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Harnessing naturally occurring mutations for T-cell therapy:a potential new avenue to enhance treatment efficacy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1799-1801页

作者： michael Hiltensperger j.rgen Ruland Kilian Schober Mikrobiologisches Institut-Klinische Mikrobiologie Immunologie und HygieneFriedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany Institute of Clinical Chemistry and Pathobiochemistry School of MedicineTechnical University of MunichMunichGermany TranslaTUM Center for Translational Cancer ResearchTechnical University of MunichMunichGermany German Cancer Consortium(DKTK) HeidelbergGermany German Center for Infection Research(DZIF) partner site MunichMunichGermany FAU Profile Center Immunomedicine Friedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany

In a recent study published in Nature,Garcia et *** a sophisticated approach to identify fitness-enhancing mutations for T cells that was inspired by cancer evolution.1 The identified CARD11-PIK3R3 gene fusion enhanced tumor rej.ction and persistence of engineered T cells in multiple tumor models and might have the potential to improve efficacy of adoptive T-cell therapies in cancer patients.

关键词： cancer potential

Mathematical beauty and Palladian architecture:Measuring and comparing visual complexity and diversity

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Frontiers of Architectural Research 2024年第4期13卷 729-740页

作者： j. Hyun Lee michael j.Ostwald School of Built Environment Faculty of ArtsDesign&ArchitectureThe University of New South WalesSydneyNSW 2052Australia

Palladio’s design principles,including proportion and harmony,have often been associated with mathematical definitions of ***,the geometric and semantic properties of his fac¸ades have rarely been analysed in a holistic *** is little evidence of how mathematical beauty may be embodied in his *** research investigates complexity(fractal dimension or D)and diversity(perplexity or PP)as aesthetic indices,aiming to capture distinct characteristics of Palladian *** D and PP values of 22 Palladian villa fac¸ades are measured and analysed,before being compared with those of three Renaissance facades by Sebastiano *** combination of D and PP captures the geometric and semantic aesthetic qualities of architectural ***,the developed scatter plot of D and PP results supports the identification of four distinct aesthetic types of Palladian fac¸ade *** novel combination of D and PP measures contributes to a better understanding of one definition of the mathematical beauty of architecture,wherein“the whole is other than the sum of the parts”in compositional terms(a famous Gestalt principle).Specifically,this research provides new mathematical insights into the visual character of Palladian architecture and compares two important measures thereof.

关键词： Palladian architecture Complexity Diversity Mathematical beauty Perplexity Fac¸ade design

Use of donepezil for neurocognitive recovery after brain inj.ry in adult and pediatric populations:a scoping review

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Neural Regeneration Research 2024年第8期19卷 1686-1695页

作者： Avery L.Miller Nathan K.Evanson j.michael Taylor University of Cincinnati College of Medicine CincinnatiOHUSA Department of Pediatrics University of CincinnatiCincinnatiOHUSA Department of Neurology and Rehabilitation Medicine University of CincinnatiCincinnatiOHUSA Division of Pediatric Rehabilitation Medicine Cincinnati Children’s Hospital Medical CenterCincinnatiOHUSA Division of Neurology Cincinnati Children’s Hospital Medical CenterCincinnatiOHUSA

There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain inj.ry in pediatric *** inhibitors such as donepezil have been evaluated in adult patients after traumatic brain inj.ry,but relatively less is known about the effect in pediatric *** goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibito rs as a potential a dj.vant treatment fo r neurocognitive decline in pediatric patients with traumatic brain *** queried PubMed to identify literature published from database inception thro ugh j.ne 2023 desc ribing the use of donepezil in young adult traumatic brain inj.ry and pediatric patients with predefined *** on preselected search criteria,340 unique papers we re selected for title and abstra ct ***-two reco rds were reviewed in full after eliminating preclinical studies and pape rs outside the scope of the *** adult traumatic brain inj.ry,we review results from 14 papers detailing 227 subj.cts where evidence suggests donepezil is well tole rated and shows both obj.ctive and patient-reported efficacy for reducing cognitive *** children,3 pape rs report on 5 children recovering from traumatic brain inj.ry,showing limited *** additional 15 pediatric studies conducted in populations at risk for cognitive dysfunction provide a broader look at safety and efficacy in 210 patients in the pediatric age *** its promise for efficacy in adults with traumatic brain inj.ry and tole rability in pediatric patients,we believe further study of donepezil for children and adolescents with traumatic brain inj.ry is warranted.

关键词： acetylcholinesterase inhibitor adult cognition donepezil pediatrics traumatic brain inj.ry

Measurement,associations,patterns,and promotion:Unveiling vital areas in physical activity epidemiology

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j.urnal of Sport and Health Science 2024年第5期13卷 605-607页

作者： Kara M.Whitaker Guest editor michael j.LaMonte Department of Health&Human Physiology University of IowaIowa CityIA 52242USA Department of Epidemiology and Environmental Health University of BuffaloBuffaloNY 14214 USA

Physical activity(PA)epidemiology first emerged as a new field of study around the 1950s with publication of seminal investigations on London civil servants1 and has continued to evolve as a scientific discipline to present *** subdiscipline of epidemiology studies the frequencies,distributions,and dynamics of PA and its impact on human health,morbidity,and *** over the past 75 years has demonstrated numerous health benefits of *** on these research findings,the World Health Organization recommends adults aged 18-64 years engage in at least 150-300 min of moderate-intensity aerobic PA per week,or at least 75-150 min of vigorous-intensity aerobic PA per week,or a combination of both intensities.

关键词： epidemiology promotion continued

Evaluating Methods of Visual Assistance for Workers to Improve Quality and Usability in Individualized Kitchen Cabinet Assembly

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j.urnal of Computer and Communications 2024年第2期12卷 156-172页

作者： Albert Eff michael S. j. Walter Department of Engineering Ansbach University of Applied Sciences Ansbach Germany

In times of digitalisation, visual assistance systems in assembly are increasingly important. The design of these assembly systems needs to be highly complex to meet the requirements. Due to the increasing number of variants in production processes, as well as shorter innovation and product life cycles, assistance systems should improve quality and reduce complexity of assembly processes. However, many large kitchen manufacturers still assemble kitchen cabinets manually, due to the high variety of components, such as rails and fittings. This paper focuses on the analysis and evaluation of virtual assistance systems to improve quality and usability in individualised kitchen cabinet assembly processes at a large German manufacturer. A solution is identified and detailed.

关键词： Digitalisation Assembly Process Visual Assistance Usability Human-Centred Assembly Design

Buechel Pappas Resurfacing Shoulder Replacement: Evolution and over 40 Years of Clinical Experience

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Open j.urnal of Orthopedics 2024年第5期14卷 218-228页

作者： Frederick F. Buechel michael j. Pappas Rutgers Nj.Medical School Newark NJ USA South Mountain Orthopaedic Associates South Orange NJ USA New j.rsey Institute of Technology Newark NJ USA

Background: Early exploration of the semi constrained “Floating-Socket” total shoulder replacement (TSR) in 1974 led to a proliferation of various unconstrained designs that allowed resection or retention of the humeral head, depending upon the pathological process involved. Degenerative glenohumeral arthritis with mild to moderate involvement of subchondral bone allowed for a resurfacing option, while severe humeral head involvement required a partial or full humeral head replacement attached to an intramedullary stem for fixation. All components evolved from cemented to cementless application by 1982. The purpose of this paper is to describe the progression of Buechel-Pappas (B-P) shoulder replacement development from the early 1970’s in both cemented and cement less applications. Methods: Clinical evaluations of “Floating-Socket” TSR, followed by B-P stem-type, resurfacing types, bipolar-type and revision components, all of which comprise the B-P Shoulder Replacement System, were performed over a 49-year period. Results: “Floating-Socket” implants improved the results of simple, constrained ball-in-socket designs, but generally failed by glenoid component loosening in both chimpanzee and human applications. Unconstrained resurfacing-type components, both anatomical humeral head and full proximal humeral components, were quite successful, with minimal failures observed in long-term studies. Bipolar salvage implants, used for severe proximal deficiencies, revisions and massive rotator cuff arthropathy, were also very successful;providing overhead range of motion in many patients. Conclusions: Resurfacing hemiarthroplasty, in patients with intact or repairable rotator cuff mechanisms, gave the most satisfactory results and were the least technically complicated to perform, requiring minimal instrumentation. Resurfacing of full proximal humeral deficiencies, using femoral resurfacing components, gave similar clinical results to more complex semi-constrained devices,

关键词： Total Shoulder Replacement Resurfacing Shoulder Replacement

Back to the drawing board:Overview of the next generation of combination therapy for inflammatory bowel disease

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World j.urnal of Gastroenterology 2024年第25期30卷 3182-3184页

作者： j.ffrey A Lowell michael j.Farber Keith Sultan Department of Medicine Zucker School of Medicine at HofstraNorth Shore University Hospital-Long Island Jewish Medical CenterManhassetNY 11030United States Preclinical Studies New York Institute of Technology College of Osteopathic MedicineGlen HeadNY 11545United States Division of Gastroenterology Northwell HealthNorth Shore University Hospital and Long Island Jewish Medical CenterGreat NeckNY 10021United States

Inflammatory bowel disease(IBD)is entering a potentially new era of combined *** et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this *** importance of controlled trials should be stressed in establishing new treatment *** prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.

关键词： Inflammatory bowel disease Biologics Immunomodulators Dual-therapy Combination therapy

The Global Energy and Water Exchanges(GEWEX)Proj.ct in Central Asia:The Case for a Regional Hydroclimate Proj.ct

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Advances in Atmospheric Sciences 2024年第5期41卷 777-783页

作者： michael BRODY Maksim KULIKOV Sagynbek ORUNBAEV Peter j.VAN OEVELEN International Agricultural University Tashkent 111200Uzbekistan George Mason University FairfaxVirginia 22030USA University of Central Asia Bishkek 720001Kyrgyz Republic American University of Central Asia Bishkek 720060Kyrgyz Republic International GEWEX proj.ct George Mason UniversityFairfaxVirginia 22030USA

Central Asia consists of the former Soviet Republics,Kazakhstan,Kyrgyz Republic,Taj.kistan,Turkmenistan,and *** region’s climate is continental,mostly semi-arid to *** is a significant part of the region’s *** its nature of intensive water use,agriculture is extremely vulnerable to climate *** growth and irrigation development have significantly increased the demand for water in the *** climate change issues include melting glaciers and a shrinking snowpack,which are the foundation of the region’s water resources,and a changing precipitation *** glaciers are located in Kyrgyzstan and Taj.kistan,leading to transboundary water resource *** already has extremely high *** indicate that Central Asia has been warming and precipitation might be *** warming is expected to increase,but its spatial and temporal distribution depends upon specific global *** of future precipitation show significant uncertainties in type,amount,and *** Hydroclimate Proj.cts(RHPs)are an approach to studying these *** steps to develop an RHP began in 2021 with a widely distributed online survey about these climate *** was followed up with an online workshop and then,in 2023,an in-person workshop,held in Tashkent,*** for the Global Energy and Water Exchanges(GEWEX)proj.ct for the region include both observations and modeling,as well as development of better and additional precipitation observations,all of which are topics for the next workshop.A well-designed RHP should lead to reductions in critical climate uncertainties in policy-relevant timeframes that can influence decisions on necessary investments in climate adaptation.

关键词： GEWEX Central Asia climate change agriculture

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Rethinking the egg

National Science Review 2024年第06期 81-82页

作者： michael j.Benton School of Earth Sciences University of Bristol

Our image of early dinosaur eggs must change. Early dinosaur eggs are portrayed as soft-shelled, like those of modern lizards or snakes [1], and yet all the evidence is that early dinosaurs at least laid leathery-shel...

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