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5-Fluorouracil dose escalation generated desensitized colorectal cancer cells with reduced expression of protein methyltransferases and no epithelial-to-mesenchymal transition potential

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Oncology Research 2024年第6期32卷 1047-1061页

作者： kimberly FENECH ISAAC MICALLEF BYRON BARON Centre for Molecular Medicine and Biobanking University of MaltaMsidaMSD 2080Malta Department of Tumor Genetics and Biology Graduate School of Medical SciencesFaculty of Life SciencesKumamoto UniversityKumamoto860-8556Japan

Background:Colorectal cancer(CRC)is one of the most frequently diagnosed *** many cases,the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluorouracil(5-FU).The epithelial-to-mesenchymal transition(EMT)and dysregulation in protein methylation are two mechanisms associated with chemoresistance in many *** study looked into the effect of 5-FU dose escalation on EMT and protein methylation in *** and Methods:HCT-116,Caco-2,and DLD-1 CRC cell lines were exposed to dose escalation treatment of *** motility and invasive potentials of the cells before and after treatment with 5-FU were investigated through wound healing and invasion *** was followed by aWestern blot which analyzed the protein expressions of the epithelial marker E-cadherin,mesenchymal marker vimentin,and the EMT transcription factor(EMTTF),the snail family transcriptional repressor 1(Snail)in the parental and desensitized *** blotting was also conducted to study the protein expressions of the protein methyltransferases(PMTs),Euchromatic histone lysine methyltransferase 2(EHMT2/G9A),protein arginine methyltransferase(PRMT5),and SET domain containing 7/9(SETD7/9)along with the global lysine and arginine methylation ***:The dose escalation method generated 5-FU desensitized CRC cells with distinct morphological features and increased tolerance to high doses of *** 5-FU desensitized cells experienced a decrease in migration and invasion when compared to the parental *** was reflected in the observed reduction in E-cadherin,vimentin,and Snail in the desensitized cell ***,the protein expressions of EHMT2/G9A,PRMT5,and SETD7/9 also decreased in the desensitized cells and global protein lysine and arginine methylation became dysregulated with 5-FU ***:This study showed that continuous,dose-escalation treatment of 5-FU in CRC cells generated 5-FU

关键词： Chemoresistance Epithelial-to-mesenchymal transition Protein methylation Protein methyltransferases

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巴西亚马孙河流域雅诺马马人体内的有机汞含量

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AMBIO－人类环境杂志 2003年第7期32卷 434-439页

作者： kimberly anne sing Daniel Hryhorczuk Giovanni Saffirio Thomas Sinks Daniel C.Paschal John Sorensen Edwin H.Chen 郝春玲加利福尼亚大学洛杉矶分校伊利诺斯大学公共卫生系匹兹堡大学美国疾病预防和控制中心明尼苏达大学德卢斯分校考古定年学实验室伊利诺斯大学芝加哥分校公共卫生系

位于巴西北部的Catrimani河流域是雅诺马马人的居住地,且自1980年以来,一直是采金场所。金矿开采活动释放入环境中的无机汞会被转化为有机汞,且在水域生态系统会发生生物放大作用。摄食被汞污染鱼的人群,如雅诺马马人有可能会受到危害... 详细信息

位于巴西北部的Catrimani河流域是雅诺马马人的居住地,且自1980年以来,一直是采金场所。金矿开采活动释放入环境中的无机汞会被转化为有机汞,且在水域生态系统会发生生物放大作用。摄食被汞污染鱼的人群,如雅诺马马人有可能会受到危害。我们分别于1994年和1995年对居住在采矿河流附近和非采矿河流附近的雅诺马马村民进行了调查,并且对被其捕捞的水虎鱼体内的汞含量进行了分析。我们分别于1994和1995年对5个村庄的90名雅诺马马印地安人和3个村庄的62名雅诺马马印地安人进行了调查研究。于1994年所调查的5个村庄中,有4个位于Catrimani河沿岸,大约在距过去金矿开采活动场所下游140～160km处。另一个村庄位于没有开采活动的Ajaraní河沿岸。于1995年所调查的3个村庄中,有两个位于Catrimani河沿岸的村庄再一次被调查,另一个位于没有采矿活动的Pacu河。在被调查的所有村民中,其血液中有机汞含量的变化范围为0～62.6μg/L(每个村庄的平均值在21.2～43.1μg/L之间)。采自有采矿活动的Catrimani河的水虎鱼汞含量的变化范围为235～1084ppb。在所测的13个水虎鱼样品中,有9个体长在30cm或更长的水虎鱼样品总汞含量超过了世界卫生组织和巴西卫生部规定的鱼中汞消费限值(500ppb)。不幸的是,在没有开采活动的Ajaraní和Pacu河附近的居民和鱼体内都呈现出了较高的汞水平,这表明间接的汞源也会对亚马孙河流域造成环境污染。

关键词：巴西亚马孙河流域雅诺马马人体内汞含量采样方法血样饮食习惯

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Cost-Effective Method of Gene Synthesis by Sequencing from Microchip-Derived Oligos for Droplet Cloning

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Advances in Bioscience and Biotechnology 2024年第8期15卷 474-485页

作者： kimberly Wang Jericho Senior High School Jericho NY USA

Gene synthesis has provided important contributions in various fields including genomics and medicine. Current genes are 7 - 30 cents depending on the assembly and sequencing methods performed. Demand for gene synthesis has been increasing for the past few decades, yet available methods remain expensive. A solution to this problem involves microchip-derived oligonucleotides (oligos), an oligo pool with a substantial number of oligo fragments. Microchips have been proposed as a tool for gene synthesis, but this approach has been criticized for its high error rate during sequencing. This study tests a possible cost-effective method for gene synthesis utilizing fragment assembly and golden gate assembly, which can be employed for quicker manufacturing and efficient execution of genes in the near future. The droplet method was tested in two trials to determine the viability of the method through the accuracy of the oligos sequenced. A preliminary research experiment was performed to determine the efficacy of oligo lengths ranging from two to four overlapping oligos through Gibson assembly. Of the three oligo lengths tested, only two fragment oligos were correctly sequenced. Two fragment oligos were used for the second experiment, which determined the efficacy of the droplet method in reducing gene synthesis cost and speed. The first trial utilized a high-fidelity polymerase and resulted in 3% correctly sequenced oligos, so the second trial utilized a non-high-fidelity polymerase, resulting in 8% correctly sequenced oligos. After calculating, the cost of gene synthesis lowers down to 0.8 cents/base. The final calculated cost of 0.8 cents/base is significantly cheaper than other manufacturing costs of 7 - 30 cents/base. Reducing the cost of gene synthesis provides new insight into the cost-effectiveness of present technologies and protocols and has the potential to benefit the fields of bioengineering and gene therapy.

关键词： Cost-Effective Gene Synthesis Microchip Oligo Droplet Cloning

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The Role of Impulsivity and Addiction in Gambling Behaviors: How Applied Neuroscience Research Can Help in the Monitoring and Management of Mental Health Issues

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Open Journal of Medical Psychology 2024年第1期13卷 11-24页

作者： Yingzhen Jia kimberly Rose Clark College of Arts and Sciences Boston University Boston MA USA Department of Psychological and Brain Sciences Dartmouth College Hanover NH USA

One in five Americans experience symptoms associated with at least one mental health disorder every year. These include behavioral addictions, which have long been overlooked despite their similar neural bases with substance addictions. Gambling addiction, a type of behavioral addiction, deserves particular attention given the significant negative effects, this addiction has on financial and interpersonal health. The purpose of this paper is to review the available literature concerning the behavioral and neural processes involved in gambling addiction, including: the anticipation of reward, the role of dopamine, and the neural substrates of the decision-making processes involved in gambling addiction. Market research has also identified solutions that integrate applied neuroscience and self-tracking systems to monitor and manage mental health issues associated with gambling addiction. The authors then propose a gambling treatment-focused mobile app solution that addresses outstanding issues with a special design aimed at reversing plasticity in order to relieve the effects of gambling addiction. .

关键词： Applied Neuroscience Gambling Addiction Mental Health Management

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Neurocircuit regeneration by extracellular matrix reprogramming

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Neural Regeneration Research 2025年第8期20卷 2300-2301页

作者： Shengzhang Su Ian N.Levasseur kimberly M.Alonge Department of Medicinal Chemistry University of WashingtonSeattleWAUSA Department of Chemistry University of WashingtonSeattleWAUSA Department of Medicine University of Washington Medicine Diabetes InstituteSeattleWAUSA

The brain's extracellular matrix(ECM),which is comprised of protein and glycosaminoglycan(GAG)scaffolds,constitutes 20%-40% of the human brain and is considered one of the largest influencers on brain cell functioning(Soles et al.,2023).Synthesized by neural and glial cells,the brain's ECM regulates a myriad of homeostatic cellular processes,including neuronal plasticity and firing(Miyata et al.,2012),cation buffering(Moraws ki et al.,2015),and glia-neuron interactions(Anderson et al.,2016).Considering the diversity of functions,dynamic remodeling of the brain's ECM indicates that this understudied medium is an active participant in both normal physiology and neurological diseases.

关键词： matrix programming

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Citrobacter Causing Septic Arthritis: A Case Report

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Infectious Diseases & Immunity 2024年第3期4卷 146-148页

作者： kimberly K.Levine Mary Dahl Abubakar Tauseef Joseph Thirumalareddy Department of Internal Medicine Creighton University School of MedicineOmaha 68124NEUSA

The genus Citrobacter commonly found in water and soil as well as the intestinal and urinary tracts of animals and *** Citrobacter infections are infrequently diagnosed in environmental contexts,the rising incidence of nosocomial manifestations underscores the importance of considering this organism in the differential diagnosis of hospital-acquired *** present a case of patient with septic arthritis of the shoulder who had been originally admitted for the management of acute-on-chronic congestive heart failure exacerbation and severe *** hospital day 1,joint aspiration cultures and Gram stain confirmed the presence of Citrobacter koseri,a pathogen not commonly associated with septic arthritis,and ceftriaxone was administered to target *** hospital day 7,antibiotic was transitioned to levofloxacin,every other day for 4 *** patient was discharged to an acute rehabilitation facility after a 14-day hospital *** case stresses the importance of maintaining a broad differential diagnosis for any patients who present with fever and joint inflammation or swelling,especially in a postoperative setting.

关键词： Citrobacter koseri Bacteremia Septic arthritis

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A Case Report: Emergency Management of a Pregnant Trauma Patient—An Anesthesiologist’s Perspective and Role

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Open Journal of Anesthesiology 2024年第2期14卷 25-39页

作者： Kalpana Tyagaraj Candice Ibarra kimberly Moy Nina Luksanapol Gianna Torre Raymond Powers Anuj Bapodra Maimonides Medical Center New York USA

Trauma is the leading cause of death for all women of childbearing age. Motor vehicle accidents account for almost two-thirds of all maternal non-obstetric, trauma-related deaths, while falls and domestic violence comprise a large percentage of the rest. The leading causes of obstetric trauma are motor vehicle accidents, falls, assaults, and gunshots, and ensuing injuries are classified as blunt abdominal trauma, pelvic fractures, or penetrating trauma . The causes are different with different life styles and different socio-economic and cultural background. Pregnant trauma victims tend to be younger, less severely injured, and more likely African American or of Hispanic descent compared with nonpregnant victims of trauma. Drugs and alcohol are a factor in about 20 percent of maternal trauma. With pregnancy comes the challenge and responsibility of caring for two patients at once, the mother and the fetus. In general, providing optimal maternal care is the best strategy to optimize fetal survival. Decision-making including the condition of the mother, gestational age, status of the fetus, and interventions are based on these key factors. Many providers are involved in the care of the pregnant patient: at the trauma scene, in the emergency department, and in the operating room. The anesthesiologist plays a key role in the care and management of the pregnant trauma patient. All anesthesiologists have ample training in obstetric anesthesia during their residency and frequently cover obstetric units in hospitals where pregnant patients are cared for. On the other hand, most nonobstetric physicians have little obstetric exposure and may be uncomfortable caring for the pregnant patient because of unfamiliarity with the physiologic changes of pregnancy or the evaluation of fetal well-being. This is not only a source of stress for other trauma providers, but can put maternal well-being at risk. Non-obstetric physicians may hesitate to order necessary diagnostic and therapeu

关键词： Obstetric Anesthesiology Ob Trauma Maternal and Fetal Resuscitation

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Key Factors to Consider When Introducing a New Vaccine in Low-Income Settings: Lessons from Malawi Expanded Program on Immunization

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World Journal of Vaccines 2024年第1期14卷 1-23页

作者： Samuel Mpinganjira kimberly Konono Joseph Mwaka Adidja Amani Habtamu Anteneh Michael Ngigi Boston Zimba Atupele Kapito Institute for Global Health Santa Chiara Lab Universita degli Studi di Siena Siena Italy School of Public and Global Health Kamuzu University of Health Sciences Blantyre Malawi Faculty of Medicine and Biomedical Sciences of the University of Yaound 1 Yaound Cameroon Department of Public Health University of Glasgow Glasgow UK

Introduction: As new vaccines become available, countries must assess the relevance to introduce them into their vaccination schedules. Malawi has recently introduced several new vaccines and plans to introduce more. This study was conducted to identify key factors that need to be considered when deciding to introduce a new vaccine and current challenges faced by low and middle income countries using Malawi as an example. Methodology: The study employed a desk review approach, examining published literature from various sources such as PubMed, Medline, and Google Scholar. Policy documents from organizations like the World Health Organization, GAVI the Alliance, and the Ministry of Health for Malawi were also included. A total of 99 articles and documents on new vaccine introduction, challenges of immunization, policy documents in immunization and health systems strengthening were included. The review focused on addressing five key areas critical to new vaccine introduction namely: the need for a vaccine, availability of the vaccine, safety and effectiveness of the vaccine, demand for the vaccine, and the prudent use of public or private funds. Results: Malawi considered the burden of cervical cancer and the significance of malaria in the country when introducing the HPV and malaria vaccines. The country opted for vaccines that can be handled by the cold chain capacity and available human resources. Despite that malaria vaccine and Typhoid Conjugate Vaccine trials were done in country, there are limited vaccine safety and efficacy trials conducted in Malawi, leading to a reliance on WHO-prequalified vaccines. Demand for newly introduced vaccines varied, with high demand for Oral Cholera Vaccine during a cholera outbreak, while demand for COVID-19 vaccines decreased over time. Although cost-effectiveness studies were limited in the country, 2 studies indicated that Typhoid Conjugate Vaccine and malaria vaccine would be cost effective. All these have been implemented d

关键词： Vaccine Introduction Implementation Expanded Program on Immunization Low-Income Stakeholders

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护理专业国际学生短期访学教育项目的设计与实施

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International Journal of Nursing Sciences 2024年第1期11卷 83-90页

作者： Ubolrat Piamjariyakul Saima Shafique Dana L.Friend kimberly A.Adams Wiyakarn Sanghuachang Trisha M.Petitte Stephanie Young School of Nursing West Virginia UniversityMorgantownWVUSA Boromarajonani College of Nursing Saraburi SaraburiThailand

目的旨在描述制定及评估一项短期留学生研究和教育项目。方法研究分为项目制定与实施及评价2部分。根据1名国际学生的短期访学需求,护理学院的全球护理项目协调员和首席导师共同确定项目基本内容和团队成员。该项目学习活动考虑了该国... 详细信息

目的旨在描述制定及评估一项短期留学生研究和教育项目。方法研究分为项目制定与实施及评价2部分。根据1名国际学生的短期访学需求,护理学院的全球护理项目协调员和首席导师共同确定项目基本内容和团队成员。该项目学习活动考虑了该国际学生对老年人和居家临终关怀的兴趣,包括4项内容:.开展研究工作,参与教学活动,参与临床实践活动,以及特殊活动和专业发展培训课程。在为期6个月的访学结束时,对参与此次教学活动的教师、研究生及留学生进行访谈和简短问卷调查。结果通过访谈了解到3个方面的内容:通过参与该项目中获得的经验(增强了教育和研究的多样性,获得了新的全球医疗保健知识,对文化意识的自我反思和促进);项目实施的障碍和挑战(签证申请过程,英语语言障碍,缺乏公共交通设施,时间安排冲突);克服这些障碍和挑战的策略(在课程中增加文化多样性信息;与其他同学一起学习英语;使用不同的沟通技巧;在签证申请过程中与大学全球事务办公室持续合作;提供互动体验)。所有项目参与者都对该项目表示非常满意(4.67±0.50),认为对他们在科研、教学和临床实践方面的护理技能有很大影响(4.67±0.50)。结论此次项目的参与者均获得了相关经验,可用于今后的教学指导活动。国际护理专业学生需要得到帮助才能更好地适应访学环境,教师必须具有文化敏感性,了解学生的学习需求,并倡导营造适合学生学习的环境。

关键词：评价国际学生护理教育课程

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Evolutionary responses to climate change and contaminants： Evidence and experimental approaches

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Current Zoology 2015年第4期61卷 690-701页

作者： David A. kimberly Department of Biology Westminster College 442 Meldrum Science Center Salt Lake City UT 84105 USA Department of Environmental Toxicology The Institute of Environmental and Human Health Texas Tech University 1207 Gilbert Drive Lubbock Texas 79416 USA Environmental Science and Studies Program Towson University 8000 York Rd. Towson MD 21252 USA

A fundamental objective within ecotoxicology lies in understanding and predicting effects of contaminants. This ob- jective is made more challenging when global climate change is considered as an environmental stress that co-occurs with con- taminant exposure. In this multi-stressor context, evolutionary processes are particularly important. In this paper, we consider several non-＂omic＂ approaches wherein evolutionary responses to stress have been studied and discuss those amenable to a mul- tiple stressor context. Specifically, we discuss common-garden designs, artificial and quasi-natural selection, and the estimation of adaptive potential using quantitative genetics as methods for studying evolutionary responses to contaminants and climate change in the absence of expensive molecular tools. While all approaches shed light on potential evolutionary impacts of stressor exposure, they also have limitations. These include logistical constraints, difficulty extrapolating to real systems, and responses tied strongly to specific taxa, populations, and/or testing conditions. The most effective way to lessen these inherent limitations is likely through inclusion of complementary physiological and molecular tools, when available. We believe that an evolutionary context to the study of contaminants and global climate change is a high priority in ecotoxicology and we outline methods that can be implemented by almost any researcher but will also provide valuable insights [Current Zoology 61 （4）： 690-701, 2015].

关键词： Climate change Multiple stressors Adaptation Experimental evolution Quantitative genetics

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