profiling

剖析
  • 文章类型: Journal Article
    背景:疫苗犹豫是一个全球关注的复杂问题。由于护士在提供患者护理和塑造疫苗公众意见方面发挥着至关重要的作用,必须采取干预措施来解决护理中的疫苗犹豫。因此,确定导致犹豫的特征和态度的概况可能有助于确定针对量身定制的全球疫苗接种运动的特定重点领域.这项研究的目的是概述护理界对COVID-19和流感疫苗犹豫不决的特征和态度。
    方法:这种多站点,横断面研究从英国招募了1967名注册护士和1230名护理学生,芬兰,和意大利在2023年3月至9月之间。
    方法:数据收集涉及采用疫苗接种态度检查(VAX)量表的在线调查,卑尔根社交媒体成瘾量表,以及与社会人口统计学和职业特征有关的问题。基于VAX量表,使用k均值聚类分析来识别各种犹豫簇。单因素方差分析和卡方检验用于确定社会人口统计学特征的显著差异,职业因素,疫苗接种的态度,和集群之间的社交媒体使用情况。
    结果:确定了三个不同的簇。概况A显示了很高的疫苗信心,配置文件B显示出轻微的犹豫,配置文件C报告了高度的犹豫。在配置文件C中,在年轻人中发现了更高水平的疫苗犹豫,文化程度较低的护士经验不足。虽然受过高等教育的老年护士,担任高级角色的人,对疫苗更有信心,并且有一致的接受流感和COVID-19疫苗接种的历史(概况A)。研究发现意大利护士非常犹豫(简介C),英国护士高度自信(简介A),和芬兰护士均匀分布在自信之间,有点犹豫,高度犹豫(简介A,B,C,分别)。此外,Instagram和TikTok的更频繁使用与疫苗犹豫有关(配置文件B和C),LinkedIn和X在对疫苗有信心的个体中更为常见(概况A)。
    结论:这项研究在国际护士样本中确定了与疫苗犹豫相关的特定社会人口统计学和职业因素。此外,确定了导致犹豫的态度,对疫苗未来不可预见的影响的担忧被认为是一种批评态度,可能会削弱信心,增加护理方面的犹豫。这项研究还揭示了社交媒体平台对疫苗犹豫的影响,因此,指出哪些平台可以有效地向全球护理社区传播疫苗接种运动。
    结论:全球疫苗接种运动应侧重于具体概况和集群,以促进国际护理界的疫苗接种。在职业生涯早期赋予护士权力将有助于灌输积极的疫苗接种行为,确保在整个个人职业生涯中以及以后持续接种疫苗,对促进公共卫生层面的疫苗接种也有影响。
    BACKGROUND: Vaccine hesitancy is a complex issue of global concern. As nurses play a vital role in delivering patient care and shaping public opinions on vaccines, interventions to address vaccine hesitancy in nursing are imperative. As such, identifying profiles of characteristics and attitudes contributing to hesitancy may help identify specific areas of focus to target tailored global vaccination uptake campaigns. The purpose of this study was to profile the characteristics and attitudes contributing to hesitancy toward COVID-19 and Influenza vaccines in the nursing community.
    METHODS: This multisite, cross-sectional study recruited 1967 registered nurses and 1230 nursing students from the United Kingdom, Finland, and Italy between March and September 2023.
    METHODS: Data collection involved an online survey adopting the Vaccination Attitudes Examination (VAX) Scale, the Bergen Social Media Addiction Scale, and questions pertaining to sociodemographic and occupational characteristics. A k-means cluster analysis was used to identify various clusters of hesitancy based on the VAX Scale. One-way ANOVA and chi-square tests were used to identify significant differences in sociodemographic characteristics, occupational factors, vaccination attitudes, and social media usage between the clusters.
    RESULTS: Three distinct clusters were identified. Profile A showed high vaccine confidence, profile B displayed slight hesitancy, and profile C reported high levels of hesitancy. In profile C, higher levels of vaccine hesitancy were identified in younger, less experienced nurses with lower educational attainment. While older nurses with higher educational attainment, who were in senior roles, were more vaccine-confident and had a consistent history of accepting the Influenza and COVID-19 vaccinations (profile A). The study found Italian nurses highly hesitant (profile C), British nurses highly confident (profile A), and Finnish nurses evenly distributed between confident, slightly hesitant, and highly hesitant (profiles A, B, and C, respectively). In addition, more frequent usage of Instagram and TikTok was associated with vaccine hesitancy (profiles B and C), and LinkedIn and X were more common among vaccine-confident individuals (profile A).
    CONCLUSIONS: This study has identified specific sociodemographic and occupational factors that are related to vaccine hesitancy in an international sample of nurses. Additionally, attitudes contributing to hesitancy were identified, with worries about unforeseen future effects of the vaccine being identified as a critical attitude that may undermine confidence and increase hesitancy in nursing. This study also sheds light on the influence that social media platforms have on vaccine hesitancy and, as such, indicates which platforms are effective to disseminate vaccination campaigns to global nursing communities.
    CONCLUSIONS: Global vaccination campaigns should focus on specific profiles and clusters to promote vaccination in the international nursing community. Empowering nurses early in their careers will help to instill positive vaccination behaviors, ensuring a sustained uptake of vaccinations throughout the individual\'s career and beyond, with an impact on promoting vaccination at the public health level as well.
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  • 文章类型: Journal Article
    背景:移动健康(mHealth)解决方案可以提高质量,可访问性,和卫生服务的公平性,促进早期康复。对于听力损失的人,mHealth应用程序可能旨在支持听觉诊断中的决策过程,并向用户提供治疗建议(例如,助听器需要)。对于一些人来说,这样的mHealth应用程序可能是与听力诊断服务的第一次接触,应该激励听力损失的用户有针对性地寻求专业帮助。然而,个性化的治疗建议是可能的,只有通过了解个人的资料有关的结果的兴趣。
    目的:本研究旨在表征重复使用基于应用程序的听力测试后或多或少倾向于寻求专业帮助的个体。目标是得出相关的听力相关特征和个性特征,为mHealth听力解决方案的用户提供个性化治疗建议。
    方法:总共,185名(n=106,57.3%的女性)患有主观听力损失的无辅助老年人(平均年龄63.8,SD6.6y)参加了一项移动研究。我们收集了一系列全面的83项听力相关和心理测量的横截面和纵向数据,这些测量先前发现可以预测听力帮助寻求。在研究结束时和2个月后,将寻求帮助的准备度评估为结果变量。参与者使用几种有监督的机器学习算法(随机森林,天真贝叶斯,和支持向量机)。使用特征重要性分析确定了用于预测的最相关特征。
    结果:算法正确预测了65.9%(122/185)至70.3%(130/185)的研究结束时寻求帮助的行动,随访时分类准确率达到74.8%(98/131)。除了听力表现之外,最重要的分类特征是日常生活中听力损失的感知后果,对助听器的态度,寻求帮助的动机,身体健康,感官敏感性人格特质,神经质,和收入。
    结论:这项研究有助于识别个体特征,预测自我报告听力损失的老年人寻求帮助。建议在个人分析算法中实施它们,并在mHealth听力应用程序中得出有针对性的建议。
    BACKGROUND: Mobile health (mHealth) solutions can improve the quality, accessibility, and equity of health services, fostering early rehabilitation. For individuals with hearing loss, mHealth apps might be designed to support the decision-making processes in auditory diagnostics and provide treatment recommendations to the user (eg, hearing aid need). For some individuals, such an mHealth app might be the first contact with a hearing diagnostic service and should motivate users with hearing loss to seek professional help in a targeted manner. However, personalizing treatment recommendations is only possible by knowing the individual\'s profile regarding the outcome of interest.
    OBJECTIVE: This study aims to characterize individuals who are more or less prone to seeking professional help after the repeated use of an app-based hearing test. The goal was to derive relevant hearing-related traits and personality characteristics for personalized treatment recommendations for users of mHealth hearing solutions.
    METHODS: In total, 185 (n=106, 57.3% female) nonaided older individuals (mean age 63.8, SD 6.6 y) with subjective hearing loss participated in a mobile study. We collected cross-sectional and longitudinal data on a comprehensive set of 83 hearing-related and psychological measures among those previously found to predict hearing help seeking. Readiness to seek help was assessed as the outcome variable at study end and after 2 months. Participants were classified into help seekers and nonseekers using several supervised machine learning algorithms (random forest, naïve Bayes, and support vector machine). The most relevant features for prediction were identified using feature importance analysis.
    RESULTS: The algorithms correctly predicted action to seek help at study end in 65.9% (122/185) to 70.3% (130/185) of cases, reaching 74.8% (98/131) classification accuracy at follow-up. Among the most important features for classification beyond hearing performance were the perceived consequences of hearing loss in daily life, attitude toward hearing aids, motivation to seek help, physical health, sensory sensitivity personality trait, neuroticism, and income.
    CONCLUSIONS: This study contributes to the identification of individual characteristics that predict help seeking in older individuals with self-reported hearing loss. Suggestions are made for their implementation in an individual-profiling algorithm and for deriving targeted recommendations in mHealth hearing apps.
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  • 文章类型: Journal Article
    这篇全面的综述探讨了放射治疗在癌症治疗中的关键作用。强调遗传分析的多样化应用。这篇综述强调了预测辐射毒性的遗传标记,实现个性化的治疗计划。它深入研究了基因分析对各种癌症类型的放射治疗策略的影响,讨论与治疗反应相关的研究结果,预后,和治疗抗性。基因分析的整合被证明可以改变癌症治疗范式,提供个性化放射治疗方案的见解,并在标准协议可能达不到的情况下指导决策。最终,该综述强调了基因谱分析在提高患者预后和推进肿瘤学精准医疗方面的潜力.
    This comprehensive review explores the pivotal role of radiotherapy in cancer treatment, emphasizing the diverse applications of genetic profiling. The review highlights genetic markers for predicting radiation toxicity, enabling personalized treatment planning. It delves into the impact of genetic profiling on radiotherapy strategies across various cancer types, discussing research findings related to treatment response, prognosis, and therapeutic resistance. The integration of genetic profiling is shown to transform cancer treatment paradigms, offering insights into personalized radiotherapy regimens and guiding decisions in cases where standard protocols may fall short. Ultimately, the review underscores the potential of genetic profiling to enhance patient outcomes and advance precision medicine in oncology.
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  • 文章类型: Journal Article
    纳米药物包含多种成分,和颗粒密度被认为是调节施用的纳米药物的生物分布的重要性质。纳米颗粒的密度通过离心法表征,如分析超速离心。粒度和分布是纳米药物的关键物理化学和质量属性。在这项研究中,我们开发了一种适用于脂质体和脂质纳米颗粒(LNP)的新型分析方法,根据粒度和密度,使用离心场流分馏(CF3)。我们使用CF3评估了具有各种阿霉素(DOX)加载量的不同大小的PEG化脂质体的洗脱曲线。该方法用于评价DOX脂质体的药物释放度。批次内和批次间差异,AmBisome®的重建再现性,和COVID-19疫苗(Comirnaty®和SpikevaxTM)中LNP的洗脱特征。本研究中获得的数据强调了所提出方法的重要性,并强调了使用CF3分形图和多角度光散射检测器对脂质体和LNP进行表征和表征的重要性。
    Nanomedicines comprise multiple components, and particle density is considered an important property that regulates the biodistribution of administered nanomedicines. The density of nanoparticles is characterized by centrifugal methods, such as analytical ultracentrifugation. Particle size and distribution are key physicochemical and quality attributes of nanomedicines. In this study, we developed a novel profiling method applicable to liposomes and lipid nanoparticles (LNPs), based on particle size and density, using centrifugal field-flow fractionation (CF3). We evaluated the elution profiles of PEGylated liposomes of different sizes with various doxorubicin (DOX)-loading amounts using CF3. This method was applied to evaluate the drug release of DOX-loaded liposomes, intra- and inter-batch variability, reconstitution reproducibility of AmBisome®, and elution characteristics of LNPs in COVID-19 vaccines (Comirnaty® and SpikevaxTM). The data obtained in the present study underscore the significance of the proposed methodology and highlight the importance of profiling and characterizing liposomes and LNPs using CF3 fractograms and a multi-angle light-scattering detector.
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  • 文章类型: Journal Article
    已知在可可豆发酵过程中会发生一些发芽。这种生物过程对可可发酵过程的影响是未知的,因此进行了研究。为了确定发芽在分子水平以及对风味的影响,使用超高效液相色谱-电喷雾电离-飞行时间-质谱(UPLC-ESI-ToF-MS)的非靶向代谢组学方法,同时采集低和高碰撞能质谱(MSe)。测量了相同来源的生可可豆和发芽可可豆的提取物,并通过无监督的主成分分析比较了特征差异。OPLS-DA显示12-羟基茉莉酸(HOJA)硫酸盐,()-儿茶素和(-)-表儿茶素是大多数下调的化合物,以及两种羟甲基戊二酰(HMG)葡糖苷A和B,是发芽材料中决定性的上调化合物。此外,通过与分离和合成的参考化合物共洗脱,可以首次在可可中进一步鉴定出HMG葡糖苷和12-羟基茉莉酸。HOJA硫酸盐,这在可可中被假定,和HOJA被发现具有苦涩的味道。
    Some germination is known to occur during the process of fermentation in cocoa beans. The impact of this biological process on the course of cocoa fermentation is not known and was thus investigated. In order to determine the impact of germination at the molecular level as well as on flavor, an untargeted metabolomics approach using Ultra Performance Liquid Chromatography-Electrospray Ionization-Time of Flight-Mass Spectrometry (UPLC-ESI-ToF-MS) with simultaneous acquisition of low- and high-collision energy mass spectra (MSe) was performed. Extracts of raw and germinated cocoa beans of the same origin were measured and compared for characteristic differences by unsupervised principal component analysis. OPLS-DA revealed 12-hydroxyjasmonic acid (HOJA) sulfate, (+)-catechin and (-)-epicatechin as most down-regulated compounds as well as two hydroxymethylglutaryl (HMG) glucosides A and B among others as decisive up-regulated compounds in the germinated material. Additionally, further HMG glucosides and 12-hydroxyjasmonic acid could be identified in cocoa for the first time by coelution with isolated and synthesized reference compounds. HOJA sulfate, which has been postulated in cocoa, and HOJA were revealed to impart bitter and astringent taste qualities.
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  • 文章类型: Journal Article
    色胺是中枢神经系统的神经调质。它也是一种生物胺,由L-色氨酸的微生物脱羧形成。几乎没有检查过干酪中色胺的积累。没有关于可能影响其积累的因素的研究。确定色胺含量并确定影响其积累的因素可能有助于设计富含色胺的功能性奶酪,而不会达到潜在的毒性浓度。我们报告了代表201个品种的300个奶酪样品的色胺浓度。16%的样品积累了色胺,在3.20mgkg-1和3012.14mgkg-1之间(平均29.21mgkg-1)。4.7%的奶酪积累的色胺水平高于被描述为潜在毒性的水平。此外,确定了与含色胺奶酪相关的三种技术/代谢/环境概况,以及反映每一个的标志性品种。这些知识对于乳制品行业控制其产品的色胺含量可能很有用。
    Tryptamine is a neuromodulator of the central nervous system. It is also a biogenic amine, formed by the microbial decarboxylation of L-tryptophan. Tryptamine accumulation in cheese has been scarcely examined. No studies are available regarding the factors that could influence its accumulation. Determining the tryptamine content and identifying the factors that influence its accumulation could help in the design of functional tryptamine-enriched cheeses without potentially toxic concentrations being reached. We report the tryptamine concentration of 300 cheese samples representing 201 varieties. 16% of the samples accumulated tryptamine, at between 3.20 mg kg-1 and 3012.14 mg kg-1 (mean of 29.21 mg kg-1). 4.7% of cheeses accumulated tryptamine at higher levels than those described as potentially toxic. Moreover, three technological/metabolic/environmental profiles associated with tryptamine-containing cheese were identified, as well as the hallmark varieties reflecting each. Such knowledge could be useful for the dairy industry to control the tryptamine content of their products.
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  • 文章类型: Journal Article
    背景:jirovecii肺孢子虫是引起急性和致命性肺炎感染的最新出现的危及生命的健康问题。对于患有白血病和免疫缺陷疾病的患者来说,这是罕见的,更具传染性。因此,到目前为止还没有治疗这种感染的方法,需要开发针对这种病原体的任何治疗方法。
    方法:在这项工作中,我们使用了比较蛋白质组学,强大的免疫信息学,和反向疫苗学,通过靶向外膜蛋白和跨膜蛋白来创建针对jirovecii肺孢子虫的mRNA疫苗。使用两种肺孢子虫蛋白质组的比较消减蛋白质组学分析,选择了不同的非冗余肺孢子虫(菌株SE8)蛋白质组。基于亲水性,从该蛋白质组中选择了七个jirovecii肺孢子虫跨膜蛋白,本质,毒力,抗原性,途径相互作用,蛋白质-蛋白质网络分析,和过敏原性。
    目的:反向疫苗学方法用于预测主要组织相容性复合体(MHC)I的免疫原性和抗原表位,II和B细胞从选定的蛋白质的基础上,它们的抗原性,毒性和致敏性。将这些免疫原性表位连接在一起以构建基于mRNA的疫苗。为了增强免疫原性,合适的佐剂,接头(GPGPG,KK,和CYY),和PRDRE序列被使用。
    结果:通过Ramachandran图的预测建模和确认,我们评估了二级和三维结构。掺入佐剂RpfE以增强疫苗构建体的免疫原性(GRAVY指数:-0.271,不稳定性指数:39.53,抗原性:1.0428)。疫苗构建体的理化分析被预测为抗原性,高效,和潜在的疫苗。值得注意的是,在疫苗构建体和TLR-3/TLR-4(-1301.7kcal/mol-1和-1374.7kcal/mol-1)之间观察到强相互作用。
    结论:结果预测基于mRNA的疫苗会引发细胞和体液免疫反应,使疫苗成为对抗jirovecii肺孢子虫的潜在候选物,并且更适合用于体外分析和验证以证明其有效性。
    BACKGROUND: Pneumocystis jirovecii is the most emerging life-threating health problem that causes acute and fatal pneumonia infection. It is rare and more contagious for patients with leukemia and immune-deficiency disorders. Until now there is no treatment available for this infection therefore, it is needed to develop any treatment against this pathogen.
    METHODS: In this work, we used comparative proteomics, robust immune-informatics, and reverse vaccinology to create an mRNA vaccine against Pneumocystis jirovecii by targeting outer and transmembrane proteins. Using a comparative subtractive proteomic analysis of two Pneumocystis jirovecii proteomes, a distinct non-redundant Pneumocystis jirovecii (strain SE8) proteome was chosen. Seven Pneumocystis jirovecii transmembrane proteins were chosen from this proteome based on hydrophilicity, essentiality, virulence, antigenicity, pathway interaction, protein-protein network analysis, and allergenicity.
    OBJECTIVE: The reverse vaccinology approach was used to predict the immunogenic and antigenic epitopes of major histocompatibility complex (MHC) I, II and B-cells from the selected proteins on the basis of their antigenicity, toxicity and allergenicity. These immunogenic epitopes were linked together to construct the mRNA-based vaccine. To enhance the immunogenicity, suitable adjuvant, linkers (GPGPG, KK, and CYY), and PRDRE sequences were used.
    RESULTS: Through predictive modeling and confirmation via the Ramachandran plot, we assessed secondary and 3D structures. The adjuvant RpfE was incorporated to enhance the vaccine construct\'s immunogenicity (GRAVY index: -0.271, instability index: 39.53, antigenicity: 1.0428). The physiochemical profiling of vaccine construct was predicted it an antigenic, efficient, and potential vaccine. Notably, strong interactions were observed between the vaccine construct and TLR-3/TLR-4 (-1301.7 kcal/mol-1 and -1374.7 kcal/mol-1).
    CONCLUSIONS: The results predicted that mRNA-based vaccines trigger a cellular and humoral immune response, making the vaccine potential candidate against Pneumocystis jirovecii and it is more suitable for in-vitro analysis and validation to prove its effectiveness.
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  • 文章类型: Journal Article
    背景:这项研究的目的是确定应纳入功能的关键方面,以构成发育协调障碍(DCD)儿童的干预前评估概况;更具体地说,DCD涉及功能的哪些方面?它们的相对影响是什么?
    方法:进行了系统综述和荟萃分析,Pubmed,WebofScience,搜索了Scopus和Proquest(最新更新:2023年4月,PROSPERO:CRD42023461619)。包括病例对照研究,以确定在不同功能领域中基于现场测试的性能的点估计。评估了偏见的风险,和估计的证据水平。进行了随机效应荟萃分析,以计算功能域的汇总标准化平均差异,并对临床相关子域进行了分组。用I2测定异质性。
    结果:121篇论文被纳入分析。纳入了5923名DCD儿童(59.8%的男孩)和23619名典型发育(TD)儿童(45.8%的男孩)的数据。TD儿童的DCD组的平均(SD)年龄为10.3y(1.2)和9.3y(1.3)。发现了运动性能的适度证据,执行功能,感官加工和感知,DCD患儿认知功能和运动休闲活动受影响。
    结论:两组之间的差异因功能域而异。这强调了DCD儿童中存在的多样性,并为解释该患者组中的异质性提供了理论依据。然而,结果强调了所有这些领域的潜在参与,并呼吁临床医生不仅要检查运动技能困难,还要检查功能的其他方面。结果表明,需要为每个DCD儿童制定个性化的干预前多维评估档案。它还支持临床医生在跨学科团队中发挥的重要作用,以解决DCD儿童遇到的困难。
    BACKGROUND: Purpose of this study was to determine what key aspects of function should be incorporated to make up a pre-intervention assessment profile of a child with Developmental Coordination Disorder (DCD); more specifically, what aspects of functioning are implicated in DCD and what is their relative impact?
    METHODS: A systematic review and meta-analysis were conducted, for which Pubmed, Web of Science, Scopus and Proquest were searched (last update: April 2023, PROSPERO: CRD42023461619). Case-control studies were included to determine point estimates for performances on field-based tests in different domains of functioning. Risk of bias was assessed, and level of evidence estimated. Random-effect meta-analyses were performed to calculate the pooled standardized mean differences for domains of functioning and subgrouping was done for clinically relevant subdomains. Heterogeneity was determined with I2.
    RESULTS: 121 papers were included for analyses. Data of 5 923 children with DCD were included (59.8% boys) and 23 619 Typically Developing (TD) children (45.8% boys). The mean (SD) age of the DCD group was 10.3y (1.2) and 9.3y (1.3) for the TD children. Moderate evidence was found for motor performance, executive functions, sensory processing and perceptions, cognitive functions and sports and leisure activities to be affected in children with DCD.
    CONCLUSIONS: Differences between the two groups varied per domain of functioning. This emphasizes the diversity present within children with DCD and provides a rationale for explaining the heterogeneity in this patient group. Yet, results highlight the potential involvement of all these domains and call for clinicians to be alert not only to examine motor skill difficulties but also other aspects of function. Results indicate the need to develop an individualized pre-intervention multi-dimensional assessment profile for each child with DCD. It also supports the important role that clinicians play in an interdisciplinary team to tackle the difficulties encountered by children with DCD.
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  • 文章类型: Journal Article
    随着下一代测序在软组织病理学中的应用越来越多,特别是在不符合任何世界卫生组织(WHO)类别的肿瘤中,EWSR1融合相关软组织肿瘤的范围已显著扩大。尽管复发性EWSR1::ATF1融合最初仅限于间质肿瘤三联征,包括软组织透明细胞肉瘤,血管瘤样纤维组织细胞瘤和恶性胃肠道神经外胚层肿瘤(MGNET),这个家庭一直在扩大。我们在此描述了4种未分类的腹外软组织(n=3)和骨(n=1)肿瘤,表现出上皮样和圆形细胞形态,并带有EWSR1::ATF1融合。受影响的是3名男性和1名女性,年龄在20-56岁之间。所有原发性肿瘤均为腹外和深层(胸壁,纵隔,三角肌,和咽旁软组织)。它们的大小范围为4.4-7.5厘米(中位数,6.2).一名患者出现体质症状。有(2)或没有(1)新/辅助治疗的手术是治疗。在最后一次随访(8-21个月),2例患者发展为进行性疾病(1例复发;1例远处转移)。这些肿瘤的免疫表型可能会误导EMA的可变表达(3个中的2个),pankeratin(4个中的2个),突触素(2/3),MUC4(1/3),和ALK(3个中的1个)。所有肿瘤均为S100和SOX10阴性。这些观察结果指出,迄今为止,软组织和骨骼的上皮样和圆形细胞肿瘤的存在,由EWSR1::ATF1融合驱动,但与已建立的EWSR1::ATF1相关软组织实体不同。它们的整体形态和免疫表型概括了新兴的EWSR1/FUS::CREB融合相关的腹内上皮样/圆形细胞肿瘤。我们的案例指出了潜在的攻击性临床行为。认识到这种肿瘤类型是强制性的,以描绘任何固有的生物学和/或治疗上的区别,在鉴别诊断中更广为人知的肉瘤,包括硬化性上皮样纤维肉瘤。
    With the increasing use of next generation sequencing in soft tissue pathology, particularly in neoplasms not fitting any World Health Organization (WHO) category, the spectrum of EWSR1 fusion-associated soft tissue neoplasms has been expanding significantly. Although recurrent EWSR1::ATF1 fusions were initially limited to a triad of mesenchymal neoplasms including clear cell sarcoma of soft tissue, angiomatoid fibrous histiocytoma and malignant gastrointestinal neuroectodermal tumor (MGNET), this family has been expanding. We herein describe 4 unclassified extra-abdominal soft tissue (n = 3) and bone (n = 1) neoplasms displaying epithelioid and round cell morphology and carrying an EWSR1::ATF1 fusion. Affected were 3 males and 1 female aged 20-56 years. All primary tumors were extra-abdominal and deep-seated (chest wall, mediastinum, deltoid, and parapharyngeal soft tissue). Their size ranged 4.4-7.5 cm (median, 6.2). One patient presented with constitutional symptoms. Surgery with (2) or without (1) neo/adjuvant therapy was the treatment. At last follow-up (8-21 months), 2 patients developed progressive disease (1 recurrence; 1 distant metastasis). The immunophenotype of these tumors is potentially misleading with variable expression of EMA (2 of 3), pankeratin (2 of 4), synaptophysin (2 of 3), MUC4 (1 of 3), and ALK (1 of 3). All tumors were negative for S100 and SOX10. These observations point to the existence of heretofore under-recognized group of epithelioid and round cell neoplasms of soft tissue and bone, driven by EWSR1::ATF1 fusions, but distinct from established EWSR1::ATF1-associated soft tissue entities. Their overall morphology and immunophenotype recapitulate that of the emerging EWSR1/FUS::CREB fusion associated intra-abdominal epithelioid/round cell neoplasms. Our cases point to a potentially aggressive clinical behavior. Recognizing this tumor type is mandatory to delineate any inherent biological and/or therapeutic distinctness from other, better-known sarcomas in the differential diagnosis including sclerosing epithelioid fibrosarcoma.
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  • 文章类型: Journal Article
    背景:丹参属,唇形科的一员,是具有广泛药用特性的基石属。它具有丰富的代谢物来源,长期以来一直用于治疗不同的疾病。
    目的:由于丹参属的非靶向代谢组学缺乏,这项工作试图研究一个全面的质谱库匹配,计算数据注释,排他性生物标志物,特定的化学型,种内代谢物谱变异,以丹参的五种药用物种为例进行了代谢产物富集研究。
    方法:对每个物种的地上部分进行基于非靶向代谢物的QTRAP液相色谱-串联质谱(LC-MS/MS)分析工作流程。利用MetaboAnalyst6.0和全球天然产物社会分子网络(GNPS)网络平台对代谢物数据集进行了全面和多变量分析。
    结果:非目标方法通过文库匹配和通过自动匹配注释的92个节点,增强了117个代谢物的鉴定能力。一种机器学习算法作为子结构主题建模,MS2LDA,进一步实施以探索代谢物亚结构,导致四个Mass2Motifs。该自动化文库新发现了总共23种代谢物。此外,87个验证的生物标志物的文库匹配,GNPS的58个生物标志物注解,筛选出11种特定的化学型。
    结论:GNPS平台的综合光谱库匹配和自动注释通过工作流程提供了全面的代谢物分析。此外,具有多变量分析的QTRAPLC-MS/MS揭示了有关种间和种内分化水平的可靠信息。代谢物谱分析的严格调查为化学分类学和药物研究提供了大规模的概述和新的见解。
    BACKGROUND: The genus Salvia L., a member of the family Lamiaceae, is a keystone genus with a wide range of medicinal properties. It possesses a rich metabolite source that has long been used to treat different disorders.
    OBJECTIVE: Due to a deficiency of untargeted metabolomic profiling in the genus Salvia, this work attempts to investigate a comprehensive mass spectral library matching, computational data annotations, exclusive biomarkers, specific chemotypes, intraspecific metabolite profile variation, and metabolite enrichment by a case study of five medicinal species of Salvia.
    METHODS: Aerial parts of each species were subjected to QTRAP liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis workflow based on untargeted metabolites. A comprehensive and multivariate analysis was acquired on the metabolite dataset utilizing MetaboAnalyst 6.0 and the Global Natural Products Social Molecular Networking (GNPS) Web Platform.
    RESULTS: The untargeted approach empowered the identification of 117 metabolites by library matching and 92 nodes annotated by automated matching. A machine learning algorithm as substructural topic modeling, MS2LDA, was further implemented to explore the metabolite substructures, resulting in four Mass2Motifs. The automated library newly discovered a total of 23 metabolites. In addition, 87 verified biomarkers of library matching, 58 biomarkers of GNPS annotations, and 11 specific chemotypes were screened.
    CONCLUSIONS: Integrative spectral library matching and automated annotation by the GNPS platform provide comprehensive metabolite profiling through a workflow. In addition, QTRAP LC-MS/MS with multivariate analysis unveiled reliable information about inter and intraspecific levels of differentiation. The rigorous investigation of metabolite profiling presents a large-scale overview and new insights for chemotaxonomy and pharmaceutical studies.
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