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Genome-wide Studies Reveal Genetic Risk Factors for Hepatic Fat Content

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Genomics, Proteomics & Bioinformatics 2024年第2期22卷 57-68页

作者： Yanni Li eline H.van den Berg Alexander Kurilshikov Dasha V.Zhernakova Ranko Gacesa Shixian Hu esteban A.Lopera-Maya Alexandra Zhernakova Lifelines Cohort Study Vincent e.de Meijer Serena Sanna Robin P.F.Dullaart Hans Blokzijl eleonora A.M.Festen Jingyuan Fu Rinse K.Weersma Department of Gastroenterology and Hepatology University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Genetics University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300052China Laboratory of Genomic Diversity Center for Computer TechnologiesITMO UniversitySaint Petersburg 199034Russia Institute of Precision Medicine the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Department of Surgery Section of Hepatobiliary Surgery and Liver TransplantationUniversity of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of endocrinology University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Pediatrics University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands 不详

Genetic susceptibility to metabolic associated fatty liver disease(MAFLD)is complex and poorly *** characterization of the genetic background of hepatic fat content would provide insights into disease etiology and causality of risk *** performed genome-wide association study(GWAS)on two noninvasive definitions of hepatic fat content:magnetic resonance imaging proton density fat fraction(MRI-PDFF)in 16,050 participants and fatty liver index(FLI)in 388,701 participants from the United Kingdom(UK)Biobank(UKBB).Heritability,genetic overlap,and similarity between hepatic fat content phenotypes were analyzed,and replicated in 10,398 participants from the University Medical Center Groningen(UMCG)Genetics Lifelines Initiative(UGLI).Meta-analysis of GWASs of MRI-PDFF in UKBB revealed five statistically significant loci,including two novel genomic loci harboring CReB3L1(rs72910057-T,P=5.40e−09)and GCM1(rs1491489378-T,P=3.16e−09),respectively,as well as three previously reported loci:PNPLA3,TM6SF2,and *** of FLI in UKBB identified 196 genome-wide significant loci,of which 49 were replicated in UGLI,with top signals in ZPR1(P=3.35e−13)and FTO(P=2.11e−09).Statistically significant genetic correlation(rg)between MRI-PDFF(UKBB)and FLI(UGLI)GWAS results was found(rg=0.5276,P=1.45e−03).Novel MRI-PDFF genetic signals(CReB3L1 and GCM1)were replicated in the FLI *** identified two novel genes for MRI-PDFF and 49 replicable loci for *** a difference in hepatic fat content assessment between MRI-PDFF and FLI,a substantial similar genetic architecture was *** is identified as an easy and reliable approach to study hepatic fat content at the population level.

关键词： Hepatic fat content MAFLD Genome-wide association study Fatty liver index Magnetic resonance imaging proton density fat fraction

Cell-type-specific transcriptomics reveals that root hairs and endodermal barriers play important roles in beneficial plant-rhizobacterium interactions

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Molecular Plant 2023年第7期16卷 1160-1177页

作者： eline H.Verbon Louisa M.Liberman Jiayu Zhou Jie Yin CornéM.J.Pieterse Philip N.Benfey loannis A.Stringlis Ronnie de Jonge Plant-Microbe Interactions Department of BiologyScience4LifeUtrecht UniversityP.0.Box 800.563508 TB Utrechtthe Netherlands Howard Hughes Medical Institute Duke UniversityDurhamNC 27708USA Department of Biology Duke UniversityDurhamNC 27708USA Laboratory of Plant Pathology Agricultural University of Athens75 lera Odos str11855 AthensGreece

Growth-and health-promoting bacteria can boost crop productivity in a sustainable *** simiae WCS417is sucha bacterium that efficiently colonizes roots,modifiesthe architecture of the root systemto increase its size,and induces systemic resistance to make plants more resistant to pests and *** previous work suggested that WCS417-induced phenotypes are controlled by root cell-type-specific ***,it remains unclear how WCS417 affects these *** this study,we transcriptionally profiled five Arabidopsis thaliana root cell types following WCS417 *** found that the cortex and endodermis have the most differentially expressed genes,even though they are not in direct contact with this epiphytic *** of these genes are associated with reduced cell wall biogenesis,and mutant analysis suggests that this downregulation facilitates WCS417-driven root architectural ***,we observed elevated expression of suberin biosynthesis genes and increased deposition of suberin in the endodermis of WCS417-colonized *** an endodermal barrier mutant,we showed the importance of endodermal barrier integrity for optimal plant-beneficial bacterium *** of the transcriptome profiles in the two epidermal cell types that are in direct contact with WcS417-trichoblasts that form root hairs and atrichoblasts that do not-implies a difference in potential for defense gene *** both cell types respond to WCS417,trichoblasts displayed both higher basal and WCS417-dependent activation of defense-related genes compared with *** suggests that root hairs may activate root immunity,a hypothesis that is supported by differential immune responses in root hair *** together,these results highlight the strength of cell-type-specific transcriptional profiling to uncover"masked"biological mechanisms underlying beneficial plant-microbe associations.

关键词： FACs cell-type-specific transcriptomics root immunity beneficial rhizobacteria suberin root hair

Strategic options for syphilis control in Papua New Guineae impact and cost-effectiveness projections using the syphilis interventions towards elimination (SITe) model

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Infectious Disease Modelling 2021年第1期6卷 584-597页

作者： Shepherd Machekera Peniel Boas Poruan Temu Zimmbodilion Mosende Namarola Lote Angela Kelly-Hanku S.Guy Mahiane Robert Glaubius Jane Rowley Anup Gurung eline Korenromp Government of Papua New Guinea National Department of HealthAOPI CenterWaigani DrivePO Box5896Port MoresbyPapua New Guinea World Vision International Ruta PlaceMorata StGordons.P.O Box 4254BorokoNational Capital DistrictPort MoresbyPapua New Guinea UNAIDS Papua New Guinea Country Office Port MoresbyPapua New Guinea WHO Papua New Guinea Country Office Communicable Disease&Health Emergency Dept.AOPI CentreWaigani DrivePort MoresbyPapua New Guinea Papua New Guinea Institute of Medical Research 441 Homate StreetPO Box 60GorokaEastern Highland ProvincePapua New Guinea Kirby Institute UNSW SydneyWallace Wurth BuildingHigh StreetUNSW Australia KensingtonNSW 2052SydneyAustralia Avenir Health ModellingPlanning and Policy Analysis Dept.655 Winding Brook DriveGlastonburyCT06033USA Independent Consultant 135 Gloucester TerraceW26DXLondonUK Avenir Health ModellingPlanning and Policy Analysis Dept.150 Route de FerneyPO box 2100CH-1211 Geneva 2Switzerland

Objectives:Papua New Guinea(PNG)has among the highest rates of sexually transmitted infections(STIs)globally and is committed to reducing their *** Syphilis Interventions Towards elimination(SITe)model was used to explore the expected impact and cost of alternative syphilis intervention scale-up ***:SITe is a dynamical model of syphilis transmission among adults 15-49 *** are divided into nine groups based on sexual behaviour and into six stages of *** model was calibrated to PNG using data from routine surveillance,biobehavioural surveys,research studies and program *** included syphilis prevalence,risk behaviours,intervention coverage and service delivery unit *** compared different interventions(clinical treatment,contact tracing,syphilis screening,and condom promotion)for incidence and cost per infection averted over ***:Increasing treatment coverage of symptomatic primary/secondary-stage syphilis cases from 25-35%in 2020 to 60%from 2023 onwards reduced estimated incidence over 2021-2030 by 55%,compared to a scenario assuming constant coverage at 2019-2020 *** introduction of contact tracing in 2020,assuming 0.4 contacts per symptomatic person treated,reduced incidence over 2021-2030 by 10%.Increasing screening coverage by 20-30 percentage points from the 2019-2020 level reduced incidence over 2021-2030 by 3e16%depending on the target ***-up clinical,symptom-driven treatment and contact tracing had the lowest cost per infection averted,followed by condom promotion and periodic screening of female sex workers and men who have sex with ***:PNG could considerably reduce its syphilis burden by scaling-up clinical treatment and contact tracing alongside targeted behavioural risk reduction *** is a useful tool countries can apply to inform national STI programming and resource allocation.

关键词： Syphilis Prevention Treatment Cost-effectiveness Resource allocation National program strategy

THe eNVIRONMeNTAL IMPACT OF FLOODING OF A DeNSeLY POPULATeD POLDeR DISTRICT IN THe NeTHeRLANDS

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THE ENVIRONMENTAL IMPACT OF FLOODING OF A DENSELY POPULATED ...

Adult female syphilis prevalence,congenital syphilis case incidence and adverse birth outcomes,Mongolia 2000e2016:estimates using the Spectrum STI tool

第19届国际灌排大会

作者： Louis C.P.M.Stuyt eline e.van der Hoek Johan e.A.Reinders ellen G.M.Hermans Menzo de Muinck Keizer Centre for Water and Climate （CWK） Alterra Wageningen URP.O.Box 47NL-6700 AA WageningenThe Netherlands.

＜正＞Model studies into the consequences of flooding events are usually focused on damage to buildings, infrastructure, economic losses and casualties thus ignoring the risk of environmental damage. In this project, a model study was made to assess the environmental consequences of the release of pollutants during the flooding of a polder district in the Netherlands following a river dike breach. A conceptual framework was established for the sequence of events or ’chain reaction’ during a flood. A dike breach is formed, the scour of the flood waters and/or high water levels may damage or destroy objects like homes, industrial complexes and farms;damaged objects release hazardous substances that will be dispersed in the flood waters including suspended matter and the released chemicals will affect people and ecosystems in the inundated area. The analyses were made in the 50,000 ha case study area ’Krimpen’, located in the western Netherlands near the cities of Rotterdam, Delft and The Hague. The simulated period of flooding was ten days. The failure of objects where hazardous chemicals are stocked was linked to water height and velocity. The release and migration of pollutants like volatile aromatics, germs, sum PAH, PCB, LNAPL, DNAPL, heavy metals, nutrients and pesticides was simulated with an innovative, integrated modelling tool. The assessed impact of the pollutants on the environment was found to be substantial. Small yet numerous sources like cars may release substantial amounts of toxic chemicals to the flood waters and suspended sediments during and after the flood, while large installations like chemical plants only give problems near the dike breach where high flow velocities prevail. The simulated concentrations of toxic substances frequently exceeded the legal threshold levels.

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Infectious Disease Modelling 2018年第1期3卷 13-22页

作者： erdenetungalag enkhbat eline L.Korenromp Jugderjav Badrakh Setsen Zayasaikhan Purevsuren Baya enkhjargal Orgiokhuu Narantuya Jadambaa Sergelen Munkhbaatar Delgermaa Khishigjargal Narantuya Khad Guy Mahiane Naoko Ishikawa Davaalkham Jagdagsuren Melanie M.Taylor Mongolia National Centre for Communicable Disease AIDS/STI Surveillance and Research DepartmentUlaanbaatar210648Bayanzurkh DistrictNam-Yan-Ju StreetMongolia Avenir Health GenevaSwitzerland1 route de Morillons/150 Route de Ferney(WCCOffice 164)PO Box 2100CH-1211 Geneva 2Switzerland World Health Organization Post Box 663Ulaanbaatar-13Mongolia Mongolia Global Fund Supported Project on AIDS and TB Peace Avenue 13/3Sukhbaatar DistrictUlaanbaatarMongolia Mongolia Center for Health Development Enkhtaivan Street-13bSukhbaatar DistrictUlaanbaatarMongolia Avenir Health 655 Winding Brook DriveGlastonburyCTCT-06033USA World Health Organization Western Pacific Regional OfficePO Box 2932(United Nations Avenue)1000 ManilaPhilippines World Health Organization Department of Reproductive Health and Research8 Avenue Appia(L152)1211 GenevaSwitzerland Centers for Disease Control and Prevention Atlanta GAUSA

Introduction:Mongolia's health ministry prioritizes control of Sexually Transmitted Infections,including syphilis screening and treatment in antenatal care(ANC).Methods:Adult syphilis prevalence trends were fitted using the Spectrum-STI estimation tool,using data from ANC surveys and routine screening over *** were combined with programmatic data to estimate numbers of treated and untreated pregnant women with syphilis and associated incidence congenital syphilis(CS)and CS-attributable adverse birth outcomes(ABO),which we compared with CS case ***:Syphilis prevalence in pregnant women was estimated at 1.7%in 2000 and 3.0%in *** estimated 652 CS cases,of which 410 ABO,in *** larger,annually increasing numbers of CS cases and ABO were estimated to have been prevented:1654 cases,of which 789 ABO in 2016thanks to increasing coverages of ANC(99%in 2016),ANC-based screening(97%in 2016)and treatment of women diagnosed(81%in 2016).The 42 CS cases reported nationally over 2016(liveborn infants only)represented 27%of liveborn infants with clinical CS,but only 7%of estimated CS cases among women found syphilis-infected in ANC,and 6%of all estimated CS cases including those born to women with undiagnosed ***/Conclusion:Mongolia's ANC-based syphilis screening program is reducing CS,but maternal prevalence remains *** eliminate CS(target:es per 100,000 live births),Mongolia should strengthen ANC services,limiting losses during referral for treatment,and under-diagnosis of CS including still-births and neonatal deaths,and expand syphilis screening and prevention programs.

关键词： Syphilis Congenital syphilis Surveillance Screening Antenatal care epidemiological modelling

A new hemostatic agent composed of Zn^(2+)-enriched Ca^(2+)alginate activates vascular endothelial cells in vitro and promotes tissue repair in vivo

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Bioactive Materials 2022年第12期7卷 368-382页

作者： Anne-Charlotte Ponsen Richard Proust Sabrina Soave Françoise Mercier-Nom´e Isabelle Garcin Laurent Combettes Jean-Jacques Lataillade Georges Uzan INSeRM UMRS-MD 1197 Universit´e Paris-SaclayInstitut Andr´e LwoffHˆopital Paul BrousseVillejuifFrance Plateforme d’Histologie Immunopathologie de Clamart(PHIC) Universit´e Paris-SaclayINSERMCNRSInstitut Paris Saclay d’Innovation Th´erapeutiqueChˆatenay-MalabryFrance Universit´e Paris-Saclay INSERMInflammationMicrobiome and ImmunosurveillanceClamartFrance INSeRM UMRS 1174 Universit´e Paris-SaclayOrsayFrance Centre de Transfusion Sanguine des Arm´ees ClamartFrance

To control capillary bleeding, surgeons may use absorbable hemostatic agents, such as Surgicel® and TachoSil®. Due to their slow resorption, their persistence in situ can have a negative impact on tissue repair in the resected organ. To avoid complications and obtain a hemostatic agent that promotes tissue repair, a zinc-supplemented calcium alginate compress was developed: HeMO-IONIC®. This compress is non-absorbable and is therefore removed once hemostasis has been achieved. After demonstrating the hemostatic efficacy and stability of the blood clot obtained with HeMO-IONIC, the impact of Surgicel, TachoSil, and HeMO-IONIC on cell activation and tissue repair were compared (i) in vitro on endothelial cells, which are essential to tissue repair, and (ii) in vivo in a mouse skin excision model. In vitro, only HeMO-IONIC maintained the phenotypic and functional properties of endothelial cells and induced their migration. In comparison, Surgicel was found to be highly cytotoxic, and TachoSil inhibited endothelial cell migration. In vivo, only HeMO-IONIC increased angiogenesis, the recruitment of cells essential to tissue repair (macrophages, fibroblasts, and epithelial cells), and accelerated maturation of the extracellular matrix. These results demonstrate that a zinc-supplemented calcium alginate, HeMO-IONIC, applied for 10 min at the end of surgery and then removed has a long-term positive effect on all phases of tissue repair.

关键词： Hemostatic agent Alginate Surgery Hemostasis endothelial cells Tissue repair

非溃疡性消化不良的跨文化问卷调查表的建立及其调查效能研究:阿雷格里港消化不良症状调查表

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世界核心医学期刊文摘（胃肠病学分册） 2005年第8期1卷 5-6页

作者： Sander G.B Mazzoleni L.e Fernando C 李翔 RamiroBarcellos 1660 apto. 501 CEP 90035-002Porto Alegre RS Brazil.Dr

Despite its high prevalence, nonulcer dyspepsia is still difficult to study, d ue to the lack of adequate tools to measure significant outcomes. The objective of this study was to develop and validate a symptom-focused, disease- -specific questionnaire to evaluate patients with nonulcer dyspepsia. For tha t, the questionnaire was carefully written following widely accepted terminology , so as to facilitate translation and validation in other languages and cultures . The questionnaire was developed using Rome I terminology for symptoms, which w ere evaluated according to their intensity, duration, and frequency when applica ***-one patients with nonulcer dyspepsia, as well as 31 sex and age-mat ched volunteers without digestive problems were used to assess the internal cons istency, reproducibility,responsiveness, content validity, and discriminant vali dity of the questionnaire. Another 31 functional dyspeptic patients were enrolle d for assessment of criterion validity. Cronbach’s αcoefficient was 0.82. The intraclass correlation coefficient for the scores obtained 7 days apart was 0.86 . The mean score obtained after 3 months of treatment was 16.4, vs. 23.03 at bas eline (P = 0.001). Two blinded gastroenterologists agreed that the questionnaire adequately evaluated nonulcer *** median symptoms score for controls was 0, vs. 22.5 for dyspeptic patients (P = 0.001). An inverse correlation was o bserved between quality of life and dyspeptic symptoms (R=-0.28, P = 0.026). Th e proposed questionnaire has high degrees of both reproducibility and responsive ness. As this questionnaire was based on Rome I International Consensus terminol ogy, it is expected that it will be easy to translate and validate.

关键词：消化不良症状效能研究阿雷格里港消化道疾病问卷调查可重复性双盲控制标准术语问卷表持续时间