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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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Monoamine Oxidase-B Inhibitor Rasagiline Effects on Motor and Non-Motor Symptoms in Individuals with Parkinson’s Disease: A Systematic Review and Meta-Analysis

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Advances in Parkinson's Disease 2024年第3期13卷 27-56页

作者： Paula Abola mitchell Wolden Department of Clinical Research University of Jamestown Jamestown United States of America

Objective: In the manuscript titled Monoamine Oxidase-B Inhibitor Rasagiline Effects on Motor and Non-Motor Symptoms in Individuals with Parkinsons Disease: A Systematic Review and Meta-Analysis, the objective was to conduct a systematic review with meta-analysis to investigate the effects that Rasagiline has on motor and non-motor symptoms in individuals with PD. Introduction: Rasagiline is a second-generation monoamine oxidase-B (MAO-B) inhibitor used both as monotherapy and adjunctive therapy for Parkinsons Disease (PD). Methods: A systematic literature search and meta-analysis were performed with randomized control trials that investigated the effects of Rasagiline on motor and non-motor symptoms in individuals with PD. The systematic search was conducted in PubMed, Cochrane, and EBSCO databases. Methodological quality was assessed using the Cochrane Grading Recommendations Assessment, Development and Evaluation approach. Results: Fourteen studies were included in our review. There were trivial to small and statistically significant improvements in motor symptoms for individuals with PD treated with Rasagiline compared to placebo. Non-motor symptoms showed no significant improvement with Rasagiline compared to placebo in five of six meta-analyses. Results were based on very low to moderate certainty of evidence. Conclusion: 1 mg/day Rasagiline significantly improved Parkinsonian motor symptoms in individuals with PD compared with placebo. For all outcomes, the 1 mg/day Rasagiline group was favored over the placebo group.

关键词： Parkinson’s Disease Monoamine Oxidase-B Inhibitor Rasagiline Non-Motor Symptoms Motor Symptoms UPDRS PDQ-39 OFF Time

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Digital Empowerment

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ChinAfrica 2024年第7期16卷 14-15页

作者： EHIZUELEN MICHAEL mitchell OMORUYI Centre for Nigerian Studies Institute of African StudiesZhejiang Normal University

How China’s tech cooperation with Africa is boosting the continent’s industrial modernisation Given the rate at which youth population in numerous African countries is growing,the continent promises to emerge as a major consumption market in the coming *** than 70 percent of Africa’s population is under the age of 35,and by 2030,42 percent of the world’s young people are expected to reside on the continent.

关键词： boosting Africa cooperation

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Improving Lives China-Africa cooperation propels space industry,drives socio-economic progress

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ChinAfrica 2024年第5期16卷 28-29页

作者： EHIZUELEN MICHAEL mitchell OMORUYI Centre for Nigerian Studies Institute of African StudiesZhejiang Normal University

In the past,outer space was primarily the domain of a few powerful countries and generally considered separate from broader concerns of human security and ***,in recent times,space technology development has been a dynamic arena in which the majority of the world’s countries,including countries across the continent of Africa,are actively engaged to address their most pressing socio-economic *** the turn of the millennium,countries across Africa have demonstrated growing interest in developing their space capabilities to address their most pressing challenges,including but not limited to climate change,poverty,terrorism,and forced migration.

关键词： Africa primarily challenges

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Promoting Human Rights Through Development

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ChinAfrica 2024年第3期16卷 32-33页

作者： EHIZUELEN MICHAEL mitchell OMORUYI Centre for Nigerian Studies Institute of African Studies Zhejiang Normal University

China’s human rights practice focuses on the rights of subsistence and development,China always regards rights to subsistence and development as primary and basic human *** a goal humanity has pursued for a long time,the Chinese people have worked tirelessly to protect human rights for *** with its rising global stature,the nation has moved from its traditionally more defensive posture to a more activist role in the field of global human rights protection,especially in the United Nations Human Rights Council.

关键词： Human traditionally Rights

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Scavenging and release of REE and HFSE by Na-metasomatism in magmatic-hydrothermal systems

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Fundamental Research 2024年第2期4卷 315-323页

作者： Wu-Bin Yang He-Cai Niu Ning-Bo Li Pete Hollings Shannon Zurevinski Roger H.mitchell Key Laboratory of Mineralogy and Metallogeny/Guangdong Provincial Key Laboratory of Mineral Physics and Materials Guangzhou Institute of GeochemistryChinese Academy of SciencesGuangzhou 510640China CAS Center for Excellence in Deep Earth Science Guangzhou 510640China Department of Geology Lakehead UniversityThunder BayON P7B 5E1Canada

Exploitable or potentially exploitable deposits of critical metals,such as rare-earth(REE)and high-field-strength elements(HFSE),are commonly associated with alkaline or peralkaline igneous ***,the origin,transport and concentration of these metals in peralkaline systems remains poorly *** study presents the results of a mineralogical and geochemical investigation of the Na-metasomatism of alkali amphiboles and clinopyroxenes from a barren peralkaline granite pluton in NE China,to assess the remobilization and redistribution of REE and HFSE during magmatic-hydrothermal *** amphiboles and aegirine-augites from the peralkaline granites show evolutionary trends from sodic-calcic to sodic compositions,with increasing REE and HFSE concentrations as a function of increasing Na-index[Na^(#),defined as molar Na/(Na+Ca)ratios].The Na-amphiboles(i.e.,arfvedsonite)and aegirine-augites can be subsequently altered,or breakdown,to form hydrothermal aegirine during late-or post-magmatic *** compositions analyzed by insitu LA-ICPMS show that the primary aegirine-augites have high and variable REE(2194-3627 ppm)and HFSE(4194-16,862 ppm)contents,suggesting that these critical metals can be scavenged by alkali amphiboles and *** to the primary aegirine-augites,the presentative early replacement aegirine(Aeg-I,Na^(#)=0.91-0.94)has notably lower REE(1484-1972)and HFSE(4351-5621)*** contrast,the late hydrothermal aegirine(Aeg-II,Na^(#)=0.92-0.96)has significantly lower REE(317-456 ppm)and HFSE(6.44-72.2 ppm)*** that the increasing Na^(#)from aegirine-augites to hydrothermal aegirines likely resulted from Na-metasomatism,a scavenging-release model can explain the remobilization of REE and HFSE in peralkaline granitic *** scavenging and release of REE and HFSE by Na-metasomatism provides key insights into the genesis of globally significant REE and HFSE *** high Na-index of th

关键词： Critical metals Alkali amphiboles Na-metasomatism REE and HFSE Na-index(Na^(#))

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Des racines et des ailes La culture du droit humain a la subsistance en Chine

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中国与非洲（法文版） 2024年第3期16卷 32-33页

作者： EHIZUELEN MICHAEL mitchell OMORUYI Centre d'etudes nigerianes Institut d'etudes africainesUniversite normale du Zhejiang

La Chine met en avant les droits a la subsistance et au développement commeétant les plus fondamentaux des droits *** peuple chinois s'est engage avec determination dans la protection des droits de I'homme,un idéal que I'humanite cherche a atteindre depuis de nombreuses *** son influence croissante sur la scene mondiale,la Chine aévolue d'une posture traditionnellement defensive vers un engagement plus actif dans la defense des droits de I'homme a I'eéchelle internationale,notamment au sein du Conseil des droits de I'homme des Nations unies.

关键词： des les culture

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Voûtes célestes,terresfertiles La collaboration sino-africaine dynamise l'industrie spatiale et stimule le développement socio-économique

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中国与非洲（法文版） 2024年第5期16卷 28-29页

作者： EHIZUELEN MICHAEL mitchell OMORUYI 不详

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Neurosurgical and pharmacological management of dystonia

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World Journal of Psychiatry 2024年第5期14卷 624-634页

作者： Ali Ahmed Mohamed Steven Faragalla Asad Khan Garrett Flynn Gersham Rainone Phillip mitchell Johansen Brandon Lucke-Wold Charles E Schmidt College of Medicine Florida Atlantic UniversityBoca RatonFL 33431United States Department of Neurosurgery and Brain Repair University of South FloridaTampaFL 33606United States Department of Neurosurgery University of FloridaGainesvilleFL 32611United States

Dystonia characterizes a group of neurological movement disorders characterized by abnormal muscle movements,often with repetitive or sustained contraction resulting in abnormal *** types of dystonia present based on the affected body regions and play a prominent role in determining the potential efficacy of a given *** most patients afflicted with these disorders,an exact cause is rarely identified,so treatment mainly focuses on symptomatic *** agents,such as oral anticholinergic administration and botulinum toxin injection,play a major role in the initial treatment of *** more severe and/or refractory cases,focal areas for neurosurgical intervention are identified and targeted to improve quality of *** brain stimulation(DBS)targets these anatomical locations to minimize dystonia *** ablation procedures and peripheral denervation surgeries also offer potential treatment to patients who do not respond to *** management options grant providers and patients the ability to weigh the benefits and risks for each individual patient *** review article explores these pharmacological and neurosurgical management modalities for dystonia,providing a comprehensive assessment of each of their benefits and shortcomings.

关键词： Botulinum toxin Magnetic resonance imaging-guided focused ultrasound Surgical ablation Deep brain stimulation Peripheral denervation surgery Antipsychotics

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Liquid Subcutaneous Levodopa-Carbidopa ND0612 Effects on Motor Symptoms in Individuals with Parkinson’s Disease: A Systematic Review and Meta-Analysis

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Advances in Parkinson's Disease 2024年第2期13卷 9-25页

作者： Paula Abola mitchell Wolden Kristin Lefebvre Department of Clinical Research University of Jamestown Jamestown ND USA

Objective: In the manuscript titled “Liquid subcutaneous Levodopa-Carbidopa ND0612 effects on motor symptoms in individuals with Parkinson’s Disease: A systematic review and meta-analysis”, the objective was to conduct a systematic review with meta-analysis to investigate the effects ND0612 24-hour dosing regimen has on motor symptoms in individuals with Parkinson’s Disease (PD). Introduction: ND0612 is a novel minimally invasive continuous subcutaneous delivery system of liquid Levodopa-Carbidopa being investigated for the treatment of PD in individuals experiencing motor symptoms. Methods: A systematic literature search was conducted in PubMed, Cochrane, and EBSCO databases to identify randomized controlled trials investigating the effects of ND0612 on motor symptoms in individuals with PD. Outcomes included the Unified Parkinson’s Disease Rating Scale (UPDRS) Part II and Part III scores. Methodological quality was assessed using the Cochrane Grading of Recommendations Assessment, Development, and Evaluation approach. Meta-analysis was performed using a random effects model with the DerSimonian and Laird method to estimate the effects of the ND0612 24-hour dosing regimen on UPDRS Part II and Part III scores. Results: Three studies were included in our review. There were statistically significant reductions in UPDRS Part II scores (mean difference (MD) −3.299;95% confidence interval (CI) −3.438, −3.159) and in UPDRS Part III scores (MD −12.695;95% CI −24.428, −0.962) in the ND0612 24-hour dosing regimen. Results were based on very low certainty of evidence. Conclusion: Based on very low certainty evidence, the ND0612 24-hour dosing regimen is effective at improving motor symptoms in individuals with PD. Our findings suggest that ND0612 is more effective at improving UPDRS Part II and Part III scores in individuals with PD than other pharmacological and non-pharmacological treatments, warranting further study.

关键词： Parkinson’s Disease ND0612 Levodopa-Carbidopa Motor Symptoms Motor Complications UPDRS

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