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Liver-specific glucocorticoid action in alcoholic liver disease:Study of glucocorticoid receptor knockout and knockin mice

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Academic productivity correlates with industry earnings in foot and ankle fellowship programs in the United States:A retrospective analysis

肝脏研究（英文） 2024年第2期8卷 91-104页

作者： Yazheng Wang conor Fahy Hong Lu Department of Pharmacology SUNY Upstate Medical UniversitySyracuseNYUSA

Background and aim:Glucocorticoids are the only first-line drugs for severe alcoholic hepatitis(AH),with limited efficacy and various side effects on extrahepatic ***-targeting glucocorticoid therapy may have multiple advantages over systemic glucocorticoid for *** aim of this study was to determine the role of hepatocellular glucocorticoid receptor(GR)in alcohol-associated steatosis(AS)and AH.Materials and methods:AS was induced by a high-fat diet plus binge alcohol in adult male and female mice with liver-specific knockout(LKO)and heterozygote of *** was induced by chronic-plus-binge in middle-aged male mice with liver-specific knockin of *** in hepatic mRNA and protein expression were determined by quantitative real-time polymerase chain reaction and Western blot.Results:GR-LKO aggravated steatosis and decreased hepatic expression and circulating levels of albumin in both genders of AS mice but only increased markers of liver injury in male AS *** steatosis in GR-LKO mice was associated with induction of lipogenic genes and down-regulation of bile acid synthetic *** protein levels of GR,hepatocyte nuclear factor 4 alpha,and phosphorylated signal transducer and activator of transcription 3 were gene-dosage-dependently decreased,whereas that of lipogenic ATP citrate lyase was increased in male GR heterozygote and LKO ***,hepatic expression of estrogen receptor alpha(ERα)was induced,and the essential estrogen-inactivating enzyme sulfotransferase 1e1 was gene-dosage-dependently down-regulated in GR heterozygote and knockout AS mice,which was associated with induction of ERα-target ***-specific knockin of GR protected against liver injury and steatohepatitis in middle-aged AH mice.conclusions:Hepatic GR deficiency plays a crucial role in the pathogenesis of AS induced by high-fat diet plus binge,and liver-specific overexpression/activation of GR protects against chronic-plus-binge-induced AH in middl

关键词： Glucocorticoid receptor (GR) Alcohol-associated steatosis (AS) Alcoholic hepatitis (AH) Heterozygote Liver-specific knockout Liver-specific knockin Hepatic protection

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World Journal of Orthopedics 2024年第2期15卷 129-138页

作者： Albert T Anastasio Anthony N Baumann Kempland c Walley Kyle J Hitchman conor O’Neill Jonathan Kaplan Samuel B Adams Department of Orthopedic Surgery Duke University HospitalDurhamNC 27710United States college of Medicine Northeast Ohio Medical UniversityRootstownOH 44272United States Department of Orthopedic Surgery University of MichiganAnn ArborMI 48109United States School of Osteopathic Medicine Campbell UniversityLillingtonNC 27546United States

BAcKGROUND The study investigates the connection between academic productivity and industry earnings in foot and ankle orthopedic surgery *** metrics like the H-index and Open Payments Database(OPD)data,it addresses a gap in understanding the relationship between scholarly achievements and financial outcomes,providing a basis for further exploration in this specialized medical *** To elucidate the trends between academic productivity and industry earnings across foot and ankle orthopedic surgery fellowship programs in the United *** This study is a retrospective analysis of the relationship between academic productivity and industry earnings of foot and ankle orthopedic surgery fellowships at an individual faculty and fellowship *** productivity was defined via H-index and recorded from the Scopus *** earnings were recorded from the *** Forty-eight foot and ankle orthopedic surgery fellowships(100%of fellowships)in the United States with a combined total of 165 physicians(95.9%of physicians)were *** individual physician(n=165)total life-time earnings reported on the OPD website was United States Dollar(USD)451430.30±1851084.89(range:USD 25.16-21269249.85;median:USD 27839.80).Mean physician(n=165)H-index as reported on Scopus is 14.24±12.39(range:0-63;median:11).There was a significant but weak correlation between individual physician H-index and individual physician total life-time earnings(Pcant and moderate positive correlation between combined fellowship H-index and total life-time earnings per fellowship(P=0.004,Spearman’s rho=0.409).cONcLUSION There is a significant and positive correlation between academic productivity and industry earnings at foot and ankle orthopedic surgery fellowships in the United *** observation is true on an individual physician level as well as on a fellowship level.

关键词： Sunshine act Foot and ankle Orthopedic surgery Orthopedic fellowship Industry earnings

Perceived value of microfinance and SME performance: The role of exploratory innovation

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International Journal of Innovation Studies 2024年第2期8卷 172-185页

作者： christian Sarfo Jing A.Zhang conor O'Kane Paula O'Kane Department of Management University of LincolnBrayford PoolLincoln LN67TSUnited Kingdom Department of Management Otago Business SchoolUniversity of OtagoPO Box 56Dunedin9054New Zealand

This study examines how perceived value of microfinance and exploratory innovation affect small and medium-sized enterprises(SME)performance in the context of a developing *** on the strategic innovation and microfinance literature,we hypothesize that(1)perceived value of microfinance affects exploratory innovation and SME performance,and(2)exploratory innovation serves as an effective mechanism through which microfinance enhances SME *** employ partial least squares structural equation modeling(PLS-SEM)to test our *** a sample of 581 Ghanaian SMEs with microfinance,the results of the PLS SEM support our *** further conducted a qualitative analysis of comments provided by the SMEs(n=144)to gain a deeper understanding of exploratory innovation in developing *** findings show that SMEs purposefully attempt to strengthen their exploratory inno-vation in *** discuss the theoretical and practical implications of these findings as well as future research avenues.

关键词： Perceived value of microfinance Exploratory innovation SME performance

Human-artificial intelligence interaction in gastrointestinal endoscopy

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World Journal of Gastrointestinal Endoscopy 2024年第3期16卷 126-135页

作者： John R campion Donal B O'connor conor Lahiff Department of Gastroenterology Mater Misericordiae University HospitalDublin D07 AX57Ireland School of Medicine University College DublinDublin D04 C7X2Ireland Department of Surgery Trinity College DublinDublin D02 R590Ireland

The number and variety of applications of artificial intelligence(AI)in gastr-ointestinal(GI)endoscopy is growing *** technologies based on machine learning(ML)and convolutional neural networks(cNNs)are at various stages of development and deployment to assist patients and endoscopists in preparing for endoscopic procedures,in detection,diagnosis and classification of pathology during endoscopy and in confirmation of key performance *** based on ML and cNNs require regulatory approval as medical *** between humans and the technologies we use are complex and are influenced by design,behavioural and psychological *** to the substantial differences between AI and prior technologies,important differences may be expected in how we interact with advice from AI ***-AI interaction(HAII)may be optimised by developing AI algorithms to minimise false positives and designing platform interfaces to maximise *** factors influencing HAII may include automation bias,alarm fatigue,algorithm aversion,learning effect and *** of these areas merits further study in the specific setting of AI applications in GI endoscopy and professional societies should engage to ensure that sufficient emphasis is placed on human-centred design in development of new AI technologies.

关键词： Artificial intelligence Machine learning Human factors computer-aided detection colonoscopy Adenoma detection rate

Helicobacter pylori:High dose amoxicillin does not improve primary or secondary eradication rates in an Irish cohort

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World Journal of clinical cases 2024年第16期12卷 2773-2779页

作者： conor costigan Aoife M O'Sullivan Jim O'connell Shreyashee Sengupta Thomas Butler Stephen Molloy Fintan John O'Hara Barbara Ryan Niall Breslin Sarah O'Donnell Anthony O'connor Sinead Smith Deirdre McNamara Trinity Academic Gastroenterology Group School of Medicine-Trinity College DublinDublin D2Ireland Department of Gastroenterology Tallaght University HospitalDublin D24 NR0AIreland

BAcKGROUND Helicobacter pylori(***)eradication rates have fallen globally,likely in large part due to increasing antibiotic resistance to traditional *** areas of high clarithromycin and metronidazole resistance such as ours,Maastricht VI guidelines suggest high dose amoxicillin dual therapy(HDADT)can be considered,subject to evidence for local *** this study we assess efficacy of HDADT therapy for *** eradication in an Irish *** To assess the efficacy of HDADT therapy for *** eradication in an Irish cohort as both first line,and subsequent therapy for patients diagnosed with *** All patients testing positive for *** in a tertiary centre were treated prospectively with HDADT(amoxicillin 1 g tid and esomeprazole 40 mg bid×14 d)over a period of 8 *** was confirmed with Urea Breath Test at least 4 wk after cessation of therapy.A delta-over-baseline>4%was considered *** demographics and treatment outcomes were recorded,analysed and controlled for basic demographics and prior *** *** One hundred and ninety-eight patients were identified with *** infection,10 patients were excluded due to penicillin allergy and 38 patients refused follow up *** all 139 were included in the analysis,55%(n=76)were female,mean age was 46.6 ***,93(67%)of patients were treatment-naïve and 46(33%)had received at least one previous course of *** groups were statistically ***-reported compliance with HDADT was 97%,mild side-effects occurred in 7%.There were no serious adverse drug *** the eradication rate for our cohort was 56%(78/139).Eradication rates were worse for those with previous treatment[43%(20/46)vs 62%(58/93),P=0.0458,odds ratio=2.15].Age and Gender had no effect on eradication *** Overall eradication rates with HDADT were *** being a simple and possibly better tolerated regime,these results do not

关键词： Helicobacter pylori eradication Helicobacter pylori High dose amoxicillin High dose amoxicillin dual therapy Triple therapy

chimeric Antigen Receptors and Regulatory T cells:The Potential for HLA-Specific Immunosuppression in Transplantation

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Engineering 2022年第3期8卷 30-43页

作者： Sabrina Wright conor Hennessy Joanna Hester Fadi Issa Nuffield Department of Surgical Sciences University of OxfordOxford OX39DUUK

chimeric antigen receptors(cARs)are a breakthrough in genetic engineering that have revolutio nized the field of adoptive cellular therapy(AcT).cells expressing these receptors are rerouted to a predefined target by the inclusion of an antigen-specific binding region within the synthetic cAR *** advantage of cells with programmed specificity has been demonstrated clinically in the field of oncology,and it is clear that such cells have greater accuracy,potency,and reduced off-target therapeutic effects compared with their unmodified *** contrast to conventional T cells(Tconvs),regulatory T cells(Tregs)play a major role in suppressing immune activation and regulating the host immune *** expression within Tregs has been proposed as a therapy for autoimmune and inflammatory diseases,graft-versus-host disease(GVHD),and organ transplant rejectio *** the latter,they hold immense potential as mediators of immune tolerance for recipients of ***,current research into cAR-Treg engineering is extremely limited,and there is uncertainty regarding optimal design for therapeutic *** review examines the rationale behind the development of cAR-Tregs,their significance for human transplantation,potential designs,safety considerations,and comparisons of cAR-Tregs in transplantation models to date.

关键词： chimeric antigen receptors T cell Treg Alloimmunity Bioengineering Transplant Autoimmunity

Genome and clonal hematopoiesis stability contrasts with immune,cfDNA,mitochondrial,and telomere length changes during short duration spaceflight

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Precision clinical Medicine 2024年第1期7卷 1-13页

作者： J.Sebastian Garcia-Medina Karolina Sienkiewicz S.Anand Narayanan Eliah G.Overbey Kirill Grigorev Krista A.Ryon Marissa Burke Jacqueline Proszynski Braden Tierney caleb M.Schmidt Nuria Mencia-Trinchant Remi Klotz Veronica Ortiz Jonathan Foox christopher chin Deena Najjar Irina Matei Irenaeus chan carlos cruchaga Ashley Kleinman JangKeun Kim Alexander Lucaci conor Loy Omary Mzava Iwijn De Vlaminck Anvita Singaraju Lynn E.Taylor Julian c.Schmidt Michael A.Schmidt Kelly Blease Juan Moreno Andrew Boddicker Junhua Zhao Bryan Lajoie Andrew Altomare Semyon Kruglyak Shawn Levy Min Yu Duane c.Hassane Susan M.Bailey Kelly Bolton Jaime Mateus christopher E.Mason Department of Physiology and Biophysics Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for computational Biomedicine Weill Cornell MedicineNew YorkNY 10021USA Department of Immunology Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA Department of Stem cell Biology and Regenerative Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Space Exploration Technologies corporation HawthomeCA 90250USA Sovaris Aerospace BoulderCO 80302USA Advanced Pattern Analysis&Human Performance Group BoulderCO 80302USA children's cancer and Blood Foundation Laboratories Departments of Pediatrics and Cell and Developmental BiologyDrukier Institute for Children's HealthMeyer Cancer CenterWeill Cornell MedicineNew YorkNY 10021USA Meyer cancer center Weill Cornell MedicineNew YorkNY 10065USA Department of Nutrition and Integrative Physiology Florida State UniversityTallahasseeFL 32306USA Department of Systems Engineering Colorado State UniversityFort CollinsCO 80523USA Element Biosciences San DiegoCA 10055USA Department of Environmental and Radiological Health Sciences Colorado State UniversityFort CollinsCO 80523USA cell and Molecular Biology Program Colorado State UniversityFort CollinsCO 80523USA BioAstra Inc New YorkNYUSA Washington University St Louis Oncology Division St.LouisMO 63100USA Meinig School of Biomedical Engineering Cornell UniversityIthacaNY 14853USA The Feil Family Brain and Mind Research Institute Weill Cornell MedicineNY 10021USA WorldQuant Initiative for Quantitative Prediction Weill Cornell MedicineNew YorkNY 10021USA

Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic *** advances,there remains much to learn about human adaptation to spaceflight's unique challenges,including microgravity,immune system perturbations,and radiation *** To provide a detailed genetics analysis of the mission,we collected dried blood spots pre-,during,and post-flight for DNA *** length was measured by quantitative PcR,while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations.A robust bioinformatic pipeline was used for data analysis,including variant calling to assess mutational *** Telomere elongation occurred during spaceflight and shortened after return to ***-free DNA analysis revealed increased immune cell signatures *** significant clonal hematopoiesis of indeterminate potential(cHIP)or whole-genome instability was *** long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months *** Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to *** sequencing data will serve as a reference point for studying the early development of cHIP in astronauts,an understudied phenomenon as previous studies have focused on career *** study will serve as a reference point for future commercial and non-commercial spaceflight,low Earth orbit(LEO)missions,and deep-space exploration.

关键词： genomes clonal hematopoiesis stability immune mitochondria ribosomes spaceflight

Neurocognitive Dysfunction After Treatment for Pediatric Brain Tumors:Subtype-Specific Findings and Proposal for Brain Network-Informed Evaluations

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Neuroscience Bulletin 2023年第12期39卷 1873-1886页

作者： charlotte Sleurs Paul Fletcher conor Mallucci Shivaram Avula Thankamma Ajithkumar Department of cognitive Neuropsychology Tilburg University5037 ABTilburgThe Netherlands Department of Oncology KU Leuven3000LeuvenBelgium Department of Psychiatry University of CambridgeAddenbrookes HospitalCambridgeCB20QQUK Wellcome Trust MRc Institute of Metabolic Science University of CambridgeCambridge Biomedical CampusCambridgeCB20QQUK Department of Neurosurgery Alder Hey Children’s NHS Foundation TrustLiverpoolL145ABUK Department of Radiology Alder Hey Children’s NHS Foundation TrustLiverpoolL145ABUK Department of Oncology Cambridge University Hospital NHS TrustCambridgeCB20QQUK

The increasing number of long-term survivors of pediatric brain tumors requires us to incorporate the most recent knowledge derived from cognitive neuroscience into their oncological *** the lesion itself,as well as each treatment,can cause specific neural damage,the long-term neurocognitive outcomes are highly complex and challenging to *** number of neurocognitive studies in this population grows exponentially worldwide,motivating modern neuroscience to provide guidance in follow-up before,during and after *** this review,we provide an overview of structural and functional brain connectomes and their role in the neuropsychological outcomes of specific brain tumor *** on this information,we propose a theoretical neuroscientific framework to apply appropriate neuropsychological and imaging follow-up for future clinical care and rehabilitation trials.

关键词： connectome Pediatric brain tumor Neuroimaging Neurocognition-Neuropsychological assessment

cascade electrocatalytic reduction of carbon dioxide and nitrate to ethylamine

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Journal of Energy chemistry 2022年第2期31卷 367-370页

作者： Zixu Tao Yueshen Wu Zishan Wu Bo Shang conor Rooney Hailiang Wang Department of chemistry Yale UniversityNew HavenCT 06520United States Energy Sciences Institute Yale UniversityWest HavenCT 06516United States

cO_(2) utilization,including electrochemical reduction of cO_(2) to fuels and useful chemicals,is explored to valorize carbon emissions[1–12].The value of cO_(2) electroreduction products originates from their c–H,c–c,and c–O *** further increase the value and expand the scope of products,it is desirable to integrate c–N bond formation with the electrochemical reduction of cO_(2).

关键词： nitrate dioxide carbon