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Considerations for the use of porcine organ donation models in preclinical organ donor intervention research

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Animal Models and Experimental Medicine 2024年第3期7卷 283-296页

作者： Frazer I.Heinis Shaheed Merani Nicholas W.Markin Kim F.Duncan Michael J.Moulton Lance Fristoe william E.Thorell Raechel A.Sherrick Tami R.Wells Matthew T.Andrews Marian Urban School of Natural Resources Institute of Agriculture and Natural ResourcesUniversity of Nebraska-LincolnLincolnNebraskaUSA Division of Transplantation and Vascular Surgery Department of SurgeryUniversity of Nebraska Medical CenterOmahaNebraskaUSA Department of Anesthesiology University of Nebraska Medical CenterOmahaNebraskaUSA Division of Cardiothoracic Surgery Department of SurgeryUniversity of Nebraska Medical CenterOmahaNebraskaUSA Clinical Perfusion Nebraska Medicine-Nebraska Medical CenterOmahaNebraskaUSA Department of Neurosurgery University of Nebraska Medical CenterOmahaNebraskaUSA Nutrition and Health Sciences College of Education and Human SciencesUniversity of Nebraska-LincolnLincolnNebraskaUSA Department of Comparative Medicine University of Nebraska Medical CenterOmahaNebraskaUSA

Use of animal models in preclinical transplant research is essential to the optimization of human allografts for clinical *** models of organ donation and preservation help to advance and improve technical elements of solid organ recovery and facilitate research of ischemia-reperfusion injury,organ preservation strategies,and future donor-based *** considerations include cost,public opinion regarding the conduct of animal research,translational value,and relevance of the animal model for clinical *** present an overview of two porcine models of organ donation:donation following brain death(DBD)and donation following circulatory death(DCD).The cardiovascular anatomy and physiology of pigs closely resembles those of humans,making this species the most appropriate for pre-clinical *** are also considered a potential source of organs for human heart and kidney *** is imperative to minimize animal loss during procedures that are surgically *** present our experience with these models and describe in detail the use cases,procedural approach,challenges,alternatives,and limitations of each model.

关键词： animal model brain death circulatory death organ transplantation

An update on hormonal regulation of early embryo-fallopian tube interactions: insights for improvements of assisted reproductive technology outcomes

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Reproductive and Developmental Medicine 2024年第1期8卷 39-49页

作者： Suranga P.Kodithuwakku Ernest H.Y.Ng william S.B.Yeung Kai-Fai Lee Department of Obstetrics and Gynaecology LKS Faculty of MedicineThe University of Hong KongHong Kong SAR 999077China Department of Animal Science Faculty of AgricultureUniversity of PeradeniyaPeradeniya 20400Sri Lanka Shenzhen Key Laboratory of Fertility Regulation.The University of Hong Kong-Shenzhen Hospital Shenzhen 518053China

Human fallopian tubes(FTs)play important roles in the whole reproductive *** are the site for the final maturation of gametes,fertilization,transport of preimplantation embryos,and early embryonic development before entering the *** these functions are critical in the establishment of a successful *** the embryo is in transit through the FT,the FT microenvironment changes through endocrine,paracrine,autocrine,and juxtacrine mechanisms which involve various hormones and bioactive substances mainly from the neighboring ***,the interactions between the embryo and the FT may be the earliest embryo-maternal communications that are essential for the establishment of *** review critically discusses the evidence of various hormonal and bioactive mediated control of the microenvironment in the FTs during the earliest embryo-maternal ***,we highlight existing gaps in the knowledge and the importance of exploring more of the physiology of FTs which will hold the key to producing high-quality embryos for patients seekingin vitro fertilization(IVF)treatments.

关键词： Fallopian tube Embryo Maternal-embryo communication Hormonal control

The secondary injury cascade after spinal cord injury:an analysis of local cytokine/chemokine regulation

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Neural Regeneration Research 2024年第6期19卷 1308-1317页

作者： Daniel J.Hellenbrand Charles M.Quinn Zachariah J.Piper Ryan T.Elder Raveena R.Mishra Taylor L.Marti Phoebe M.Omuro Rylie M.Roddick Jae Sung Lee william L.Murphy Amgad S.Hanna Department of Neurosurgery University of Wisconsin-Madison School of Medicine and Public HealthMadisonWIUSA Department of Biomedical Engineering University of Wisconsin-MadisonMadisonWIUSA Department of Orthopedics and Rehabilitation University of Wisconsin-MadisonMadisonWIUSA Department of Materials Science and Engineering University of Wisconsin-MadisonMadisonWIUSA Forward BIO Institute University of Wisconsin-MadisonMadisonWIUSA

After spinal cord injury,there is an extensive infiltration of immune cells,which exacerbates the injury and leads to further neural ***,a major aim of current research involves targeting the immune response as a treatment for spinal cord *** much research has been performed analyzing the complex inflammatory process following spinal cord injury,there remain major discrepancies within previous literature regarding the timeline of local cytokine *** objectives of this study were to establish an overview of the timeline of cytokine regulation for 2 weeks after spinal cord injury,identify sexual dimorphisms in terms of cytokine levels,and determine local cytokines that significantly change based on the severity of spinal cord *** were inflicted with either a mild contusion,moderate contusion,severe contusion,or complete transection,7 mm of spinal cord centered on the injury was harvested at varying times post-injury,and tissue homogenates were analyzed with a Cytokine/Chemokine 27-Plex *** demonstrated pro-inflammatory cytokines including tumor necrosis factorα,interleukin-1β,and interleukin-6 were all upregulated after spinal cord injury,but returned to uninjured levels within approximately 24 hours post-injury,while chemokines including monocyte chemoattractant protein-1 remained upregulated for days *** contrast,several anti-inflammatory cytokines and growth factors including interleukin-10 and vascular endothelial growth factor were downregulated by 7 days *** spinal cord injury,tissue inhibitor of metalloproteinase-1,which specifically affects astrocytes involved in glial scar development,increased more than all other cytokines tested,reaching 26.9-fold higher than uninjured *** a mild injury,11 cytokines demonstrated sexual dimorphisms;however,after a severe contusion only leptin levels were different between female and male *** conclusion,pro-inflammatory cytokines in

关键词： astrocytes chemokines cytokines inflammation macrophages microglia secondary damage spinal cord injury

Extrahepatic cholestasis associated with paracoccidioidomycosis:Challenges in the differential diagnosis of biliopancreatic neoplasia

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2531-2540页

作者： Jose Sebastiao dos Santos Vitor de Moura Arrais william Jose Rosseto Ferreira Ricardo Ribeiro Correa Filho Mariangela Ottoboni Brunaldi Rafael Kemp Ajith Kumar Sankanrakutty Jorge Elias Junior Fernando Bellissimo-Rodrigues Roberto Martinez Edson Zangiacomi Martinez Jose Celso Ardengh Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo(FMRP-USP) Departamento de Cirurgia e AnatomiaRibeirao Preto 14049-900Sao PauloBrazil Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo(FMRP-USP)Departamento de PatologiaRibeirao Preto 14048900Sao PauloBrazil Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo(FMRP-USP)Departamento de Imagens MédicasHematologia e Oncologia ClínicaRibeirao Preto 14048900Sao PauloBrazil Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo(FMRP-USP)Departamento de Medicina SocialRibeirao Preto 14015-010Sao PauloBrazil Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo(FMRP-USP)Departamento de Clínica MédicaRibeirao Preto 14015-010Sao PauloBrazil Universidade de Sao Paulo Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo(FMRP-USP)Departamento de Cirurgia e AnatomiaRibeirao Preto 14049-900Sao PauloBrazil and Hospital MoriahServico de Endoscopia DigestivaSao Paulo 04084-002Sao PauloBrazil

BACKGROUND Paracoccidioidomycosis(PCM)may involve the hepatic pedicle and peripan creatic lymph nodes,cause damage to the bile duct and manifest,exceptionally,in combination with extrahepatic cholestasis(EHC),making investigation and treatment *** To investigate the management of patients with visceral PCM admitted with *** All patients diagnosed with PCM treated in a public,tertiary teaching hospital between 1982 and 2020 were retrospectively *** also identified with EHC were allocated to two groups according to the treatment approach for the purpose of comparing clinical,laboratory,and imaging findings,resources used for etiological diagnosis,treatment results,and *** analyses were performed using the linear mixed-effects model(random and fixed effects),which was adjusted using the PROC MIXED procedure of the SAS®9.0 software,and Fisher’s exact *** Of 1645 patients diagnosed with PCM,40(2.4%)had *** these,20(50.0%)lived in the rural area and 29(72.5%)were men,with a mean age of 27.1 years(3-65 years).Jaundice as first symptom and weight loss of at least 10 kg were observed in 16 patients(40.0%),and a mass in the head of the pancreas was observed in 8(20.0%).The etiological diagnosis was made by tissue collection during surgery in 4 cases(10.0%)and by endoscopic methods in 3 cases(7.5%).Twenty-seven patients(67.5%)received drug treatment alone(Group 1),whereas 13(32.5%)underwent endoscopic and/or surgical procedures in combination with drug treatment(Group 2).EHC was significantly reduced in both groups(40.7% in Group 1,with a mean time of 3 months;and 38.4% in Group 2,with a mean time of 7.5 months),with no statistically significant difference between *** recurrence rates,associated mainly with treatment nonadherence,were similar in both groups:37% in Group 1 and 15.4% in Group *** mortality rate was 18.5% in Group 1 and 23% in Group 2,with survival estimates of 71.3% and 72.5%,respectively,with

关键词： Cholestasis Jaundice Obstructive Blastomycosis Paracoccidioides Diagnosis Treatment

Interaction design for paediatric emergency VR training

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Virtual Reality & Intelligent Hardware 2020年第4期2卷 330-344页

作者： TJ matthews Feng TIAN Tom DOLBY Centre for Digital Entertainment Bournemouth UniversityUK Faculty of Science&Technology Bournemouth UniversityUK Head of Simulations AiSolveUK

Background Virtual reality(VR)in healthcare training has increased adoption and support,but efforts are still required to mitigate usability *** This study conducted a usability study of an in-use emergency medicine VR training application,available on commercially available VR hardware and with a standard interaction *** users without prior VR experience but with relevant medical expertise completed two simulation scenarios for a total of 18 recorded *** completed NASA Task Load Index and System Usability Scale questionnaires after each session,and their performance was recorded for the tracking of user *** and Conclusions Our results showed a medium(and potentially optimal)Workload and an above average System Usability *** was significant improvement in several factors between users'first and second sessions,notably increased Performance *** errors with the strongest correlation to usability were not directly tied to interaction design,however,but to a limited'possibility space'.Suggestions for closing this'gulf of execution'were presented,including'voice control'and'hand-tracking',which are only feasible for this commercial product now with the availability of the Oculus Quest ***,wider implications for VR medical training were outlined,and potential next steps towards a standardized design identified.

关键词： Virtual reality Medical training Human-Centred design Interaction design

Storylines of family medicine Ⅹ:standing up for diversity,equity and inclusion

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Family Medicine and Community Health 2024年第S3期12卷 89-98页

作者： william B Ventres Leslie A Stone Wayne W Bryant Jr Mario F Pacheco Edgar Figueroa Francis N Chu Shailendra Prasad David N Blane Na'amah Razon Ranit Mishori Robert L Ferrer Garrett S Kneese Family and Preventive Medicine University of Arkansas for Medical Sciences College of MedicineLittle RockArkansasUSA Family and Community Medicine University of New Mexico School of MedicineAlbuquerqueNew MexicoUSA Medicine Weill Cornell Medical CollegeNew YorkNew YorkUSA San Jose Family Medicine Residency Kaiser PermanenteSan JoseCaliforniaUSA Family Medicine and Community Health University of Minnesota Medical School—Twin Cities CampusMinneapolisMinnesotaUSA School of Health and Wellbeing University of GlasgowGlasgowUK Family and Community Medicine University of CaliforniaDavisSacramentoCaliforniaUSA Family Medicine Georgetown University School of MedicineWashingtonDistrict of ColumbiaUSA Family and Community Medicine UT Health San Antonio Long School of MedicineSan AntonioTexasUSA UC San Diego Family Medicine Residency Program San DiegoCaliforniaUSA

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine as interpreted by individual family physicians and medical educators in the USA and elsewhere around the ***‘Ⅹ:standing up for diversity,equity and inclusion’,authors address the following themes:‘The power of diversity—why inclusivity is essential to equity in healthcare’,‘Medical education for whom?’,‘Growing a diverse and inclusive workforce’,‘Therapeutic judo—an inclusive approach to patient care’,‘Global family medicine—seeing the world“upside down”’,‘The inverse care law‘,‘Social determinants of health as a lens for care’,‘Why family physicians should care about human rights’and‘Toward health equity—the opportunome’.May the essays that follow inspire readers to promote change.

关键词： illustration education family

Molecular Docking Studies on Streptomycin Antileishmanial Activity

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Open Journal of Physical Chemistry 2024年第2期14卷 36-48页

作者： Todd A. Young Matthew George Jr. Ayele Gugssa william M. Southerland Yayin Fang Clarence M. Lee Department of Biology Howard University Washington DC United States Department of Biochemistry and Molecular Biology Howard University Washington DC United States

Resistance to pentavalent antimonial drugs and the lack of vaccines make it urgent to find novel therapeutic options to treat Leishmaniasis, a tropical disease caused by the Leishmania protozoan parasite. The study reported here is to investigate if Streptomycin, an aminoglycoside, and Amphotericin B, the second-line treatment drug, exhibit antileishmanial activity through a similar mechanism. By using MOE (Molecular Operating Environment), we performed molecular docking studies on these drugs binding to a range of targets including ribosome targets in Leishmania and H. sapiens. Our study shows that the two drugs do not bind to the same pockets in Leishmania targets but to the same pockets in the human ribosome, with some differences in interactions. Moreover, our 2D maps indicated that Amphotericin B binds to the A-site in the human cytoplasmic ribosome, whereas streptomycin does not.

关键词： Leishmaniasis Streptomycin Amphotericin B Molecular Docking Aminoglycosides Antileishmanial

A field parcel-oriented approach to evaluate the crop cover-management factor and time-distributed erosion risk in Europe

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International Soil and Water Conservation Research 2023年第1期11卷 43-59页

作者： Francis matthews Gert Verstraeten Pasquale Borrelli Panos Panagos European Commission Joint Research Centre(JRC)IspraItaly Department of Earth and Environmental Sciences KU LeuvenBelgium Department of Science Roma Tre University00146RomeItaly

The crop cover-management(C-)factor in arable landscapes describes the soil erosion susceptibility associated with seasonally cultivated *** informatic and computational limitations have led many modelling studies to prescribe C-factor values and assume spatial and temporal ***,the multiple influencing factors ranging from parcel-scale crop cultivation and management to regional-scale rainfall regimes motivates new methods to capture this variation when identifying at-risk ***,we define a multi-component method to derive the C-factor by associating time series of canopy and residue surface cover from Sentinel-2 and climate-specific rainfall erosivity with Integrated Administration and Control System(IACS)field parcel data from European Union member states.A scalable and standardised method is emphasised to increase the future interoperability and inter-comparability of soil erosion modelling studies deploying the ***,field parcel simu-lation units with associated crop declarations provide a new reference scale to link predictions of soil erosion risk with specific management decisions and declarations by *** implementing the method on a homogenised subsample of 8600 field parcels covering available IACS regions,several key findings are outlined:1)time series information provides new opportunities to predict the time-criticality of erosion in specific crop cultivations,2)the varying(a-)synchronicity between seasonal crop canopy cover and heavy rainstorms means that spatial variability is inherent within the C-factor across Europe,and 3)the addition of agricultural management practices(*** practice de-scriptions)to open-access IACS repositories can facilitate more comprehensive evaluations of the C-factor and soil erosion risk.

关键词： C-factor Soil erosion Modelling Remote sensing Crop-phenology IACS data Soil conservation Europe

The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

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Genes & Diseases 2024年第3期11卷 155-187页

作者： Michael Yu Kevin Qin Jiaming Fan Guozhi Zhao Piao Zhao Wei Zeng Connie Chen Annie Wang Yonghui Wang jiamin Zhong Yi Zhu william Wagstaff Rex C.Haydon Hue H.Luu Sherwin Ho Michael J.Lee Jason Strelzow Russell R.Reid Tong-Chuan He School of Medicine Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Orthopedic Surgery The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Department of Orthopaedic Surgery Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China

The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across *** proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling *** behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling *** signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various *** includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem *** signaling has also been implicated in tumor cells that exhibit stem cell-like *** signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone *** surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including *** of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and ***,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt *** with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

关键词： β-Catenin Cancer Canonical Wnt Disease Non-canonical Wnt Stem cells Targeted therapy Wnt signaling