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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

predictors of the placebo response in a nutraceutical randomized controlled trial for depression

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journal of Integrative Medicine 2024年第1期22卷 46-53页

作者： Rosemary Arnold jenifer Murphy-Smith Chee H.Ng David Mischoulon gerard j.Byrne Chad A.Bousman Con Stough Michael Berk jerome Sarris professorial Unit the Melbourne ClinicDepartment of PsychiatryUniversity of MelbourneRichmond 3121Australia Depression Clinical and Research program Department of PsychiatryMassachusetts General HospitalHarvard Medical SchoolBostonMA 02115USA Faculty of Medicine Discipline of PsychiatryCentre for Clinical ResearchRoyal Brisbane&Women’s HospitalHerstonthe University of QueenslandBrisbane 4006Australia Departments of Medical Genetics PsychiatryPhysiology&Pharmacology and Community Health SciencesUniversity of CalgaryCalgaryAB T2N 1N4Canada Department of psychiatry the University of MelbourneMelbourne 3052Australia Centre for Human psychopharmacology Swinburne UniversityMelbourne 3122Australia The Institute for Mental and physical Health and Clinical Translation School of MedicineBarwon HealthDeakin UniversityGeelong 3220Australia The Centre of Excellence in Youth Mental Health the University of MelbourneParkville 3052Australia Florey Institute of Neuroscience and Mental Health the University of MelbourneParkville 3052Australia NICM Health Research Institute Western Sydney UniversityWestmeadNSW 2145Australia

Objective The placebo response in depression studies is the change in symptoms amongst those who receive an inactive *** well-designed randomized controlled trials(RCTs)of depression have a high proportion of placebo responders,with little understanding as to *** present study assesses characteristics associated with the placebo response in a nutraceutical trial with a large proportion of placebo *** This is a secondary analysis of a nutraceutical depression RCT which identified no overall treatment benefit relative to placebo(n=69 in placebo group).We investigated participant characteristics such as socio-demographics,clinical features,and recruitment methods,and their association with the placebo *** genetic polymorphisms were also *** response was measured based on change in Montgomery-Asberg Depression Rating Scale *** association of these hypothesis-driven variables of interest and the placebo response was examined using linear mixed effects *** Greater levels of education,particularly pursuing post-high school education,better self-reported general health,marriage/de facto,greater improvement in the first trial week,and more failed antidepressant therapies in the current depressive episode were associated with greater placebo *** increased placebo response was not found in those recruited via social media nor in those with concomitant antidepressant *** nucleotide polymorphisms from the tryptophan hydroxylase 1(TpH1)gene(A779C and A218C)were weakly associated with greater placebo response,although the evidence was attenuated after accounting for multiple *** This is,to our knowledge,the first study within nutraceutical research for depression to assess the association between participant characteristics and variation in the placebo *** variables appeared to predict the placebo *** findings may encourage future trial design

关键词： Randomized controlled trial placebo Depression Nutraceutical psychiatry

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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

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：诊断治疗原发性硬化性胆管炎 pSC 消化系统

Current and future opportunities for liquid biopsy of circulating biomarkers to aid in early cancer detection

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journal of Cancer Metastasis and Treatment 2022年第1期8卷 334-344页

作者： Susan H.Gawel Laurel jackson Nicolette jeanblanc gerard j.Davis Abbott Diagnostics Division Abbott LaboratoriesAbbott ParkIL 60064USA

Early diagnosis of cancer can significantly improve treatment and survival *** and tissue biopsy are the gold standard diagnostic approaches but are costly,invasive,and often unable to detect early-stage *** past decade has marked an acceleration in the discovery and development of liquid biopsy tests for aiding in the detection of various types of tumor markers in non-tissue samples,such as *** biopsy markers include circulating tumor cells,as well as tumor cell fragments,nucleic acids,and *** biopsy may be useful in screening patients considered to be at high risk of developing cancer,for refining diagnosis when combined with other test results,and for early detection of *** in big data analytics,informatics,and artificial intelligence will make it possible to combine patient history,clinical data,and liquid biopsy marker profiles to achieve more accurate and earlier *** this review,we summarize the current use of liquid biopsy in cancer care,including the development of multi-analyte panels to improve diagnostic accuracy and detect several cancer types in a single *** highlight recent advances for potential future applications of liquid biopsy to aid in the diagnosis of early-stage lung *** also discuss the opportunities and challenges of integrating liquid biopsy into current algorithms for cancer screening and diagnosis.

关键词： Cancer early detection diagnostic algorithm biomarkers blood serum analyte

Glade and Forest-Edge plant Community Attributes for Three Glade Types in Arusha National park, Tanzania

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American journal of plant Sciences 2022年第4期13卷 457-472页

作者： Ladislaus W. Kahana gerard Malan Teresa j. Sylvina College of African Wildlife Management Mweka Moshi Tanzania Tshwane University of Technology Pretoria South Africa Bush-To-Base Solutions Inc. Christiansburg VA USA

The aim of the study was to compare glade and forest-glade edge plant community attributes for man-made, upper and lower natural glades. Two plots were set up in twelve glades at 2.5, 12.5 m and three plots in thirteen glades at 2.5, 12.5 and 22.5 m depending on the size of the glade. The results showed that plants total abundance, percentage basal cover, species richness and species diversity for upper and lower natural glades differed significantly p p pectively and species diversity for man-made glades p plant species abundance, richness and diversity were highest at the forest-glade edge and decreased towards the glade interior. plant species composition of the three glades types differed significantly (MRpp: T = -4.51, p pecies richness and forbs species diversity differed significantly for man-made glades p pper natural glades, grasses species richness was highly significant p pecies richness and diversity were significant p pecies richness and species diversity differed significantly p p pectively. Growth forms in the lower natural glades were associated with the forest-glade edge or glade interior χp>2p> = 15.95, df = 4, p Eleusine jaegeri, Heterogon contortus, Senna mimisoides, Digitaria scalarum, Clutia abyssinica) were habitat indicators for disturbed areas, wet humid grey/black clay soils for upper natural glades and three (Solanum incanum, Senna didymobotrya, and pennistem mezianum, were indicators of overgrazed areas and black clay soils for man-made glades. In conclusion, plant species abundance, richness and diversity were highest at the forest-glade edge and decreased towards the glade interior, while plant species composition differed significantly between the three-glade types. The plant growth form for lower natural glades was associa

关键词： Forest Glade-Edge Glade Interior plant Indicator Species plant Species Diversity plant Species Richness

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

Microstructure and magnetocaloric properties of partially crystallized Gd_(60)Co_(30)Fe_(10)amorphous alloy prepared by different solidification cooling rates

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Rare Metals 2022年第1期41卷 246-253页

作者： Hui-Yan Zhang Zi-Yang Zhang Ya-Fang Xu Ai-Lin Xia Wei-Huo Li Fa-Chao Wang Shuang-Shuang Chen gerard Sisó Key Laboratory of Green Fabrication and Surface Technology of Advanced Metal Materials(Anhui University of Technology) Ministry of Education School of Materials Science and Engineering Anhui University of Technology Departament d’Enginyeria Electro`nica-Escola d’Enginyeria Universitat Autònoma de Barcelona

The Gd_(60)Co_(30)Fe_(10)alloy ribbons with different solidification cooling rates were prepared by modifying the melt-spinning speed of 6.0,12.5,25.0 and 50.0 m·s^(-1)·With cooling rate decreasing,the(Fe,Co)5 Gd and hcp-Gd nanocrystalline was in situ precipitated among the amorphous matrix,which resulted in the composition change of the amorphous *** of the only slight amount of crystalline phase in Gd_(60)Co_(30)Fe_(10)alloys,the magnetic and magnetocaloric properties mainly depend on the amorphous phase,and all the magnetic entropy change versus temperature(|Δ|SMI-T)curves are table-like,indicating the suitability for Ericsson *** magnetic transition temperature of the Gd_(60)Co_(30)Fe_(10)alloy at a melt-spinning speed of 6.0 m·s^(-1) shifted obviously to the lower value with the applied magnetic fields *** peak value of magnetic entropy change(|ΔSMpk|)is 2.19 j·kg^(-1)·K^(-1)at217 K under the magnetic field change of 0-2 T,and the table-like region is 200-230 *** was proved that the moderate reduction of the cooling rate will not deteriorate the magnetocaloric performance of the Gd_(60)Co_(30)Fe_(10)ribbons seriously.

关键词： Magnetic refrigeration Amorphous-nanocrystalline composite In situ precipitation Magnetocaloric effect

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