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CD4^(+)T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors

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Cellular & Molecular Immunology 2024年第4期21卷 374-392页

作者： Xin Lei Daniël C.de Groot Marij j.P.Welters Tom de Wit Ellen Schrama Hans van Eenennaam Saskia j.Santegoets Timo Oosenbrug Annemarthe van der Veen joris L.Vos Charlotte L.Zuur Noel F.C.C.de Miranda Heinz jacobs Sjoerd H.van der Burg jannie Borst Yanling Xiao Department of Immunology Leiden University Medical CenterLeidenThe Netherlands Oncode Institute Leiden University Medical CenterLeidenThe Netherlands Department of Tumor Biology and Immunology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Medical Oncology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands IMMIOS B.V. OssThe Netherlands Division of Medical Oncology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Otorhinolaryngology Leiden University Medical Center LeidenThe Netherlands Department of Pathology Leiden University Medical CenterLeidenThe Netherlands

CD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDC1s)to induce CD8^(+)cytotoxic T lymphocyte(CTL)anticancer responses,as proven in mouse *** recently identified cDC1s with a transcriptomic imprint of CD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting ***,we delineate the mechanism of cDC1 licensing by CD4^(+)T cells in *** CD4^(+)T cells produce IFNβvia the STING pathway,which promotes MHC-I antigen(cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer *** cooperation with CD40 ligand(L),IFNβalso optimizes the costimulatory and other functions of cDC1s required for CTL response ***-I-producing CD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to CTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDCs and tumor-reactive CD8^(+)T *** agreement with this scenario,the presence of IFN-I-producing CD4^(+)T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

关键词： CD4^(+)T-cell help cDC1 licensing IFN-I signaling CD40 costimulation (cross-)presentation CTL priming Tumor control

Inbreeding and genetic load in a pair of sibling grouse species:Tetrastes sewersowi and ***

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Avian Research 2024年第2期15卷 265-270页

作者： Kai Song Tom van der Valk Bin Gao Peter Halvarsson Yun Fang Wendong Xie Siegfried Klaus Zhiming Han Yue-Hua Sun jacob Hoglund Key Laboratory of Animal Ecology and Conservation Biology Institute of ZoologyChinese Academy of SciencesBeijing100101China Animal Ecology Department of Ecology and GeneticsUppsala UniversityNorbyvagen 18DUppsala75236Sweden Department of Cell and Molecular Biology Uppsala75273Sweden Unit of Parasitology Department of Biomedicine and Veterinary Public HealthSwedish University of Agricultural SciencesPO Box 7036Uppsala75007Sweden Lindenhohe 5 JenaD-07749Germany The State Key Laboratory of Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing100101China

Genetic load and inbreeding are recognized as important factors to be considered in conservation *** levels of both can increase the risk of population extinction by negatively impacting fitness-related characters in many species of plants and animals,including humans(inbreeding depression).Genomic tech-niques are increasingly used in measuring and understanding genetic load and inbreeding and their importance in evolution and *** used whole genome resequencing data from two sibling grouse species in subarctic Eurasia to quantify *** found a large range of inbreeding measured as FROH(fraction of runs of homozygosity)in individuals from different populations of Chinese Grouse(Tetrastes sewerzowi)and Hazel Grouse(***).FROH estimated from genome-wide runs of homozygosity(ROH)ranged from 0.02 to 0.24 among Chinese Grouse populations and from 0.01 to 0.44 in Hazel *** from a population of Chinese Grouse residing in the Qilian mountains and from the European populations of Hazel Grouse(including samples from Sweden,Germany and Northeast Poland)were the most inbred(FROH ranged from 0.10 to 0.23 and 0.11 to 0.44,respectively).These levels are comparable to other highly inbred populations of *** Grouse from northern China and Chinese Grouse residing in the Qinghai-Tibetan Plateau showed relatively lower inbreeding *** of the ratio between deleterious missense mutations and synonymous mutations revealed higher levels in Chinese Grouse as compared to Hazel *** results are possibly explained by higher fixation rates,mutational melt down,in the range-restricted Chinese Grouse compared to the wide-ranging Hazel ***,when we compared the relatively more severe class of loss-of-function muta-tions,Hazel Grouse had slightly higher levels than Chinese Grouse,a result which may indicate that purifying selection(purging)has been more efficient in Chinese Grouse on this class of mutations.

关键词： Genetic load Inbreeding Purifying selection Qinghai-Tibetan Plateau ROH Tetrastes

Drug repurposing screen identifies vidofludimus calcium and pyrazofurin as novel chemical entities for the development of hepatitis E interventions

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Virologica Sinica 2024年第1期39卷 123-133页

作者： Hongbo Guo Dan Liu Kuan Liu Yao Hou Chunyang Li Qiudi Li Xiaohui Ding Monique M.A.Verstegen jikai Zhang Lingli Wang Yibo Ding Renxian Tang Xiucheng Pan Kuiyang Zheng Luc j.Wvan der Laan Qiuwei Pan Wenshi Wang Department of Pathogen Biology and Immunology Jiangsu Key Laboratory of Immunity and MetabolismJiangsu International Laboratory of Immunity and MetabolismXuzhou Medical UniversityXuzhou221004China Department of Gastroenterology and Hepatology Erasmus MC-University Medical CenterRotterdamNL-3015 CNthe Netherlands Department of Surgery Erasmus MC Transplant InstituteUniversity Medical CenterRotterdam3015CENL-3015 CNthe Netherlands Department of Infectious Diseases The Affiliated Hospital of Xuzhou Medical UniversityXuzhou221002China

Hepatitis E virus(HEV)infection can cause severe complications and high mortality,particularly in pregnant women,organ transplant recipients,individuals with pre-existing liver disease and immunosuppressed ***,there are still unmet needs for treating chronic HEV ***,we screened a best-in-class drug repurposing library consisting of 262 drugs/*** screening,we identified vidofludimus calcium and pyrazofurin as novel anti-HEV *** calcium is the next-generation dihydroorotate dehydrogenase(DHODH)inhibitor in the phase 3 pipeline to treat autoimmune diseases or SARS-CoV-2 *** selectively targets uridine monophosphate synthetase(UMPS).Their anti-HEV effects were further investigated in a range of cell culture models and human liver organoids models with wild type HEV strains and ribavirin treatment failure-associated HEV ***,both drugs exhibited a sizeable therapeutic window against *** instance,the IC50 value of vidofludimus calcium is 4.6–7.6-fold lower than the current therapeutic doses in ***,their anti-HEV mode of action depends on the blockage of pyrimidine ***,two drugs robustly inhibited ribavirin treatment failure-associated HEV mutants(Y1320H,G1634R).Their combination with IFN-αresulted in synergistic antiviral *** conclusion,we identified vidofludimus calcium and pyrazofurin as potent candidates for the treatment of HEV *** on their antiviral potency,and also the favorable safety profile identified in clinical studies,our study supports the initiation of clinical studies to repurpose these drugs for treating chronic hepatitis E.

关键词： Hepatitis Evirus(HEV) Drug repurposing Vidofludimus calcium Pyrazofurin Pyrimidine biosynthesis

Cost projections for microwave plasma CO production using renewable energy

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journal of Energy Chemistry 2022年第8期31卷 507-513,I0014页

作者： Remko j.Detz Bob van der Zwaan Netherlands Organisation for Applied Scientific Research(TNO) Amsterdam 1043 NTThe Netherlands Faculty of Science(HIMS and IAS) University of AmsterdamAmsterdam 1090 GDThe Netherlands School of Advanced International Studies(SAIS) Johns Hopkins UniversityBologna 40126Italy

Successful deployment of renewable fuel production requires substantial cost reduction along the entire value chain of the underlying manufacturing *** improve their performance,renewable fuel production technologies should follow a cost-reducing learning *** this article,we adopt recent evidence that learning-by-doing is directly influenced by the technology unit size and explore three scenarios for microwave plasma CO_(2)conversion in which the learning rate varies between 10%,15%,and 20%.Our projections reveal that the total investments required to deploy this CO_(2)conversion technology at an exajoule scale decline from 83 down to 23 billion euros under a 10%increase in the value of the learning *** CO_(2) production costs in 2050 amount to 247–346€(2019)/t CO_(2),in which the range is determined by the value of the learning *** under substantial learning until 2050 the levelized CO production cost is unlikely to become competitive with conventional natural gas-based CO_(2) production processes,except when a CO_(2)tax is applied of up to 150€(2019)/t CO_(2).To optimally exploit effects of learning-by-doing,we recommend developing several CO production technologies simultaneously with multiple unit sizes,so as to improve the chance of ultimately selecting the process with the highest learning rate.

关键词： CO_(2)utilization Synthetic fuels Renewable chemicals Learning curves Unit size

A Space-Time Interior Penalty Discontinuous Galerkin Method for the Wave Equation

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Communications on Applied Mathematics and Computation 2022年第3期4卷 904-944页

作者： Poorvi Shukla j.j.W.van der Vegt Department of Applied Mathematics University of TwenteP.O.Box 2177500 AE EnschedeThe Netherlands

A new higher-order accurate space-time discontinuous Galerkin(DG)method using the interior penalty flux and discontinuous basis functions,both in space and in time,is pre-sented and fully analyzed for the second-order scalar wave *** attention is given to the definition of the numerical fluxes since they are crucial for the stability and accuracy of the space-time DG *** theoretical analysis shows that the DG discre-tization is stable and converges in a DG-norm on general unstructured and locally refined meshes,including local refinement in *** space-time interior penalty DG discre-tization does not have a CFL-type restriction for *** order of accuracy is obtained in the DG-norm if the mesh size h and the time stepΔt satisfy h≅CΔt,with C a positive *** optimal order of accuracy of the space-time DG discretization in the DG-norm is confirmed by calculations on several model *** calculations also show that for pth-order tensor product basis functions the convergence rate in the L∞and L2-norms is order p+1 for polynomial orders p=1 and p=3 and order p for polynomial order p=2.

关键词： Wave equation Space-time methods Discontinuous Galerkin methods Interior penalty method A priori error analysis

The impact of prehospital blood sampling on the emergency department process of patients with chest pain:a pragmatic non-randomized controlled trial

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World journal of Emergency Medicine 2023年第4期14卷 257-264页

作者： johan L.van Nieuwkerk M.Christien van der Linden Rolf j.Verheul Merel van Loon-van Gaalen Marije janmaat Naomi van der Linden Emergency Department Haaglanden Medical Centre&Emergency Medical Services Haaglandenthe Hague 2501 CBthe Netherlands Research and Development Haaglanden Medical Centrethe Hague 2501 CKthe Netherlands Laboratory Services Haaglanden Medical Centrethe Hague 2501 CKthe Netherlands Emergency Department Haaglanden Medical Centrethe Hague 2501 CKthe Netherlands Faculty of Health University of Applied Sciences LeidenLeiden 2300 AJthe Netherlands Faculty of Technology Policy and ManagementDelft University of TechnologyDelft 2628 BXthe Netherlands

BACKGROUND:In patients with chest pain who arrive at the emergency department(ED)by ambulance,venous access is frequently established prehospital,and could be utilized to sample *** blood sampling may save time in the diagnostic *** this study,the association of prehospital blood draw with blood sample arrival times,troponin turnaround times,and ED length of stay(LOS),number of blood sample mix-ups and blood sample quality were ***:The study was conducted from October 1,2019 to February 29,*** patients who were transported to the ED with acute chest pain with low suspicion for acute coronary syndrome(ACS),outcomes were compared between cases,in whom prehospital blood draw was performed,and controls,in whom blood was drawn at the *** analyses were used to assess the association of prehospital blood draw with the time ***:Prehospital blood draw was performed in 100 *** 406 patients,blood draw was performed at the *** blood draw was independently associated with shorter blood sample arrival times,shorter troponin turnaround times and decreased LOS(P0.05).CONCLUSION:For patients with acute chest pain with low suspicion for ACS,prehospital blood sampling is associated with shorter time intervals,while there were no significant differences between the two groups in the validity of the blood samples.

关键词： Blood specimen collection Crowding Emergency medical services Troponin

Artificial intelligence for characterization of diminutive colorectal polyps:A feasibility study comparing two computer-aided diagnosis systems

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Artificial Intelligence in Gastrointestinal Endoscopy 2024年第1期5卷 11-22页

作者： Quirine Eunice Wennie van der Zander Ramon M Schreuder Ayla Thijssen Carolus H j Kusters Nikoo Dehghani Thom Scheeve Bjorn Winkens Mirjam C M van der Ende-van Loon Peter H N de With Fons van der Sommen Ad A M Masclee Erik j Schoon Department of Gastroenterology and Hepatology Maastricht University Medical CenterMaastricht 6202 AZNetherlands GROW School for Oncology and ReproductionMaastricht UniversityMaastricht 6200 MDNetherlands Division of Gastroenterology and Hepatology Catharina Hospital EindhovenEindhoven 5602 ZANetherlands Department of Electrical Engineering Eindhoven University of TechnologyEindhoven 5600 MBNetherlands Department of Methodology and Statistics Maastricht UniversityPostbus 6166200 MD MaastrichtNetherlands School for Public Health and Primary Care Maastricht UniversityMaastricht 6200 MDNetherlands

BACKGROUND Artificial intelligence(AI)has potential in the optical diagnosis of colorectal *** To evaluate the feasibility of the real-time use of the computer-aided diagnosis system(CADx)AI for ColoRectal Polyps(AI4CRP)for the optical diagnosis of diminutive colorectal polyps and to compare the performance with CAD EYE^(TM)(Fujifilm,Tokyo,japan).CADx influence on the optical diagnosis of an expert endoscopist was also *** AI4CRP was developed in-house and CAD EYE was proprietary software provided by *** CADxsystems exploit convolutional neural *** polyps were characterized as benign or premalignant and histopathology was used as gold ***4CRP provided an objective assessment of its characterization by presenting a calibrated confidence characterization value(range 0.0-1.0).A predefined cut-off value of 0.6 was set with values0.76).Self-critical AI4CRP’s diagnostic performances excluded low confidence *** AI4CRP use was feasible and performed on 30 patients with 51 colorectal ***-critical AI4CRP,excluding 14 low confidence characterizations[27.5%(14/51)],had a diagnostic accuracy of 89.2%,sensitivity of 89.7%,and specificity of 87.5%,which was higher compared to *** EYE had a 83.7%diagnostic accuracy,74.2%sensitivity,and 100.0%*** performances of the endoscopist alone(before AI)increased nonsignificantly after reviewing the CADx characterizations of both AI4CRP and CAD EYE(AI-assisted endoscopist).Diagnostic performances of the AI-assisted endoscopist were higher compared to both CADx-systems,except for specificity for which CAD EYE performed *** Real-time use of AI4CRP was *** confidence values provided by a CADx is novel and self-critical AI4CRP sho

关键词： Artificial intelligence Colorectal polyp characterization Computer aided diagnosis Diminutive colorectal polyps Optical diagnosis Self-critical artificial intelligence

One-Step Reverse Osmosis Based on Riverbank Filtration for Future Drinking Water Purification

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Engineering 2022年第2期8卷 27-34页

作者： Yujia Zhai Gang Liu Walter G.j.van der Meer Oasen Drinkwater Gouda 2800 ACNetherlands Faculty of Science and Technology University of TwenteEnschede 7500 AENetherlands Key Laboratory of Drinking Water Science and Technology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China Sanitary Engineering Research Group Department of Water ManagementFaculty of Civil Engineering and GeosciencesDelft University of TechnologyDelft 2600 GANetherlands

The presence of newly emerging pollutants in the aquatic environment poses great challenges for drink-ing water treatment *** to their low concentrations and unknown characteristics,emerging pol-lutants cannot be efficiently removed by conventional water treatment processes,making technically,economically,and environmentally friendly water purification technologies increasingly *** article introduces a one-step reverse osmosis(OSRO)concept consisting of riverbank filtration(RBF)and reverse osmosis(RO)for drinking water *** OSRO concept combines the relatively low-cost natural pretreatment of river water with an advanced engineered purification *** pro-vides a continuous natural source of water with stable water quality and a robust barrier for *** the pre-removal of particles,organic matter,organic micro-pollutants(OMPs),and microbes,RBF becomes an ideal source for a purification system based on RO membranes,in comparison with the direct intake of surface *** treatment removes almost 99.9%of the particles,pathogens,viruses,and OMPs,as well as the vast majority of nutrients,and thus meets the requirements for the chlorine-free delivery of drinking water with high *** OSRO treatment is cost effective com-pared with the standard conventional series of purification steps involving sprinkling filters,softening,and activated *** bank filtration(ABF),which functions as an artificial recharge in combi-nation with a sand filtration system,is proposed as an alternative for RBF in the OSRO concept to supply drinking water from locally available *** is also suggested that the OSRO concept be imple-mented with wind power as an alternative energy source in order to be more sustainable and *** OSRO-based decentralized water system is proposed for water reclaiming and *** is suggested that future water treatment focus on the combination of natural and engineered systems to pro

关键词： Drinking water treatment River bank filtration Reverse osmosis Artificial bank filtration Water reclamation and reuse

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肺动脉高压患者骨形态发生蛋白受体2突变

中华高血压杂志 2016年第3期24卷 299-299页

作者： van der Bruggen CE Happé CM Dorfmüller P Trip P Spruijt OA Rol N Hoevenaars F Houweling AC Girerd B Marcus jT Mercier O Humbert M Handoko ML van der velden j Vonk Noordegraaf A Bogaard Hj Goumans Mj de Man FS 刘莉叶鹏

骨形态发生蛋白受体2（bone morphogenetic protein receptor 2,BMPR2）基因突变对肺动脉高压（pulmonary arterial hypertension,PAH）患者右心室压力负荷的影响尚未知。研究人员通过体内功能检查联合右、左心室分子与组织学分析,对伴... 详细信息

骨形态发生蛋白受体2（bone morphogenetic protein receptor 2,BMPR2）基因突变对肺动脉高压（pulmonary arterial hypertension,PAH）患者右心室压力负荷的影响尚未知。研究人员通过体内功能检查联合右、左心室分子与组织学分析,对伴或不伴BMPR2突变的PAH患者的右心室功能进行评估。方法与结果：纳入原发性或家族性PAH患者95例进行基因筛选,结果示28例患者存在BMPR2突变,67例无突变。应用右心导管术和心脏核磁共振检测。

关键词：骨形态发生蛋白受体基因突变肺动脉高压患者 hypertension 受体2 receptor arterial