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A Pilot Trial Testing the Feasibility of Using Molecular-Guided Therapy in Patients with Recurrent Neuroblastoma

Journal of Cancer Therapy 2012年第5期3卷 602-612页

作者： Giselle L. Saulnier Sholler William Ferguson Genevieve Bergendahl Erika Currier Shannon R. Lenox Jeffrey Bond Marni Slavik William Roberts Deanna Mitchell don eslin Jacqueline Kraveka Joel Kaplan Nehal Parikh Suman Malempati Gina Hanna Emily Eugster David Cherba Jeremy Miller Craig Webb Cardinal Glennon Children’s Hospital Saint Louis University School of Medicine St. Louis University St. Louis USA Center for Cancer Genomics and Computational Biology Pediatric Oncology Translational Research Program at the Van Andel Research Institute in Grand Rapids Grand Rapids USA Center for Children’s Cancer and Blood Disorders Arnold Palmer Hospital for Children MD Anderson Cancer Center Orlando Orlando USA Department of Pediatric Oncology Helen DeVos Children’s Hospital Michigan State University Grand Rapids USA Department of Pediatric Oncology Oregon Health Science University Portland USA Division of Hematology/Oncology 2J Connecticut Children’s Medical Center Hartford USA Pediatric Hematology/Oncology Medical University of South Carolina Charleston USA Pediatric Oncology Levine Children’s Hospital Charlotte USA Rady Children’s Hospital San Diego University of California San Diego School of Medicine at the University of California San Diego San Diego USA Vermont Cancer Center Department of Medicine University of Vermont Burlington USA

Background: Neuroblastoma is the most common extracranial solid tumor in children, and treatment options for recurrent neuroblastoma are limited. Using molecular profiling to target the molecular vulnerabilities of neuroblastoma with existing therapeutic agents may result in a rational, data-driven approach with potential to improve clinical outcomes. Methods: The primary objective of this pilot study was to evaluate the feasibility of supporting real-time treatment decisions through predictive modeling of genome-wide mRNA gene expression data from neuroblastoma tumor biopsies. Feasibility was defined as completion of tumor biopsy, histopathological evaluation, RNA extraction and quality control, gene expression profiling within a CLIA-certified laboratory, bioinformatic analysis, generation of a drug predicttion report, molecular tumor board review yielding a formulated treatment plan, and independent medical monitor review within a 2-week period. Results: Five patients with multiply relapsed or refractory neuroblastoma were enrolled between April and June 2010. All biopsies passed histopathology and RNA quality control. Generation of gene expression data and its analysis (3-7 days), reports which linked this data into medically actionable drug candidates (1-5 days), molecular tumor board (1-3 days) and independent medical monitor review (1 day) were all completed in real-time. The average time was 10.5 days for all patients. Conclusion: This study shows that it is feasible to create therapeutic treatment plans based on genomic profiling in less than 12 days. This warrants further testing in a Phase I study to determine safety of predicted treatments and evaluate whether the information obtained in these analyses would result in patient benefit.

关键词： Neuroblastoma Molecular Guided Therapy Predictive Therapies Molecular Profiling Genomic Profiling Pediatric Cancer

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Lecanemab Unveiled:Exploring Alzheimer’s Treatment Advancements,Assessing Strengths,Limitations,and Its Therapeutic Landscape Position

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Biomedical and Environmental Sciences 2024年第4期37卷 428-431页

作者： VICTOR Abiola Adepoju OKECHUKWU Innocent Onyezue SAFAYET Jamil OLALEKAN John Okesanya don Eliseo Lucero-Prisno Ⅲ Department of HIV and Infectious Diseases Jhpiegoan affiliate of John Hopkins UniversityAbujaNigeria Department of Prevention and Community Directorate APIN Public Health InitiativesAbujaNigeria Department of Public Health Daffodil International UniversityDhaka-1216Bangladesh Department of Public Health and Maritime Transport University of ThessalyVolosGreece Department of Global Health and Development London School of Hygiene and Tropical MedicineLondonUnited Kingdom

In the ever-evolving landscape of Alzheimer’s treatment,lecanemab(Leqembi)has emerged as a promising *** conventional therapies that merely alleviate symptoms,lecanemab is a humanized monoclonal antibody with a distinct *** targets protofibrils,insoluble fibrils,amyloid oligomers,and soluble amyloid-beta protofibrils,which are known to be especially damaging to neurons,with high accuracy.

关键词： Alzheimer amyloid Therapeutic

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Robotic-assisted retroperitoneal lymph node dissection for stage II testicular cancer

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Asian Journal of Urology 2024年第1期11卷 121-127页

作者： George McClintock Ahmed S.Goolam don Perera Ryan Downey Scott Leslie Peter Grimison Henry Woo Peter Ferguson Nariman Ahmadi Department of Urology Chris O'Brien LifehouseSydneyNSWAustralia Department of Anaesthesia Chris O'Brien LifehouseSydneyNSWAustralia The University of Sydney SydneyNSW2006Australia Department of Medical Oncology Chris O'Brien LifehouseSydneyNSWAustralia

Objective:To evaluate the perioperative as well as early oncological outcomes of patients undergoing robotic retroperitoneal lymph node dissection for treatment of testicular ***:We conducted a prospective consecutive case series of patients undergoing robotic assisted retroperitoneal lymph node dissection for metastatic testicular cancer between May 2018 and July 2021 at our *** were collected on patient and tumour characteristics,intraoperative and postoperative parameters,and functional and oncological *** statistics are ***:Nineteen patients were identified;18(94.7%)completed the procedure robotically and one was converted to open surgery;78.9%of patients had stage≥IIB and 12(63.2%)patients had undergone prior *** median operative time was 300(interquartile range[IQR]240-315)*** blood loss was 100(IQR 50-175)*** length of stay was 2(range 1-11)*** robotically completed patients commenced diet and passed flatus on Day 1 and were discharged by Day *** median lymph node yield was 40.5(IQR 38-51)*** patients undergoing nerve-sparing procedures recovered antegrade ejaculatory *** patient had a Clavien-Dindo III complication(chylous ascites requiring drainage).At a median follow-up of 22.3(IQR 16.3-24.9)months,one patient developed retroperitoneal recurrence,which was successfully treated with second-line chemotherapy;no other patients have had ***:Robotic retroperitoneal lymph node dissection is a safe and feasible alternative to open surgery in appropriately selected patients,offering low *** oncological outcomes are *** cohorts and longer follow-ups are required to validate our institution's findings.

关键词： Retroperitoneal lymph node dissection Robotic surgery Testicular cancer Retroperitoneal node dissection

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藏族英雄史诗格萨尔王传形式基础(续)

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中国藏学 2024年第1期 106-114,215页

作者：丹珠昂奔中央民族大学北京100081

形式基础是格萨尔研究的基本理论问题,涉及史诗产生、发展、传播的特定时代的社会文化基础,渊源深长。格萨尔的形式集中于“两‘仲’、三要素、一模式”。仲与德乌、苯都是青藏高原古老的文化形式,当格萨尔作为史诗萌芽时,艺人们借用了... 详细信息

形式基础是格萨尔研究的基本理论问题,涉及史诗产生、发展、传播的特定时代的社会文化基础,渊源深长。格萨尔的形式集中于“两‘仲’、三要素、一模式”。仲与德乌、苯都是青藏高原古老的文化形式,当格萨尔作为史诗萌芽时,艺人们借用了他们最熟悉的“仲”的形式,形成了格萨尔王传的形式基础。深刻认识把握这一形式基础,既是认识格萨尔光辉存在的一把钥匙,也是传承、弘扬格萨尔史诗,汲取其精神精华的桥梁,有利于我们传承、研究、弘扬、开发、利用格萨尔的既有成果,确立文化自信,构建各民族共有精神家园。

关键词：格萨尔形式仲仲肯音乐

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Quasi-Static, Poiseuille Flow of Analgesics from an Elastomeric Pump: Theoretical Determination of Infusion Times and Toxicity Conditions

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Journal of Biosciences and Medicines 2024年第9期12卷 251-265页

作者： Clare B. Lipscombe Trevor C. Lipscombe don S. Lemons Division of General Surgery Vanderbilt University Medical Center Nashville TN USA Catholic University of America Press Washington DC USA Department of Physics Bethel College North Newton KS USA

Background : Elastomeric pumps (elastic balls into which analgesics or antibiotics can be inserted) push medicines through a catheter to a nerve or blood vessel. Since elastomeric pumps are small and need no power source, they fit easily into a pocket during infusion, allowing patient mobility. Elastomeric pumps are widely used and widely studied experimentally, but they have well-known problems, such as maintaining reliable flow rates and avoiding toxicity or other peak-and-trough effects. Objectives : Our research objective is to develop a realistic theoretical model of an elastomeric pump, analyze its flow rates, determine its toxicity conditions, and otherwise improve its operation. We believe this is the first such theoretical model of an elastomeric pump consisting of an elastic, medicine-filled ball attached to a horizontal catheter. Method : Our method is to model the system as a quasi-Poiseuille flow driven by the pressure drop generated by the elastic sphere. We construct an engineering model of the pressure exerted by an elastic sphere and match it to a solution of the one-dimensional radial Navier-Stokes equation that describes flow through a horizontal, cylindrical tube. Results : Our results are that the model accurately reproduces flow rates obtained in clinical studies. We also discover that the flow rate has an unavoidable maximum, which we call the “toxicity bump”, when the radius of the sphere approaches its terminal, unstretched value—an effect that has been observed experimentally. Conclu sions : We conclude that by choosing the properties of an elastomeric pump, the toxicity bump can be restricted to less than 10% of the earlier, relatively constant flow rate. Our model also produces a relation between the length of time that the analgesic fluid infuses and the physical properties of the fluid, of the elastomeric sphere and the tube, and of the blood vessel into which the analgesic infuses. From these, we conclude that elastomeric pumps can be

关键词： Elastomeric Pump Infusion Therapy Bio-Fluids Medical Devices Antibiotic Delivery Analgesic Delivery

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小老鼠、红草莓和大饿熊

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阅读 2024年第44期 14-19页

作者： don Audrey Wood

绘本导读：欢乐的“六一”儿童节，你打算和伙伴们一起做点什么呢？不如跟着绘本来玩一场有意思的游戏吧！你看，有一只小老鼠，他一大早就跑去摘了一颗熟透了的红草莓，辛苦地扛回了家。可是，竟然有个声音一直对他说：有一只饥饿的大...

绘本导读：欢乐的“六一”儿童节，你打算和伙伴们一起做点什么呢？不如跟着绘本来玩一场有意思的游戏吧！你看，有一只小老鼠，他一大早就跑去摘了一颗熟透了的红草莓，辛苦地扛回了家。可是，竟然有个声音一直对他说：有一只饥饿的大坏熊，离得老远就能闻到草莓的香气，正准备冲过来抢走红草莓呢！于是，一场关于红草莓的“保卫战”开始了……

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远程工作是否可行?

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空中英语教室（高级版．彭蒙惠英语） 2024年第1期 16-17,42页

作者： don Lee 不详

10经历过疫情之后,巴特·瓦尔德兹有着和许多传统老板一样的心态。他认为远程工作是一种反常现象,希望所有人都能尽快回到办公桌前。“在我成长的环境里,人们都穿西装打领带,早上8点就出现在公司——没有任何借口。”这位60岁的Ingenovi... 详细信息

10经历过疫情之后,巴特·瓦尔德兹有着和许多传统老板一样的心态。他认为远程工作是一种反常现象,希望所有人都能尽快回到办公桌前。“在我成长的环境里,人们都穿西装打领带,早上8点就出现在公司——没有任何借口。”这位60岁的Ingenovis公司首席执行官说。

关键词：反常现象首席执行官瓦尔德远程办公桌老板

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Endoscopic ultrasound-guided portal pressure gradient identifies patients with previously undiagnosed clinically significant portal hypertension

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Portal Hypertension & Cirrhosis 2024年第2期3卷 67-74页

作者： Jerome C.Edelson Scott F.D.Edelson John G.Quiles Cyrus V.Edelson Eric M.Montminy Christian L.Horn John P.Magulick don C.Rockey Department of Gastroenterology and Hepatology Brooke Army Medical CenterFort Sam HoustonTexasUSA Department of Medicine Uniformed Services University of the Health SciencesBethesdaMarylandUSA Department of Medicine Brooke Army Medical CenterFort Sam HoustonTexasUSA John H.Stroger Jr.Hospital of Cook County ChicagoIllinoisUSA Digestive Disease Research Center Medical University of South CarolinaCharlestonSouth CarolinaUSA

Aims:Portal hypertension(PH)is a complication of cirrhosis that leads to hepatic *** the portal pressure gradient(PPG)provides valuable information for disease assessment,staging,and *** this study,we aimed to report the utilization of endoscopic ultrasound(EUS)-guided PPG(EUS-PPG)measurements in a real-world ***:This retrospective analysis included patients at a tertiary care center who underwent EUS-PPG between February 2021 and May *** most common indication was to establish or exclude the diagnosis of cirrhosis,followed by an assessment of surgical risk in the setting of suspected *** demographic and clinical data were collected,and statistical analysis was performed using the Student's t ***:Eighteen patients underwent *** success was achieved in 17 of the 18 *** complications were *** mean scores of Child-Pugh,Model for End-Stage Liver Disease-Sodium,and Fibrosis-4 scores were 5.1±0.5,9.0±3.0,and 3.7±4.5,*** the 18 patients,two presented with esophageal varices and six with portal hypertensive *** mean PPG was 5.8±4.5 mmHg,and five patients exhibited clinically significant PH(CSPH).Of the 18 patients,15 underwent concurrent EUS-liver biopsy,which was 100%successful and provided diagnostic histology for all *** PPG data led to changes in the clinical management of 17 ***:EUS-PPG is safe and technically *** Child-Pugh score did not correlate well with the presence of CSPH;however,PPG measurements resulted in changes in the management of almost all *** studies correlating EUS-PPG with other assessments of liver diseases are required.

关键词： EUS portal hypertension portal pressure gradient

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北美机车车队的更新

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国外铁道机车与动车 2024年第2期 5-7页

作者： [美]don Graab 焦国超(译) 不详

2016年以来,北美电传动内燃机车制造业务持续下滑;2021年购置5台内燃机车后,至今未购入一台新造机车。这种情况可能还将持续:相较于购置新车,铁路公司更倾向于对现有机车进行翻新改造。何时能够恢复对新型机车的需求仍是未知,这主要取... 详细信息

2016年以来,北美电传动内燃机车制造业务持续下滑;2021年购置5台内燃机车后,至今未购入一台新造机车。这种情况可能还将持续:相较于购置新车,铁路公司更倾向于对现有机车进行翻新改造。何时能够恢复对新型机车的需求仍是未知,这主要取决于机车改后使用寿命的延长情况。现状持续时间越久,铁路制造企业面临的困难和挑战就越大。

关键词：北美电传动内燃机车铁路公司机车改造

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《吐蕃大事纪年》中关于地名“热达合”的认定

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攀登（藏文版） 2024年第1期 79-88页

作者：李加东知甘肃省法官学院

根据敦煌本《吐蕃大事纪年》记载,公元8世纪初吐蕃赞普指派多麦地区的臣属主持会盟,会盟地点为“热达合”,文献记载显示吐蕃在“热达合”前后四次主持召开过会盟,足以见“热达合”这一地点的重要性。虽然学术界对此有过一些探讨,但至今... 详细信息

根据敦煌本《吐蕃大事纪年》记载,公元8世纪初吐蕃赞普指派多麦地区的臣属主持会盟,会盟地点为“热达合”,文献记载显示吐蕃在“热达合”前后四次主持召开过会盟,足以见“热达合”这一地点的重要性。虽然学术界对此有过一些探讨,但至今仍未形成研究共识。为此,基于前人研究基础,结合实地调研和查阅相关藏文史籍,认为“热达合”一词系多麦地区“热西多”和“旦斗”的统称。其中,“热西多”为今青海省循化县清水镇区域范围,“旦斗”为今青海省化隆县金源乡丹斗寺区域。

关键词：《吐蕃大事纪年》 “热达合” 会盟地点

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