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Effects of prolonged methylphenidate treatment on amygdala reactivity and connectivity:a randomized controlled trial in stimulant treatment-naive,male participants with ADHD

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Psychoradiology 2021年第3期1卷 152-163页

作者： Antonia Kaiser marco A.Bottelier michiel B.de Ruiter michelle m.Solleveld Hyke G.H.Tamminga Cheima Bouziane hilde m.geurts Ramon J.L.Lindauer J.J.Sandra Kooij Paul J.Lucassen Anouk Schrantee Liesbeth Reneman Amsterdam UmC University of AmsterdamDepartment of Radiology and Nuclear MedicineAmsterdam NeuroscienceAmsterdam1105 AZthe Netherlands 2University Medical Center GroningenChild Study CenterAccareGroningen9713GZthe Netherlands 3Netherlands Cancer InstituteDivision of Psychosocial Research and EpidemiologyAmsterdam1066CXthe Netherlands 4University of AmsterdamDutch Autism&ADHD Research CenterDepartment of PsychologyAmsterdam1018WTthe Netherlands 5Amsterdam UMCUniversity of AmsterdamDepartment of Child and Adolescent PsychiatryAmsterdam1105AZthe Netherlands 6Academic Centre for Child and Adolescent PsychiatryLevvelAmsterdam1076ECthe Netherlands 7Expertise Center Adult ADHDPsyQThe Hague2512VAthe Netherlands 8Amsterdam UMCVrije UniversiteitAmsterdam Public Health Research InstituteDepartment of PsychiatryAmsterdam1105AZthe Netherlands 9University of AmsterdamBrain Plasticity GroupSwammerdam Institute for Life SciencesAmsterdam1012WXThe Netherlands

Background:Problems with emotional processing are widely reported in individuals with attentiondeficit/hyperactivity disorder(ADHD).Although methylphenidate(mPH)effectively alleviates inattention and hyperactivity symptoms in ADHD,its effects on emotional processing and internalizing symptoms have remained *** we previously found that acute mPH administration modulated neural mechanisms underlying emotional processing in an age-dependent manner,the effects of prolonged administration remained ***:Therefore,we investigated:(i)whether prolonged mPH treatment influences neural substrates(amygdala reactivity and connectivity)of emotional processing,and(ii)whether these effects are modulated by ***:The“effects of Psychotropic drugs On Developing brain-mPH”(“ePOD-mPH”)randomized controlled trial was a 16-week double-blind,placebo-controlled,multi-center trial with mPH in 50 boys(10–12 years of age)and 49 men(23–40 years of age),all stimulant treatment-naive and diagnosed with *** performed an emotional face-matching task during functional magnetic resonance *** assessed their symptoms of ADHD and internalizing symptoms at baseline,during the trial(8 weeks),and 1 week after the trial end(17 weeks).Results and Conclusions:We did not find effects of prolonged mPH treatment on emotional processing,as measured by amygdala reactivity and connectivity and internalizing symptoms in this trial with stimulant treatment-naive *** differs from our findings on emotional processing following acute mPH administration and the effects of prolonged mPH treatment on the dopamine system,which were both modulated by ***,prolonged mPH treatment did improve ADHD symptoms,although depressive and anxiety symptoms showed a medication-independent ***,our data indicate that baseline internalizing symptoms may be used to predict mPH treatment effects on ADHD symptoms,particularly in(male)adults with ADH

关键词： ADHD fmRI emotional dysregulation internalizing symptoms amygdala face-matching paradigm

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Validation of a liquid chromatographic method for the pharmaceutical quality control of products containing elacridar

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Journal of Pharmaceutical Analysis 2016年第4期6卷 268-275页

作者： Emilia Sawicki michel J.Hillebrand hilde Rosing Jan H.m.Schellens Bastiaan Nuijen Jos H.Beijnen Department of Pharmacy & Pharmacology The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital Division of Clinical Pharmacology Department of Medical OncologyThe Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital Division of Pharmacoepidemiology & Clinical Pharmacology.Department of Pharmaceutical Sciences Faculty of Science.Utrecht University

many anticancer drugs have an impaired bioavailability and poor brain penetration because they are substrates to drug efflux pumps such as P-glycoprotein and Breast Cancer Resistance *** is a strong inhibitor of these two drug efflux pumps and therefore has great potential to improve oral absorption and brain penetration of many anticancer ***,a clinical formulation of elacridar is unavailable and therefore the pharmaceutical development of a drug product is highly *** also necessitates the availability of an analytical method for its quality control.A reverse-phase high-performance liquid chromatographic method with ultraviolet detection was developed for the pharmaceutical quality control of products containing elacridar as the active pharmaceutical *** analytical method was validated for linearity,accuracy,precision,selectivity,carry-over,stability of stock and reference solutions,stability of the final extract,stability-indicating capability and impurity *** found that elacridar is unstable in aqueous solutions that are exposed to light because a hydroxylation product of elacridar is ***,sample solutions with elacridar must be protected from light.

关键词： GF120918 Solid dispersion Dissolution Hydroxylation HPLC-UV

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Candidate colorectal cancer predisposing gene variants in Chinese early-onset and familial cases

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World Journal of Gastroenterology 2015年第14期21卷 4136-4149页

作者： Jun-Xiao Zhang Lei Fu Richarda m de Voer marc-manuel Hahn Peng Jin Chen-Xi Lv Eugène TP Verwiel marjolijn JL Ligtenberg Nicoline Hoogerbrugge Roland P Kuiper Jian-Qiu Sheng Ad geurts van Kessel Department of Human Genetics Radboud University Medical CenterRadboud Institute for Molecular Life Sciences Department of Gastroenterology General Hospital of Beijing Military Region Third military medical University Chongqing 400038China Department of Human Genetics and Department of Pathology Radboud University Medical Center

AIm: To investigate whether whole-exome sequencing may serve as an efficient method to identify known or novel colorectal cancer(CRC) predisposing genes in early-onset or familial CRC ***: We performed whole-exome sequencing in 23 Chinese patients from 21 families with nonpolyposis CRC diagnosed at ≤ 40 years of age, or from multiple affected CRC families with at least 1 firstdegree relative diagnosed with CRC at ≤ 55 years of *** DNA from blood was enriched for exome sequences using the Sure Select Human All Exon Kit, version 2(Agilent Technologies) and sequencing was performed on an Illumina Hi Seq 2000 *** were processed through an analytical pipeline to search for rare germline variants in known or novel CRC predisposing ***: In total, 32 germline variants in 23 genes were identified and confirmed by Sanger *** 6 of the 21 families(29%), we identified 7 mutations in 3 known CRC predisposing genes including mLH1(5 patients), mSH2(1 patient), and mUTYH(biallelic, 1 patient), five of which were reported as *** remaining 15 families, we identified 20 rare and novel potentially deleterious variants in 19 genes, six of which were truncating *** previously unreported variant identified in a conserved region of EIF2AK4(***738_Asp739insA rgA rg) was found to represent a local Chinese variant, which was significantly enriched in our early-onset CRC patient cohort compared to a control cohort of 100 healthy Chinese individuals scored negative by colonoscopy(33.3% vs 7%, P me sequencing of early-onset or familial CRC cases serves as an efficient method to identify known and potential pathogenic variants in established and novel candidate CRC predisposing genes.

关键词： Colorectal cancer Cancer predisposition Early-onse

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Rhizobium Lipo-chitooligosaccharide Signaling Triggers Accumulation of Cytokinins in medicago truncatula Roots

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molecular Plant 2015年第8期8卷 1213-1226页

作者： Arjan van Zeijl Rik H.m. Op den Camp Eva E. Deinum Tatsiana Charnikhova Henk Franssen Huub J.m. Op den Camp Harro Bouwmeester Wouter Kohlen Ton Bisseling Rene geurts Department of Plant Sciences Laboratory of Molecular Biology Wageningen University Droevendaalsesteeg 16708 PB Wageningen The Netherlands Department of Systems Biophysics FOM institute AMOLF Science Park 104 1098 XG Amsterdam The Netherlands Department of Plant Sciences Laboratory of Plant Physiology Wageningen University Droevendaalsesteeg 1 6708 PB Wageningen The Netherlands Department of microbiology IWWR Radboud University Nijmegen Heyendaalseweg 135 6525 AJ Nijmegen The Netherlands College of Science King Saud University Post Office Box 2455 Riyadh 11451 Saudi Arabia

Legume rhizobium symbiosis is initiated upon perception of bacterial secreted lipo-chitooligosaccharides （LCOs）. Perception of these signals by the plant initiates a signaling cascade that leads to nodule formation. Several studies have implicated a function for cytokinin in this process. However, whether cytokinin accu- mulation and subsequent signaling are an integral part of rhizobium LCO signaling remains elusive. Here, we show that cytokinin signaling is required for the majority of transcriptional changes induced by rhizo- bium LCOs. In addition, we demonstrate that several cytokinins accumulate in the root susceptible zone 3 h after rhizobium LCO application, including the biologically most active cytokinins, trans-zeatin and iso- pentenyl adenine. These responses are dependent on calcium- and calmodulin-dependent protein kinase （CCamK）, a key protein in rhizobial LCO-induced signaling. Analysis of the ethylene-insensitive mtein21 mtsickle mutant showed that LCO-induced cytokinin accumulation is negatively regulated by ethylene. Together with transcriptional induction of ethylene biosynthesis genes, it suggests a feedback loop negatively regulating LCO signaling and subsequent cytokinin accumulation. We argue that cytokinin accumulation is a key step in the pathway leading to nodule organogenesis and that this is tightly controlled by feedback loops.

关键词： medicago truncatula cytokinin ethylene rhizobium lipo-chitooligosaccharides CRE1

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A protocol paper:community engagement interventions for cardiovascular disease prevention in socially disadvantaged populations in the UK:an implementation research study

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Global Health Research and Policy 2020年第1期5卷 335-343页

作者： Papreen Nahar Harm van marwijk Linda Gibson Geofrey musinguzi Sibyl Anthierens Elizabeth Ford Stephen A.Bremner mark Bowyer Jean Yves Le Reste Tholene Sodi hilde Bastiaens Department of Global Health and Infection Brighton and Sussex Medical SchoolThe University of SussexBrightonUK Department of Primary Care and Public Health Brighton and Sussex Medical SchoolThe University of SussexBrightonUK School of Social Sciences Nottingham Trent UniversityNottinghamUK Department of Disease Control and Environmental Health School of Public HealthCollege of Health SciencesMakerere UniversityKampalaUganda Department of Primary and Interdisciplinary Care University of AntwerpAntwerpBelgium EA 7479 SPURBO Facultéde Médecine et des Sciences de la SantéUniversitéde Bretagne OccidentaleBrestFrance Department of Psychology University of LimpopoMankwengSouth Africa

Background:Cardiovascular disorders(CVD)are the single greatest cause of mortality *** the UK,the National Health Service(NHS)has launched an initiative of health checks over and above current care to tackle ***,the uptake of Health Checks is poor in disadvantaged *** protocol paper sets out a UK-based study(Sussex and Nottingham)aiming to co-produce a community delivered CVD risk assessment and coaching intervention to support community members to reduce their risk of *** overall aim of the project is to implement a tailored-to-context community engagement(CE)intervention on awareness of CVD risks in vulnerable populations in high,middle and low-income *** specific objectives of the study are to enhance stakeholder’engagement;to implement lifestyle interventions for cardiovascular primary prevention,in disadvantaged populations and motivate uptake of NHS health ***:This study uses both qualitative and quantitative methods in three phases of evaluation,including pre-,per-and *** ensure contextual appropriateness the‘Scaling-up Packages of Interventions for Cardiovascular disease prevention in selected sites in Europe and Sub-Saharan Africa:An implementation research’(SPICES)project will organize a multi-component community-engagement *** the qualitative component,the pre-implementation phase will involve a contextual assessment and stakeholder mapping,exploring potentials for CVD risk profiling strategies and led by trained Community Health Volunteers(CHV)to identify accessibility and *** per-implementation phase will involve healthy lifestyle counselling provided by CHVs and evaluation of the outcome to identify fidelity and *** post-implementation phase will involve developing sustainable community-based strategies for CVD risk *** three components will include a process evaluation.A stepped wedge cluster randomised trial of the roll out will

关键词： Implementation research CVD risk prevention Community engagement Stepped-wedge cluster randomised trial

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Trends in treatment and overall survival among patients with proximal esophageal cancer

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World Journal of Gastroenterology 2019年第47期25卷 6835-6846页

作者： Judith de Vos-Geelen Sandra mE geurts Liselot BJ Valkenburg-van Iersel Evelien Jm de Jong Vivianne CG Tjan-Heijnen margreet van Putten Valery EPP Lemmens Heike I Grabsch Nadia Haj mohammad Frank JP Hoebers Chantal V Hoge Paul m Jeene Hanneke Wm van Laarhoven Tom Rozema marije Slingerland Grard AP Nieuwenhuijzen Department of Internal medicine Division of Medical OncologyGROW-School for Oncology and Developmental BiologyMaastricht University Medical CenterMaastricht 6202 AZNetherlands Department of Research Netherlands Comprehensive Cancer Organization(IKNL)Eindhoven 5612 HZNetherlands Department of Pathology GROW-School for Oncology and Developmental BiologyMaastricht University Medical CenterMaastricht 6202 AZNetherlands Pathology and Data Analytics Leeds Institute of Medical Research at St James”sUniversity of LeedsLeeds LS97TFUnited Kingdom Department of medical Oncology University Medical Center UtrechtUtrecht 3584 CXNetherlands Department of Radiation Oncology(mAASTRO clinic) GROW-School for Oncology and Developmental BiologyMaastricht University Medical CenterMaastricht 6229 ETNetherlands Department of Internal medicine Division of GastroenterologyMaastricht University Medical CenterMaastricht 6202 AZNetherlands Department of Radiotherapy RadiotherapiegroepDeventer 7416 SENetherlands Department of medical Oncology Amsterdam University Medical CentersUniversity of AmsterdamAmsterdam 1105 AZNetherlands Department of Radiotherapy Insituut VerbeetenTilburg 5042 SBNetherlands Department of medical Oncology Leiden University Medical CenterLeiden 2333 ZANetherlands Department of Surgery Catharina Hospital EindhovenEindhoven 5623 EJNetherlands Department of Public Health Erasmus Medical Center RotterdamRotterdam 3015 GDNetherlands

BACKGROUND The management of proximal esophageal cancer differs from that of tumors located in the mid and lower part of the esophagus due to the close vicinity of vital ***-surgical treatment options like radiotherapy and definitive chemoradiation(CRT)have been *** trends in(non-)surgical treatment and its impact on overall survival(OS)in patients with proximal esophageal cancer are unclear,related to its rare disease *** optimize treatment strategies and counseling of patients with proximal esophageal cancer,it is therefore essential to gain more insight through real-life *** To establish trends in treatment and OS in patients with proximal esophageal *** In this population-based study,patients with proximal esophageal cancer diagnosed between 1989 and 2014 were identified in the Netherlands Cancer *** proximal esophagus consists of the cervical esophagus and the upper thoracic section,extending to 24 cm from the *** in radiotherapy,chemotherapy,and surgery,and OS were *** were stratified by presence of distant *** Cox proportional hazards regression analyses was performed to assess the effect of period of diagnosis on OS,adjusted for patient,tumor,and treatment *** In total,2783 patients were *** the study period,the use of radiotherapy,resection,and CRT in non-metastatic disease changed from 53%,23%,and 1%in 1989-1994 to 21%,9%,and 49%in 2010-2014,*** metastatic disease,the use of chemotherapy and radiotherapy increased over *** OS of the total population increased from 7.3 mo[95%confidence interval(CI):6.4-8.1]in 1989-1994 to 9.5 mo(95%CI:8.1-10.8)in 2010-2014(logrank Pmetastatic disease,5-year OS rates improved from 5%(95%CI:3%-7%)in 1989-1994 to 13%(95%CI:9%-17%)in 2010-2014(logrank Pmultivariable regression analysis demonstrated a significant treatment effect over time on ***

关键词： Esophagus Esophageal cancer Proximal Cervical Upper thoracic Trends Treatment Survival Outcome

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Development of mRPC technology for STAR-TOF

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Nuclear Science and Techniques 2005年第4期16卷 231-237页

作者： SUN Yong-Jie LI Cheng SHAO ming CHEN Hong-Fang G. EPPLEY F.geurts H. HUANG HUANG Sheng-Li W.J. LIOPE T. NUSSBAUm RUAN Li-Juan J. SCHAmBACH WANG Xiao-Lian WU Jian Z. XU Department of modern Physics University of Science and Technology of China Hefei 230026 China Rice University Bonner Nuclear Lab Houston TX 77005 USA University of California- Los Angeles Los Angeles CA90095 USA Brookhaven National Laboratory Upton New York 11973 USA University of Texas Austin TX 78712 USA）

A prototype of multi-gap resistive plate chamber (mRPC) modules with 6 gas gaps of 220 μm used for the time-of-flight (TOF) detectors has been developed by STAR TOF group. A tray (TOFr) composed of 28 mRPC modules was constructed and operated in STAR for the d+Au collisions and Au+Au collisions during 2003 RHIC and 2004 RHIC run. Results show its time resolution is 85 ps with the average efficiency of 95% and clear identification of K/π up to 1.6 GeV and proton/ K up to 3.0 GeV.

关键词： mRPC技术 STAR-TOF RHIC PID 气体电力探测技术

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运用7.0TmR磁化预备的3D-FLAIR和3D-DIR序列对多发性硬化病灶的检测

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国际医学放射学杂志 2012年第2期 194-195页

作者： W.L.de Graaf J.J.Zwanenburg F.Visser m.P.Wattjes P.J.W.Pouwels J.J.G.geurts 卞读军 Department of Radiology VU University Medical Center AmsterdamDe Boelelaan 1117NL-1081 HVAmsterdamthe Netherlands

目的为了探讨7.0TmR三维T2加权液体衰减反转恢复(FLAIR)和双反转恢复(DIR)mR成像序列对多发性硬化(mS)病灶检测的可行性和价值。方法选10例mS病人和5名健康志愿者,7.0TmR扫描设备,将磁化预备

关键词： mRI,方法成像三维多发性硬化/诊断学多发性硬化,病理学大脑皮质,病理学

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3DmR减影成像对活动性多发性硬化病灶检出率提高的研究

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国际医学放射学杂志 2010年第3期 282-283页

作者：张竞文 B. moraal m.P. Wattjes J.J. G. geurts D.L. Knol R.A. von Schijndel P. J. W. Pouwels Department of Radiology MS Center Amsterdam VU University Medical Center

摘要目的观察近各向同性的单层块三维(3D)mRI技术在减影成像中的优势,并与二维(2D)减影影像相比较,评价其对活动性多发

关键词：检出率病灶 mRI 减影活动性

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功能mRI上脑网络动态性的下降是多发性硬化病人认知损害的征兆

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国际医学放射学杂志 2019年第5期 619-619页

作者： A.J.C.Eijlers A.m.Wink K.A.meijer L.Douw J.J.G.geurts m.m.Schoonheim 王艾博 Departments of Anatomy and Neurosciences and Radiology and Nuclear medicine MS Center Amsterdam Amsterdam UMCLocatie VUmc Amsterdam Neuroscience

摘要既往研究表明,多发性硬化(mS)病人存在广泛的脑功能网络紊乱,表现为脑网络效能降低。而近期研究提示脑网络的动态性与认知功能存在强相关性。目的对认知功

关键词：多发性硬化病动态性 mRI

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