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

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

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Neuron-to-astrocyte proteostatic stress signaling in response to tau pathology

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Neural Regeneration Research 2024年第3期19卷 505-506页

作者： Kevin Llewelyn Batenburg Wiep Scheper amsterdam umc location Vrije Universiteit amsterdam Department of Human GeneticsAmsterdam Neuroscience-NeurodegenerationAmsterdamThe Netherlands Department of Functional Genomics Center for Neurogenomics and Cognitive ResearchVrije Universiteit AmsterdamAmsterdam Neuroscience-NeurodegenerationAmsterdamThe Netherlands

Maintenance of protein homeostasis or“proteostasis”is essential for the functioning and viability of *** is in particular the case for cells like neurons that cannot self-renew and acquire unique functional properties during their *** proteostatic stress responses are in place to protect cells from damage in case of proteostatic *** integrated stress response(ISR)is one of the key proteostatic stress responses in the cell(Costa-Mattioli and Walter,2020).The ISR is the downstream convergence point for the four stress-induced eIF2αkinases(EIF2AK1-4)that control stress-regulated protein translation via phosphorylation of the translation factor eIF2α.ISR activation results in a transient reduction of global translation while it concomitantly enhances the translation of specific mRNAs,including that encoding the activating transcription factor 4(ATF4).Together,the translational control mediated by the ISR results in a temporary reduction of the overall protein load and the selectively increased expression of proteins that contribute to restoration of the proteostatic balance.

关键词： translation stress Together

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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

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Deciding on life-saving treatment after a violent suicide attempt:an ethical case report

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General Psychiatry 2024年第2期37卷 289-291页

作者： Robert Wichers Hanna M Heller Sisco van Veen Department of Child and Adolescent Psychiatry&Psychosocial Care Amsterdam University Medical CenterLocation AMCAmsterdamThe Netherlands amsterdam Public Health Mental Health programAmsterdamThe Netherlands Department of Hospital Psychiatry Amsterdam University Medical CenterLocation VUmcAmsterdamThe Netherlands Research Department 113 Suicide PreventionAmsterdamThe Netherlands Department of Psychiatry&Department of Ethics Law and HumanitiesAmsterdam University Medical CenterAmsterdamThe Netherlands GGZ inGeest Mental Health Care AmsterdamThe Netherlands

To the editor:In the USA alone,there were 1.7 million suicide attempts in 2021.1 Although the majority of suicide attempts are not fatal,immediate medical attention is often necessary,especially when violent methods are used.2 These methods include jumping from heights,using a firearm,crashing a motor vehicle,and lying down or jumping in front of a moving object.

关键词： treatment editor alone

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A novel homozygous missense variant in ARSK causes MPS X,a new subtype of mucopolysaccharidosis

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Genes & Diseases 2024年第3期11卷 87-90页

作者： Miao Sun Cornelia K.Kaminsky Philip Deppe Mai-Brittllse Frederic M.Vaz Barbara Plecko Torben Lubke Linda M.Randolph Division of Genomic Medicine Department of Pathology and Laboratory MedicineChildren's Hospital Los Angeles/Keck School of Medicine of USCLos AngelesCA 90027USA Department of Radiology Children's Hospital Los Angeles/Keck School of Medicine of USCLos AngelesCA 90027USA Department of Chemistry BiochemistryBielefeld UniversityBielefeld 33615Germany amsterdam umc Location university of amsterdam Department of Clinical Chemistry and PediatricsLaboratory Genetic Metabolic DiseasesEmma Children's HospitalMeibergdreef 9Amsterdam 1100 DEthe Netherlands amsterdam Gastroenterology Endocrinology Metabolism Inborn Errors of MetabolismAmsterdam 1105 BKthe Netherlands Core Facility Metabolomics Amsterdam UMC Location University of AmsterdamAmsterdam 1100DDthe Netherlands Department of Pediatrics Division of General PediatricsMedical Universityof GrazGraz8036Austria Division of medical Genetics Department of PediatricsChildren's Hospital Los Angeles/Keck School of Medicine of USCLos AngelesCA 90027USA

Mucopolysaccharidoses(MPS)are a group of rare inborn errors of metabolism caused by defective lysosomal enzymes which prevent cells from degrading and recycling certain carbohydrates and fats,resulting in the storage of glycosaminoglycans in cells throughout the *** leads to multisystem abnormalities involving bone,connective tissues,brain,blood,spinal cord,skin,and other tissues.

关键词： metabolism doses polys

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Blood-brain barrier pathology in cerebral small vessel disease

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Neural Regeneration Research 2024年第6期19卷 1233-1240页

作者： Ruxue Jia Gemma Solé-Guardia Amanda J.Kiliaan Department of medical Imaging AnatomyRadboud University Medical CenterDonders Institute for BrainCognition&BehaviorCenter for Medical NeurosciencePreclinical Imaging Center PRIMERadboud Alzheimer CenterNijmegenthe Netherlands

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the *** at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of *** signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease *** pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier ***,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel ***,the purpose of this review is to provide a new foundation in the study of small vessel disease ***,we discuss the main structural domains and functions of the blood-brain ***,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel ***,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

关键词： blood-brain barrier dysfunction cerebral blood flow cerebral hypoperfusion endothelial dysfunction hypertension inflammation magnetic resonance imaging neurovascular unit oxidative stress small vessel disease tight junctions transcytosis

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Movement Trend Alterations in the Periaqueductal Gray(PAG)-Employed Ratbot Navigation Are Correlated with Stimulation Parameters

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Journal of Bionic Engineering 2024年第2期21卷 866-876页

作者： Sina Khajei Abed Khorasani Mohammad Reza Afarinesh Vahid Sheibani Neuroscience Research center Institute of NeuropharmacologyKerman University of Medical SciencesKerman***Iran Cognitive Neuroscience Research center Institute of NeuropharmacologyKerman University of Medical SciencesKerman***Iran

In previous studies,Periaqueductal Gray(PAG)stimulation was used to stop ratbots from *** to the homology between the PAG and the intercollicular nucleus,which has been used for forward movement in birds,we investigated the possibility of PAG application to induce forward locomotion for the first *** a corridor maze,the traveled distances via PAG electrical stimulation were examined in nine Wistar male rats during three sessions.A custom-designed stimulator was developed to apply the *** results showed reductions in responses to stimulation over ***,the traveled distances had negative slopes during the consecutive trials(in 8 out of the 9 rats),and the slope mean was significantly different from *** was a strong correlation between the stimulation parameters(electric Charge per Phase(CPP)and the Number of Pulses(NP))and the observed *** negative Movement Slopes(MS)were highly correlated with the CPP and the NP,as the Pearson's linear correlation coefficients were−0.87 and−0.79,*** MS-CPP coefficients of determination(R-squared)were also between 0.76 and *** addition,the MS-NP coefficients of determination were between 0.63 and ***,it is concluded that the electrical stimulation parameters influence the behavioral outcomes ***,the PAG area may be considered a suitable candidate for forward locomotion control in the future if the area is harnessed effectively to prevent undesirable chaotic behaviors.

关键词： Periaqueductal Gray(PAG) Navigation Ratbot Animal-robot Forward locomotion Movement slope

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Mid-term survival of the Optimys short stem: A prospective case series of 500 patients

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World Journal of Orthopedics 2024年第3期15卷 257-265页

作者： Bryan Hamans Sheryl de Waard Sjoerd Kaarsemaker Esther R C Janssen Inger N Sierevelt Gino M M J Kerkhoffs Daniël Haverkamp Department of Orthopaedic Surgery Xpert ClinicAmsterdam 1101EANetherlands Department of Orthopedic Surgery Amsterdam University Medical CenterAmsterdam 1105 AZNetherlands Esther R C Janssen Department of Orthopaedic SurgeryViecuri Medisch CentrumVenlo 5912 BLNetherlands Centre for Orthopaedic Research Spaarne ZiekenhuisHoofddorp 2134 TMNetherlands Department of Orthopaedic Surgery and Sports Medicine Amsterdam UMC-Location AMCAmsterdam 1105 AZNetherlands Department of Orthopedic Surgery Xpert Orthopedic Surgery ClinicAmsterdam 1101 EANetherlands

BACKGROUND In recent years,there has been an increase in the number of total hip arthroplasty procedures in the younger patient *** active group has higher expectations of their prosthesis in comparison to the older population,and there is a greater physical demand for the *** femoral stems were in-troduced to retain proximal bone stock and joint biomechanics and became more common to implant in this specific ***,the long-term survival and functional outcomes of various short stems are still being investigated in different *** To determine the 5-year survival of the Optimys hip *** This was a prospective multicenter cohort study of 500 patients conducted in two hospitals in the *** patients received the Optimys short stem(Mathys Ltd,Bettlach,Switzerland).The primary outcome measure was survival of the hip stem,with revision as the *** secondary outcome measurements included patient-reported outcome measures(PROMs).Kaplan-Meier analysis was used to calculate the 5-year survival ***-minus-log transformation was performed to calculate the 95%confidence interval(95%CI).Mixed model analyses were performed to assess the course of the PROMs during the 1st 2 years after *** were modeled separately for the 1st and 2nd years to calculate the yearly change in PROMs during both follow-up periods with accompanying 95%*** The mean age of the total 500 patients was 62.3 years(standard deviation:10.6)and 202 were male(40%).At a median follow-up of 5.5 years(interquartile range:4.5-6.7),7 patients were deceased and 6 revisions were registered,for infection(n=3),subsidence(n=2)and malposition(n=1).This resulted in an overall 5-year survival of 98.8%(95%CI:97.3-99.5).If infection was left out as reason for revision,a stem survival of 99.4%(95%CI:98.1-99.8)was *** questionnaires were completed by 471 patients(94%),317 patients(63%)completed the 1-year follow-up questionna

关键词： Total hip arthroplasty Femoral stem Short stem Optimys Survival 5-year survival Revision PROMs

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Targeting GPR65 alleviates hepatic inflammation and fibrosis by suppressing the JNK and NF-κB pathways

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Military medical Research 2024年第4期11卷 500-520页

作者： Kun Zhang Meng-Xia Zhang Xiao-Xiang Meng Jing Zhu Jia-Jun Wang Yi-Fan He Ye-Hua Li Si-Cong Zhao Zhe-Min Shi Li-Na Zheng Tao Han Wei Hong Department of Histology and Embryology School of Basic Medical SciencesTianjin Medical UniversityTianjin 300070China Department of Hepatology and Gastroenterology Tianjin Union Medical CenterTianjin Medical UniversityTianjin Union Medical Center Affiliated to Nankai UniversityTianjin 300000China

Background:G-protein coupled receptors(GPCRs)are recognized as attractive targets for drug ***,it remains poorly understood how GPCRs,except for a few chemokine receptors,regulate the progression of liver ***,we aimed to reveal the role of GPR65,a proton-sensing receptor,in liver fibrosis and to elucidate the underlying ***:The expression level of GPR65 was evaluated in both human and mouse fibrotic ***,Gpr65-deficient mice were treated with either bile duct ligation(BDL)for 21 d or carbon tetrachloride(CCl4)for 8 weeks to investigate the role of GPR65 in liver fibrosis.A combination of experimental approaches,including Western blotting,quantitative real-time reverse transcription-polymerase chain reaction(qRT-PCR),and enzyme-linked immunosorbent assay(ELISA),confocal microscopy and rescue studies,were used to explore the underlying mechanisms of GPR65’s action in liver ***,the therapeutic potential of GPR65 inhibitor in the development of liver fibrosis was ***:We found that hepatic macrophage(HM)-enriched GPR65 was upregulated in both human and mouse fibrotic ***,knockout of Gpr65 significantly alleviated BDL-and CCl4-induced liver inflammation,injury and fibrosis in vivo,and mouse bone marrow transplantation(BMT)experiments further demonstrated that the protective effect of Gpr65knockout is primarily mediated by bone marrow-derived macrophages(BMMs).Additionally,in vitro data demonstrated that Gpr65 silencing and GPR65 antagonist inhibited,while GPR65 overexpression and application of GPR65 endogenous and exogenous agonists enhanced the expression and release of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and transforming growth factor-β(TGF-β),all of which subsequently promoted the activation of hepatic stellate cells(HSCs)and the damage of hepatocytes(HCs).Mechanistically,GPR65 overexpression,the acidic pH and GPR65 exogenous agonist induced up-regulation of

关键词： GPR65 Hepatic fibrosis Hepatic macrophages Inflammation c-Jun N-terminal kinase Nuclear factorκB

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A combined nanotherapeutic approach targeting farnesoid X receptor,ferroptosis,and fibrosis for nonalcoholic steatohepatitis treatment

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2228-2246页

作者： Jiangtao Fu Pingping Zhang Zhiguo Sun Guodong Lu Qi Cao Yiting Chen Wenbin Wu Jiabao Zhang Chunlin Zhuang Chunquan Sheng Jiajun Xu Ying Lu Pei Wang The center for Basic Research and Innovation of Medicine and Pharmacy(MOE) School of PharmacyNaval Medical UniversityShanghai 200433China National Demonstration center for Experimental Pharmaceutical Education Naval Medical University/Second Military Medical UniversityShanghai 200433China Department of Diving and Hyperbaric Medicine Naval Special Medical CenterNaval Medical UniversityShanghai 200433China

Obeticholic acid(OCA),a farnesoid X receptor(FXR)agonist with favorable effects on fatty and glucose metabolism,has been considered the leading candidate drug for nonalcoholic steatohepatitis(NASH)***,its limited effectiveness in resolving liver fibrosis and lipotoxicity-induced cell death remains a major ***,a newly recognized form of cell death characterized by uncontrolled lipid peroxidation,is involved in the progression of *** oxide(NO)is a versatile biological molecule that can degrade extracellular *** this study,we developed a PEGylated thiolated hollow mesoporous silica nanoparticles(MSN)loaded with OCA,as well as a ferroptosis inhibitor liproxsatin-1 and a NO donor S-nitrosothiol(ONL@MSN).Biochemical analyses,histology,multiplexed flow cytometry,bulk-tissue RNA sequencing,and fecal 16S ribosomal RNA sequencing were utilized to evaluate the effects of the combined nanoparticle(ONL@MSN)in a mouse NASH *** with the OCA-loaded nanoparticles(O@MSN),ONL@MSN not only protected against hepatic steatosis but also greatly ameliorated fibrosis and ***@MSN also displayed enhanced therapeutic actions on the maintenance of intrahepatic macrophages/monocytes homeostasis,inhibition of immune response/lipid peroxidation,and correction of microbiota *** findings present a promising synergistic nanotherapeutic strategy for the treatment of NASH by simultaneously targeting FXR,ferroptosis,and fibrosis.

关键词： Nonalcoholic steatohepatitis Nanotherapy Farnesoid X receptor Ferroptosis Fibrosis Obeticholic acid S-Nitrosothiol Liproxstatin-1

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