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journal of Molecular Cell Biology 2020年第8期12卷 644-653页

作者： Tijmen H.Booij Wouter N.Leonhard Hester Bange Kuan Yan Michiel Fokkelman Anna j.plugge Kimberley A.M.Veraar johannes G.Dauwerse gerard j.p.van westen Bob van de Water Leo S.price Dorien j.M.peters Division of Toxicology Leiden Academic Centre for Drug Research(LACDR)Leiden UniversityLeidenThe Netherlands present address:NEXUS personalized Health Technologies ETH ZurichSwitzerland Department of Human Genetics Leiden University Medical Center(LUMC)LeidenThe Netherlands OcellO B.V. LeidenThe Netherlands Division of Medicinal Chemistry Leiden Academic Centre for Drug Research(LACDR)LeidenThe Netherlands

polycystic kidney disease(pKD)is a prevalent genetic disorder,characterized by the formation of kidney cysts that progressively lead to kidney *** currently available drug tolvaptan is not well tolerated by all patients and there remains a strong need for alternative *** signalling rewiring in pKD that drives cyst formation is highly complex and not fully *** a consequence,the effects of drugs are sometimes difficult to *** previously established a high-throughput microscopy phenotypic screening method for quantitative assessment of renal cyst ***,we applied this 3D cyst growth phenotypic assay and screened 2320 small drug-like molecules,including approved *** identified 81 active molecules that inhibit cyst ***-parametric phenotypic profiling of the effects on 3D cultured cysts discriminated molecules that showed preferred pharmacological effects above genuine toxicological ***,a triterpenoid from Tripterygium wilfordii,was identified as a potent inhibitor of cyst growth in *** an in vivo iKspCre-pkd1^lox,lox mouse model for pKD,celastrol inhibited the growth of renal cysts and maintained kidney function.

关键词： pKD celastrol pyrvinium pamoate high-content screening 3D

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基于GIS的滑坡预测模型的预测率及其作用

岩石力学与工程学报 2007年第2期26卷 285-291页

作者：喻根 B.H.p.Maathuis C.j.van westen 合肥工业大学资源与环境工程学院安徽合肥230009 荷兰国际地理信息科学与地球观测学院

滑坡预测模型的选择直接影响到滑坡预测的准确性,是滑坡预测的关键所在。该研究利用意大利Alpago地区的滑坡数据和其他相关地理空间数据,以模糊伽马模型、模糊代数积模型、模糊代数和模型以及模糊最小模型等4个定量滑坡预测模型为例,探... 详细信息

滑坡预测模型的选择直接影响到滑坡预测的准确性,是滑坡预测的关键所在。该研究利用意大利Alpago地区的滑坡数据和其他相关地理空间数据,以模糊伽马模型、模糊代数积模型、模糊代数和模型以及模糊最小模型等4个定量滑坡预测模型为例,探讨滑坡预测模型的预测率在对比、评价和选择不同模型方面的作用。滑坡预测模型的预测率是,模型预测结果图的各个级别类型中,未用于建模的滑坡面积百分比的累积分布函数。在地理信息系统中,利用已知的滑坡分布数据和模型的预测结果图,可以计算滑坡预测模型的预测率。研究结果表明,滑坡模型的预测率是滑坡预测模型自身特性的度量,在输入图层和滑坡类型确定的条件下,滑坡预测模型的预测率可作为对比、评价和选择不同模型的定量指标,可以用来确定最合适的预测模型。

关键词：边坡工程地理信息系统滑坡预测模型预测率

From spatio-temporal landslide susceptibility to landslide risk forecast

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Geoscience Frontiers 2024年第2期15卷 220-235页

作者： Tengfei Wang Ashok Dahal Zhice Fang Cees van westen Kunlong Yin Luigi Lombardo Faculty of Engineering China University of GeosciencesWuhan 430074China Faculty of Geo-Information Science and Earth Observation(ITC) University of TwenteEnschedeAE 7500Netherlands Institute of Geophysics and Geomatics China University of GeosciencesWuhan 430074China

The literature on landslide susceptibility is rich with examples that span a wide range of ***,the component that pertains to the extension of the susceptibility framework toward space–time modeling is largely *** statement holds true,particularly in the context of landslide risk,where few scientific contributions investigate risk dynamics in space and *** manuscript proposes a modeling protocol where a dynamic landslide susceptibility is obtained via a binomial Generalized Additive Model whose inventories span nine years(from 2013 to 2021).For the analyses,the data cube is organized with a mapping unit consisting of 26,333 slope units repeated over an annual temporal unit,resulting in a total of 236,997 *** phase already includes several interesting modeling experiments that have rarely appeared in the landslide literature(e.g.,variable interaction plots).However,the main innovative effort is in the subsequent phase of the protocol we propose,as we used climate projections of the main trigger(rainfall)to obtain future estimates of yearly susceptibility *** estimates are then combined with projections of urban settlements and associated populations to create a dynamic risk model,assuming vulnerability=***,this manuscript presents a unique example of such a modeling routine and offers a potential standard for administrations to make informed decisions regarding future urban development.

关键词： Space-time statistics Dynamic landslide susceptibility Landslide risk Future projections

Minimizing carbon deposition in plasma-induced methane coupling with structured hydrogenation catalysts

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journal of Energy Chemistry 2021年第7期30卷 271-279页

作者： Nuria García-Moncada Toine Cents gerard van Rooij Leon Lefferts Catalytic processes and Materials(CpM) TNW FacultyUniversity of TwenteP.O.Box 2177500 AE EnschedeThe Netherlands Sasol Holding Netherlands B.V. 7544 GG EnschedeThe Netherlands Nonequilibrium Fuel Conversion DIFFER5612 AJ EindhovenThe Netherlands

The effect of temperature and hydrogen addition on undesired carbonaceous deposit formation during methane coupling was studied in DBD-plasma catalytic-wall reactors with pd/Al2 O3, using electrical power to drive the *** with thin catalyst layers allowed comparison of the performance of empty reactors and catalytic wall reactors without significantly influencing the plasma *** product distribution varies strongly in the temperature window between 25 and 200℃Minimal formation of deposits is found at an optimal temperature around 75℃ in the catalytic-wall *** selectivity to deposits was c.a.10% with only 9 mg of catalyst loading instead of 45% in the blank reactor,while decreasing methane conversion only ***-feeding H2 to an empty reactor causes a similar decrease in selectivity to deposits,but in this case methane conversion also decreased *** of deposits formation in the catalytic-wall reactor at 75℃ is due to catalytic hydrogenation of mainly acetylene to *** the empty reactor,H2 co-feed decreases conversion but does not change the product *** catalytic-wall reactors can be regenerated with H2-plasma at room temperature,which produces more added-value hydrocarbons.

关键词： Dielectric barrier discharge(DBD)plasma-catalysis Structured reactor Methane coupling H_(2)co-feed Temperature optimization Carbon deposits

pharmacological interventions targeting nuclear factor-kappa B signaling in multiple sclerosis

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Neural Regeneration Research 2021年第10期16卷 2023-2025页

作者： Kim M.A.De Kleijn gerard j.M.Martens Department of Molecular Animal physiology Donders Institute for BrainCognition and BehaviourCentre for NeuroscienceFaculty of ScienceRadboud University6525AJ NijmegenThe Netherlands NeuroDrug Research Ltd 6525ED NijmegenThe Netherlands(De Kleijn KMAMartens GJM)Department of Molecular Animal PhysiologyDonders Institute for BrainCognition and BehaviourCentre for NeuroscienceFaculty of ScienceRadboud University6525AJ NijmegenThe Netherlands

Multiple sclerosis(MS)is an inflammatory neurodegenerative disease of the central nervous system(CNS).pathological characteristics of the disease include activation of CNS-intrinsic immune cells,such as microglia and astrocytes,and loss of neuronal connections,myelin and blood-brain barrier(BBB)integrity as well as peripheral immune cell infiltration into the *** has long been considered a predominantly immunological disease,which has led to the development of essentially only immune-directed *** this traditional“outside-in”MS hypothesis,a dysregulation of the peripheral immune system causes immune cell infiltration into the CNS,leading to autoreactivity against myelin sheath components and secondary BBB ***,recent findings indicate that overactivation of microglia and astrocytes represents an important first step in MS pathology,as appears to be the case for other neurodegenerative diseases such as Alzheimer’s disease(AD)and parkinson’s disease(pD).

关键词： sclerosis outside essentially

Burns in the elderly:a nationwide study on management and clinical outcomes

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Burns & Trauma 2020年第1期8卷 71-81页

作者： Harold Goei Margriet E.van Baar jan Dokter j Vloemans gerard I.j.M.Beerthuizen Esther Middelkoop Kees H.van der Vlies the Dutch Burn Repository group Association of Dutch Burn Centres Burn CentreMaasstad HospitalRotterdamthe Netherlands Department of plastic Reconstructive and Hand SurgeryAmsterdam Movement SciencesVU University Medical CentreAmsterdamthe Netherlands Burn Centre Maasstad Hospital Rotterdamthe Netherlands Burn Centre Red Cross Hospital Beverwijkthe Netherlands Burn Centre Martini HospitalGroningenthe Netherlands Association of Dutch Burn Centres Burn Centre Red Cross HospitalBeverwijkthe Netherlands Department of public Health Erasmus Medical CentreRotterdamthe Netherlands 不详

Background:In modern-day burn care,advanced age remains an important predictor for mortality among burn *** this study,we compared the complete treatment trajectory(including prehospital and surgical treatment)and the outcomes between an elderly burn population and a younger adult burn ***:In this nationwide study,data from the Dutch Burn Repository were *** is a uniform national registration for Dutch specialized burn *** adult patients that were admitted to one of the three Dutch burn centres from the period 2009 to 2015 were included in the *** patients were considered as elderly when≥65 years of age,and were then further subdivided into three age categories:65–74,75–85 and 85+*** adults in the age category 18–64 years were used as the reference *** managementwas studied comprehensively and included timing of surgery,the number of procedures and details on the surgical technique,especially the technique used for debridement and the grafting technique that was *** the comparison of clinical outcome,the following parameters were included:mortality,wound infections,length of stay/TBSA(total body surface area)burned,discharge disposition and secondary ***:During the study period,3155 adult patients were included(elderly,n=505).Burn severity,reflected by the median TBSA,varied between 3.2–4.0%and was comparable,but aetiology and pre-hospital care were different between elderly and the younger adult reference *** treatment was initiated significantly faster in elderly burn patients(ppatients(hydrosurgery,42.0%vs 23.5–22.6%),and on the other hand more avulsion(5.3%vs 7.3–17.6%)and primary wound closure(6.7%vs 24.5%).The most frequently used grafting technique was meshed skin grafts(79.2–88.6%);this was not related to *** increased rapidly with a higher age and showed a h

关键词： Burns Nationwide study Elderly Surgical management Clinical outcomes

primary sclerosing cholangitis: Updates in diagnosis and therapy

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World journal of Gastroenterology 2005年第1期11卷 7-16页

作者： piero portincasa Michele Vacca Antonio Moschetta Michele petruzzelli Giuseppe palasciano Karel j.van Erpecum gerard p.van Berge-Henegouwen Section of Internal Medicine Department of Gastroenterology and Hepatology

primary sclerosing cholangitis (pSC) is a chronic cholestatic syndrome of unknown origin mostly found in males, and characterized by diffuse inflammation and fibrosis of both intra- and extra-hepatic bile ducts. So far, pSC is considered as an autoimmune hepatobiliary disease. In most cases the progression of pSC towards liver cirrhosis and liver failure is slow but irreversible, and liver transplantation is currently the only definitive treatment. In recent years,pSC has been an area of active research worldwide with great interest in etiology, pathogenesis, diagnosis, and therapeutic options such as hydrophilic ursodeoxycholic acid and immunosuppressive agent tacrolimus. Recent updates on clinical and therapeutic aspects of pSC are discussed in the present review.

关键词： Sclerosing cholangitis Diagnosis Therapy

prevalence of-and risk factors for work disability in Dutch patients with inflammatory bowel disease

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World journal of Gastroenterology 2017年第46期23卷 8182-8192页

作者： Lieke M Spekhorst Bas Oldenburg Ad A van Bodegraven Dirk j de jong Floris Imhann Andrea E van der Meulen-de jong Marieke j pierik janneke C van der Woude gerard Dijkstra Geert D'Haens Mark Lowenberg Rinse K Weersma Eleonora AM Festen 无 Department of Gastroenterology and Hepatology University of Groningen and University Medical Centre Groningen Department of Genetics University of Groningen and University Medical Centre Groningen Department of Gastroenterology and Hepatology University Medical Center Utrecht Department of Gastroenterology and Hepatology VU University Medical Center Department of Gastroenterology and Hepatology University Medical Center St. Radboud Department of Gastroenterology and Hepatology Leiden University Medical Center Department of Gastroenterology and Hepatology University Medical Center Maastricht Department of Gastroenterology and Hepatology Erasmus Medical Center Department of Gastroenterology and Hepatology Amsterdam Medical Center parelsnoer Institute and the Dutch Initiative on Crohn and Colitis

AIM To determine the prevalence of work disability in inflammatory bowel disease(IBD), and to assess risk factors associated with work *** For this retrospective cohort study, we retrieved clinical data from the Dutch IBD Biobank on july 2014, containing electronic patient records of 3388 IBD patients treated in the eight University Medical Centers in the Netherlands. prevalence of work disability was assessed in 2794 IBD patients and compared with the general Dutch population. Multivariate analyses were performed for work disability(sick leave, partial and full disability) and long-term full work disability(> 80% work disability for > 2 years).RESULTS prevalence of work disability was higher in Crohn's disease(CD)(29%) and ulcerative colitis(UC)(19%) patients compared to the general Dutch population(7%). In all IBD patients, female sex, a lower education level, and extra-intestinal manifestations, were associated with work disability. In CD patients, an age > 40 years at diagnosis, disease duration > 15 years,smoking, surgical interventions, and anti-TNFα use were associated with work disability. In UC patients, an age > 55 years, and immunomodulator use were associated with work disability. In CD patients, a lower education level(OR = 1.62, 95%CI: 1.02-2.58), and in UC patients, disease complications(OR = 3.39, 95%CI: 1.09-10.58) were associated with long-term full work *** The prevalence of work disability in IBD patients is higher than in the general Dutch population. Early assessment of risk factors for work disability is necessary, as work disability is substantial among IBD patients.

关键词： Inflammatory bowel disease Crohn’s disease Ulcerative colitis Work disability Health care costs

Digital blinding of radiographs to mask allocation in a randomized control trial

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World journal of Orthopedics 2017年第10期8卷 785-789页

作者： gerard p Slobogean Lukasz Soswa Giuliana Rotunno peter j O'Brien Kelly A Lefaivre Department of Orthopaedics University of Maryland School of Medicine Department of Orthopaedics University of British Columbia University of Maryland School of Medicine

AIM To demonstrate the effectiveness of a digital radiographic altering technique in concealing treatment allocation to blind outcome assessment of distal femur fracture *** Digital postoperative anteroposterior and lateral radiographs from a sample of 33 randomly-selected patients with extra-articular distal femur fractures treated by surgical fixation at a Level 1 trauma center were included. Using commercially available digital altering software, we devised a technique to blind the radiographs by overlaying black boxes over the implant hardware while preserving an exposed fracture site for assessment of fracture healing. Three fellowship-trained surgeons evaluated a set of blinded radiographs twice and a control set of unblinded radiographs once. Each set of radiographs were reviewed independently and in a randomly-assigned order. The degrees of agreement and disagreement among evaluators in identifying implant type while reviewing both blinded and unblinded radiographs were assessed using the Bang Blinding Index and james Blinding Index. The degree of agreement in fracture union was assessed using kappa *** The assessment of blinded radiographs with both the Bang Blinding Index(BBI) and james Blinding Index(jBI) demonstrated a low degree of evaluator success at identifying implant type(Mean BBI, far cortical locking:-0.03, SD: 0.04; Mean BBI, standard screw: 0, SD: 0; jBI: 0.98, SD: 0), suggesting near perfect blinding. The assessment of unblinded radiographs with both blinding indices demonstrated a high degree of evaluator success at identifying implant type(Mean BBI, far cortical locking: 0.89, SD: 0.19; Mean BBI, standard screw: 0.87, SD: 0.04; jBI: 0.26, SD: 0.12), as expected. There was moderate agreement with regard to assessment of fracture union among the evaluators in both the blinded(Kappa: 0.38, 95%CI: 0.25-0.52) and unblinded(Kappa: 0.35, 95%CI: 0.25-0.45) arms of the study. There was no statistically significant differen

关键词： Methods Randomized controlled trials patient outcome assessment Fracture healing Femoral fractures

Irritable bowel syndrome: A microbiome-gut-brain axis disorder?

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World journal of Gastroenterology 2014年第39期20卷 14105-14125页

作者： paul j Kennedy john F Cryan Timothy G Dinan gerard Clarke 1.15 Biosciences Institute Department of Psychiatry Alimentary Pharmabiotic Centre University College Cork Cork Ireland Department of Anatomy and Neuroscience Alimentary Pharmabiotic CentreUniversity College CorkCork Ireland

Irritable bowel syndrome(IBS) is an extremely prevalent but poorly understood gastrointestinal disorder. Consequently, there are no clear diagnostic markers to help diagnose the disorder and treatment options are limited to management of the symptoms. The concept of a dysregulated gut-brain axis has been adopted as a suitable model for the disorder. The gut microbiome may play an important role in the onset and exacerbation of symptoms in the disorder and has been extensively studied in this context. Although a causal role cannot yet be inferred from the clinical studies which have attempted to characterise the gut microbiota in IBS, they do confirm alterations in both community stability and diversity. Moreover, it has been reliably demonstrated that manipulation of the microbiota can influence the key symptoms, including abdominal pain and bowel habit, and other prominent features of IBS. A variety of strategies have been taken to study these interactions, including probiotics, antibiotics, faecal transplantations and the use of germ-free animals. There are clear mechanisms through which the microbiota can produce these effects, both humoral and neural. Taken together, these findings firmly establish the microbiota as a critical node in the gut-brain axis and one which is amenable to therapeutic interventions.

关键词： Irritable bowel syndrome Microbiome Anxiety Tryptophan Abdominal pain Gastrointestinal motility Cognition