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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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Consilience and unity in ocular anterior segment research

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1173-1183页

作者： Houmam Araj department of health and human services National Eye Institute/National Institutes of Health(NEI/NIH)BethesdaMaryland 20892USA

In his beautiful book,Consilience:The Unity of Knowledge,the eminent biologist Edward O Wilson,advocates the need for integration and reconciliation across the *** defines consilience as“literally a‘jumping together’of knowledge with a linking of facts…to create a common groundwork of explanation”.It is the premise of this paper that as much as basic biomedical research is in need of data generation using the latest available techniques–unifying available knowledge is just as *** involves the necessity to resolve contradictory findings,reduce silos,and acknowledge *** take the cornea and the lens as case studies of our ***,in this perspective,we discuss the conflicting and fragmented information on protein aggregation,oxidative damage,and *** are fields of study that are integrally tied to anterior segment *** goal is to highlight the vital need for Wilson’s consilience and unity of knowledge which in turn should lead to enhanced rigor and reproducibility,and most importantly,to greater understanding and not simply knowing.

关键词： anterior segment ocular surface cornea lens cataract posterior capsular opacification protein aggregation oxidative damage antioxidants fibrosis wound healing consilience

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NetBCE: An Interpretable Deep Neural Network for Accurate Prediction of Linear B-cell Epitopes

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Genomics, Proteomics & Bioinformatics 2022年第5期20卷 1002-1012页

作者： Haodong Xu Zhongming Zhao Center for Precision health School of Biomedical InformaticsThe University of Texas Health Science Center at HoustonHoustonTX 77030USA human Genetics Center School of Public HealthThe University of Texas Health Science Center at HoustonHoustonTX 77030USA The University of Texas MD Anderson Cancer Center UThealth houston Graduate School of Biomedical Sciences HoustonTX 77030USA department of Biomedical Informatics Vanderbilt University Medical CenterNashvilleTN 37203USA

Identification of B-cell epitopes(BCEs)plays an essential role in the development of peptide vaccines and immuno-diagnostic reagents,as well as antibody design and *** this work,we generated a large benchmark dataset comprising 124,879 experimentally supported linear epitope-containing regions in 3567 protein clusters from over 1.3 million B cell *** of this curated dataset showed large pathogen diversity covering 176 different *** accuracy in linear BCE prediction was found to strongly vary with different features,while all sequencederived and structural features were *** search more efficient and interpretive feature representations,a ten-layer deep learning framework for linear BCE prediction,namely Net BCE,was *** BCE achieved high accuracy and robust performance with the average area under the curve(AUC)value of 0.8455 in five-fold cross-validation through automatically learning the informative classification *** BCE substantially outperformed the conventional machine learning algorithms and other tools,with more than 22.06%improvement of AUC value compared to other tools using an independent *** investigating the output of important network modules in Net BCE,epitopes and non-epitopes tended to be presented in distinct regions with efficient feature representation along the network layer *** Net BCE is freely available at https://***/bsml320/Net BCE.

关键词： prediction network value

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The Risk of Risk Assessment

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Biomedical and Environmental Sciences 1989年第1期2卷 48-53页

作者： VERNON N.HOUK Center for Environmental health and Injury Control Centers for Disease Control Public Health Service U.S. Department of Health and Human Services Atlanta Georgia 30333

Appropriate risk management can only be based on sound risk assessment. The sources of uncertainty involved in risk assessment are discussed and a number of approaches to improving such assessments are recommended.

关键词： The Risk of Risk Assessment

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Age-dependent changes in the association between sleep duration and impaired glucose metabolism

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World Journal of Diabetes 2017年第8期8卷 397-406页

作者： Kei Nakajima Kaname Suwa Kenji Toyama School of Nutrition and Dietetics Faculty of Health and Social Services Kanagawa University of Human Services Yokosuka department of Endocrinology and Diabetes Saitama Medical Center Saitama Medical University Saitama health Promotion Corporation

AIM To investigate whether the association between sleep duration and impaired glucose metabolism varies among younger and older *** We reviewed data of self-reported habitual sleep duration per night, HbA1c levels, and clinically relevant factors in a cross-sectional checkup database of 75472 Japanese from the general population aged 20-79 years(51695 men and 23777 women). Associations of prediabetes(HbA1c ≥ 5.7% and/or diabetic pharmacotherapy) or diabetes(HbA1c ≥ 6.5% and/or diabetic pharmacotherapy) with short and long sleep durations compared with a reference sleep duration(7 h) were investigated by multivariate logistic regression analysis. We controlled for potential relevant confounders, including age, sex, and work duration per day according to younger and older *** As age advanced, sleep duration became longer and this increase in the 40 s and 50 s was two times greater in men than in women. This finding was accompanied by a deterioration in HbA1c levels. In subjects aged youngerthan 40 years(n = 32929), HbA1c levels were inversely and linearly correlated with sleep duration in both sexes. However, in subjects aged 40 years or older(n = 42543), HbA1c levels showed a non-linear relationship against sleep duration with a nadir at 7 h. Multivariate logistic regression analysis showed that in younger subjects, short durations of sleep(≤ 5 h and 6 h) were positively associated with prediabetes(both P < 0.001), but a long duration of sleep(≥ 8 h) was inversely associated with prediabetes(P < 0.001). These associations remained significant after adjustment for relevant confounders, including age, sex, and work duration per day(ORs = 1.20, 95%CI: 1.05-1.37, P < 0.001; ORs = 1.12, 95%CI: 1.02-1.24, P < 0.05; and ORs = 0.84, 95%CI: 0.72-0.99, P < 0.05, respectively). In contrast, in older subjects, besides an association of prediabetes with a short duration of sleep(≤ 5 h)(ORs = 1.12, 95%CI: 1.03-1.21, P < 0.01), diabetes was significant

关键词： Sleep Prediabetes Diabetes HbA1c Aging

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health centres and social determinants of health: an analysis of enabling services provision and clinical quality

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Family Medicine and Community health 2023年第3期11卷 1-9页

作者： Michael Topmiller Jessica McCann Hank Hoang Jennifer Rankin Jene Grandmont Molly Pelzer Alek Sripipatana healthLandscape American Academy of Family PhysiciansLeawoodKansasUSA US department of health and human services Health Resources and Services AdministrationBureau of Primary Health CareRockvilleMarylandUSA

Objective It is well known that social determinants of health(SDOH),including poverty,education,transportation and housing,are important predictors of health *** Resources and services Administration(HRSA)-funded health centres serve a patient population with high vulnerability to barriers posed by SDOH and are required to provide services that enable health centre service utilisation and assist patients in navigating barriers to *** study explores whether health centres with higher percentages of patients using these enabling services experience better clinical performance and *** and setting The analysis uses organisational characteristics,patient demographics and clinical quality measures from HRSA’s 2018 Uniform Data *** centres(n=875)were sorted into quartiles with quartile 1(Q1)representing the lowest utilisation of enabling services and quartile 4(Q4)representing the *** researchers calculated a service area social deprivation score weighted by the number of patients for each health centre and used ordinary least squares to create adjusted values for each of the clinical quality process and outcome *** of variance was used to test differences across enabling services *** After adjusting for patient characteristics,health centre size and social deprivation,authors found statistically significant differences for all clinical quality process measures across enabling services quartiles,with Q4 health centres performing significantly better than Q1 health centres for several clinical process ***,these Q4 health centres performed poorer in outcome measures,including blood pressure and haemoglobin A1c *** These findings emphasise the importance of how enabling services(eg,translation services,transportation)can address unmet social needs,improve utilisation of health services and reaffirm the challenges inherent in overcoming SDOH to improve health outcomes.

关键词： centre services representing

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Therapeutic potential and pharmacological mechanism of visnagin

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Journal of Integrative Medicine 2024年第4期22卷 399-412页

作者： Poonam Yadav Sumeet Kumar Singh Sayantap Datta Saloni Verma Aarti Verma Arnab Rakshit Anjana Bali Jasvinder Singh Bhatti Amit Khurana Umashanker Navik department of Pharmacology School of Health SciencesCentral University of PunjabBathindaPunjab 151401India department of Pharmacological and Pharmaceutical Sciences College of PharmacyUniversity of HoustonHoustonTX 77204-5000USA department of human Genetics and Molecular Medicine School of Health SciencesCentral University of PunjabBathindaPunjab 151401India

Visnagin is a furanochromone and one of the most important compound in the Ammi visnaga(L.)Lam(a synonym of Visnaga daucoides Gaertn.)plant,which is used to cure various *** investigations into the bioactive properties of visnagin have been studied to *** literature on visnagin demonstrates its biological properties,including anti-inflammatory,anti-diabetic,and beneficial effects in cardiovascular and renal ***,visnagin improves sperm quality parameters,stimulates steroidogenesis,and increases serum gonadotropins and testosterone levels,while decreasing proinflammatory cytokines,oxidative damage,genomic instability,and it modulates ***,visnagin has emerged as an exciting lead for further research,owing to its potential in various unmet clinical *** current review summarized its basic structure,pharmacokinetics,and pharmacological effects,focusing on its mechanisms of *** review will help to understand the potential of visnagin as an alternative treatment strategy for several diseases and provide insight into research topics that need further exploration for visnagin’s safe clinical use.

关键词： Visnagin Phytochemical Anti-inflammatory Ammi visnaga L. Visnaga daucoides Gaertn Cancer

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Unhealthy eating habits around sleep and sleep duration: To eat or fast?

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World Journal of Diabetes 2018年第11期9卷 190-194页

作者： Kei Nakajima School of Nutrition and Dietetics Faculty of Health and Social Services Kanagawa University of Human Services department of Endocrinology and Diabetes Saitama Medical Center Saitama Medical University

Traditionally, breakfast skipping(BS), and recently latenight dinner eating(LNDE), have attracted attention in public health because they can predispose to cardiometabolic conditions such as obesity and type 2 diabetes. Intriguingly, it has become evident that short duration of sleep elicits similar health risks. As LNDE, BS, and short sleep can be closely related and can aggravate each other, these three should not be considered separately. In this context, LNDE(or its equivalents, snacking or heavy alcohol consumption after dinner) and BS may be representative unhealthy eating habits around sleep(UEHAS). While it is important to take energy in the early morning for physical and intellectual activities, attaining a fasting state is essential for metabolic homeostasis. Our previous UEHAS studies have shown that BS without LNDE, i.e., BS alone, is not associated with obesity and diabetes, suggesting the possibility that BS or taking a very low energy breakfast, which could yield fasting for a while, may prevent obesity and diabetes in people with inevitable LNDE. Further studies considering UEHAS and short sleep simultaneously are needed to elucidate the effects of these unhealthy lifestyles on cardiometabolic diseases.

关键词： Breakfast skipping Late-night dinner eating Sleep Fasting Hungry

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Fasting biochemical hypoglycemia and related-factors in nondiabetic population: Kanagawa Investigation of Total Check-up Data from National Database-8

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World Journal of Diabetes 2021年第7期12卷 1131-1140页

作者： Kotone Tanaka Ryoko Higuchi Kaori Mizusawa Teiji Nakamura Kei Nakajima Graduate School of health Innovation Kanagawa University of Human ServicesKawasaki 210-0821Japan School of Nutrition and Dietetics Faculty of Health and Social ServicesKanagawa University of Human ServicesYokosuka 238-8522Japan department of Endocrinology and Diabetes Saitama Medical CenterSaitama Medical UniversityKawagoe 350-8550Japan

BACKGROUND In healthy people,the lowest daily blood glucose concentration is usually observed in the early morning,after overnight ***,the clinical relevance and the prevalence of fasting biochemical hypoglycemia(FBH)are poorly understood in people who do not have diabetes,although the clinical implications of such hypoglycemia have been extensively studied in patients with *** can be influenced by many factors,including age,sex,body mass,smoking,alcohol drinking,exercise levels,medications,and eating behaviors,such as breakfast skipping and late-night *** To determine the prevalence of FBH and investigated its association with potential risk factors in a population without *** Clinical parameters and lifestyle-related factors were assessed in a cross-sectional study of 695613 people aged 40-74 years who had undergone a health check-up(390282 men and 305331 women).FBH was defined as fasting plasma glucose<70 mg/dL(3.9 mmol/L)after overnight fasting,regardless of any *** absence of diabetes was defined as HbA1c<6.5%,fasting plasma glucose<126 mg/dL(7.0 mmol/L),and no pharmacotherapy for *** logistic regression analysis,with adjustment for confounding factors,was used to identify *** FBH was present in 1842 participants(0.26%).There were significantly more women in the FBH group(59.1%)than in the non-FBH group(43.9%).Values of most of the clinical parameters,but not age,were significantly lower in the FBH group than in the non-FBH *** regression analysis showed that a body mass index of≤20.9 kg/m2(reference:21-22.9 kg/m2)and current smoking were significantly associated with FBH,and this was not altered by adjustment for age,sex,and pharmacotherapy for hypertension or *** sex was associated with *** the data were analyzed according to sex,men in their 60s or 70s appeared more likely to experience FBH compared with their 40s,whereas men in their 50s and

关键词： Hypoglycemia Body mass index Age Smoking Women Breakfast skipping

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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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