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Management of distal cholangiocarcinoma with arterial involvement: Systematic review and case series on the role of neoadjuvant therapy

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World Journal of Gastrointestinal Surgery 2024年第8期16卷 2689-2701页

作者： Lewis A Hall Duncan Loader Santiago Gouveia Marta Burak James Halle-Smith Peter Labib Moath Alarabiyat Ravi Marudanayagam Bobby V Dasari keith J Roberts Syed S Raza Michail Papamichail David C Bartlett Robert P Sutcliffe Nikolaos A Chatzizacharias Department of Hepatopancreatobiliary Surgery and Liver Transplantation University Hospitals Birmingham NHS Foundation TrustBirmingham B152GWUnited Kingdom Institute of Immunology and Immunotherapy University of BirminghamBirmingham B152TTUnited Kingdom College of Medical and Dental Sciences University of BirminghamBirmingham B152TTUnited Kingdom Institute of Clinical Sciences University of BirminghamBirmingham B152TTUnited Kingdom

BACKGROUND The use of neoadjuvant therapy(NAT)in distal cholangiocarcinoma(dCCA)with regional arterial or extensive venous involvement,is not widely accepted and evidence is *** To synthesise evidence on NAT for dCCA and present the experience of a highvolume tertiary-centre managing dCCA with arterial *** A systematic review was performed according to PRISMA guidance to identify all studies reporting outcomes of patients with dCCA who received *** patients from 2017 to 2022 who were referred for NAT for dCCA at our centre were retrospectively collected from a prospectively maintained *** characteristics,NAT type,progression to surgery and oncological outcomes were *** Twelve studies were *** definition of“unresectable”locally advanced dCCA was *** studies reported outcomes for 9 patients who received NAT for dCCA with extensive vascular involvement.R0 resection rate ranged between 0 and 100%but without survival benefit in most *** studies considered either NAT in resectable dCCA or inclusive with extrahepatic *** presented case series includes 9 patients(median age 67,IQR 56-74 years,male:female 5:4)referred for NAT for borderline resectable or locally advanced *** patients progressed to surgery and 2 were *** patient died at 14 months with evidence of recurrence at 6 months and the other died at 51 months following recurrence 6 months *** Evidence for benefit of NAT is *** on criteria for uniform definition of resectability for dCCA is *** propose using the established National-Comprehensive-Cancer-Network®criteria for pancreatic ductal adenocarcinoma.

关键词： Cholangiocarcinoma Neoadjuvant therapy Arterial involvement Locally advanced Systematic review

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RNA m^(6)A reader YTHDF2 facilitates precursor miR-126 maturation to promote acute myeloid leukemia progression

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Genes & Diseases 2024年第1期11卷 382-396页

作者： Zheng Zhang Keren Zhou Li Han Andrew Small Jianhuang Xue Huilin Huang Hengyou Weng Rui Su Brandon Tan Chao Shen Wei Li Zhicong Zhao Ying Qing Xi Qin Kitty Wang keith Leung Mark Boldin Chun-Wei Chen David Ann Zhijian Qian Xiaolan Deng Jianjun Chen Zhenhua Chen Department of Systems Biology Beckman Research Institute of City of HopeMonroviaCA 91016USA Irell and Manella Graduate School of Biological Sciences Beckman Research Institute of City of HopeDuarteCA 91010USA Gehr Family Center for Leukemia Research City of HopeDuarteCA 91010USA Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdong 510060China Guangzhou Laboratory GuangzhouGuangdong 510005China Bioland Laboratory GuangzhouGuangdong 51005China Department of Liver Surgery Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China Department of Diabetes Complications and Metabolism Beckman Research Institute of City of HopeDuarteCA 91010USA Department of Biochemistry and Molecular Biology University of FloridaGainesvilleFL 32603USA Tongji Hospital Affiliated to Tongji University Frontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China School of Pharmacy China Medical UniversityShenyangLiaoning 110001China

As the most common internal modification of mRNA,Ne-methyladenosine(m^(6)A)and its regulators modulate gene expression and play critical roles in various biological and patholog-ical processes including *** was reported previously that m^(6)A methyltransferase(writer),methyltransferase-like 3(METTL3)adds m^(6)A in primary microRNAs(pri-miRNAs)and fa-cilitates its processing into precursor miRNAs(pre-miRNAs).However,it is unknown whether m^(6)A modification also plays a role in the maturation process of pre-miRNAs and(if so)whether such a function contributes to ***,we found that YTHDF2 is aberrantly overexpressed in acute myeloid leukemia(AML)patients,especially in relapsed patients,and plays an onco-genic role in ***,YTHDF2 promotes expression of miR-126-3p(also known as miR-126,as it is the main product of precursor miR-126(pre-miR-126)),a miRNA that was reported as an oncomiRNA in AML,through facilitating the processing of pre-miR-126 into mature ***,YTHDF2 recognizes m^(6)A modification in pre-miR-126 and recruits AGO2,a regulator of pre-miRNA processing,to promote the maturation of ***2 posi-tively and negatively correlates with miR-126 and miR-126's downstream target genes,respec-tively,in AML patients,and forced expression of miR-126 could largely rescue YTHDF2/Ythdf2 depletion-mediated suppression on AML cell growth/proliferation and leukemogenesis,indi-cating that miR-126 is a functionally important target of YTHDF2 in ***,our studies not only reveal a previously unappreciated YTHDF2/miR-126 axis in AML and highlight the ther-apeutic potential of targeting this axis for AML treatment,but also suggest that m^(6)A plays a role in pre-miRNA processing that contributes to tumorigenesis.

关键词： AML miR-126 N^(6)-methyladenosine Pre-miRNA maturation YTHDF2

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Five Principles as Relevant Today as 70 Years Ago

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今日中国（英文版） 2024年第8期 18页

作者： keith BENNETT

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Embracing the Year ofthe Dragon

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今日中国（英文版） 2024年第2期

作者： keith BENNETT

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Prehospital transdermal glyceryl trinitrate for ultra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- controlled ambulance trial

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Stroke & Vascular Neurology 2024年第1期9卷 38-49,I0035-I0046页

作者： Jason Philip Appleton Lisa J Woodhouse Craig S Anderson Sandeep Ankolekar Lesley Cala Mark Dixon Timothy J England Kailash Krishnan Grant Mair keith W Muir John Potter Christopher I Price Marc Randall Thompson G Robinson Christine Roffe Else C Sandset Jeffrey L Saver Angela Shone Aloysius Niroshan Siriwardena Joanna M Wardlaw Nikola Sprigg Philip M Bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Applied HealthResearch University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trials Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Faculty of Medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University Health Science Center BeijingChina Neurology Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia Department of Neurology King's College Hospital NHS Foundation TrustLondonUK Faculty of Health and Medical Sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East Midlands Ambulance Service NHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK Centre for Clinical Brain Sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurology and Psychology University of GlasgowGlasgowUK Bob Champion Research and Education Building University of East AngliaNorwichUK Institute of Neuroscience Newcastle UniversityNewcastle upon TyneUK Department of Neurology Leeds Teaching Hospitals NHS TrustLeedsUK Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre University of LeicesterLeicesterUK Stroke Research in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK Department of Neurology Oslo University HospitalOsloNorway Research and Development Norwegian Air Ambulance FoundationOsloNorway Department of Neurology and Comprehensive Stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA Research and Graduate Services University of NottinghamNottinghamUK Community and Health Research Unit University of LincolnLincolnUK

Background The effect of transdermal glyceryl trinitrate(GTN,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is ***,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).Methods RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4hours of *** primary outcome was a shift in scores on the modified Rankin scale(mRS)at day *** outcomes included death;a global analysis(Wei-Lachin test)containing Barthel Index,EuroQol-5D,mRS,telephone interview for cognitive status-modified and Zung depression scale;and neuroimaging-determined‘brain frailty’*** were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWD)with 95%*** 597 of 1149(52%)patients had a final diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Glasgow Coma Scale 14(2)and time from onset to randomisation 67[45,108]***‘brain frailty’was common:median score 2[2,3](range 0–3).At day 90,GTN did not influence the primary outcome(acOR for increased disability 1.15,95%CI 0.85 to 1.54),death or global analysis(MWD 0.00,95%CI-0.10 to 0.09).In subgroup analyses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe *** In patients who had an ischaemic stroke,ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital *** IS ALREADY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those w

关键词： Glasgow nitrate random

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A PERSONAL MEMOIR OF WEIMIN ZHENG-“A MAN FOR ALL SEASONS”

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Journal of Systems Science and Systems Engineering 2013年第4期22卷 499-504页

作者： keith W.HIPEL Department of Systems Design Engineering University of Waterloo

In 1951 Professor Weimin Zheng returned to the People＇s Republic of China from the United Kingdom to assist in building his country into a modern nation. Rather than pursue a doctoral degree at the California Institute of Technology, or Caltech as it is popularly called, Professor Zheng, unselfishly and patriotically, decided that he would devote his many talents to providing a first-class education to Chinese students within a strong university system. In particular,

关键词： A MAN FOR ALL SEASONS A PERSONAL MEMOIR OF WEIMIN ZHENG

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Prostate-associated gene 4 （PAGE4）, an intrinsically disordered cancer/testis antigen, is a novel therapeutic target for prostate cancer

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Asian Journal of Andrology 2016年第5期18卷 695-703页

作者： Prakash Kulkarni A keith Dunker keith Weninge John Orban Institute for Bioscience and Biotechnology Research University of Maryland Rockville MD 20850 USA Center for Computational Biology and Bioinformatics Department of Biochemistry and Molecular Biology Indiana University School of Medicine and Informatics Indianapolis IN 46202 USA Department of Physics North Carolina State University Raleigh NC 27695 USA Department of Chemistry and Biochemistry University of Maryland College Park MD 20742 USA.

Prostate-associated gene 4 （PAGE4） is a remarkably prostate-specific Cancer/Testis Antigen that is highly upregulated in the human fetal prostate and its diseased states but not in the adult normal gland. PAGE4 is an intrinsically disordered protein （IDP） that functions as a stress-response protein to suppress reactive oxygen species as well as prevent DNA damage. In addition, PAGE4 is also a transcriptional regulator that potentiates transactivation by the oncogene c-Jun, c-Jun forms the AP-1 complex by heterodimerizing with members of the Fos family and plays an important role in the development and pathology of the prostate gland, underscoring the importance of the PAGE4/c-Jun interaction. HIPK1, also a component of the stress-response pathway, phosphorylates PAGE4 at T51 which is critical for its transcriptional activity. Phosphorylation induces conformational and dynamic switching in the PAGE4 ensemble leading to a new cellular function. Finally, bioinformatics evidence suggests that the PAGE4 mRNA could be alternatively spliced resulting in four potential isoforms of the polypeptide alluding to the possibility of a range of conformational ensembles with latent functions. Considered together, the data suggest that PAGE4 may represent the first molecular link between stress and prostate cancer （PCa）. Thus, pharmacologically targeting PAGE4 may be a novel opportunity for treating and managing patients with PCa, especially patients with low-risk disease.

关键词： prostate-associated Gene 4 cancer/testis antigen intrinsically disordered protein prostate cancer c-Jun AP-1 proteininteraction networks homeodomain-interacting protein 1

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Effects of novel vaccines on weight loss in diet-induced-obese(DIO) mice

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Journal of Animal Science and Biotechnology 2012年第3期3卷 136-142页

作者： keith N Haffer Braasch Biotech LLC 421 Rose AvenueGarrestonSD 570303-0430USA

The purpose of the study was to test the therapeutic effects of novel vaccines for reducing weight gain and increasing weight loss in diet induced obesity （DIO） model. Male C57BL/6 J mice, fed a 60% Kcal fat diet for 8 weeks prior to the start of the study, were vaccinated via the intraperitoneal route with two formulations （JH17 ＆ JH]8） of chimeric-somatostatin vaccines at 1 and 22 days of the study. Control mice were injected with PBS. All mice continued to be feed the 60% Kcal fat diet for the week and food intake was measured weekly. At week 6 6 week study. Body weights were measured two times a mice were euthanized and a terminal bleed was made and antibody levels to somatostatin and levels of insulin-like growth factor 1 （IGF-1） were determined. Vaccination with both vaccine formulations induced a statistically significant body weight change over the study period, as compared with PBS controls. Percentage of baseline body weight was also significantly affected by vaccination during the study period. Vaccinates finished the study at 104% and 107% of baseline weight, JHI7 ＆ JH18 respectively, while untreated controls reached 115% of baseline weight. Food intake per mouse was similar in all mouse groups during the entire study. Control mice did not demonstrate any antibody titers to somatostatin, while all vaccinated mice had measurable antibody responses （〉 1：500,000 titer）. IGF-1 levels were not statistically significant among the groups, but were elevated in the JH18 vaccinates （mean 440.4 ng/mL） when compared with PBS controls （mean 365.6 ng/mL）. Vaccination with either JH17 or JH18 chimeric -somatostatin vaccines produced a statistically significant weight loss as compared with PBS controls （P 〈 0.0001）, even though the DIO mice with continually fed a 60% Kcal fat diet. The weight loss/lower weight gain observations were even more significant, as all mice consumed similar amounts of food for the entire study. The presence of high levels of anti-somatostatin

关键词： Obesity Treatment Vaccines Weight loss Weight management

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MODEL, GUESS, CHECK: Wordle as a primer on active learning for materials research

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npj Computational Materials 2022年第1期8卷 937-939页

作者： keith A.Brown Department of Mechanical Engineering Physics Departmentand Division of Materials Science&EngineeringBoston UniversityBostonMAUSA

Research and games both require the participant to make a series of *** learning is a process borrowed from machine learning for algorithmically making choices that has become increasingly used to accelerate materials *** this process may seem opaque to researchers outside the field of machine learning,examining active learning in games provides an accessible way to showcase the process and its ***,we examine active learning through the lens of the game Wordle to both explain the active learning process and describe the types of research questions that arise when using active learning for materials research.

关键词： Wordle learning outside

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EMDS 3.0:A modeling framework for coping with complexity in environmental assessment and planning

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Science China(Technological Sciences) 2006年第z1期49卷 63-75页

作者： keith M.Reynolds U.S.Dept.Agriculture Forest ServicePacific Northwest Research Station3200 SW Jefferson WayCorvallisOR 97331USA

The Ecosystem Management Decision Support (EMDS) system is an application framework for knowledge-based decision support of ecological assessments at any geographic scale. The system integrates state-of-the-art geographic information system (GIS) as well as knowledge-based reasoning and decision modeling technologies to provide decision support for a substantial portion of the adaptive management process of ecosystem management. EMDS 3.0 is implemented as an ArcMap extension and integrates the logic engine of NetWeaver to perform landscape evaluations, and the decision modeling engine of Criterium DecisionPlus for evaluating management priorities. Key features of the system's evaluation component include abilities to (1) reason about large, abstract, multi-faceted ecosystem management problems, (2) perform useful evaluations with incomplete information, (3) evaluate the influence of missing information, and (4) determine priorities for missing information. A key feature of the planning component is the ability to determine priorities for management activities, taking into account not only ecosystem condition, but also criteria that account for the feasibility and efficacy of potential management actions. Both components include powerful and intuitive diagnostic features that facilitate communicating the explanation of modeling results to a broad audience.

关键词： natural resources, modeling, assessment, analysis, planning, software, ecosystem management.

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