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腔隙性梗死后的认知障碍和神经代谢产物变化的关系

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世界核心医学期刊文摘（神经病学分册） 2005年第8期1卷 43-44页

作者： van Zandvoort M.j.E. van der grond j. Kappelle L.j. DeHaan E.H.F. 赵正卿 Utrecht University Van Unnikgebouw Psychol. Laboratory Heidelberglaan 23584 CS Utrecht Netherlands Dr.

In contrast to earlier observations, recent studies have demonstrated that sup ratentorial lacunar infarcts in the white matter may cause mild neuropsychologic al impairments. The origin of these cognitive disturbances is yet unknown. In th e current study proton magnetic resonance spectroscopy ( 1HMRS) was used to eluc idate the hypothesized relation between a lacunar infarct, metabolic alterations , and neuropsychological function. Patients with a single supratentorial lacunar infarct(n=26) were compared with patients with a mild myocardial infarct (n=12) and healthy controls (n=12) on a comprehensive neuropsychological examination, and on the N-acetyl-aspartate/creatine, choline/creatine and lactate/creatine ratios. The volume of interest of the MRI/MRS examination was locatedin normal- appearing white matter of the centrum semiovale ata distance from the infarct, i n both the ipsilateral and contralateral hemisphere. On neuropsychological exami nation patients with a lacunar infarct performed worse than both patients with a myocardial infarct and healthy controls. The N-acetyl-aspartate/creatine rati o was decreased in patients with a lacunar infarct compared with the other two g roups. More important,this decrease in neurometabolites was significantly correl ated to the level of cognitive functioning for the ipsilateral hemisphere and, a lthough to a lesser extent, for the contralateral *** conclude that a single symptomatic lacunar infarct in the white matter is associated with (distant) disturbances in neuro metabolites and that this decrease is related to a reduced cognitive capacity.

关键词：腔隙性梗死认知障碍神经心理代谢产物大脑半球磁共振质子波谱心肌梗死组乳酸盐半卵圆中心肌酸

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 j.ris L.Vos Charlotte L.Zuur Noel F.C.C.de Miranda Heinz j.cobs Sj.erd H.van der Burg j.nnie 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

Clinical-based phenotypes in children with pediatric post-COVID-19 condition

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World j.urnal of Pediatrics 2024年第7期20卷 682-691页

作者： Lieke C.E.Noij.j.lle M.Blankestij. Coen R.Lap Marlies A.van Houten Giske Biesbroek Anke-Hilse Maitland-van der Zee Mahmoud I.Abdel-Aziz j.hannes B.van Goudoever Mattij. W.Alsem Caroline L.H.Brackel Kim j.Oostrom Simone Hashimoto Suzanne W.j.Terheggen-Lagro Department of Pediatric Pulmonology and Allergy Amsterdam UMCLocation AMCEmma Children’s HospitalAmsterdam University Medical CenterRoom G2-222Meibergdreef 91105AZAmsterdamThe Netherlands Department of Pulmonary Medicine Amsterdam UMCAmsterdamThe Netherlands Department of Pediatrics Spaarne GasthuisHoofddorpThe Netherlands Department of Pediatrics Emma Children’s HospitalAmsterdam University Medical CenterAmsterdamThe Netherlands Department of Rehabilitation Medicine Amsterdam Movement SciencesMeibergdreef 9AmsterdamThe Netherlands Department of Paediatric Pulmonology Department of PaediatricsTergooi MCHilversumThe Netherlands Department of Child and Adolescent Psychiatry and Psychosocial Care Amsterdam UMCAmsterdam Reproduction and DevelopmentAmsterdamThe Netherlands

Background Pediatric post coronavirus disease 2019(COVID-19)condition(PPCC)is a heterogeneous syndrome,which can significantly affect the daily lives of *** study aimed to identify clinically meaningful phenotypes in children with PPCC,to better characterize and treat this *** Participants were children with physician-diagnosed PPCC,referred to the academic hospital Amsterdam UMC in the Netherlands between November 2021 and March *** factors and information on post-COVID symptoms,comorbidities,and impact on daily life were *** clusters were identified using an unsupervised and unbiased approach for mixed data *** Analysis of 111 patients(aged 3–18 years)revealed three distinct clusters within *** 1(n=62,median age=15 years)predominantly consisted of girls(74.2%).These patients suffered relatively more from exercise intolerance,dyspnea,and smell *** 2(n=33,median age=13 years)contained patients with an even gender distribution(51.5%girls).They suffered from relatively more sleep problems,memory loss,gastrointestinal symptoms,and *** 3(n=16,median age=11 years)had a higher proportion of boys(75.0%),suffered relatively more from fever,had significantly fewer symptoms(median of 5 symptoms compared to 8 and 10 for clusters 1 and 2 respectively),and experienced a lower impact on daily *** This study identified three distinct clinical PPCC phenotypes,with variations in sex,age,symptom patterns,and impact on daily *** findings highlight the need for further research to understand the potentially diverse underlying mechanisms contributing to post-COVID symptoms in children.

关键词： Adolescents Clusters Long COVID Pediatric Phenotypes Post-COVID syndrome

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 j.cob 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

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全脑血流量增高与脑白质损害减轻有关

世界核心医学期刊文摘（神经病学分册） 2005年第6期1卷 29-29页

作者： Bisschops R.H.C. van der Graaf Y. Mali W.P.Th.M. van der grond j. 李锐 Department of Radiology E01.132 University Medical Center Utrecht PO Box 85500 3508 GA Utrecht Netherlands Dr.

Background Low cerebral blood flow (CBF) has been associated with the presence of white matter lesions (WMLs). However, the power of these studies was insufficient (n = 20- 35) to determine whether flow is associated with WMLs. Purpose The aim of this study was to investigate whether total cerebral blood flow (tCBF) is associated with the severity of white matter lesions (WMLs) in a large patient sample. Subj.cts and methods 228 patients with clinical symptoms of cardiovascular disease had MRI of the brain, consisting of a T2- w FLAIR and a 2D phasecontrast flow measurement of the internal carotid arteries and the basilar artery. WMLs were graded according to prevalence and size of deep and periventricular WMLs. To determine the relation between tCBF and WMLs we used linear and logistic regression analysis adj.sted for age, gender, intima media thickness and hypertension. Results We observed an inverse association between the tCBF and the total number of WMLs adj.sted for age, gender, intima media thickness and hypertension [B = - 1,0 WML 95 % CI (- 2.0 to 0.0, p = 0.045) per 100 mL increase in tCBF]. The adj.sted odds ratio for the presence of severe WMLs in patients with high tCBF ( > 675 mL/min) was 0.5 (95% CI 0.2- 1.0) compared with patients with normal tCBF. Conclusion In this study we found that high tCBF is associated with a decrease in presence and severity of WMLs.

关键词：全脑血流量脑白质基底动脉颈内动脉心血管疾病膜厚度样本量线性回归临床症状测量方法

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 j.kai 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

Physical Simulation of Thermally Induced Martensite Formation from Retained Austenite in TRIP Steels

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j.urnal of Materials Science & Technology 2003年第Z1期19卷 105-108页

作者： Lie ZHAO Fred j. VERMOLEN j.lt SIETSMA Sybrand van der ZWAAG Netherlands Institute for Metals Research P.O.Box 5008 2600 GA Delft The Netherlands Department of Materials Science Delft University of Technology R otterdamseweg 137 2628 AL Delft The Netherlands Department of Applied Mathematics Delft University of Technology Mekelweg 4 2628 CD Delft The Netherlands Department of Materials ScienceDelft University of TechnologyRotterdamseweg 1372628 AL DelftThe Netherlands Netherlands Institute for Metals Research P.O.Box 5008 2600 GA Delft The Netherlands Faculty of Aerospace Engineering Delft University of Technology Kluyverweg 1 2629 HS Delft The Netherlands

The present work analyses the total free energy of the material during the martensitic transformation. A general expression for the martensite fraction as a function of temperature is derived, assuming that the nonchemical free energyis proportional to the volume of martensite. This expression indicates that the temperature-dependent martensitefraction can be predicted once the characteristic transformation temperatures and the relation between the chemicalfree energy and temperature of the martensite and austenite are known. An advantage of this development is thatthe proposed equation is valid for all types of relations between the chemical free energy and temperature. Thissimulation is successfully applied to the martensitic transformation upon further cooling of retained austenite in alow-alloyed TRIP steel, in which the relation between chemical free energy and temperature is quadratic and thefraction is determined from a thermo-magnetic measurement.

关键词： Thermodynamics, Martensitic transformation, Retained austenite, TRIP steels.

Cost proj.ctions for microwave plasma CO production using renewable energy

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j.urnal 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 proj.ctions reveal that the total investments required to deploy this CO_(2)conversion technology at an exaj.ule 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

Late Quaternary sinistral slip rate along the Altyn Tagh fault and its structural transformation model

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Science China Earth Sciences 2005年第3期48卷 384-397页

作者： P. Tapponnier j. van der Woerd F. j. Ryerson A.S. Meriaux Laboratoire de Tectonique Institut de Physique du Globe de Paris FranceLaboratoire de Tectonique Institut de Physique du Globe de Paris FranceIGPP Lawrence Livermore Laboratory Livermore CA 94550 USALaboratoire de Tectonique Institut de Physique du Globe de Paris France

Based on technical processing of high-resolution SPOT images and aerophotos, detailed mapping of offset landforms in combination with field examination and displacement measurement, and dating of offset geomorphic surfaces by using carbon fourteen (14C), cos- mogenic nuclides (10Be+26Al) and thermoluminescence (TL) methods, the Holocene sinistral slip rates on different segments of the Altyn Tagh Fault (ATF) are obtained. The slip rates reach 17.5 ±2 mm/a on the central and western segments west of Aksay Town, 11±3.5 mm/a on the Subei-Shibaocheng segment, 4.8±1.0 mm/a on the Sulehe segment and only 2.2±0.2 mm/a on the Kuantanshan segment, an easternmost segment of the ATF. The sudden change points for loss of sinistral slip rates are located at the Subei, Shibaocheng and Shulehe triple j.nctions where NW-trending active thrust faults splay from the ATF and propagate southeastward. Slip vector analyses indicate that the loss of the sinistral slip rates from west to east across a triple j.nction has structurally transformed into local crustal shortening perpendicular to the active thrust faults and strong uplifting of the thrust sheets to form the NW-trending Danghe Nanshan, Daxueshan and Qilianshan Ranges. Therefore, the eastward extrusion of the northern Qing- hai-Tibetan Plateau is limited and this is in accord with “the imbricated thrusting transforma- tion-limited extrusion model”.

关键词： Altyn Tagh Fault, sinistral strike-slip rate, structural transformation, extrusion tectonics.