluidics has greatly advanced lab-on-a-chip applications due to their unique and powerful attributes,including high-precision manipulation,versatility,integrability,biocompatibility,contactless nature,and rapid ***,the development of SAW microfluidic devices is limited by complex and time-consuming micro/nanofabrication techniques and access to cleanroom facilities for multistep photolithography and vacuum-based *** simplify the fabrication of SAW microfluidic devices with customizable dimensions and functions,we utilized the additive manufacturing technique of aerosol j.t *** successfully fabricated customized SAW microfluidic devices of varying materials,including silver nanowires,graphene,and poly(3,4-ethylenedioxythiophene)polystyrene sulfonate(PEDOT:PSS).To characterize and compare the acoustic actuation performance of these aerosol j.t printed SAW microfluidic devices with their cleanroom-fabricated counterparts,the wave displacements and resonant frequencies of the different fabricated devices were directly measured through scanning laser Doppler ***,to exhibit the capability of the aerosol j.t printed devices for lab-on-a-chip applications,we successfully conducted acoustic streaming and particle concentration ***,we demonstrated a novel solution-based,direct-write,single-step,cleanroom-free additive manufacturing technique to rapidly develop SAW microfluidic devices that shows viability for applications in the fields of biology,chemistry,engineering,and medicine.

关键词： printing wave fluid

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Angling of hybrid sunfish from a hatchery pond with potential implications for community fisheries

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Aquaculture and Fisheries 2023年第1期8卷 91-95页

作者： brian G.Blackwell Matthew j.ward Todd M.Kaufman South Dakota Department of Game Fish and Parks603 East 8th AvenueWebsterSD57274USA South Dakota Department of Game Fish and Parks44437139A StreetWaubaySD57273USA

Hatcheries are frequently called upon to produce catchable-sized fish for stocking community fishing *** attributes of fish selected for stocking into community ponds are that they are easy to produce in a hatchery system to sizes anglers are interested in catching and they provide anglers with high catch rates once *** sunfish[male Bluegill(Lepomis macrochirus)×female Green Sunfish(***)]have attributes that potentially make them attractive for use in community fishing *** assessed initial angler catch rates of 100 stocked hybrid sunfish in a 0.12-ha hatchery pond and after being subj.cted to angling(four,1-hr catch-and-release fishing events with five anglers).We also investigated whether catch rates would change following a supplemental stocking of an additional 100 hybrid sunfish(four,1-hr catch-and-release fishing events with five anglers).The anal fin of each fish in the second stocking was hole punched to differentiate them from those of the first stocking and fish caught by anglers were hole punched in the caudal fin each time they were caught before being released back into the *** catch rates were highest during initial fishing events that followed stocking(9.2 fish/angler hr and 18.0 fish/angler hr)and substantially declined in subsequent events(≤3.4 fish/angler hr).Catches of the newly stocked fish and previously stocked fish contributed to the high catch following the supplemental ***(80%)of the fish were caught in the first 30 min of each event and 45%were caught during the first 10 *** were able to catch 88%of the fish from the first stocking and 67%from the second stocking at least *** mortality occurred during the study as all fish were recovered when the pond was *** results suggest that hybrid sunfish will potentially provide high initial catch rates following stocking into community ponds,but managers should expect reduced catch rates following initial fishing even without h

关键词： Hybrid sunfish Angling Community fishing ponds

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Walleye Egg Survival Was Unaffected by Four Semen Inclusion Techniques during Artificial Fertilization

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Open j.urnal of Animal Sciences 2023年第2期13卷 199-204页

作者： Matthew j. ward brian G. Blackwell South Dakota Department of Game Fish and Parks Blue Dog State Fish Hatchery Waubay USA South Dakota Department of Game Fish and Parks District Office Webster USA

Improving the percent hatch during artificial spawning of walleye (Sander vitreus) could save agencies substantial resources. Semen inclusion techniques used to artificially fertilize walleye eggs may have a subsequent influence on the percent hatch. We compared walleye egg survival to the early embryo stage across four semen inclusion techniques used during fertilization to determine if one or more of the techniques would result in a higher percent hatch. Six mL of freshly collected (within 2 h) semen was presented to common pools of walleye eggs separated into 250 mL lots by either 1) pouring semen on top of the eggs before sperm activation, 2) placing 3 mL of semen below and above the eggs before sperm activation, 3) pouring 3 mL of semen on top of the eggs, activating sperm, and adding the remaining 3 mL of semen after 30 s, or 4) activating the sperm by adding semen to 1 L of water, mixing and pouring the solution on the eggs within 3 s. All treatments received 1 L of filtered lake water for sperm activation and fertilization. Mean egg survival was similar ranging from 49.5% to 56.7% among the four techniques and was not significantly different across methods. These results suggest that any of the semen inclusion techniques will likely provide a similar percent hatch for walleye eggs when 250 mL of eggs, 6 mL of semen, and 1 L of water are used during fertilization.

关键词： Walleye Egg Collection Walleye Propagation Walleye Spawning Operations

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

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

作者： Viktor H Ahlqvist Christina Dardani Paul Madley-Dowd Harriet Forbes j.ssica Rast Caichen Zhong Renee M Gardner Christina Dalman Kristen Lyal cRAIG Newschaffer Torbj.rn 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 j.bsen 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

Background 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 linkage 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(adj.sted 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,p<0.001)—a correlation that was more pronounced in focal epilepsy(r=0.23,95%CI 0.09 to 0.36,p<0.001).Findings from 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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Crystalline compounds for remediation of rare-earth fission products:A review

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j.urnal of Rare Earths 2022年第3期40卷 365-380,I0001页

作者： Saehwa Chong brian j.Riley Zayne j.Nelson Pacific Northwest National Laboratory RichlandWA99352USA

Rare earth(RE)-containing crystals have been investigated as media for the immobilization of RE fission products from nuclear waste *** reprocessing of spent nuclear fuel,fission products including REs,alkalis,and alkaline earths released from the *** viable option to immobilize the RE fission products is to incorporate them into chemically durable crystalline phases in specific waste *** study summarizes the crystal structures and synthesis methods of six RE-containing compounds that have applications in remediation of RE fission *** compounds include oxyapatite(AE_(2)RE_(8)(SiO_(4))_(6)O_(2)),oxychloride(REOCl),borosilicate(RE_(3)BSi_(2)O_(10)),pyrochlore(RE_(2)M_(2)O_(7)),monazite(REPO_(4)),and perovskite(REMO_(3))where AE denotes alkaline earth metals and M denotes transition *** review provides an overview of literature on the usage of these six compounds for immobilizing RE fission products and summarizes different synthesis methods for producing these *** of structural parameters with different REs in each compound are also discussed.

关键词： Rare-earth compounds Nuclear waste forms Crystal structures Synthesis of rare-earth compounds

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