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The concept of gene therapy for glaucoma:the dream that has not come true yet

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Neural Regeneration Research 2024年第1期19卷 92-99页

作者： Robert Sulak Xiaonan Liu adrian Smedowski Department of Physiology Faculty of Medical Sciences in KatowiceMedical University of Silesia in KatowiceKatowicePoland Institute of Biotechnology HiLIFEUniversity of HelsinkiHelsinkiFinland GlaucoTech Co. KatowicePoland

Gene therapies,despite of being a relatively new therapeutic approach,have a potential to become an important alternative to current treatment strategies in *** glaucoma is not considered a single gene disease,the identified goals of gene therapy would be rather to provide neuroprotection of retinal ganglion cells,especially,in intraocular-pressure-independent *** most commonly reported type of vector for gene delivery in glaucoma studies is adeno-associated virus serotype 2 that has a high tro pism to retinal ganglion cells,res ulting in long-term expression and low immunogenic *** gene thera py studies recruit inducible and genetic animal models of optic neuropathy,like DBA/2j mice model of high-tension glaucoma and the optic nerve *** gene therapy-based neuroprotection of retinal ganglion cells is targeting specific genes translating to growth factors(i.e.,brain derived neurotrophic factor,and its receptor TrkB),regulation of apoptosis and neurodegeneration(i.e.,Bcl-xl,Xiap,FAS system,nicotinamide mononucleotide adenylyl transferase 2,Digit3 and Sarm1),immunomodulation(i.e.,Crry,C3 complement),modulation of neuroinflammation(i.e.,e rythropoietin),reduction of excitotoxicity(i.e.,Com KIlα)and transcription regulation(i.e.,Max,Nrf2).On the other hand,some of gene therapy studies focus on lowering intra ocular pressure,by impacting genes involved in both,decreasing aqueous humor production(i.e.,aquaporin 1),and increasing outflow facility(i.e.,COX2,prostaglandin F2a receptor,RhoA/RhoA kinase signaling pathway,MMP1,Myocilin).The goal of this review is to summarize the current stateof-art and the direction of development of gene therapy strategies for glaucomatous neuropathy.

关键词： adeno-associated virus gene editing gene therapy glaucoma IOP lowering IOP-independent mechanisms neuroprotection optic nerve optic neuropathy retinal ganglion cells

Feeding ecology and interactions with mammal hosts in a symbiotic genus of birds(Buphagus spp.)in Namibia

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Avian Research 2024年第3期15卷 336-344页

作者： Michael S.Lukubwe Daniel Velarde-Garcéz Fernando Sequeira Susana Lopes adrian j.F.K.Craig Vanessa A.Mata Department of Zoology and Entomology Rhodes UniversityMakhandaSouth Africa Department of Wildlife Management and Tourism Studies University of NamibiaKatima Mulilo CampusNamibia Departamento de Biologia Faculdade de CiênciasUniversidade do PortoPortoPortugal CIBIO Centro de Investigação em Biodiversidade e Recursos GenéticosInBIO Laboratório AssociadoCampus de VairãoVairãoPortugal BIOPOLIS Program in Genomics Biodiversity and Land PlanningCIBIOCampus de VairãoVairãoPortugal

As the sole obligate symbiotic birds in Africa,oxpeckers offer a unique model for studying symbiotic *** to the multitrophic level they occupy and the context dependent foraging behavior they exhibit,the type of symbiotic relationship can be *** addition to providing a cleaning service to the host by removing ticks,oxpeckers frequently feed on blood,mucus,and saliva,inflicting potential damage on the ***,we used DNA metabarcoding on faecal samples to analyze the taxonomic composition of the trophic interactions of the Yellow-billed Oxpecker(Buphagus africanus)and Red-billed Oxpecker(***)in northeastern *** contrast to conventional methods,DNA metabarcoding allows for a detailed identification of dietary resources encompassing both mammal hosts and consumed arthropods within the same *** this information,we examined differences in the diet composition between oxpecker species and localities,as well as the co-occurrence between host and arthropod *** findings revealed that oxpeckers predominantly source their diet from mammals,ticks,and flies;however,ticks and flies rarely co-occur in the diet of an *** observed variability among individuals in their feeding ecology,which is strongly correlated with locality and,to a lesser extent,with the mammal *** noted a high degree of mobility between hosts within relatively short periods,with 32%of the samples showing traces of at least two mammal *** study illustrates the dynamic foraging behavior of these specialized symbiotic birds,shedding light on their potential role in pest control services and disease transmission.

关键词： Commensalism Diet DNA metabarcoding Oxpeckers Parasitism Trophic ecology

Explainable Artificial Intelligence(XAI)Model for Cancer Image Classification

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Computer Modeling in Engineering & Sciences 2024年第10期141卷 401-441页

作者： Amit Singhal Krishna Kant Agrawal Angeles Quezada adrian Rodriguez Aguiñaga Samantha jiménez Satya Prakash Yadav Department of Computer Science&Engineering Raj Kumar Goel Institute of TechnologyGhaziabad201017India Department of School of Computing Science and Engineering Galgotias UniversityGreater Noida203201India Tecnológico Nacional de México Campus Tijuana Baja California22414México Universidad Autónoma de Baja California TijuanaBaja California22414México Department of Computer Science and Engineering G.LBajaj Institute of Technology and Management(GLBITM)Affiliated to Dr.A.P.J.Abdul Kalam Technical UniversityLucknow201306India School of Computer Science Engineering and Technology(SCSET) Bennett UniversityGreater Noida201310India

The use of Explainable Artificial Intelligence(XAI)models becomes increasingly important for making decisions in smart healthcare *** is to make sure that decisions are based on trustworthy algorithms and that healthcare workers understand the decisions made by these *** models can potentially enhance interpretability and explainability in decision-making processes that rely on artificial ***,the intricate nature of the healthcare field necessitates the utilization of sophisticated models to classify cancer *** research presents an advanced investigation of XAI models to classify cancer *** describes the different levels of explainability and interpretability associated with XAI models and the challenges faced in deploying them in healthcare *** addition,this study proposes a novel framework for cancer image classification that incorporates XAI models with deep learning and advanced medical imaging *** proposed model integrates several techniques,including end-to-end explainable evaluation,rule-based explanation,and useradaptive *** proposed XAI reaches 97.72%accuracy,90.72%precision,93.72%recall,96.72%F1-score,9.55%FDR,9.66%FOR,and 91.18%*** will discuss the potential applications of the proposed XAI models in the smart healthcare *** will help ensure trust and accountability in AI-based decisions,which is essential for achieving a safe and reliable smart healthcare environment.

关键词： Explainable artificial intelligence artificial intelligence XAI healthcare cancer image classification

Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi juan Pablo de Rivero Vaccari jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang j.adrian Tyndall Binu Tharakan Firas Kobeissy Department of Surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

Vaccines for prevention of non-viral cancers

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Vaccines for prevention of non-viral cancers

第十二届全国免疫学学术大会

作者： Olivera j.finn Department of Immunology University of Pittsburgh School of Medicine

Discovery almost three decades ago of the first few human tumor antigens,targets of human antibodies and T cells,started a new field of therapeutic cancer *** of molecules that were found to be differentially expressed on tumors versus normal cells were incorporated in various forms into vaccines to be administered to patients in hope of boosting preexisting immunity or eliciting new immune responses to control tumor *** such antigen was the epithelial mucin MUCl that is overexpressed and hypoglycosylated on tumor

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新天鹅护理休闲区,本特利,澳大利亚

世界建筑 2024年第6期 66-71页

作者：无 adrian Iredale finn Pedersen Martyn Hook Tom See Hoo Rebecca Angus Mary McAree Rebecca Hawkett Catherine Dupuy Gian Tonossi jordan Blagaich jake Gethin Daniel Martin Peter Bennetts(摄影) 伊代尔-佩德森-霍克建筑事务所不详

新天鹅护理休闲区旨在通过减少隔离、鼓励安全的活动和社交互动来改善居民的健康和福祉,并欢迎朋友、家人和周边居民的到来。Iph建筑事务所挑战了之前的总体规划,将车辆和道路从中心空间移除,取而代之的是一条宽阔、笔直且清静的人行林... 详细信息

新天鹅护理休闲区旨在通过减少隔离、鼓励安全的活动和社交互动来改善居民的健康和福祉,并欢迎朋友、家人和周边居民的到来。Iph建筑事务所挑战了之前的总体规划,将车辆和道路从中心空间移除,取而代之的是一条宽阔、笔直且清静的人行林荫道。林荫大道从天鹅护理中心的主要入口街道(阿迪苑)延伸至新的休闲区,并继续通向到远处的老年人关怀设施。一条蜿蜒曲折的小路与林荫大道相接,方便人们慢步闲逛。随着总体规划逐渐深化,这些小路将继续延伸,为老年痴呆症患者提供安全的活动空间。

关键词：护理中心建筑事务所主要入口林荫大道本特利休闲区蜿蜒曲折林荫道

When evidence is lacking:a mixed-methods approach for the development of practice guidance in liver transplantation

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Gastroenterology Report 2021年第1期9卷 22-30,I0001页

作者： Lisa B.VanWagner Blessing Aghaulor Tasmeen Hussain Megan Kosirog Patrick Campbell Stewart Pine Amna Daud Daniel j.finn josh Levitsky Donald M.Lloyd-jones jane L.Holl Division of Gastroenterology and Hepatology Department of MedicineNorthwestern University Feinberg School of MedicineChicagoILUSA Department of Preventive Medicine Northwestern University Feinberg School of MedicineChicagoILUSA Comprehensive Transplant Center Northwestern University Feinberg School of MedicineChicagoILUSA Division of Cardiology Department of MedicineNorthwestern University Feinberg School of MedicineChicagoILUSA Department of Pediatrics Northwestern University Feinberg School of MedicineChicagoILUSA Center for Healthcare Delivery Science and Innovation and Department of Neurology Biological Sciences DivisionUniversity of ChicagoChicagoILUSA

Background Most interventions for conditions with a small cohort size,such as transplantation,are unlikely to be part of a clinical *** condition-specific evidence is lacking,expert consensus can offer more precise guidance to improve *** of cardiovascular risk in liver-transplant recipients is one example for which clinicians have,to date,adapted evidence-based guidelines from studies in the general ***,even when consensus is achieved,implementation of practice guidance is often inadequate and *** report on a novel mixed-methods approach,the Northwestern MethodVC,for the development of clinical-practice guidance when condition-specific evidence is *** illustrate the method through the development of practice guidance for managing cardiovascular risk in liver-transplant *** The Northwestern MethodVC consists of(i)adaptation of relevant,existing,evidence-based clinical-practice guidelines for the target population;(ii)consensus by experts of the proposed practice guidance;(iii)identification of barriers to guidance adherence in current practice;and(iv)recommendation for implementation and dissemination of the practice *** method is based on an iterative,user-centered approach in which the needs,wants,and limitations of all end users,including patients,are attended to at each stage of the design and development *** The Northwestern MethodVC for clinical-practice-guidance development uses a mixed-methods approach to bring together broad representation from multiple disciplines and practice settings to develop consensus considering the unique needs and preferences of patients,caregivers,and practitioners who are directly impacted by clinical-practice-guidance *** hypothesize that a priori involvement of end users in the guidance-development process will lead to sustainable implementation of guidance statements into clinical practice.

关键词： liver transplantation practice guideline consensus methodology

Update on risk scoring systems for patients with upper gastrointestinal haemorrhage

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World journal of Gastroenterology 2012年第22期18卷 2739-2744页

作者： adrian j Stanley Gastrointestinal Unit Glasgow Royal Infirmary Glasgow G4 OSF United Kingdom

Upper gastrointestinal haemorrhage (UGIH) remains a common medical emergency worldwide. It is increasingly recognised that early risk assessment is an important part of management, which helps direct appropriate patient care and the timing of endoscopy. Several risk scores have been developed, most of which include endoscopic findings, although a minority do not. These scores were developed to identify various end-points including mortality, rebleeding or clinical intervention in the form of transfusion, endoscopic therapy or surgery. Recent studies have reported accurate identification of a very low risk group on presentation, using scores which require simple clinical or laboratory parameters only. This group may not require admission, but could be managed with early out-patient endoscopy. This article aims to describe the existing pre- and post-endoscopy risk scores for UGIH and assess the published data comparing them in the prediction of outcome. Recent data assessing their use in clinical practice, in particular the early identification of low-risk patients, are also discussed.

关键词： Upper gastrointestinal haemorrhage Bleeding Endoscopy Risk assessment Scoring systems Bla-tchford Rockall

A Rare Case of Concordant Atrioventricular Connection to L-Looped Ventricles in Situs Solitus:4-Dimensional Magnetic Resonance Imaging and 3D Printing

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Congenital Heart Disease 2022年第4期17卷 387-392页

作者： Gregory Perens Takegawa Yoshida j.Paul finn UCLA Mattel Children’s Hospital Children’s Heart CenterLos AngelesCAUSA Diagnostic Cardiovascular Imaging Laboratory Department of Radiology12222 David Geffen School of Medicine at UCLALos AngelesCAUSA

An infant male presented with the rare anatomy consisting of situs solitus,concordant atrioventricular connections to L-looped ventricles,double outlet right ventricle(DORV),and hypoplastic aortic arch.6 months after neonatal aortic arch repair,the morphologic right ventricle function deteriorated,and surgical evaluation was undertaken to determine if either biventricular repair with a systemic morphologic left ventricle or right ventricular exclusion was *** initial echocardiography,magnetic resonance imaging(MRI)was used to create detailed axial and 4-dimensional(4D)images and 3-dimensional(3D)printed *** detailed anatomy of this rare,complex case and its use in pre-surgical planning is presented.

关键词： Magnetic resonance imaging cardiac segments 3D printing