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Exploiting fly models to investigate rare human neurological disorders

Neural Regeneration Research 2025年第1期20卷 21-28页

作者： Tomomi Tanaka Hyung-Lok Chung Department of Neurology Houston Methodist Research InstituteHoustonTXUSA Department of Neurology Weill Cornell Medical CollegeNew YorkNYUSA

Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological *** attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted *** investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary *** tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological *** boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug *** can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical *** this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic *** discuss rare diseases associated with both neuron-expressed and glial-expressed *** cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal *** we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell ***-of-fun

关键词： ACOX1 Drosophila melanogaster glia lipid metabolism model organisms neuroinflammation neurologic disorders neuron rare disease VLCFA

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Glial progenitor heterogeneity and plasticity in the adult spinal cord

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Neural Regeneration Research 2024年第12期19卷 2567-2568页

作者： Haichao Wei Jia Qian Wu Department of Neurosurgery McGovern Medical SchoolThe University of Texas Health Science Center at HoustonHoustonTXUSA Center for Stem Cell and Regenerative medicine UT Brown Foundation Institute of Molecular MedicineHoustonTXUSA MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences HoustonTXUSA

Glial progenitor cells were reported to have the capacity to generate various types of cells in both the central nervous system(CNS)and peripheral nervous *** progenitor cells can respond to diverse environmental signals and transform into distinct populations,each serving specific ***,the adult spinal cord hosts various populations of glial progenitors,a region integral to the central nervous *** development,glial progenitors express glial fibrillary acidic protein(GFAP;Dimou and Gotz,2014).However,the specific identities of GFAP-expressing progenitors in the adult spinal cord were not thoroughly investigated.

关键词： functions plasticity thoroughly

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Cell-type resolved transcriptomic approaches for dissecting selective vulnerability in neurodgeneration

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Neural Regeneration Research 2024年第7期19卷 1411-1413页

作者： Caleb A.Wood Nicholas M.Tran Department of Neuroscience Baylor College of MedicineHoustonTXUSA Department of Molecular and Human Genetics Baylor College of MedicineHoustonTXUSA

A common feature among neurodegenerative conditions is that ce rtain neuronal populations are selectively vulnerable to loss(Fu et al.,2018).By corollary,other neurons are selectively resilient,suggesting they may possess unique features that support their survival.U nderstanding the basis of neuronal resilience or vulnerability would provide a logical strategy to identify factors that could be targeted therapeutically.

关键词： selective targeted

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SARS-CoV-2 triggers Dickkopf-1(Dkk-1)modulation of T helper cells and lung pathology in mice

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Genes & Diseases 2024年第4期11卷 9-12页

作者： Yifan Wu Freedom M.Green Stephen A.Shaw Lauren J.Bonilla Shannon E.Ronca Maria Elena Bottazzi Farrah Kheradmand Jill E.Weatherhead Department of Pathology&Immunology One Baylor PlazaHoustonTX 77030USA Department of Pediatrics One Baylor PlazaHoustonTX 77030USA Department of medicine One Baylor PlazaHoustonTX 77030USA National School of Tropical medicine One Baylor PlazaHoustonTX 77030USA Molecular Virology&Microbiology One Baylor PlazaHoustonTX77030USA Biologyof Inflammation Center Baylor College of MedicineOne BaylorPlazaHoustonTX77030USA Michael E.DeBakey VA Center for Translational Research on Inflammatory Diseases HoustonTX 77030USA

Severe acute respiratory syndrome coronavirus 2(SARSCov-2)is the etiologic agent of the coronavirus disease 19(COVID-19)*** viral infections like SARS-CoV-2,a robust anti-viral type 1 immune response,including upregulation of type 1 CD4+T helper cells(Th1),is required for effective viral clearance while minimizing end-organ pathology and collateral tissue damage.

关键词： pathology acute respiratory

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Application of artifcial intelligence in cataract management:current and future directions

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Eye and Vision 2024年第1期10卷 21-30页

作者： Laura Gutierrez Jane Sujuan Lim Li Lian Foo Wei Yan Ng Michelle Yip Gilbert Yong San Lim Melissa Hsing Yi Wong Allan Fong Mohamad Rosman Jodhbir Singth Mehta Haotian Lin Darren Shu Jeng Ting Daniel Shu Wei Ting Singapore Eye Research institute SingaporeSingapore Singapore National Eye Center 11 Third Hospital AvenueSingapore 168751Singapore academic Ophthalmology School of MedicineUniversity of NottinghamNottinghamUK Zhongshan Ophthalmic Center Sun Yet Sen UniversityGuangzhouChina

The rise of artifcial intelligence(AI)has brought breakthroughs in many areas of *** ophthalmology,AI has delivered robust results in the screening and detection of diabetic retinopathy,age-related macular degeneration,glaucoma,and retinopathy of *** management is another feld that can beneft from greater AI *** is the leading cause of reversible visual impairment with a rising global clinical *** diagnosis,monitoring,and surgical management are necessary to address this *** addition,patients in large developing countries often sufer from limited access to tertiary care,a problem further exacerbated by the ongoing COVID-19 *** on the other hand,can help transform cataract management by improving automation,efcacy and overcoming geographical ***,AI can be applied as a telediagnostic platform to screen and diagnose patients with cataract using slit-lamp and fundus *** utilizes a deep-learning,convolutional neural network(CNN)to detect and classify referable cataracts ***,some of the latest intraocular lens formulas have used AI to enhance prediction accuracy,achieving superior postoperative refractive results compared to traditional ***,AI can be used to augment cataract surgical skill training by identifying diferent phases of cataract surgery on video and to optimize operating theater workfows by accurately predicting the duration of surgical ***,some AI CNN models are able to efectively predict the progression of posterior capsule opacifcation and eventual need for YAG laser *** advances in AI could transform cataract management and enable delivery of efcient ophthalmic *** key challenges include ethical management of data,ensuring data security and privacy,demonstrating clinically acceptable performance,improving the generalizability of AI models across heterogeneous populations,and improving the trust of e

关键词： Artifcial intelligence Telemedicine Cataract Cataract screening Cataract surgery IOL calculations Biometry Machine learning

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DNA-delivered monoclonal antibodies targeting the p53 R175H mutant epitope inhibit tumor development in mice

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Genes & Diseases 2024年第4期11卷 368-380页

作者： Dafei Chai Xu Wang Praveen Neeli Shan Zhou Xingfang Yu Kanaga Sabapathy Yong Li Department of medicine Section of Epidemiology and Population SciencesDan L Duncan Comprehensive Cancer CenterBaylor College of MedicineHoustonTX 77030USA Division of Cellular&Molecular Research Humphrey Oei Institute of Cancer ResearchNational Cancer Centre SingaporeSingapore 168583Singapore

tThe tumor suppressor p53 is the most common mutated gene in cancer,with the R175H as the most frequent p53 missense ***,there are currently no approved targeted therapies or immunotherapies against mutant ***,we characterized and inves-tigated a monoclonal antibody(mAb)that recognizes the mutant p53-R175H for its affinity,specificity,and activity against tumor cells in *** then delivered DNA plasmids expres-sing the anti-R175H mAb or a bispecific antibody(BsAb)into mice to evaluate their therapeutic *** results showed that the anti-R175H mAb specifically bound to the p53-R175H an-tigen with a high affinity and recognized the human mutant p53-R175H antigen expressed on HEK293T or MC38 cells,with no cross-reactivity with wild-type *** cultured cells,the anti-R175H mAb showed higher cytotoxicity than the control but did not induce antibody-dependent cellular *** made a recombinant MC38 mouse cell line(MC38-p53-R175H)that overexpressed the human p53-R175H after knocking out the endogenous mutant p53 *** vivo,administration of the anti-R175H mAb plasmid elicited a robust anti-tumor effect against MC38-p53-R175H in *** administration of the anti-R175H BsAb plasmid showed no therapeutic effects,yet potent anti-tumor activity was observed in combination with the anti-PD-1 *** results indicate that targeting specific mutant epitopes using DNA-delivered mAbs or BsAbs presents a form of improved natural immunity derived from tumor-infiltrating B cells and plasma cells against intracellular tumor antigens.

关键词： BsAb Cytotoxicity mAb Mutant p53 PD-1 R175H

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Association between balloon atrial septostomy and prostaglandin E1 therapy until repair of transposition of the great arteries in neonates

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Pediatric Investigation 2024年第2期8卷 135-138页

作者： Samantha Gilg Sebastian Acosta Rohit S.Loomba Claire Rizk Gary E.Stapleton David Faraoni Fabio Savorgnan Department of Pediatrics Divisions of Critical Care Medicine and CardiologyTexas Children’s Hospital and Baylor College of MedicineHoustonTexasUSA Department of Pediatrics Division of CardiologyTexas Children’s Hospital and Baylor College of MedicineHoustonTexasUSA Department of Pediatrics The Heart InstituteAdvocate Children’s HospitalChicago Medical School and Rosalind Franklin University of Medicine and ScienceOak LawnIllinoisUSA Department of Anesthesiology Arthur S.Keats Division of Pediatric Cardiovascular AnesthesiaPerioperative and Pain MedicineTexas Children’s HospitalBaylor College of MedicineHoustonTexasUSA

The standard of care in the management of d-transposition of the great arteries(TGA)includes the arterial switch operation(ASO).1,2 Although some institutions have begun to publish the results of performing the ASO within the first few hours of life,most centers continue to"electively"delay ASO for several days to allow for a reduction in pulmonary vascular resistance and the stabilization of renal and liver function.1,2 The early initiation of prostaglandin E1(PGE)infusion to maintain ductal patency is a nearly universal component of therapy in order to maintain adequate arterial oxygen saturation and systemic oxygen delivery during the pre-operative period via intercirculatory mixing at the atrial septal and patent ductus arteriosus levels1,3.

关键词： balloon maintain stabilization

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Cardiac Piezo1 Exacerbates Lethal Ventricular Arrhythmogenesis by Linking Mechanical Stress with Ca^(2+) Handling After Myocardial Infarction

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Research 2024年第1期2023卷 583-594页

作者： Sheng-an Su Yuhao Zhang Wudi Li Yutao Xi Yunrui Lu Jian Shen Yuankun Ma Yaping Wang Yimin Shen Lan Xie Hong Ma Yao Xie Meixiang Xiang Department of Cardiology Cardiovascular Key Laboratory of Zhejiang ProvinceThe Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Department of Endocrinology The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Texas Heart institute HoustonTX 77030USA

Ventricular arrhythmogenesis is a key cause of sudden cardiac death following myocardial infarction(MI).Accumulating data show that ischemia,sympathetic activation,and inflammation contribute to ***,the role and mechanisms of abnormal mechanical stress in ventricular arrhythmia following MI remain *** aimed to examine the impact of increased mechanical stress and identify the role of the key sensor Piezo1 in ventricular arrhythmogenesis in *** with increased ventricular pressure,Piezo1,as a newly recognized mechano-sensitive cation channel,was the most up-regulated mechanosensor in the myocardium of patients with advanced heart ***1 was mainly located at the intercalated discs and T-tubules of cardiomyocytes,which are responsible for intracellular calcium homeostasis and intercellular communication.

关键词： ventricular homeostasis Ventricular

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Device-measured physical activity and sedentary time in the Nordic countries:A scoping review of population-based studies

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Journal of Sport and Health Science 2024年第5期13卷 650-660页

作者： Ing-Mari Dohrn Jakob Tarp Jostein Steene-Johannessen Tommi Vasankari Maria Hagströmer Division of Physiotherapy Department of NeurobiologyCare Sciences and SocietyKarolinska Institutet14183 HuddingeSweden Department of Sports medicine Norwegian School of Sports Sciences0806 OsloNorway UKK institute for Health Promotion Research 33500 TampereFinland Faculty of medicine and Health Technology Tampere University33100 TampereFinland academic Primary Health Care Centre Region Stockholm13365 StockholmSweden

Purpose:The purpose of this scoping review was to summarize and describe the methodology and results from population-based studies of physical activity and sedentary time measured with devices in the Nordic countries(Denmark,Finland,Iceland,Norway,and Sweden)and published in 2000 or ***:A systematic search was carried out in PubMed and Web of Science in June 2023 using predefined search ***:Fourteen unique research projects or surveillance studies were ***,2 surveillance studies published by national agencies were included,resulting in a total of 16 studies for *** surveillance systems exist in Finland and Norway,with regular survey waves in school-aged children/adolescents and *** Denmark,recent nationally representative data have been collected in school children *** far,Sweden has no regular national surveillance system using device-based data *** studies were found from *** first study was conducted in 2001 and the most recent in 2022,with most data collected from 2016 to *** studies included children/adole scents 6-18 years,no study included *** total 11 studies included adults,of which 8 also covered older *** study focused specifically on older *** analytical sample size ranged from 205 to 27,*** methodology is presented,such as information on sampling strategy,device type and placement,wear protocols,and physical activity classification *** of physical activity and sedentary time in children/adolescents,adults,and older adults across the Nordic countries are ***:A growing implementation of device-based population surveillance of physical activity and sedentary behavior in the Nordic countries has been *** variety of devices,placement,and data procedures both within and between the Nordic countries highlights the challenges when it comes to comparing study outcomes as well as the need for more standa

关键词： Accelerometer Light intensity Moderate-vigorous intensity Surveillance Wearable devices

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Clinical associations of corneal neuromas with ocular surface diseases

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Neural Regeneration Research 2024年第1期19卷 140-147页

作者： Charmaine Jan Li Toh Chang Liu Isabelle Xin Yu Lee Molly Tzu Yu Lin Louis Tong Yu-Chi Liu Lee Kong Chian School of medicine Nanyang Technological UniversitySingapore Singapore Eye Research institute Singapore Department of Cornea and External Eye Disease Singapore National Eye CentreSingapore Ophthalmology and Visual Sciences academic Clinical Program Duke-NUS Medical SchoolSingapore

Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or *** formation of corneal neuromas results from damage to corneal nerves,such as following corneal pathology or corneal or intraocular surge ***,denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers,and later injured axons regenerate and new sprouts called neuromas *** recent years,analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy,a non-invasive imaging technique with microscopic resolution,has been used to evaluate corneal neuropathy and ocular surface *** neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes,and are a promising surrogate biomarker for ocular surface diseases,such as neuropathic corneal pain,dry eye disease,diabetic corneal neuropathy,neurotrophic keratopathy,Sjogren's syndrome,bullous keratopathy,post-refra ctive surgery,and *** this review,we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas,as well as elaborated on their pathogenesis,visualization via in vivo confocal microscopy,and utility in monitoring treatment *** current quantitative analysis on neuromas mainly relies on manual annotation and quantification,which is user-dependent and labor-intensive,future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner,allowing it to be applied in clinical settings more *** imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.

关键词： cornea corneal diseases corneal nerve corneal neuropathy in vivo confocal microscopy microneuroma neuroma ocular surface diseases

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