LOT

LOT
  • 文章类型: Review
    2022年WHO泌尿和男性生殖器肿瘤分类引入了几种新型肾脏实体,表现出具有特定突变背景的嗜酸性粒细胞/嗜酸性细胞特征。因此,分子技术,例如下一代测序(NGS),变得更常用于他们的评估。我们研究了12例肾脏低度嗜酸性细胞肿瘤(LOT)(来自11例患者),在一组210个嗜酸性粒细胞/嗜酸性细胞肾肿瘤中发现,在2019年10月至2023年5月期间在我们机构诊断,在此期间占所有嗜酸性粒细胞/嗜酸性细胞肾肿瘤的5.7%(12/210)。我们回顾了他们的临床病理,组织学,和免疫组织化学特征,以及它们的突变特征。我们还回顾了有关LOT的NGS衍生数据的文献,通过选择根据最初提出的标准进行LOT诊断的论文。中位年龄为65岁(平均:63.5;范围43-79),中位肿瘤大小为2.0cm(平均:2.2;范围:0.9-3.1)。所有肿瘤均为PAX8、CK7和GATA3阳性,CD117/KIT阴性或局灶性阳性。我们发现以下基因突变:MTOR((6/11),54.5%)),TSC1((2/11),18.2%)),1名同时患有NOTCH1和NOTCH4((1/11),9.1%))。在2/11(18.2%)患者中发现了野生型状态,并且一个肿瘤无法分析。对包括79个LOT的8项先前研究的回顾显示,调节哺乳动物雷帕霉素靶蛋白(mTOR)途径的基因中经常发生突变:MTOR(32/79(40.5%)),TSC1(21/79(26.6%)),和TSC2(9/79(11.4%))。其他突变基因包括PIK3CA,NF2和PTEN,通常不知道会影响mTOR途径,但可能充当上游和下游效应物。我们的研究表明,当应用适当的诊断标准时,LOT在常规实践中得到越来越多的诊断。我们还证实mTOR通路主要通过MTOR与该肿瘤的发病机制密切相关。TCS1和TSC2突变,但是其他基因也可能参与该途径的激活,尤其是在没有“规范”突变的LOT中。
    The 2022 WHO classification of urinary and male genital tumors introduced several novel kidney entities exhibiting eosinophilic/oncocytic features with specific mutational backgrounds. Thus, molecular techniques, such as next-generation sequencing (NGS), became more commonly used for their evaluation. We studied 12 low-grade oncocytic tumors (LOT) of the kidney (from 11 patients), identified in a cohort of 210 eosinophilic/oncocytic renal tumors, diagnosed in our institution between October 2019 and May 2023, which represented 5.7% (12/210) of all eosinophilic/oncocytic renal tumors during this period. We reviewed their clinicopathologic, histologic, and immunohistochemical features, as well as their mutational profiles. We also reviewed the literature on NGS-derived data of LOT, by selecting papers in which LOT diagnosis was rendered according to the criteria proposed initially. Median age was 65 years (mean: 63.5; range 43-79) and median tumor size was 2.0 cm (mean: 2.2; range: 0.9-3.1). All tumors were positive for PAX8, CK7, and GATA3, and negative or focally positive for CD117/KIT. We found the following gene mutations: MTOR ((6/11), 54.5%)), TSC1 ((2/11), 18.2%)), and 1 had both NOTCH1 and NOTCH4 ((1/11), 9.1%)). Wild-type status was found in 2/11 (18.2%) patients and one tumor was not analyzable. A review of 8 previous studies that included 79 LOTs revealed frequent mutations in the genes that regulate the mammalian target of rapamycin (mTOR) pathway: MTOR (32/79 (40.5%)), TSC1 (21/79 (26.6%)), and TSC2 (9/79 (11.4%)). Other mutated genes included PIK3CA, NF2, and PTEN, not typically known to affect the mTOR pathway, but potentially acting as upstream and downstream effectors. Our study shows that LOT is increasingly diagnosed in routine practice when applying the appropriate diagnostic criteria. We also confirm that the mTOR pathway is strongly implicated in the pathogenesis of this tumor mainly through MTOR, TCS1, and TSC2 mutations, but other genes could also be involved in the pathway activation, especially in LOTs without \"canonical\" mutations.
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  • 文章类型: Journal Article
    嗜酸细胞肾肿瘤的鉴别诊断范围从良性实体到更具侵袭性的肾细胞癌(RCC)。最近的工作描述了一种临时的肾嗜酸细胞肿瘤,即低度嗜酸细胞肿瘤(LOT),这表明与嗜酸细胞瘤和发色细胞RCC重叠的形态学特征,但也具有独特的免疫特征(即,KRT7弥漫性阳性,KIT阴性)和mTOR途径基因改变的发生率很高(80%至100%)。鉴于嗜酸细胞肿瘤的诊断重叠,我们寻找mTOR通路突变与LOT之间的一致性.对30例低级别肾嗜酸细胞肿瘤进行了KRT7和KIT的组织学检查和免疫组织化学检查。肿瘤被归类为“确定性”(例如,LOT)对于实体瘤,嵌套或模糊的肾小管生长和弥漫性KRT7染色和阴性KIT,如果形态学和/或免疫染色不能完全支持明确的LOT诊断,或“不确定”。下一代测序是在没有任何诊断知识的情况下进行的,并在80%(12/15)的决定性肿瘤中鉴定出mTOR通路突变,与不确定组的7%(1/15)相比。1个确定的肿瘤被重新分类为乳头状RCC(MTOR突变阴性),6个不确定的肿瘤被证实为嗜酸细胞瘤(N=4)。具有相反极性的透明细胞RCC或乳头状RCC,分别。总的来说,形态的整合,免疫组织化学,和分子数据使70%的肿瘤(总共30个中的21个)最终得到了明确的诊断,与高一致性(93%)的LOT,特别是在确定组;其余9个肿瘤(30%)被归类为肾嗜酸细胞肿瘤,未指定。
    The differential diagnosis for oncocytic renal tumors spans the spectrum from benign entities to more aggressive renal cell carcinomas (RCC). Recent work has characterized a provisional renal oncocytic neoplasm, namely the low-grade oncocytic tumor (LOT), which demonstrates overlapping morphologic features with oncocytoma and chromophobe RCC, but also has a unique immunoprofile (ie, diffusely positive for KRT7, negative for KIT) and a high rate (80% to 100%) of mTOR pathway gene alterations. Given the diagnostic overlap among oncocytic tumors, we looked for concordance between mTOR pathway mutations and LOT. Thirty low-grade renal oncocytic neoplasms underwent histologic review and immunohistochemistry for KRT7 and KIT. Tumors were classified as \"determinate\" (eg, LOT) for tumors with solid, nested or vaguely tubular growth and diffuse KRT7 staining and negative KIT, or \"indeterminate\" if the morphology and/or immunostains did not fully support a definitive LOT diagnosis. Next-generation sequencing was performed without any knowledge of the diagnoses, and identified mTOR pathway mutations in 80% (12/15) of the determinate tumors, compared with 7% (1/15) in the indeterminate group. One determinate tumor was reclassified as papillary RCC (MTOR mutation negative) and 6 indeterminate tumors were confirmed to be oncocytoma (N = 4), clear cell RCC or papillary RCC with reverse polarity, respectively. Overall, integration of morphology, immunohistochemistry, and molecular data enabled a final definitive diagnosis for 70% of tumors (21 of the total 30), with a high concordance (93%) for LOT specifically in the determinate group; the remaining 9 tumors (30%) were classified as renal oncocytic neoplasm, not otherwise specified.
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  • 文章类型: Journal Article
    许多最近描述的肾肿瘤实体具有嗜酸性粒细胞/嗜酸性细胞形态,一些坚实的建筑增长模式,并倾向于呈现为低阶段肿瘤。绝大多数此类肿瘤遵循非侵袭性临床行为。在这次审查中,我们讨论形态学,免疫组织化学,和与TSC/mTOR通路突变相关的三个最新的新的/新出现的肾脏实体的分子遗传学谱。这些是嗜酸性粒细胞实性和囊性肾细胞癌,嗜酸性空泡状肿瘤,和低度嗜酸细胞肿瘤,属于一组异质性的肾肿瘤,展示了大部分坚实的建筑,嗜酸性粒细胞/嗜酸性细胞细胞质,肾嗜酸细胞瘤和嫌色细胞肾细胞癌的形态学和免疫组织化学特征重叠。所有三种肿瘤还具有mTORC1途径突变的分子遗传背景(TSC1/TSC2/mTOR/RHEB)。尽管有共同的遗传背景,具有TSC/mTOR突变的肿瘤似乎代表了一组不同的肾肿瘤.
    A number of recently described renal tumor entities share an eosinophilic/oncocytic morphology, somewhat solid architectural growth pattern, and tendency to present as low-stage tumors. The vast majority of such tumors follow a non-aggressive clinical behavior. In this review, we discuss the morphological, immunohistochemical, and molecular genetic profiles of the three most recent novel/emerging renal entities associated with TSC/mTOR pathway mutations. These are eosinophilic solid and cystic renal cell carcinoma, eosinophilic vacuolated tumors, and low-grade oncocytic tumors, which belong to a heterogeneous group of renal tumors, demonstrating mostly solid architecture, eosinophilic/oncocytic cytoplasm, and overlapping morphological and immunohistochemical features between renal oncocytoma and chromophobe renal cell carcinoma. All three tumors also share a molecular genetic background with mutations in the mTORC1 pathway (TSC1/TSC2/mTOR/RHEB). Despite the common genetic background, it appears that the tumors with TSC/mTOR mutations represent a diverse group of distinct renal neoplasms.
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  • 文章类型: Journal Article
    在保护心理健康的努力中应该包括乐观,因为它可以提供认知资源。乐观还可以减少与精神障碍的发生和复发相关的压力生活事件的负面影响。这项研究旨在评估基于社区的成年人样本中精神障碍与乐观之间的关系。这项研究是在通过随机抽样确定的三个半农村集群中进行的。根据自变量调整后,使用Logistic模型计算每种精神疾病与生活取向测验(LOT)之间的关系.总的来说,24.5%的参与者被分为至少一个精神障碍组,20.8%,3.5%,0.3%有一个,两个,或者三种精神障碍,分别。从初级保健评估精神障碍模块诊断的患者的中位LOT评分较低,除了躯体形式障碍模块。保持乐观的观点可将情绪障碍的风险降低0.86(OR;95%CI,0.81-0.91),焦虑症0.89(0.83-0.97),和可能的酒精滥用0.83(0.74-0.93)次调整后。应详细研究乐观观点在应对精神问题中的作用。
    Optimism should be included in efforts to protect mental health, as it can provide cognitive resources. Optimism also reduces the negative effects of stressful life events associated with the occurrence and recurrence of mental disorders. This study aimed to evaluate the relationship between mental disorders and optimism in a community-based sample of adults. The study was conducted in three semi-rural clusters determined via random sampling. After adjustment in accordance with the independent variables, the relationship between each psychiatric disorder and Life Orientation Test (LOT) was calculated using logistic models. Overall, 24.5% of participants were categorized into at least one mental disorder group, with 20.8%, 3.5%, and 0.3% having one, two, or three mental disorders, respectively. The median LOT score was lower in patients diagnosed from the Primary Care Evaluation of Mental Disorders modules, except for the somatoform disorder module. Maintaining an optimistic view reduced the risk of mood disorders by 0.86 (OR; 95% CI, 0.81-0.91), anxiety disorders by 0.89 (0.83-0.97), and probable alcohol abuse by 0.83 (0.74-0.93) times after adjustment. The role of an optimistic view in coping with mental problems should be investigated in detail.
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  • 文章类型: Evaluation Study
    由于生产错误的最终风险,快速即时(POC)测试的潜力一直受到质疑。因此,目的是评估商业POC侧流测试的两个单独的生产批次,用于检测针对SARS-CoV-2刺突蛋白(S1)的IgM和IgG。对照样本包括从生物样本库中收集的确诊SARS-CoV-2感染个体的血清和COVID-19前阴性血清。血清中抗S1IgM/IgG的存在通过内部基于Luminex的血清学检测(COVID-19SIA)得到证实。100个样品被验证为抗S1IgG阳性,而74个样品为抗S1IgM阳性。两百个样品被验证为抗SlIgM/IgG阴性。对于两批POC测试,IgM的敏感性分别为93.2%和87.8%,IgG的敏感性分别为93.0%和100%。IgM的特异性为100%,IgG的特异性为99.5%。IgM阳性预测值为100%,IgG阳性预测值为98.9%和99.0%。IgM阴性预测值分别为97.6%和95.7%,IgG为96.6%和100%。评估的POC测试适用于评估抗SARS-CoV-2S1IgM和IgG,作为个人水平上以前病毒暴露的量度。鼓励对单独的快速POC测试进行外部验证,以确保在引入市场之前具有高灵敏度。
    The potential of rapid point-of-care (POC) tests has been subject of doubt due to an eventual risk of production errors. The aim was therefore to evaluate the two separate production lots of a commercial POC lateral flow test, intended for the detection of IgM and IgG against the SARS-CoV-2 spike protein (S1). Control samples consisted of serum from individuals with confirmed SARS-CoV-2 infection and pre-COVID-19 negative sera gathered from a biobank. The presence of anti-S1 IgM/IgG in the sera was verified by an in-house Luminex-based serological assay (COVID-19 SIA). One hundred samples were verified as positive for anti-S1 IgG and 74 for anti-S1 IgM. Two hundred samples were verified as negative for anti-S1 IgM/IgG. For the two lots of the POC-test, the sensitivities were 93.2% and 87.8% for IgM and 93.0% and 100% for IgG. The specificities were 100% for IgM and 99.5% for IgG. The positive predictive value was 100% for IgM and 98.9% and 99.0% for IgG. The negative predictive value was 97.6% and 95.7% for IgM, and 96.6% and 100% for IgG. The evaluated POC-test is suitable to assess anti-SARS-CoV-2 S1 IgM and IgG, as a measure of previous virus exposure on an individual level. The external validation of separate lots of rapid POC-tests is encouraged to ensure high sensitivity before market introduction.
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  • 文章类型: Journal Article
    Flooding is a simple yet reliable way of discovering resources in wireless ad hoc networks such as mobile ad hoc networks (MANETs), ad hoc sensors, and recently, IoT networks. However, its operation is resource-intensive, especially in densely populated networks. Several approaches can be found in the literature to reduce the impact of flooding. Many of these approaches follow a repeal-based operation, chasing and stopping further propagation of flooding packets once the target is found. However, repeal-based protocols might end up transmitting even more packets than the original flooding. This work characterizes a maximum repeal-flooding boundary beyond which it is counterproductive to chase the original flooding. We present the Flood and Contain (F&C) algorithm, a method that can quickly establish the maximum repeal-flooding boundary for each node while making no assumptions on the underlying network. F&C\'s packet overhead increases linearly with the hop count up to the maximum repeal-flooding boundary, in which case there is no attempt to chase the original flooding. In this latter case, F&C generates only as many packets as the original flooding. Simulations show that, on average, F&C reduces the total flooding overhead (compared to traditional flooding) up to 35 percent once considering all possible destinations, with only a slight increase in resource discovery latency, and it outperforms all other repeal-based protocols, particularly for longer routes.
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  • 文章类型: Journal Article
    肾肿瘤是最异质性和多样性的肿瘤之一。该领域的不断进步反映在新肿瘤实体的出现和对不断扩大的形态学的认识上,免疫组织化学,分子,肾脏肿瘤的流行病学和临床谱。2016年世界卫生组织(WHO)对肾细胞肿瘤进行分类后的最新进展为一些新兴实体提供了新的证据。如间变性淋巴瘤激酶重排相关RCC(ALK-RCC),已作为临时实体列入世卫组织2016年分类。此外,几个以前无法识别的实体,目前不包括在世卫组织的分类中,还介绍了,如嗜酸性粒细胞实性和囊性肾细胞癌(ESCRCC),肾脏低度嗜酸细胞肾肿瘤(LOT)和高度嗜酸细胞肾肿瘤(HOT)。尽管病理学家在这些新肿瘤实体的识别和分类中起着至关重要的作用,并且处于表征它们的努力的最前沿,临床医生对这些实体的认识和接受度最终将转化为更细致的管理和改善个体患者的预后.在这次审查中,我们总结了这些新兴肾脏实体的现有知识和新数据,目的是促进他们增加的诊断识别和更好的表征,并促进进一步的研究,有望在未来的肾脏肿瘤分类中获得正式的认可和考虑。
    Kidney neoplasms are among the most heterogeneous and diverse tumors. Continuous advancement of this field is reflected in the emergence of new tumour entities and an increased recognition of the expanding morphologic, immunohistochemical, molecular, epidemiologic and clinical spectrum of renal tumors. Most recent advances after the 2016 World Health Organization (WHO) classification of renal cell tumors have provided new evidence on some emerging entities, such as anaplastic lymphoma kinase rearrangement-associated RCC (ALK-RCC), which has already been included in the WHO 2016 classification as a provisional entity. Additionally, several previously unrecognized entities, not currently included in the WHO classification, have also been introduced, such as eosinophilic solid and cystic renal cell carcinoma (ESC RCC), low-grade oncocytic renal tumor (LOT) and high-grade oncocytic renal tumor (HOT) of kidney. Although pathologists play a crucial role in the recognition and classification of these new tumor entities and are at the forefront of the efforts to characterize them, the awareness and the acceptance of these entities among clinicians will ultimately translate into more nuanced management and improved prognostication for individual patients. In this review, we summarise the current knowledge and the novel data on these emerging renal entities, with an aim to promote their increased diagnostic recognition and better characterization, and to facilitate further studies that will hopefully lead to their formal recognition and consideration in the future classifications of kidney tumors.
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  • 文章类型: Journal Article
    Within the context of the Internet of Things (IoT) and the Location of Things (LoT) service, this paper presents an interactive tool to quantitatively analyze the performance of cooperative localization techniques for wireless sensor networks (WSNs). In these types of algorithms, nodes help each other determine their location based on some signal metrics such as time of arrival (TOA), received signal strength (RSS), or a fusion of them. The developed tool is intended to provide researchers and designers a fast way to measure the performance of localization algorithms considering specific network topologies. Using TOA or RSS models, the Crámer-Rao lower bound (CRLB) has been implemented within the tool. This lower bound can be used as a benchmark for testing a particular algorithm for specific channel characteristics and WSN topology, which allows determination if the necessary accuracy for a specific application is possible. Furthermore, the tool allows us to consider independent characteristics for each node in the WSN. This feature allows the avoidance of the typical \"disk graph model,\" which is usually applied to test cooperative localization algorithms. The tool allows us to run Monte-Carlo simulations and generate statistical reports. A set of basic illustrative examples are described comparing the performance of different localization algorithms and showing the capabilities of the presented tool.
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  • 文章类型: Journal Article
    Early telencephalic development involves the migration of diverse cell types that can be identified by specific molecular markers. Most prominent among them are Cajal-Retzius (CR) cells that emanate mainly from the cortical hem and to a lesser extent from rostrolateral, septal and caudo-medial regions. One additional territory proposed to give rise to CR cells that migrate dorsally into the neocortex lies at the ventral pallium, although contradictory results question this notion. With the use of a cell-permeable fluorescent tracer in cultured embryos, we identified novel migratory paths of putative CR cells and other populations that originate from the rostrolateral telencephalon at its olfactory region. Moreover, extensive labeling on the lateral telencephalon along its rostro-caudal extent failed to reveal a dorsally-migrating CR cell population from the ventral pallium at the stages analyzed. Hence, this work reveals a novel olfactory CR cell migration and supports the idea that the ventral pallium, where diverse types of neurons converge, does not actually generate CR cells.
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  • 文章类型: Journal Article
    血液成分规格的控制是在欧洲由欧盟委员会指令和在美国由AABB标准推广的要求。在相关文献中建议使用统计过程控制方法,包括EDQM准则。控制可靠性取决于采样。然而,正确的抽样方法似乎没有系统地应用。通常,取样旨在唯一地符合所生产血液成分的1%规格。然而,从纯粹的统计角度来看,可以认为该模型与一致的抽样技术无关。这可能是检测异常模式和确保生产具有产生不合格组件的非显著概率的严重限制。本文讨论了血液机构中正在发生的事情。提出了三种统计方法:简单随机抽样,基于有限总体的比例进行抽样,并根据检验水平进行抽样。经验结果表明,这些模型在血液机构中是可行的,有助于采样的鲁棒性和相关的统计过程控制决策,以达到建议的目的。
    The control of blood components specifications is a requirement generalized in Europe by the European Commission Directives and in the US by the AABB standards. The use of a statistical process control methodology is recommended in the related literature, including the EDQM guideline. The control reliability is dependent of the sampling. However, a correct sampling methodology seems not to be systematically applied. Commonly, the sampling is intended to comply uniquely with the 1% specification to the produced blood components. Nevertheless, on a purely statistical viewpoint, this model could be argued not to be related to a consistent sampling technique. This could be a severe limitation to detect abnormal patterns and to assure that the production has a non-significant probability of producing nonconforming components. This article discusses what is happening in blood establishments. Three statistical methodologies are proposed: simple random sampling, sampling based on the proportion of a finite population, and sampling based on the inspection level. The empirical results demonstrate that these models are practicable in blood establishments contributing to the robustness of sampling and related statistical process control decisions for the purpose they are suggested for.
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