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Insect Science 2024年第3期31卷 817-834页

作者： Nathan Meijer Lisa Zoet Theo de Rijk Paul Zomer Deborah Rjkers H.j.van der Fels-Klerx joop j.A.van Loon Wageningen Food Safety Research(WFSR) Part of Wageningen University and ResearchWageningenThe Netherlands Bestico B.V. Industrieweg 6Berkel en RodenrjsThe Netherlands Plant Sciences Group Laboratory of EntomologyWageningen UniversityWageningenTheNetherlands

Black soldier fly larvae(Hermetia illucens)receive growing interest as a potential alternative animal feed *** insects may be exposed to insecticide residues in the rearing *** study aimed to investigate the effects of six different pyrethroid and organophosphate insecticides on this insect species'*** toxicity of two"model"substances for each of these classes(cypermethrin;pirimiphosmethyl)was quantified,with and without the synergist piperonyl butoxide(PBO).Critical effect doses corresponding to 10%yield(CED10)for cypermethrin(0.4 mg/kg)and pirimiphos-methyl(4.8 mg/kg)were *** addition of PBO to cypermethrin enhanced its relative potency with a factor *** data were compared against the relative toxicity of two analogue substances in each class(permethrin,deltamethrin;chlorpyrifosmethyl,malathion).Results suggest that exposure to concentrations complying with legal limits can cause significant reductions in *** to multiple substances at lower concentrations resulted in negative additive and synergistic *** the tested substances,deltamethrin was most toxic,causing 94%yield at 0.5 mg/*** results suggested that transfer of tested substances to the larval biomass was substance-and concentration-specific,but appeared to be correlated to reduced yields and the presence of *** of organophosphates was overall low(der adjusting legally allowed maximum residue levels in insect feed.

关键词： feed insects pesticides rearing substrate

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

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

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World journal of Pediatrics 2024年第7期20卷 682-691页

作者： Lieke C.E.Noij jelle M.Blankestijn Coen R.Lap Marlies A.van Houten Giske Biesbroek Anke-Hilse Maitland-van der Zee Mahmoud I.Abdel-Aziz johannes B.van Goudoever Mattijs 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 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

Outcome of direct-acting antiviral treatment for patients with chronic hepatitis C virus infection: clinical benefit proven?

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Hepatobiliary Surgery and Nutrition 2020年第2期9卷 257-259页

作者： Raoel Maan Adriaan j.van der Meer Department of Gastroenterology and Hepatology Erasmus MC University Medical Center RotterdamRotterdamthe Netherlands

The highly effective direct-acting antivirals(DAAs)for the treatment of chronic hepatitis C virus(HCV)infection were well-received by both patients and physicians as sustained virological response(SVR)was associated with an improved overall survival in patients with stable liver disease,even in case of cirrhosis(1).Yet,at that time these results were derived from retrospective cohort studies with long-term follow-up after interferon-based *** patients with compensated liver disease there is confidence that SVR is a clinically relevant endpoint based on consistent positive results with smart use of statistics in numerous cohort ***,however,there remains a need for long-term follow-up data showing a clinical benefit of DAA-induced SVR,preferably with high-quality prospective *** results from the French ANRS CO22 Hepather cohort,as published by *** and colleagues in the April issue of the Lancet,thus bring an important contribution to the field(2).It’s the first prospective cohort study with reasonable follow-up time to assess all-cause mortality after DAA therapy.

关键词： patients infection clinical

Hepatocellular carcinoma (HCC) risk stratification after virological cure for hepatitis C virus (HCV)-induced cirrhosis: time to refine predictive models

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Hepatobiliary Surgery and Nutrition 2021年第3期10卷 385-387页

作者： Raoel Maan Adriaan j.van der Meer Department of Gastroenterology and Hepatology Erasmus MC University Medical Center RotterdamRotterdamThe Netherlands

Direct-acting antivirals(DAAs)have revolutionized antiviral treatment for chronic hepatitis C virus(HCV)infection,especially with the interferon-free regimens of the past 5 *** a cure for a virus that has been identified(only)30 years ago is unique in medical ***,even in case of advanced liver disease,cohort studies showed that patients attaining a sustained virological response(SVR)have a 3-to 4-fold reduced risk of hepatocellular carcinoma(HCC)(1-3).

关键词： sustained interferon hepatitis

Are Gene Expression Microarray Analyses Reliable? A Review of Studies of Retinoic Acid Responsive Genes

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Genomics, Proteomics & Bioinformatics 2003年第1期1卷 9-14页

作者： Peter j.van der Spek Andreas Kremer Lynn Murry Michael G.Walker janssen Pharmaceutica Beerse BelgiumJanssen Pharmaceutica Beerse BelgiumIncyte Genomics Inc. CA 94087 USAIncyte Genomics Inc. CA 94087 USA

Microarray analyses of gene expression are widely used, but reports of the same analyses by different groups give widely divergent results, and raise questions regarding reproducibility and reliability. We take as an example recent published reports on microarray experiments that were designed to identify retinoic acid responsive genes. These reports show substantial differences in their results. In this article, we review the methodology, results, and potential causes of differences in these applications of microarrays. Finally, we suggest practices to improve the reliability and reproducibility of microarray experiments.

关键词： microarrays retinoic acid response gene reliability case studies

Effects of a general practitioner cooperative co-located with an emergency department on patient throughput

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World journal of Emergency Medicine 2016年第4期7卷 270-273页

作者： Michiel j.van Veelen Crispijn L.van den Brand Resi Reijnen M.Christien van der Linden Department of Emergency Medicine University of BotswanaSchool of Medicine Department of Emergency Medicine Medical Center Haaglanden

BACKGROUND:In 2013 a General Practitioner Cooperative(GPC) was introduced at the Emergency Department(ED) of our *** of the aims of this co-located GPC was to improve throughput of the remaining patients at the *** determine the change in patient flow,we assessed the number of self-referrals,redirection of self-referrals to the GPC and back to the ED,as well as ward and ICU admission rates and length of stay of the remaining ED ***:We conducted a four months' pre-post comparison before and after the implementation of a co-located GPC with an urban ED in the ***:More than half of our ED patients were *** triage,54.5%of these selfreferrals were redirected to the *** assessment at the GPC,8.5%of them were referred back to the *** number of patients treated at the ED declined with 20.3%after the introduction of the *** the remaining ED population,there was a significant increase of highly urgent patients(P<0.001),regular admissions(P<0.001),and ICU admissions(P<0.001).Despite the decline of the number of patients at the ED,the total length of stay of patients treated at the ED increased from 14 682 hours in the two months' control period to 14 962 hours in the two months' intervention period,a total increase of 270 hours in two months(P<0.001).CONCLUSION:Introduction of a GPC led to efficient redirection of self-referrals but failed to improve throughput of the remaining patients at the ED.

关键词： Emergency Service,hospital General practitioners Crowding Length of stay

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