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EZH2 inhibitors promote β-like cell regeneration in young and adult type 1 diabetes donors

Signal Transduction and Targeted Therapy 2024年第2期9卷 679-692页

作者： keith Al-Hasani Safiya Naina Marikar Harikrishnan Kaipananickal Scott Maxwell Jun Okabe Ishant Khurana Thomas Karagiannis Julia J.Liang Lina Mariana Thomas Loudovaris Thomas Kay Assam El-Osta Epigenetics in Human Health and Disease Program Baker Heart and Diabetes Institute75 Commercial RoadMelbourne 3004 VICAustralia Department of Diabetes Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia Epigenetics in Human Health and Disease Laboratory Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia School of Science STEM CollegeRMIT UniversityMelbourne 3001 VICAustralia Immunology and Diabetes Unit St Vincent’s Institute of Medical ResearchFitzroy 3065 VICAustralia Department of Medicine and Therapeutics The Chinese University of Hong KongSha TinHong Kong SAR Hong Kong Institute of Diabetes and Obesity Prince of Wales HospitalThe Chinese University of Hong Kong3/F Lui Che Woo Clinical Sciences Building30-32-Ngan Shing StreetSha TinHong Kong SAR Li Ka Shing Institute of Health Sciences The Chinese University of Hong KongSha TinHong Kong SAR Biomedical Laboratory Science Department of TechnologyFaculty of HealthUniversity College CopenhagenCopenhagenDenmark

β-cells are a type of endocrine cell found in pancreatic islets that synthesize,store and release *** type 1 diabetes(T1D),T-cells of the immune system selectively destroy the insulin-producingβ-*** of these cells leads to a lifelong dependence on exogenous insulin administration for ***,there is an urgent need to identify novel therapies that stimulateβ-cell growth and induceβ-cell *** and others have shown that pancreatic ductal progenitor cells are a promising source for regeneratingβ-cells for T1D owing to their inherent differentiation *** transcriptional suppression is refractory to exocrine reaction and tightly controls the regenerative potential by the EZH2 *** the present study,we show that transient stimulation of exocrine cells,derived from juvenile and adult T1D donors to the FDAapproved EZH2 inhibitors GSK126 and Tazemetostat(Taz)influence a phenotypic shift towards aβ-like cell *** transition from repressed to permissive chromatin states are dependent on bivalent H3K27me3 and H3K4me3 chromatin *** EZH2 is fundamental toβ-cell regenerative *** pancreatic ductal cells exhibit insulin production and secretion in response to a physiological glucose challenge ex *** pre-clinical studies underscore the potential of small molecule inhibitors as novel modulators of ductal progenitor differentiation and a promising new approach for the restoration ofβ-like cell function.

关键词： EZH2 struction inhibitors

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CI-WGAN:融合临床指标和WGAN的孤独症个体化脑功能连接网络生成

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数据采集与处理 2024年第4期39卷 813-826页

作者：孙海林严加栋张嵘 KENDRICK keith 蒋希电子科技大学生命科学与技术学院成都611731 麦吉尔大学蒙特利尔神经研究所蒙特利尔H3A 2B4 北京大学基础医学院神经生物学系北京100191 北京大学神经科学研究所北京100191 神经科学教育部重点实验室北京100191 卫健委神经科学重点实验室北京100191 北京大学医学部孤独症研究中心北京100191

脑功能连接(Functional connectivity,FC)网络作为潜在的脑影像标志物对孤独症谱系障碍(Autism spectrum disorder,ASD)的辅助诊疗研究具有重要作用。然而现有的FC生成方法大多仅基于脑影像数据,未充分考虑个体的临床指标从而易丢失疾... 详细信息

脑功能连接(Functional connectivity,FC)网络作为潜在的脑影像标志物对孤独症谱系障碍(Autism spectrum disorder,ASD)的辅助诊疗研究具有重要作用。然而现有的FC生成方法大多仅基于脑影像数据,未充分考虑个体的临床指标从而易丢失疾病的特异性信息。而且,ASD作为一种谱系障碍,其临床指标存在显著的个体化差异。因此,仅基于脑影像数据的传统生成模型在生成准确的且能反映个体化临床指标的ASD个体FC的任务上存在挑战。针对上述挑战,提出了个体化临床指标引导的沃瑟斯坦生成对抗网络模型(Clinical-indicator-aware Wasserstein generative adversarial network,CI-WGAN),用于生成孤独症个体化FC网络。该模型引入个体化临床指标引导机制,实现了高精度ASD患者FC网络的生成。基于全世界最大孤独症脑影像公开数据集之一的ABIDE I数据集进行实验,CI-WGAN生成FC与真实FC的峰值信噪比(Peak signal-to-noise ratio,PSNR)、结构相似度(Structural similarity,SSIM)与平均绝对误差(Mean absolute error,MAE)分别达到19.037、0.236与0.178,相较于其他FC生成模型分别提升了3%、12%与2%。此外基于生成FC和独立临床验证指标的表征相似度分析(Representational similarity analysis,RSA),CI-WGAN生成的FC相较其他模型生成FC最少提高了0.1倍和3.7倍,证明了CI-WGAN生成的FC包含更多的ASD个体特异性信息。本文提出的CI-WGAN模型实现了高质量个体化FC的生成,为ASD的早期诊断和个性化治疗提供了有力的技术支持。

关键词：孤独症谱系障碍大脑功能连接生成对抗网络临床指标引导机制梯度惩罚机制

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Diabetic peripheral neuropathy and neuromodulation techniques:a systematic review of progress and prospects

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Neural Regeneration Research 2025年第8期20卷 2218-2230页

作者： Rahul Mittal Keelin McKenna Grant keith Evan McKenna Joana R.N.Lemos Jeenu Mittal Khemraj Hirani Diabetes Research Institute University of Miami Miller School of MedicineMiamiFLUSA Department of Otolaryngology University of Miami Miller School of MedicineMiamiFLUSA Herbert Wertheim College of Medicine Florida International UniversityMiamiFLUSA School of Medicine and Public Health University of WisconsinMadisonWIUSA

Neuromodulation for diabetic peripheral neuropathy represents a significant area of interest in the management of chronic pain associated with this *** peripheral neuropathy,a common complication of diabetes,is characterized by nerve damage due to high blood sugar levels that lead to symptoms,such as pain,tingling,and numbness,primarily in the hands and *** aim of this systematic review was to evaluate the efficacy of neuromodulatory techniques as potential therapeutic interventions for patients with diabetic peripheral neuropathy,while also examining recent developments in this *** investigation encompassed an array of neuromodulation methods,including frequency rhythmic electrical modulated systems,dorsal root ganglion stimulation,and spinal cord *** systematic review suggests that neuromodulatory techniques may be useful in the treatment of diabetic peripheral *** the advantages of these treatments will enable physicians and other healthcare providers to offer additional options for patients with symptoms refractory to standard pharmacologic *** these efforts,we may improve quality of life and increase functional capacity in patients suffering from complications related to diabetic neuropathy.

关键词： diabetes mellitus diabetic peripheral neuropathy neuromodulation neurostimulation therapy non-pharmacological treatment pain management

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Hepatic vein reconstruction during hepatectomy:A feasible and underused technique

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 421-427页

作者： Manish Ahuja Kunal Joshi Chris Coldham Paulo Muiesan Bobby Dasari Manuel Abradelo Ravi Marudanayagam Darius Mirza John Isaac David Bartlett Nikolaos A Chatzizacharias Robert P Sutcliffe keith J Roberts Department of HPB and Liver Transplant Surgery University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Immunology and Immunotherapy University of BirminghamBirminghamUK

Complete surgical resection(R0)of liver tumors,primary or metastatic,remains the main objective in management of primary and metastatic liver tumors[1].Tumors invading to the proximity of the hepatic venous outflow pose a peculiar challenge to achieve R0 resections,because this location may render a tumor *** median survival of patients with liver tumor without surgery is less than 12 months[2].Even with surgery,post-hepatectomy liver failure and subsequently increased mortality are the main problems associated with complex resection[3].Moreover,when the vein is affected,vein resection and subsequent reconstruction are *** resection is a standard practice in liver resection and transplantation[4],for example,hepatic vein reconstruction during a living-donor liver transplant,porto-mesenteric axis reconstruction during resection of advanced pancreatic cancer and caval reconstruction during resection of retroperitoneal ***,novel techniques like total hepatic vascular exclusion(HVE)[5],veno-venous bypass[6]and ex vivo hepatic resection[7,8]have facilitated curative resections of tumors close to one or more major hepatic veins.

关键词： hepatectomy surgery mortality

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How completely are randomized controlled trials of non-pharmacological interventions following concussion reported? A systematic review

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Journal of Sport and Health Science 2024年第4期13卷 537-547页

作者： Jacqueline Josee van Ierssel Olivia Galea Kirsten Holte Caroline Luszawski Elizabeth Jenkins Jennifer O’Neil Carolyn A Emery Rebekah Mannix Kathryn Schneider keith Owen Yeates Roger Zemek Children’s Hospital of Eastern Ontario Research Institute OttawaON K1H 8L1Canada The Centre for Health Activity and Rehabilitation ResearchUniversity of OtagoDunedin 9016New Zealand Sport Injury Prevention Research Centre Faculty of KinesiologyUniversity of CalgaryCalgaryAB T2N 1N4Canada Alberta Children’s Hospital Research Institute University of Calgary CalgaryAB T2N 1N4Canada Hotchkiss Brain Institute University of CalgaryCalgaryAB T2N 4N1Canada Department of Psychology University of CalgaryCalgaryAB T2N 1N4Canada g Faculty of MedicineUniversity of OttawaOttawaON K1H 8M5Canada School of Rehabilitation Sciences University of OttawaOttawaON K1H 8M5Canada Bruyere Research Institute OttawaON K1N 5C8Canada Departments of Pediatrics and Emergency Medicine Harvard Medical SchoolBostonMA 02115USA Departments of Pediatrics and Emergency Medicine University of OttawaOttawaON K1H 8M5Canada

Purpose:The study aimed to examine the reporting completeness of randomized controlled trials(RCTs)of non-pharmacological interventions following ***:We searched MEDLINE,Embase,PsycInfo,CINAHL,and Web of Science up to May *** reviewers independently screened studies and assessed reporting completeness using the Template for Intervention Description and Replication(TIDieR),Consensus on Exercise Reporting Template(CERT),and international Consensus on Therapeutic Exercise aNd Training(i-CONTENT)*** information was sought my study authors where reporting was *** of bias(ROB)was assessed with the Cochrane ROB-2 *** examining non-pharmacological interventions following ***:We included 89 RCTs(n=53 high ROB)examining 11 different interventions for concussion:sub-symptom threshold aerobic exercise,cervicovestibular therapy,physical/cognitive rest,vision therapy,education,psychotherapy,hyperbaric oxygen therapy,transcranial magnetic stimulation,blue light therapy,osteopathic manipulation,and head/neck *** scores were:TIDieR 9/12(75%;interquartile range(IQR)=5;range:5-12),CERT 17/19(89%;IQR=2;range:10-19),and i-CONTENT 6/7(86%;IQR=1;range:5-7).Percentage of studies completely reporting all items was TIDieR 35%(31/89),CERT 24%(5/21),and i-CONTENT 10%(2/21).Studies were more completely reported after publication of TIDieR(t_(87)=2.08;p=0.04)and CERT(t_(19)=2.72;p=0.01).Reporting completeness was not strongly associated with journal impact factor(TIDieR:rs=0.27;p=0.01;CERT:r_(s)=-0.44;p=0.06;i-CONTENT:r_(s)=-0.17;p=0.48)or ROB(TIDieR:rs=0.11;p=0.31;CERT:rs=0.04;p=0.86;i-CONTENT:rs=0.12;p=0.60).Conclusion:RCTs of non-pharmacological interventions following concussion demonstrate moderate to good reporting completeness,but are often missing key components,particularly modifications,motivational strategies,and qualified *** completeness improved after TIDieR and CERT publication,but p

关键词： Concussion Intervention Randomized controlled trial Systematic review

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Tree structure and diversity shape the biomass of primary temperate mountain forests

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Forest Ecosystems 2024年第4期11卷 568-579页

作者： Dheeraj Ralhan Ruffy Rodrigo Heather keith Annemiek Irene Stegehuis Jakob Pavlin Yumei Jiang Milos Rydval Juliana Nogueira Alexandre Fruleux Marek Svitok Martin Mikolas Daniel Kozak Martin Dusatko Pavel Janda Oleh Chaskovsky Catalin-Constantin Roibu Miroslav Svoboda Czech University of Life Sciences Prague Faculty of Forestry and Wood SciencesKamycka 129Suchdol16521 Praha 6Czech Republic Department of Forest Science Biliran Province State UniversityBiliran6549Philippines Griffith Climate Action Beacon Griffith UniversityParklands DriveSouthportGold CoastQueensland4222Australia Laboratoire de Geologie IPSLCNRSUMR 8538Ecole Normale SuperieurePSL UniversityParisFrance Univ.Lille Institut Mines-TelecomUniv.ArtoisJuniaULR 4515LGCgELaboratoire de Genie Civil et Geo-EnvironnementF-59000LilleFrance Department of Biology and General Ecology Faculty of Ecology and Environmental SciencesTechnical University in ZvolenMasaryka 2496001ZvolenSlovakia Institute of Forest Management Ukrainian National Forestry UniversityLvivUkraine Forest Biometrics Laboratory–Faculty of Forestry Stefan Cel Mare University of SuceavaUniversitații Street Number.13Suceava720229Romania

Primary forests are spatially diverse terrestrial ecosystems with unique characteristics,being naturally regenerative and heterogeneous,which supports the stability of their carbon storage through the accumulation of live and dead ***,little is known about the interactions between biomass stocks,tree genus diversity and structure across a temperate montane primary ***,we investigated the relationship between tree structure(variability in basal area and tree size),genus-level diversity(abundance,tree diversity)and biomass stocks in temperate primary mountain forests across Central and Eastern *** used inventory data from726 permanent sample plots from mixed beech and spruce across the Carpathian *** used nonlinear regression to analyse the spatial variability in forest biomass,structure,and genus-level diversity and how they interact with plot-level tree age,disturbances,temperature and *** found that the combined effects of genus and structural indices were important for addressing the variability in biomass across different spatial *** processes in disturbance regimes and uneven tree age support forest hete rogeneity and the accumulation of live and dead biomass through the natural regeneration,growth and decay of the forest *** complexities in basal area index,supporte d by genus-level abundance,positively influence total biomass stocks,which was modulated by tree age and *** forests showed higher tree density and basal area than mixed beech forests,though mixed beech still contributes significantly to biomass across *** heterogeneity was strongly influenced by complexities in forest composition(tree genus diversity,structure).We addressed the importance of primary forests as stable carbon stores,achieved through structure and *** such ecosystems is critical for ensuring the stability of the primary forest,carbon store and biodiversity into the future.

关键词： Biodiversity indicators Biomass carbon stock Ecosystem functioning Forest composition Primary forest structure Tree size distribution

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