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Tenecteplase Reperfusion therapy in Acute ischaemic Cerebrovascular Events-Ⅱ (TRACE Ⅱ): rationale and design

Stroke & Vascular Neurology 2022年第1期7卷 71-76页

作者： Shuya Li bruce C V Campbell Lee H Schwamm Marc fisher Mark Parsons Hao Li Yuesong Pan Yongjun Wang China National Clinical Research Center for Neurological diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina department of Medicine and Neurology University of MelbourneMelbourneVictoriaAustralia department of Neurology and Comprehensive Stroke Center Massachusetts General HospitalHarvard Medical SchoolBostonMassachusettsUSA Neurology Beth Israel Deaconess Medical CenterBostonMassachusettsUSA department of Neurology Liverpool HospitalSouth Western Sydney Clinical SchoolSydneyNew South WalesAustralia

Background and purpose Tenecteplase(TNK)is a promising agent for treatment of acute ischaemic stroke(AIS).We hypothesised that recombinant human TNK tissue-type plasminogen activator(rhTNK-tPA)is non-inferior to rt-PA in achieving excellent functional outcome at 90 days,when administered within 4.5 hours of ischaemic stroke *** and design Tenecteplase Reperfusion therapy in Acute ischemic Cerebrovascular Events(TRACE)is a phase Ⅲ,multicentre,prospective,randomised,open-label,blinded-end point non-inferiority *** eligible for intravenous thrombolysis therapy are randomised to rhTNK-tPA 0.25 mg/kg(single bolus)to a maximum of 25 mg or rt-PA 0.9 mg/kg(10%bolus+90%infusion/1 hour)to a maximum of 90 *** considered necessary for the patient’s health may be given at the discretion of the investigator during 90-day *** outcomes The primary study outcome is excellent functional outcome defined as modified Rankin Scale(mRS)0–1 at 90 *** efficacy outcomes include favourable functional outcome defined as mRS≤2 at 90 days,ordinal distribution of mRS and major neurological improvement on the National Institutes of Health Stroke *** outcomes are symptomatic intracranial haemorrhage within 36 hours and death from any *** There is no completed registration study of TNK in AIS *** Ⅱ strives to provide evidence for a new drug application for rhTNK-tPA in AIS within 4.5 hours through a well-designed and rigorously executed randomised trial in China.

关键词： infusion acute rational

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Moving towards the chemo-free treatment of lymphoma:hype or reality?

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Journal of Cancer Metastasis and Treatment 2022年第1期8卷 631-636页

作者： bruce d.Cheson Scientific Advisor Lymphoma Research FoundationNew YorkNY 10005USA

A new generation of novel,effective targeted drugs and cellular therapies include monoclonal antibodies directed at the cell surface,such as the anti-Cd-19 tafasitamab which,combined with lenalidomide,is the first therapy approved by the Food and drug Administration for second-line treatment of diffuse large B-cell *** agents interfere with pro-survival intracellular signaling pathways including drugs that inhibit Bruton tyrosine kinase,phosphatidylinositol-3 kinase(PI3-kinase),and *** increasing number of therapies impact the microenvironment,notably checkpoint inhibitors and bispecific *** antigen receptor-T cell therapy has improved the outcome of patients with a variety of histologies of *** in the past,such therapies would be used inrelapsed and refractory settings,they are now being evaluated as initial treatment in selected *** an improved ability to individualize treatment approaches,chemo-free will be a reality for lymphoma patients.

关键词： Lymphoma targeted therapies chemo-free bispecifics BTK inhibitors PI3k inhibitors CAR-T cell

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Changing trends in colorectal cancer: possible cause and clinical implications

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Health 2010年第8期2卷 842-849页

作者： Mikhail fisher Leon fisher bruce Waxman Alexander A. fisher Academic Surgical Unit Monash University Dandenong Hospital Southern Health department of Gastroenterology Peninsula Health

OBJECTIVES: The aims of this study were to determine whether pattern of patients presenting with colorectal cancer (CRC) in the last few years differs significantly from that previously reported in Australia, and to relate the trends, if present, to use of hormone replacement therapy (HRT). METHOdS: We examined demographic and pathological characteristics of 145 consecutive CRC patients (65 females) treated in our institution in calendar years 2006-2007. Comparisons were made with data on 12536 CRC patients obtained from the Australian Association on Cancer Registries (AACR) for the year 2003, most recent available. Prescribing data for HRT were obtained from the Australian Commonwealth department of Health and Ageing. RESULTS: The distribution of colon, sigmoid and rectal cancers in our series was 40%, 24.8% and 35.2%, respectively, which differs significantly from 65%, 8.1% and 26.9% in the AACR data (p d d d 41.5% vs. 21.4%, respectively). Younger patients have more aggressive and advanced cancers. In Australia HRT use declined since 2001 and fell by a half in 2006. CONCLUSIONS: In the changing CRC pattern of greatest concern is a significantly higher proportion of younger patients, especially females, with higher prevalence of more advanced and aggressive cancers, coincident with decreased prescribing of HRT. These findings may have important implications for refining screening and preventive strategies and on demand for radiotherapy services.

关键词： Colorectal Cancer Age Gender Hormone Replacement Therapy Trends

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The new kid on the block in insect pest management:sprayable RNAi goes commercial

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Science China(Life Sciences) 2024年第8期67卷 1766-1768页

作者： Junjie Yan Ralf Nauen Stuart Reitz Andrei Alyokhin Jiang Zhang david Mota-Sanchez Yonggyun Kim Subba Reddy Palli Silvia I.Rondon Brian A.Nault Juan Luis Jurat-Fuentes Michael S.Crossley William E.Snyder Angharad M.R.Gatehouse Myron P.Zalucki bruce E.Tabashnik Yulin Gao State Key Laboratory for Biology of Plant disease and Insect Pests Institute of Plant ProtectionChinese Academy of Agricultural SciencesBeijing 100193China Bayer AG Crop Science DivisionR&DPest ControlMonheim 40789Germany department of Crop and Soil Science Oregon State UniversityOntario 97914USA School of Biology and Ecology University of MaineOrono 04469USA Shenzhen Branch Guangdong Laboratory of Lingnan Modern AgricultureKey Laboratory of Synthetic BiologyMinistry of Agriculture and Rural AffairsAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen 518000China department of Entomology Michigan State UniversityEast Lansing 48864USA department of Plant Medicals Andong National UniversityAndong 36729Republic of Korea department of Entomology University of KentuckyLexington 40503USA Oregon State University Oregon Integrated Pest Management CenterCorvallis 97838USA department of Entomology Cornell UniversityCornell AgriTechGeneva 14456USA department of Entomology and Plant Pathology University of TennesseeKnoxville 37996USA department of Entomology and Wildlife Ecology University of DelawareNewark 19716USA department of Entomology University of GeorgiaAthensGeorgia 30602USA School of Natural and Environmental Sciences Newcastle UniversityNewcastle upon TyneNE17RUUK School of the Environment University of QueenslandBrisbane 4072Australia Shandong Engineering Research Center for Environment-Friendly Agricultural Pest Management College of Plant Health and MedicineQingdao Agricultural UniversityQingdao 266109China department of Entomology University of ArizonaTucson 85721USA National Center of Excellence for Tuber and Root Crop Research Chinese Academy of Agricultural SciencesBeijing 100081China

Insect pest damage to crops is a threat to global food security(Tilman et al.,2011).Climate change,the evolution of insecticide resistance,and the phasing out of insecticides due to environmental and safety concerns exacerbate this *** urgently need safe and effective crop protection tools to sustainably generate yields that meet ever-increasing global demand.

关键词： crops damage pest

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Manipulation of the intestinal microbiome-a slow journey to primetime

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World Journal of Clinical Cases 2023年第21期11卷 4975-4988页

作者： Ofra Kriger-Sharabi Stephen d H Malnick david.fisher Institute of Gastroenterology Assuta Medical CenterAshdod 7747629Israel department of Internal Medicine Kaplan Medical CenterRehovot 76100Israel department of Endocrinology Soroka Medical CenterBeer Sheva POB 151Israel

The gut microbiota has important functions in the regulation of normal body *** of the microbiota are being increasingly linked to various disease *** microbiome has been manipulated via the administration of stool from animals or humans,for more than 1000 ***,fecal microbiota transplantation can be performed via endoscopic administration of fecal matter to the duodenum or colon or via capsules of lyophilized *** recently fecal microbial transplantation has been shown to be very effective for recurrent Clostridoides difficile infection(CdI).In addition there is some evidence of efficacy in the metabolic syndrome and its hepatic manifestation,metabolic associated fatty liver disease(MAFLd),irritable bowel syndrome(IBS)and inflammatory bowel disease(IBd).We review the current literature regarding the microbiome and the pathogenesis and treatment of CdI,MAFLd,IBS and IBd.

关键词： Gut microbiota Fecal microbiota transplantation Clostridoides difficile Metabolic associated fatty liver disease Irritable bowel syndrome Inflammatory bowel disease

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Effectiveness of hand self-shiatsu to improve sleep following sport-related concussion in young athletes: a proof-of-concept study

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Journal of Integrative Medicine 2019年第1期17卷 24-29页

作者： Pei Qin bruce d.dick Ada Leung Cary A.Brown Faculty of Rehabilitation Medicine University of Alberta department of Anesthesiology and Pain Medicine Faculty of Medicine and Dentistry University of Alberta department of Occupational Therapy Faculty of Rehabilitation Medicine University of Alberta

Objective: The prevalence of sport-related concussion(SRC) is high and results in a number of serious health consequences. One area that has received minimal research is the relationship between SRC and sleep. The literature shows that sleep deficiency is a frequent negative consequence of SRC. At the same time, sleep deficiency delays recovery from SRC and contributes added risk of symptom recurrence.A 2014 study of chronic pain patients who learned to apply the complementary and alternative medicine intervention hand self-shiatsu(HSS) had promising, sleep-promoting results that warrant further investigation with other populations. This proof-of-concept study explored the feasibility of HSS as an intervention to promote sleep onset and continuity for young adults with ***: This study employed a prospective case-series design, where participants act as their own controls. Baseline and follow-up data included standardized self-reported assessment tools and sleep ***: Seven athletes, aged between 18 and 25 years, participated in the study. Although statistically significant improvement in actigraphy sleep scores between baseline and follow-up was not achieved,metrics for sleep quality and daytime fatigue showed significant ***: These findings support the hypothesis that HSS has the potential to improve sleep and reduce daytime fatigue in young postconcussion athletes. This pilot study provides guidance to refine research protocols and lays a foundation for further, large-sample, controlled studies.

关键词： Concussion Insomnia Youth Complementary and alternative medicine Self-management

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Injury and illness in short-course triathletes:A systematic review

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Journal of Sport and Health Science 2024年第2期13卷 172-185页

作者： Sara A.Guevara Melissa L.Crunkhorn Michael drew Gordon Waddington Julien d.Périard Naroa Etxebarria Liam A.Toohey Paula Charlton University of Canberra Research Institute for Sport and Exercise(UCRISE) BruceACT 2617Australia New South Wales Institute of Sport SydneyNSW 2127Australia Queensland Academy of Sport BrisbaneQLD 4111Australia Triathlon Australia Gold CoastQLD 4227Australia Australian Institute of Sport BruceACT 2617Australia

Background:determining the incidence and prevalence of injury and illness in short-course triathletes would improve understanding of their etiologies and therefore assist in the development and implementation of prevention *** study synthesizes the existing evidence on the incidence and prevalence of injury and illness and summarizes reported injury or illness etiology and risk factors affecting short-course ***:This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses *** reporting health problems(injury and illness)in triathletes(all sexes,ages,and experience levels)training and/or competing in short-course distances were *** electronic databases(Cochrane Central Register of Controlled Trials,MEdLINE,Embase,APA PsychINFO,Web of Science Core Collection,and SPORTdiscus)were *** of bias was independently assessed by 2 reviewers using the Newcastle-Ottawa Quality Assessment *** authors independently completed data ***:The search yielded 7998 studies,with 42 studies eligible for ***-three studies investigated injuries,24 studies investigated illnesses,and 5 studies investigated both injuries and *** injury incidence rate ranged 15.7-24.3 per 1000 athlete exposures,and the illness incidence rate ranged 1.8-13.1 per 1000 athlete *** and illness prevalence ranged between 2%-15%and 6%-84%,*** injuries reported occurred during running(45%-92%),and the most frequently reported illnesses affected the gastrointestinal(7%-70%),cardiovascular(14%-59%),and respiratory systems(5%-60%).Conclusion:The most frequently reported health problems in short-course triathletes were:overuse and lower limb injuries associated with running;gastrointestinal illnesses and altered cardiac function,primarily attributable to environmental factors;and respiratory illness mostly caused by infection.

关键词： Athlete illnesses Athletic injuries Epidemiology Triathlon

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Crystal structure of HLA-B^(*)5801 with a TW10 HIV Gag epitope reveals a novel mode of peptide presentation

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Cellular & Molecular Immunology 2017年第7期14卷 631-634页

作者： Xiaolong Li Pedro A Lamothe bruce d Walker Jia-huai Wang department of Medical Oncology and Cancer Biology Dana-Farber Cancer InstituteHarvard Medical SchoolBostonMA 02215USA Ragon Institute of Massachusetts General Hospital Massachusetts Institute of TechnologyHarvard UniversityBostonMA 02139USA Howard Hughes Medical Institute Chevy ChaseMD 20815USA Institute for Medical and Engineering Sciences Massachusetts Institute of TechnologyCambridgeMA 02139USA department of Pediatrics and department of Biological Chemistry and Molecular Pharmacology Harvard Medical SchoolBostonMA 02215USA

The major histocompatibility complex(MHC)is encoded by a set of genes that play a key role in the vertebrate adaptive immune *** humans,these genes encode proteins termed human leukocyte antigens(HLAs).

关键词： leukocyte antigens Crystal

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An AMR Capable Finite Element diffusion Solver for ALE Hydrocodes

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Plasma Science and Technology 2015年第2期17卷 109-116页

作者： A.C.fisher d.S.BAILEY T.B.KAISER d.C.EdER B.T.N.GUNNEY N.d.MASTERS A.E.KONIGES R.W.ANdERSON Lawrence Livermore National Laboratory Lawrence Berkeley National Laboratory

We present a novel method for the solution of the diffusion equation on a composite AMR mesh. This approach is suitable for including diffusion based physics modules to hydrocodes that support ALE and AMR capabilities. To illustrate, we proffer our implementations of diffu- sion based radiation transport and heat conduction in a hydrocode called ALE-AMR. Numerical experiments conducted with the diffusion solver and associated physics packages yield 2nd order convergence in the L2 norm.

关键词： hydrodynamic simulation heat conduction thermal radiation adaptive meshrefinement finite element method

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A dominant Allele of Arabidopsis Pectin-Binding Wall-Associated Kinase Induces a Stress Response Suppressed by MPK6 but Not MPK3 Mutations

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Molecular Plant 2012年第4期5卷 841-851页

作者： bruce d. Kohorn Susan L. Kohorn Tanya Todorova Gillian Baptiste Kevin Stansky Meghan McCullough department of Biology Bowdoin College ME 04011 USA

The plant cell wall is composed of a matrix of cellulose fibers, flexible pectin polymers, and an array of as- sorted carbohydrates and proteins. The receptor-like Wall-Associated Kinases （WAKs） of Arabidopsis bind pectin in the wall, and are necessary both for cell expansion during development and for a response to pathogens and wounding. Mitogen Activated Protein Kinases （MPKs） form a major signaling link between cell surface receptors and both transcrip- tional and enzyme regulation in eukaryotes, and Arabidopsis MPK6 and MPK3 indeed have important roles in develop- ment and the response to stress and pathogens. A dominant allele of WAK2 requires kinase activity and activates a stress response that includes an increased ROS accumulation and the up-regulation of numerous genes involved in pathogen resistance, wounding, and cell wall biogenesis. This dominant allele requires a functional pectin binding and kinase domain, indicating that it is engaged in a WAK signaling pathway. A null mutant of the major plasma membrane ROS-producing enzyme complex, rbohd/f does not suppress the WAK2cTAP-induced phenotype. A mpk6, but not a mpk3, null allele is able to suppress the effects of this dominant WAK2 mutation, thus distinguishing MPK3 and MPK6, whose activity previously was thought to be redundant. Pectin activation of gene expression is abated in a wak2-null, but is tempered by the WAK-dominant allele that induces elevated basal stress-related transcript levels. The results suggest a mechanism in which changes to the cell wall can lead to a large change in cellular responses and help to explain how pathogens and wounding can have general effects on growth.

关键词： Wall Associated Kinases MPK3 MPK6 pectin oligogalacturonides.

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