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The interplay mechanism between IDH mutation, MGMT-promoter methylation, and PRMT5 activity in the progression of grade 4 astrocytoma: unraveling the complex triad theory

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Oncology Research 2024年第6期32卷 1037-1045页

作者： MAHER KURDI ALAA ALKHOTANI ABDULRAHMAN SABBAGH EYAD FAIZO AHMED I.LARY AHMED K.BAMAGA MAJID ALMANSOURI BADR HAFIZ THAMER ALSHARIF SALEH BAEESA department of Pathology Faculty of MedicineKing Abdulaziz UniversityRabighSaudi Arabia department of Pathology College of MedicineUmm Al-Qura UniversityMakkahSaudi Arabia department of Surgery Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia department of Surgery Faculty of MedicineUniversity of TabukTabukSaudi Arabia Section of Neurosurgery Department of SurgeryKing Abdulaziz Medical CityJeddahSaudi Arabia department of pediatrics Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia department of Clinical Biochemistry Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia department of Neurosciences King Faisal Specialist Hospital and Research CenterJeddahSaudi Arabia department of Surgery King Abdulaziz Specialist HospitalTaifSaudi Arabia

Background:The dysregulation of Isocitrate dehydrogenase(IDH)and the subsequent production of 2-Hydroxyglutrate(2HG)may alter the expression of epigenetic proteins in Grade 4 astrocytoma.The interplay mechanism between IDH,O-6-methylguanine-DNA methyltransferase(MGMT)-promoter methylation,and protein methyltransferase proteins-5(PRMT5)activity,with tumor progression has never been described.Methods:A retrospective cohort of 34 patients with G4 astrocytoma is classified into IDH-mutant and IDH-wildtype tumors.Both groups were tested for MGMT-promoter methylation and PRMT5 through methylation-specific and gene expression PCR analysis.Inter-cohort statistical significance was evaluated.Results:Both IDH-mutant WHO grade 4 astrocytomas(n=22,64.7%)and IDH-wildtype glioblastomas(n=12,35.3%)had upregulated PRMT5 gene expression except in one case.Out of the 22 IDH-mutant tumors,10(45.5%)tumors showed MGMT-promoter methylation and 12(54.5%)tumors had unmethylated MGMT.All IDH-wildtype tumors had unmethylated MGMT.There was a statistically significant relationship between MGMT-promoter methylation and IDH in G4 astrocytoma(p-value=0.006).Statistically significant differences in progression-free survival(PFS)were also observed among all G4 astrocytomas that expressed PRMT5 and received either temozolomide(TMZ)or TMZ plus other chemotherapies,regardless of their IDH or MGMT-methylation status(p-value=0.0014).Specifically,IDH-mutant tumors that had upregulated PRMT5 activity and MGMT-promoter methylation,who received only TMZ,have exhibited longer PFS.Conclusions:The relationship between PRMT5,MGMT-promoter,and IDH is not tridirectional.However,accumulation of D2-hydroxyglutarate(2-HG),which partially activates 2-OG-dependent deoxygenase,may not affect their activities.In IDH-wildtype glioblastomas,the 2HG-2OG pathway is typically inactive,leading to PRMT5 upregulation.TMZ alone,compared to TMZ-plus,can increase PFS in upregulated PRMT5 tumors.Thus,using a PRMT5 inhibitor in G4 astrocytomas may help in tumor regression.

关键词： Grade 4 astrocytoma Glioblastoma Isocitrate dehydrogenase(IDH) O-6-methylguanine-DNA methyltransferase(MGMT) Protein methyltransferase proteins-5(PRMT5) Progression-free survival(PFS)

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COVID-19 vaccination produces exercise-responsive SARS-CoV-2 specific T-cells regardless of infection history

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Journal of Sport and Health Science 2024年第1期13卷 99-107页

作者： Kyle A.Smith Tiffany M.Zúñiga Forrest L.Baker Helena Batatinha Charles R.Pedlar Shane C.Burgess Michael P.Gustafson Emmanuel Katsanis Richard J.Simpson School of Nutritional Sciences and Wellness The University of ArizonaTucsonAZ 85721USA department of pediatrics The University of ArizonaTucsonAZ 85724USA Faculty of Sport Allied Health and Performance ScienceSt.Mary's UniversityTwickenham TW14SXUK Institute of Sport Exercise and Health University College LondonLondon WC1E 7HUUK department of Animal and Comparative Biomedical Sciences The University of ArizonaTucsonAZ 85721USA The University of Arizona Cancer Center The University of ArizonaTucsonAZ 85719USA Laboratory Medicine and Pathology Mayo Clinic ArizonaPhoenixAZ 85054USA department of Immunobiology The University of ArizonaTucsonAZ 85724USA department of Medicine The University of ArizonaTucsonAZ 85724USA department of Pathology The University of ArizonaTucsonAZ 85724USA

Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb titers.Methods:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 vaccine.All major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb serology.Results:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded exercise.However,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent manner.Both groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid antigens.nAbs increased significantly during exercise only in the hybrid immunity group.Conclusion:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.

关键词： Anti-viral COVID-19 Exercise immunology SARS-CoV-2 T-Cells Vaccine

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Pediatric Hepatoblastoma: A Case Report and Review of the Literature

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Open Journal of pediatrics 2024年第2期14卷 266-271页

作者： Hanae Bahari Hanane Hajaj Hind Zahiri Ayyad Ghanam Abdeladim Babakhouya Maria Rkain department of pediatrics Mohammed VI University Hospital Oujda Morocco Medical School Mohammed First University Oujda Morocco

Introduction and Objective: Hepatoblastoma is the most frequent malignant embryonal liver tumor, and its incidence is increasing. Children under 3 years of age are particularly affected. The etiology is largely unknown, but a genetic predisposition exists. This case highlights the clinical and imaging characteristics and management strategies. Case Report: We report the case of an 18 months old male admitted for exploration of an abdominal mass and was diagnosed with hepatoblastoma. Conclusion: Hepatoblastoma is an aggressive tumor that begins locally and eventually metastasizes to the brain, lungs, lymph nodes, and other organs. Tumor stage at presentation and resectability are the most significant prognostic factors.

关键词： Hepatoblastoma Liver Children Alpha-Fetoprotein

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Sex differences in the risk of retinopathy of prematurity:a systematic review,frequentist and Bayesian meta‑analysis,and meta‑regression

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World Journal of pediatrics 2024年第4期20卷 340-352页

作者： Tamara M.Hundscheid Silvia Gulden Mohamad F.Almutairi František Bartoš Giacomo Cavallaro Eduardo Villamor Division of Neonatology Department of PediatricsMosaKids Children’s HospitalMaastricht University Medical Center(MUMC+)School for Oncology and Reproduction(GROW)Maastricht UniversityP.Debyelaan 25.P.O.Box 58006202 AZ MaastrichtThe Netherlands Neonatal Intensive Care Unit Sant’Anna HospitalComoItaly department of Psychology University of Amsterdam1001 NK AmsterdamThe Netherlands Neonatal Intensive Care Unit Fondazione IRCCS Ca’Granda Ospedale Maggiore PoliclinicoMilanItaly

Background Retinopathy of prematurity(ROP)is generally considered to be more frequent in males than in females.However,it is not known whether sex differences in ROP affect all degrees of the condition,are global and have changed as neonatology has developed.We aimed to conduct a systematic review and meta-analysis of studies addressing sex differences in the risk of developing ROP.Methods PubMed/MEDLINE and Embase databases were searched.The frequentist,random-effects risk ratio(RR)and 95%confidence interval(CI)were calculated.Bayesian model averaged(BMA)meta-analysis was used to calculate the Bayes factors(BFs).The BF10 is the ratio of the probability of the data under the alternative hypothesis(H1)over the probability of the data under the null hypothesis(H0).Results We included 205 studies(867,252 infants).Frequentist meta-analysis showed a positive association between male sex and severe ROP(113 studies,RR=1.14,95%CI=1.07–1.22)but no association with any ROP(144 studies,RR=1.00,95%CI=0.96–1.03).BMA showed extreme evidence in favor of H1 for severe ROP(BF10=71,174)and strong evidence in favor of H0 for any ROP(BF10=0.05).The association between male sex and severe ROP remained stable over time and was present only in cohorts from countries with a high or high-middle sociodemographic index.Conclusions Our study confirms the presence of a male disadvantage in severe ROP but not in less severe forms of the disease.There are variations in the sex differences in ROP,depending on geographical location and sociodemographic level of the countries.

关键词： Oxidative stress Retinopathy of prematurity Sex characteristics

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Sacrococcygeal Teratoma a Rare Tumor in Children: Case Report

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Open Journal of pediatrics 2024年第1期14卷 78-83页

作者： Hanae Bahari Hanane Hajaj Hind Zahiri Ayyad Ghanam Aziza El Ouali Abdeladim Babakhouya Maria Rkain department of pediatrics Mohammed VI University Hospital Oujda Morocco Medical School University Mohammed First Oujda Morocco

Sacrococcygeal teratomas (SCTs) are uncommon congenital tumors that typically develop in newborns, they are rarely associated with chromosomal abnormalities or other congenital anomalies. The majority of pediatric teratomas are benign in the neonatal age group, but the risk of malignancy increases with age. Diagnosis is based on a combination of clinical, radiological, and hormonal findings, but confirmed by anatomopathological study. Treatment is primarily surgical, with the aim of achieving complete resection to prevent recurrence. We present the case of a 22-month-old child who was admitted for management of a sacrococcygeal mass and was diagnosed with an immature teratoma.

关键词： Sacrococcygeal Mass Alpha-Fetoprotein Surgery

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Pre-operative visceral adipose tissue radiodensity is a potentially novel prognostic biomarker for early endoscopic post-operative recurrence in Crohn’s disease

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World Journal of Gastrointestinal Surgery 2024年第3期16卷 740-750页

作者： Phillip Gu Shishir Dube Norman Gellada So Yung Choi Susan Win Yoo Jin Lee Shaohong Yang Talin Haritunians Gil Y Melmed Eric A Vasiliauskas Niru Bonthala Gaurav Syal Andres J Yarur David Ziring Shervin Rabizadeh Phillip Fleshner Cindy Kallman Suzanne Devkota Stephan R Targan Dalin Li Dermot PB McGovern department of Medicine Cedars-Sinai Medical CenterLos AngelesCA 90048United States department of Imaging Cedars-Sinai Medical CenterLos AngelesCA 90048United States department of Biostatistics Shared Resource Cedars-Sinai Medical CenterLos AngelesCA 90048United States department of Internal Medicine Keimyung University School of MedicineDaegu 42601South Korea department of Medicine University of California at Los AngelesLos AngelesCA 90095United States department of Medicine University of California at San DiegoSan DiegoCA 92093United States department of pediatrics Cedars-Sinai Medical CenterLos AngelesCA 90048United States department of Surgery Cedars-Sinai Medical CenterLos AngelesCA 90048United States

BACKGROUND Evidence suggests inflammatory mesenteric fat is involved in post-operative recurrence(POR)of Crohn’s disease(CD).However,its prognostic value is INTRODUCTION Crohn’s disease(CD)is a debilitating chronic immune-mediated inflammatory disease(IMID)of the gastrointestinal tract that is increasing in incidence and prevalence globally[1].CD patients often undergo surgery for disease-related complic-ations and/or medically refractory disease.Unfortunately,surgery is not curative,and many patients develop post-operative recurrence(POR)of CD with a significant proportion eventually requiring additional surgeries.With advances in early detection and therapeutics,the contemporary 10-year risk of surgery has improved from 50%to 26%,but the risk of recurrent surgery has remained unchanged at 30%,suggesting a need to improve post-operative management strategies[2].Presently,there are two accepted strategies to mitigate POR,but each have potential limitations.Firstly,patients start early post-operative pharmacologic prophylaxis within 4-6 wk after surgery.This strategy can potentially overtreat a subset of patient who may not develop long-term disease recurrence off therapy.Consequently,these patients are at risk of medication-related adverse events and the direct and indirect costs associated with therapy with little or no benefit[3].The second strategy is performing early colonoscopy within 6-12 months after surgery and escalating therapy based on FOOTNOTES Author contributions:Gu P is the guarantor of the article and was involved in concept and design,data collection,statistical analysis,drafting of manuscript,and final approval of manuscript;Dube S and Choi SY were involved in statistical analysis,drafting of the manuscript,and final approval of manuscript;Gellada N,Win S,Lee YJ and Yang S were involved in the data collection,drafting of the manuscript,and final approval of manuscript;Haritunians T and Li D were involved in data analysis and interpretation,drafting of manuscript and final approval of manuscript;

关键词： Crohn’s disease Surgery Visceral adipose tissue Mesenteric adipose tissue Creeping fat Computed tomography

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Circulating microRNA expression and nonalcoholic fatty liver disease in adolescents with severe obesity

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World Journal of Gastroenterology 2024年第4期30卷 332-345页

作者： Yi-Jie Li Brittney O Baumert Nikos Stratakis Jesse A Goodrich Hao-Tian Wu Jing-Xuan He Yin-Qi Zhao Max T Aung Hong-Xu Wang Sandrah P Eckel Douglas I Walker Damaskini Valvi Michele A La Merrill Justin R Ryder Thomas H Inge Todd Jenkins Stephanie Sisley Rohit Kohli Stavra A Xanthakos Andrea A Baccarelli Rob McConnell David V Conti Lida Chatzi department of Population and Public Health Sciences Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90032United States Barcelona Institute of Global Health Barcelona Institute of Global HealthBarcelona 08036Spain department of Environmental Health Sciences Mailman School of Public HealthColumbia UniversityNew YorkNY 10032United States Gangarosa department of Environmental Health Rollins School of Public HealthEmory UniversityAtlantaGA 30329United States department of Environmental Medicine and Public Health Icahn School of Medicine at Mount SinaiNew YorkNY 10029United States department of Environmental Toxicology University of CaliforniaDavisCA 95616United States department of Surgery Lurie Children’s Hospital of ChicagoChicagoIL 60611United States Northwestern University Feinberg School of Medicine Northwestern UniversityChicagoIL 60611United States Division of Biostatistics and Epidemiology Cincinnati Children's Hospital Medical CenterCincinnatiOH 45229United States department of pediatrics University of Cincinnati College of MedicineCincinnatiOH 45229United States department of pediatrics Children’s Nutrition Research Center USDA/ARSBaylor College of MedicineHoustonTX 77030United States department of Gastroenterology Children’s Hospital Los AngelesLos AngelesCA 90027United States Division of Gastroenterology Hepatology and NutritionCincinnati Children's Hospital Medical CenterCincinnatiOH 45229United States

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases in children and adolescents.NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis(NASH),wherein hepatocellular inflammation and/or fibrosis coexist with steatosis.Circulating microRNA(miRNA)levels have been suggested to be altered in NAFLD,but the extent to which miRNA are related to NAFLD features remains unknown.This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents.AIM To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD.METHODS This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery study.Intra-operative core liver biopsies were collected from participants and used to characterize histological features of NAFLD.Plasma samples were collected during surgery for miRNA profiling.A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq platform.We examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age,sex,race,and other key covariates.Ingenuity Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of NAFLD.RESULTS We identified 16 upregulated plasma miRNAs,including miR-193a-5p and miR-193b-5p,and 22 downregulated plasma miRNAs,including miR-1282 and miR-6734-5p,in adolescents with NAFLD.Moreover,52,16,15,and 9 plasma miRNAs were associated with NASH,fibrosis,ballooning degeneration,and lobular inflammation,respectively.Collectively,16 miRNAs were associated with two or more histological features of NAFLD.Among those miRNAs,miR-411-5p was downregulated in NASH,ballooning,and fibrosis,while miR-122-5p,miR-1343-5p,miR-193a-5p,miR-193b-5p,and miR-7845-5p were consistently and positively associated with all histological features

关键词： MicroRNA Nonalcoholic fatty liver disease Non-alcoholic steatohepatitis Liver fibrosis Lobular inflammation Ballooning degeneration

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Novel variants and phenotypes of ROBO3 gene associated with horizontal gaze palsy with progressive scoliosis

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儿科学研究(英文) 2024年第1期8卷 72-74页

作者： Xie Yan Huang Lijuan Zhou Yunyu Wu Jin Li Ningdong department of Ophthalmology Beijing Children’s Hospital Capital Medical University National Center for Children’s Health Beijing China department of Ophthalmology The Second Affiliated Hospital of Fujian Medical University Fujian China department of Ophthalmology Shenzhen Children’s Hospital Guangdong China department of Ophthalmology Shanghai General Hospital Shanghai China department of Ophthalmology Children’s Hospital Capital Institute of Pediatrics Beijing China

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Anticancer effects of exercise:Insights from single-cell analysis

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Journal of Sport and Health Science 2024年第5期13卷 676-678页

作者： Abel Plaza-Florido Alejandro Lucia Shlomit Radom-Aizik Carmen Fiuza-Luces Pediatric Exercise and Genomics Research Center Department of PediatricsSchool of MedicineUniversity of California IrvineIrvineCA 92617USA Faculty of Sport Sciences Universidad Europea de MadridMadrid 28670Spain Physical Activity and Health Research Group(“PaHerg”) Research Institute of the Hospital 12 de Octubre(“imas12”)Madrid 28041Spain

A recent special topic in the Journal of Sport and Health Science reported the health benefits conferred by traditional and innovative m-health exercise and multimodal programs with respect to several types of cancer.... 详细信息

关键词： protective exercise modal

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Fetal lung growth predicts the risk for early-life respiratory infections and childhood asthma

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World Journal of pediatrics 2024年第5期20卷 481-495页

作者： Dimitra E.Zazara Olympia Giannou Steven Schepanski Mirja Pagenkemper Anastasios D.Giannou Maike Pincus Ioannis Belios Stefan Bonn Ania C.Muntau Kurt Hecher Anke Diemert Petra Clara Arck Division for Experimental Feto-Maternal Medicine Department of Obstetrics and Fetal MedicineUniversity Medical Center Hamburg-Eppendorf(UKE)Martinistraße 5220251HamburgGermany University Children’s Hospital UKEHamburgGermany Computer Engineering and Informatics department Polytechnic SchoolUniversity of PatrasPatrasGreece Institute of Developmental Neurophysiology Center for Molecular Neurobiology Hamburg(ZMNH)UKEHamburgGermany department of Obstetrics and Fetal Medicine UKEHamburgGermany department of General Visceral and Thoracic SurgeryUKEHamburgGermany Section of Molecular Immunology and Gastroenterology I.Department of MedicineUKEHamburgGermany pediatrics and Pediatric Pneumology Practice BerlinGermany Institute of Medical Systems Biology ZMNHUKEHamburgGermany Hamburg Center for Translational Immunology UKEHamburgGermany

Background Early-life respiratory infections and asthma are major health burdens during childhood.Markers predicting an increased risk for early-life respiratory diseases are sparse.Here,we identified the predictive value of ultrasound-monitored fetal lung growth for the risk of early-life respiratory infections and asthma.Methods Fetal lung size was serially assessed at standardized time points by transabdominal ultrasound in pregnant women participating in a pregnancy cohort.Correlations between fetal lung growth and respiratory infections in infancy or early-onset asthma at five years were examined.Machine-learning models relying on extreme gradient boosting regressor or classifier algorithms were developed to predict respiratory infection or asthma risk based on fetal lung growth.For model development and validation,study participants were randomly divided into a training and a testing group,respectively,by the employed algorithm.Results Enhanced fetal lung growth throughout pregnancy predicted a lower early-life respiratory infection risk.Male sex was associated with a higher risk for respiratory infections in infancy.Fetal lung growth could also predict the risk of asthma at five years of age.We designed three machine-learning models to predict the risk and number of infections in infancy as well as the risk of early-onset asthma.The models’R2 values were 0.92,0.90 and 0.93,respectively,underscoring a high accuracy and agreement between the actual and predicted values.Influential variables included known risk factors and novel predictors,such as ultrasound-monitored fetal lung growth.Conclusion Sonographic monitoring of fetal lung growth allows to predict the risk for early-life respiratory infections and asthma.

关键词： Asthma Child risk Early-life respiratory infections Prenatal lung development Sexual dimorphism

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