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Regenerative Biomaterials 2020年第4期7卷 413-425页

作者： Hamad Alsaykhan Jennifer Z.Paxton Anatomy@edinburgh Edinburgh Medical School:Biomedical SciencesThe University of EdinburghTeviot PlaceEdinburgh EH89AGUK Department of Basic medical sciences College of Medicine and Health SciencesQassim UniversityPO Box 99151911 Unaizah CampusAl-Qassim 51911Saudi Arabia

Musculoskeletal tissue interfaces are a common site of injury in the young,active *** particular,the interface between the musculoskeletal tissues of tendon and bone is often injured and to date,no single treatment has been able to restore the form and function of damaged tissue at the bone-tendon *** engineering and regeneration hold great promise for the manufacture of bespoke in vitro models or implants to be used to advance repair and so this study investigated the material,orientation and culture choices for manufacturing a reproducible 3D model of a musculoskeletal interface between tendon and bone cell *** models are essential for future studies focussing on the regeneration of musculoskeletal interfaces in ***-encapsulated fibrin hydrogels,arranged in a horizontal orientation though a simple moulding procedure,were shown to best support cellular growth and migration of cells to form an in vitro tendon-bone *** study highlights the importance of acknowledging the material and technical challenges in establishing co-cultures and suggests a reproducible methodology to form 3D co-cultures between tendon and bone,or other musculoskeletal cell types,in vitro.

关键词： tendon bone 3D co-culture hydrogels musculoskeletal interface

Defense and anti-defense mechanisms of bacteria and bacteriophages

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第3期25卷 181-196页

作者： Xiaoqing WANG Sebastian LEPTIHN school of Medicine Lishui UniversityLishui 323000China University of edinburgh medical school Biomedical SciencesCollege of Medicine&Veterinary MedicineThe University of EdinburghEdinburgh EH89JZUK HMU Health and medical University Am Anger 64/73-99084 ErfurtGermany

In the post-antibiotic era,the overuse of antimicrobials has led to a massive increase in antimicrobial resistance,leaving medical doctors few or no treatment options to fight infections caused by *** use of bacteriophages is a promising alternative to treat infections,supplementing or possibly even replacing *** phages for therapy is possible,since these bacterial viruses can kill bacteria specifically,causing no harm to the normal ***,bacteria have developed a multitude of sophisticated and complex ways to resist infection by phages,including abortive infection and the clustered regularly interspersed short palindromic repeats(CRISPR)/CRISPR-associated(Cas)*** also can evolve and acquire new anti-defense strategies to continue *** in-depth exploration of both defense and anti-defense mechanisms would contribute to optimizing phage therapy,while we would also gain novel insights into the microbial *** this paper,we summarize recent research on bacterial phage resistance and phage anti-defense mechanisms,as well as collaborative win-win systems involving both virus and host.

关键词： Bacteriophage Phage resistance Abortive infection Phage therapy

The causal relationship between neurocysticercosis infection and the development of epilepsy-a systematic review

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Infectious Diseases of Poverty 2017年第1期6卷 261-273页

作者： Lucy B.Gripper Susan C.Welburn Division of Infection and Pathway Medicine Edinburgh Infectious DiseasesEdinburgh Medical School:Biomedical SciencesCollege of Medicine and Veterinary MedicineThe University of EdinburghChancellor’s Building49 Little France CrescentEdinburgh EH164SBScotlandUK

Background:Neurocysticercosis(NCC)is a parasitic infection of the human central nervous system,the most common form of which involves infection of the brain parenchyma with the larval form of the Taenia solium tapeworm.A causal relationship between such an NCC infection and the development of epilepsy in infected individuals is acknowledged,in part supported by high levels of comorbidity in endemic countries ***:This study undertook a systematic review and critical analysis of the NCC-epilepsy relationship with the primary objective of quantifying the risk of developing epilepsy following NCC infection.A secondary aim was to analyse the proportions of NCC-associated epilepsy within different *** emphasis was placed on the importance of neuroimaging(CT or MRI)availability and use of clear guidelines for epilepsy diagnosis,in order to avoid overestimations of prevalence rates of either condition;a limitation identified in several previous ***:A common odds ratio of 2.76 was identified from meta-analysis of case-control studies,indicating that an individual infected with NCC has almost a three times higher risk of developing epilepsy than an uninfected ***,meta-analysis of studies identified a common proportion of 31.54%of epilepsy cases associated with NCC infection which suggests that amongst epileptic populations in at risk countries,approximately one-third may be associated with NCC ***:A significant finding was the lack of good clinical data to enable accurate determination of a causal *** studies that were included had noticeable limitations,including a general lack of consistency in diagnostics,and lack of accurate epidemiological *** review highlights a need for consistency in research in this *** the absence of reliable estimates of its global burden,NCC will remain of low priority in the eyes of funding agencies-a truly neglected disease.

关键词： epilepsy neglected enable

Optimized combinations of statins and azoles against Acanthamoeba trophozoites and cysts in vitro

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Asian Pacific Journal of Tropical Medicine 2019年第6期12卷 283-287页

作者： Ines Sifaoui Carmen M Martín-Navarro Atteneri López-Arencibia María Reyes-Batlle Basilio Valladares JoséE.Pinero Sutherland K Maciver Jacob Lorenzo-Morales University Institute of Tropical Diseases and Public Health of the Canary Islands University of La LagunaCanary IslandsSpain Centre for Integrative Physiology Biomedical SciencesEdinburgh Medical SchoolUniversity of EdinburghScotlandUK

Objective: To evaluate the combination of several statins(atorvastatin, fluvastatin and simvastatin) and azoles(voriconazole, posaconazole and itraconazole) against Acanthamoeba spp. Methods: The efficiency of the different drug combinations against the trophozoite stage of different Acanthamoeba strains were evaluated by Alamar Blue assay. Effect on the cyst stage was observed by inverted microscope. Cytotoxicity of combinations of azoles and statins was evaluated by measuring the release of lactate dehydrogenase from a murine macrophage cell line. Results: Combinations of any of the tested statins and voriconazole or posaconazole were more efficient in inhibiting Acanthamoeba compared to statins or azoles individually. The drug combinations at the combined inhibitory concentrations 50% showed lower toxicity compared to that of the compounds ***: The combinations of statins together with voriconazole and posaconazole are more efficient than these drugs alone, and these combinations have lower cytotoxicity in mammalian cell lines.

关键词： Keratitis Voriconazole Posaconazole Atorvastatin Fluvastatin Simvastatin

Do medical students studying in the United Kingdom have an adequate factual knowledge of basic life support?

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World Journal of Emergency Medicine 2019年第2期10卷 75-80页

作者： Robert D.Willmore Damjan Veljanoski Feray Ozdes Bethan Stephens James Mooney Seamus G.Crumley Arpan Doshi Philippa Davies Shreya Badhrinarayanan Emily Day Kristian Tattam April Wilson Nathan Crang Lorna Green Craig A.Mounsey Howell Fu Joseph Williams Michelle S.D'souza Dhanya Sebastian Liam A.Mcgiveron Matthew G.Percy James Cohen Imogen J.John Alice Lethbridge Imogen Watkins Omar Amin Mubasher A.Qamar John Gerrard Hanrahan Emily Cramond-Wong Barts Health NHS Trust Barts & the London medical school Queen Mary University of London Norwich medical school University of East Anglia Lancaster medical school Lancaster University school of Medicine Dentistry and Biomedical Sciences Queen's University Belfast Faculty of Medicine University of St Andrews Faculty of Medicine Dentistry and Health University of Sheffi eld Brighton and Sussex University Hospitals NHS Trust St George's University of London University of Liverpool school of Medicine University of Exeter medical school Faculty of Medicine University of Southampton medical sciences Division University of Oxford University of edinburgh medical school Faculty of Medicine University of Warwick University College London medical school Cardiff University school of Medicine College of medical and Dental sciences University of Birmingham College of medical Veterinary and Life Sciences University of Glasgow Guys Kings and St Thomas School of Medicine King’s College London Faculty of Life sciences & Medicine King's College London Faculty of Health sciences at the University of Nottingham

BACKGROUND: Healthcare professionals have a duty to maintain basic life support(BLS) skills. This study aims to evaluate medical students' factual knowledge of BLS and the training they ***: A cross-sectional, closed-response questionnaire was distributed to the fi rst-and fourth-year students studying at institutions in the United Kingdom. The paper questionnaire sought to quantify respondent's previous BLS training, factual knowledge of the BLS algorithm using five multiple choice questions(MCQs), and valuate their desire for further BLS training. Students received 1 point for each correctly identifi ed answer to the 5 MCQ'***: A total of 3,732 complete responses were received from 21 medical schools. Eighty percent(n=2,999) of students completed a BLS course as part of their undergraduate medical studies. There was a signifi cant difference(Pmedical students in the UK. There is a disparity in standards of knowledge across institutions and respondents indicating that they would like more training.

关键词： Emergency Medicine Basic life support medical education Resuscitation

Prediction of cell-cell communication patierns of dorsal root ganglion cells:single-cell RNA sequencing data analysis

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Neural Regeneration Research 2024年第6期19卷 1367-1374页

作者： Yanna Lian Cheng Wu Li Liu Xiangyao Li National Health Commission and Chinese Academy of medical sciences Key Laboratory of medical Neurobiology Ministry of Education Frontier Science Center for Brain Research and Brain-Machine IntegrationSchool of Brain Science and Brain MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina International Institutes of Medicine the Fourth Affiliated Hospital of Zhejiang University School of MedicineYiwuZhejiang ProvinceChina Zhejiang University-University of edinburgh Institute Zhejiang University School of MedicineZhejiang UniversityHainingZhejiang ProvinceChina biomedical sciences College of Medicine and Veterinary MedicineThe University of EdinburghEdinburghUK Core Facilities of the school of Medicine Zhejiang UniversityHangzhouZhejiang ProvinceChina

Dorsal root ganglion neurons transmit peripheral somatic information to the central nervous system,and dorsal root ganglion neuron excitability affects pain *** root ganglion stimulation is a new approach for managing pain *** of the cell-cell communication among dorsal root ganglion cells may help in the development of new pain and itch management ***,we used the single-cell RNA-sequencing(scRNA-seq)database to investigate intercellular communication networks among dorsal root ganglion *** collected scRNA-seq data from six samples from three studies,yielding data on a total of 17,766 *** on genetic profiles,we identified satellite glial cells,Schwann cells,neurons,vascular endothelial cells,immune cells,fibroblasts,and vascular smooth muscle *** analysis revealed that eight types of dorsal root ganglion neurons mediated proprioceptive,itch,touch,mechanical,heat,and cold ***,we predicted several distinct forms of intercellular communication among dorsal root ganglion cells,including cell-cell contact,secreted signals,extracellular matrix,and neurotransmitter-mediated *** data mining predicted that Mrgpra3-positive neurons robustly express the genes encoding the adenosine Adora2b(A2B)receptor and glial cell line-derived neurotrophic factor family receptor alpha 1(GFRα-1).Our immunohistochemistry results confirmed the coexpression of the A2B receptor and GFRα-*** injection of the A2B receptor antagonist PSB-603 effectively prevented histamine-induced scratching behaviour in a dose-dependent *** results demonstrate the involvement of the A2B receptor in the modulation of itch ***,our findings provide insight into dorsal root ganglion cell-cell communication patterns and *** results should contribute to the development of new strategies for the regulation of dorsal root ganglion excitability.

关键词： cell-cell communications CellChat dorsal root ganglion scRNA-Seq database

Global aspirations, local realities: the role of social science research in controlling neglected tropical diseases

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Infectious Diseases of Poverty 2014年第1期3卷 310-324页

作者： Kevin Bardosh Centre of African Studies School of Social and Political ScienceCollege of Humanities and Social ScienceThe University of Edinburgh58 George SquareEdinburgh EH89LDUK Division of Pathway Medicine and Centre for Infectious Diseases School of Biomedical SciencesCollege of Medicine and Veterinary MedicineThe University of EdinburghChancellor’s Building49 Little France CrescentEdinburgh EH164SBUK

Neglected Tropical Diseases(NTDs)are both drivers and manifestations of poverty and social *** advocacy efforts since the mid-2000s have led to ambitious new control and elimination targets set for 2020 by the World Health *** these global aspirations represent significant policy momentum,there are multifaceted challenges in controlling infectious diseases in resource-poor local contexts that need to be acknowledged,understood and *** a number of recent publications have emphasised the“neglected”status of applied social science research on *** light of the 2020 targets,this paper explores the social science/NTD literature and unpacks some of the ways in which social inquiry can help support effective and sustainable *** priority areas are discussed,including on policy processes,health systems capacity,compliance and resistance to interventions,education and behaviour change,and community *** paper shows that despite the multifaceted value of having anthropological and sociological perspectives integrated into NTD programmes,contemporary efforts underutilise this *** is reflective of the dominance of top-down information flows and technocratic approaches in global *** counter this tendency,social research needs to be more than an afterthought;integrating social inquiry into the planning,monitoring and evaluating process will help ensure that flexibility and adaptability to local realities are built into *** emphasis on social science perspectives can also help link NTD control to broader social determinants of health,especially important given the major social and economic inequalities that continue to underpin transmission in endemic countries.

关键词： Neglected tropical diseases Applied social sciences Implementation research Social determinants Community participation Policy Global health Sociology Anthropology

Evaluating the impact of targeting livestock for the prevention of human and animal trypanosomiasis,at village level,in districts newly affected with *** in Uganda

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Infectious Diseases of Poverty 2017年第1期6卷 128-139页

作者： Louise Hamill Kim Picozzi Jenna Fyfe Beatrix von Wissmann Sally Wastling Nicola Wardrop Richard Selby Christine Amongi Acup Kevin L.Bardosh Dennis Muhanguzi John D.Kabasa Charles Waiswa Susan C.Welburn edinburgh Infectious Diseases Division of Infection and Pathway MedicineEdinburgh Medical School:Biomedical SciencesThe University of EdinburghChancellor’s Building49 Little France CrescentEdinburgh EH164SBUK Department of Pharmacy Clinical and Comparative MedicineSchool of Veterinary Medicine and Animal ResourcesMakerere UniversityP.O.Box 7062KampalaUganda The Coordinating Office for Control of Trypanosomiasis in Uganda(COCTU) WandegeyaPlot 76/78 Buganda RoadP.O.Box 16345KampalaUganda

Background:Uganda has suffered from a series of epidemics of Human African Trypanosomiasis(HAT),a tsetse transmitted disease,also known as sleeping *** area affected by acute Trypanosoma brucei rhodesiense HAT(rHAT)has been expanding,driven by importation of infected cattle into regions previously free of the *** regions are also affected by African Animal Trypanosomiasis(AAT)demanding a strategy for integrated disease ***:In 2008,the Public Private Partnership,Stamp Out Sleeping Sickness(SOS)administered a single dose of trypanocide to 31486 head of cattle in 29 parishes in Dokolo and Kaberamaido *** study examines the impact of this intervention on the prevalence of rHAT and AAT trypanosomes in cattle from villages that had(HAT^(+ve))or had not(HAT^(-ve))experienced a recent case of *** herds from 20 villages were sampled and screened by PCR,pre-intervention and 6-months post-intervention,for the presence or absence of:Trypanosoma brucei s.l.;human infective ***;Trypanosoma vivax;and Trypanosoma congolense ***:Post-intervention,there was a significant decrease in the prevalence of *** *** the human infective sub-species *** in village cattle across all 20 *** prevalence of *** was reduced from 2.4%to 0.74%(P<0.0001),with the intervention showing greater impact in HAT^(-ve) *** number of villages containing cattle harbouring human infective parasites decreased from 15/20 to 8/20,with *** infection mainly persisting within cattle in HAT^(+ve) villages(six/eight).The proportion of *** *** identified as human infective *** decreased after the intervention from 8.3%(95%CI=11.1-5.9%)to 4.1%(95%CI=6.8-2.3%).Villages that had experienced a recent human case(HAT^(+ve) villages)showed a significantly higher prevalence for AAT both pre-and *** AAT the prevalence of *** was significantly red

关键词： African animal trypanosomiasis(AAT) Human African trypanosomiasis(HAT) Sleeping sickness Trypanosma brucei rhodesiense HAT(rHAT) Uganda T.b.brucei T.b.rhodesiense

Optical Detection of Distal Lung Enzyme Activity in Human Inflammatory Lung Disease

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biomedical Engineering Frontiers 2021年第1期2卷 44-54页

作者： Alicia Megia-Fernandez Adam Marshall Ahsan R.Akram Bethany Mills Sunay V.Chankeshwara Emma Scholefield Amy Miele Bruce C.McGorum Chesney Michaels Nathan Knighton Tom Vercauteren Francois Lacombe Veronique Dentan Annya M.Bruce Joanne Mair Robert Hitchcock Nik Hirani Chris Haslett Mark Bradley Kevin Dhaliwal EaStCHEM The University of Edinburgh School of ChemistryJoseph Black BuildingWest Mains RoadEdinburghUK EH93FJ Translational Healthcare Technologies Group Centre for Inflammation ResearchQueen’s Medical Research InstituteUniversity of Edinburgh47 Little France CrescentEdinburgh BioQuarterEdinburghUK EH164TJ The Roslin Institute and Royal(Dick)school of Veterinary Studies University of EdinburghEaster BushMidlothianUK EH259RG Department of biomedical Engineering University of Utah36 S Wasatch DrSalt Lake CityUT 84112USA school of biomedical Engineering&Imaging sciences King’s College LondonLondonUK SE17EH Mauna Kea Technologies 9Rue d’EnghienParisFrance 75010

Objective and Impact *** is a need to develop platforms delineating inflammatory biology of the distal human *** describe a platform technology approach to detect in situ enzyme activity and observe drug inhibition in the distal human lung using a combination of matrix metalloproteinase(MMP)optical reporters,fibered confocal fluorescence microscopy(FCFM),and a bespoke delivery *** development of new therapeutic agents is hindered by the lack of in vivo in situ experimental methodologies that can rapidly evaluate the biological activity or drug-target engagement in *** optimised a novel highly quenched optical molecular reporter of enzyme activity(FIB One)and developed a translational pathway for in-human *** demonstrate the specificity for matrix metalloproteases(MMPs)2,9,and 13 and probe dequenching within physiological levels of MMPs and feasibility of imaging within whole lung models in preclinical ***,in a first-in-human exploratory experimental medicine study of patients with fibroproliferative lung disease,we demonstrate,through FCFM,the MMP activity in the alveolar space measured through FIB One fluorescence increase(with pharmacological inhibition).*** translational in situ approach enables a new methodology to demonstrate active drug target effects of the distal lung and consequently may inform therapeutic drug development pathways.

关键词： Lung lung specificity

YTHDF2-mediated regulations bifurcate BHPF-induced programmed cell deaths

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National Science Review 2023年第12期10卷 83-97页

作者： Jiebo Lin Guankai Zhan Jinfeng Liu Yasen Maimaitiyiming Zhiping Deng Baohua Li Kunhui Su Jiafeng Chen Siqi Sun Wanlin Zheng Xianghui Yu Feng He Xiaodong Cheng Lingfang Wang Bin Shen Ziqin Yao Xinquan Yang Jian Zhang Wentao He Hengyu Wu Hua Naranmandura Kao-Jung Chang Junxia Min Jun Ma Mikael Bj?rklund Peng-Fei Xu Fudi Wang Chih-Hung Hsu Women's Hospital The Fourth Affiliated Hospitaland Department of Environmental MedicineZhejiang University School of Medicine Institute of Genetics International School of MedicineZhejiang University The Second Affiliated Hospital School of Public Health State Key Laboratory of Experimental Hematology Zhejiang University School of Medicine Department of Hematology of First Affiliated Hospital and Department of Public Health Zhejiang University School of Medicine State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products Institute of Virology and Biotechnology Zhejiang Academy of Agricultural Sciences Department of Obstetrics Women's Hospital School of Medicine Zhejiang University Women's Hospital and Institute of Genetics Zhejiang University School of Medicine Zhejiang Provincial Key Lab of Genetic and Developmental Disorders Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women's HospitalZhejiang University School of Medicine State Key Laboratory of Reproductive Medicine Center for Global HealthGusu School Women's Hospital of Nanjing Medical University Nanjing Maternity and Child Health Care Hospital Nanjing Medical University The First Affiliated Hospital Basic Medical SciencesSchool of Public HealthSchool of Pharmaceutical Science Hengyang Medical School University of South China Department of medical Research Taipei Veterans General Hospital The First Affiliated Hospital Institute of Translational MedicineCancer Center Zhejiang University School of Medicine Zhejiang University-University of edinburgh (ZJU-UoE) Institute University of edinburgh medical school Biomedical SciencesCollege of Medicine & Veterinary MedicineUniversity of Edinburgh

N6-methyladenosine(m6A) is a critical regulator in the fate of RNA, but whether and how m6A executes its functions in different tissues remains largely obscure. Here we report downregulation of a crucial m6A reader, YTHDF2, leading to tissue-specific programmed cell deaths(PCDs) upon fluorene-9-bisphenol(BHPF) exposure. Currently, Bisphenol A(BPA) substitutes are widely used in plastic *** eight common BPA substitutes, we detected BHPF in 14% serum samples of pregnant participants. In a zebrafish model, BHPF caused tissue-specific PCDs triggering cardiac and vascular ***, BHPF-mediated downregulation of YTHDF2 reduced YTHDF2-facilitated translation of m6A-gch1 for cardiomyocyte ferroptosis, and decreased YTHDF2-mediated m6A-sting1 decay for caudal vein plexus(CVP) apoptosis. The two distinct YTHDF2-mediated m6A regulations and context-dependent co-expression patterns of gch1/ythdf2 and tnfrsf1a/ythdf2 contributed to YTHDF2-mediated tissue-specific PCDs, uncovering a new layer of PCD regulation. Since BHPF/YTHDF2-medaited PCD defects were also observed in mammals, BHPF exposure represents a potential health threat.

关键词： RNA m6A modification programmed cell deaths bifurcation role of YTHDF2 environmental stress and m6A regulation fluorene-9-bisphenol (BHPF)