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Breast implant associated anaplastic large cell lymphoma (BIA-ALCL) is an emergent rare T cell non-Hodgkin lymphoma arising in association with a breast implant, particularly textured ones. Recent guidelines list cytopathological examination as the first essential step for diagnosis, routinely followed by CD30 immunohistochemistry (IHC) and flow cytometry (FC) for a T cell clone. The majority of BIA-ALCL literature regarding cytopathological evaluation describes morphology based on various preparation methods limited to cytospins and smears with the exception of at least one case report detailing cytomorphological and IHC findings on ThinPrep. This case report details initial diagnosis of BIA-ALCL rendered with CytoLyt prepared ThinPrep and cell block, including the specific antibodies used for IHC. The ThinPrep slide showed numerous singly dispersed large, atypical cells with abundant cytoplasm containing irregular nuclei with dispersed chromatin and prominent nucleoli in a background of macrophages, inflammatory cells and granular debris. TIA-1 and CD30 along with other T-cell markers, including specific antibodies, remains immunoreactive in tissue collected in CytoLyt solution. Cell size reduction, artifactual lymphoid cell aggregation and prominent nucleoli in benign and reactive conditions are among other ThinPrep cellular alterations pathologists should bear in mind. 相似文献
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Kazuko Sakai Takayuki Takahama Mototsugu Shimokawa Koichi Azuma Masayuki Takeda Terufumi Kato Haruko Daga Isamu Okamoto Hiroaki Akamatsu Shunsuke Teraoka Akira Ono Tatsuo Ohira Toshihide Yokoyama Nobuyuki Yamamoto Kazuhiko Nakagawa Kazuto Nishio 《Molecular oncology》2021,15(1):126
The WJOG8815L phase II clinical study involves patients with non‐small cell lung cancer (NSCLC) that harbored the EGFR T790M mutation, which confers resistance to EGFR tyrosine kinase inhibitors (TKIs). The purpose of this study was to assess the predictive value of monitoring EGFR genomic alterations in circulating tumor DNA (ctDNA) from patients with NSCLC that undergo treatment with the third‐generation EGFR‐TKI osimertinib. Plasma samples of 52 patients harboring the EGFR T790M mutation were obtained pretreatment (Pre), on day 1 of treatment cycle 4 (C4) or cycle 9 (C9), and at diagnosis of disease progression or treatment discontinuation (PD/stop). CtDNA was screened for EGFR‐TKI‐sensitizing mutations, the EGFR T790M mutation, and other genomic alterations using the cobas EGFR Mutation Test v2 (cobas), droplet digital PCR (ddPCR), and targeted deep sequencing. Analysis of the sensitizing—and T790M—EGFR mutant fractions (MFs) was used to determine tumor mutational burden. Both MFs were found to decrease during treatment, whereas rebound of the sensitizing EGFR MF was observed at PD/stop, suggesting that osimertinib targeted both T790M mutation‐positive tumors and tumors with sensitizing EGFR mutations. Significant differences in the response rates and progression‐free survival were observed between the sensitizing EGFR MF‐high and sensitizing EGFR MF‐low groups (cutoff: median) at C4. In conclusion, ctDNA monitoring for sensitizing EGFR mutations at C4 is suitable for predicting the treatment outcomes in NSCLC patients receiving osimertinib (Clinical Trial Registration No.: UMIN000022076).
Abbreviations
- CIs
- confidence intervals
- ctDNA
- circulating tumor DNA
- ddPCR
- droplet digital PCR
- EGFR
- epidermal growth factor receptor
- MFs
- mutant fractions
- NGS
- next‐generation sequencing
- NSCLC
- non‐small cell lung cancer
- ORR
- overall response rate
- OS
- overall survival
- PD
- progressive disease
- PFS
- progression‐free survival
- PR
- partial response
- SD
- stable disease
- TKI
- tyrosine kinase inhibitor
5.
《Drug discovery today》2022,27(6):1733-1742
Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action. 相似文献
6.
A Well-Balanced Positivity-Preserving Quasi-Lagrange Moving Mesh DG Method for the Shallow Water Equations 下载免费PDF全文
A high-order, well-balanced, positivity-preserving quasi-Lagrange moving
mesh DG method is presented for the shallow water equations with non-flat bottom
topography. The well-balance property is crucial to the ability of a scheme to simulate perturbation waves over the lake-at-rest steady state such as waves on a lake or
tsunami waves in the deep ocean. The method combines a quasi-Lagrange moving
mesh DG method, a hydrostatic reconstruction technique, and a change of unknown
variables. The strategies in the use of slope limiting, positivity-preservation limiting,
and change of variables to ensure the well-balance and positivity-preserving properties are discussed. Compared to rezoning-type methods, the current method treats
mesh movement continuously in time and has the advantages that it does not need to
interpolate flow variables from the old mesh to the new one and places no constraint
for the choice of a update scheme for the bottom topography on the new mesh. A selection of one- and two-dimensional examples are presented to demonstrate the well-balance property, positivity preservation, and high-order accuracy of the method and
its ability to adapt the mesh according to features in the flow and bottom topography. 相似文献
7.
Keith P. Reber John D. Sivey Matthew Vollmuth Priyansh D. Gujarati 《Journal of labelled compounds & radiopharmaceuticals》2022,65(9):254-263
Parabens are antimicrobial additives found in a wide array of consumer products. However, the halogenated compounds formed from parabens during wastewater disinfection are a potential environmental concern. In order to identify these transformation products and investigate their mechanism of formation, a synthetic route to ethyl parabens labeled with the stable isotope carbon-13 at specific positions within the benzene ring was developed. This efficient two-step procedure starts from commercially available 13C-labeled phenols and involves (1) initial acylation of the phenol via a Houben–Hoesch reaction with trichloroacetonitrile followed by (2) a modified haloform reaction of the resulting trichloromethyl ketone to afford the corresponding 13C-labeled ethyl parabens in 65%–80% overall yield. The scope of the modified haloform reaction was also investigated, allowing for the synthesis of other parabens derived from primary or secondary alcohols, including 13C- and deuterium-labeled esters. In addition, 4-hydroxybenzoic acid can be formed directly from the common trichloromethyl ketone intermediate upon treatment with lithium hydroxide. This protocol complements existing methods for preparing 13C-labeled paraben derivatives and offers the specific advantages of exhibiting complete regioselectivity in the Houben–Hoesch reaction (to form the para-disubstituted product) and avoiding the need for protecting groups in the modified haloform reaction that forms the paraben esters. 相似文献
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9.
Previous event-related potential (ERP) studies show that a salient lateral sound activates the visual cortex more strongly contralateral to the sound, observed as an auditory-evoked contralateral occipital positivity (ACOP). Studies showed that this activation enhances the early cortical processing of co-localized visual stimuli presented after, reflected by better detection rates, better discrimination, and sharper perceived contrast. We replicated the ACOP, using earphones, and tested whether auditory cuing can influence temporal order judgments (TOJ) for two visual stimuli (horizontal arrangement) as well as if the ACOP would predict the amplitude of this influence. A lateral salient sound was followed, after 150 or 630 ms, by the visual presentation of a pair of disks, one in left and one in right hemifield, with variable SOA. The TOJ task was to indicate which disk appeared first or which disk appeared second (controlling for response bias). We observed an ACOP at posterior electrode sites and confirmed our hypothesis that the lateral sound influenced TOJ by accelerating the perception of the disk presented on the cued side, even though the sound was irrelevant to the task. Furthermore, the ACOP amplitude was correlated to this visual perceptual change, indicating that a larger change in brain activity was associated with a faster processing of co-localized visual stimuli. 相似文献
10.
本文旨在探讨影响新疆低温乳消费市场的限制性因素及相应的对策。调研通过网络调查问卷和实地调研走访相结合的方式,从乳制品消费结构、消费能力,低温奶认知、低温奶购买意愿、购买便利性、购买偏好及健康饮奶习惯等方面分析影响新疆低温乳消费市场的因素。结果显示:32.93%的消费者不了解乳中生物活性物质(如乳铁蛋白)的热敏性,39.97%的消费者不能区分各类液态乳产品,47.64%的消费者有煮沸巴氏杀菌乳后饮用的习惯;43.21%的消费者"担心未消毒彻底,存在细菌",36.30%的消费者认为"加热后可增加营养价值和香味";72.64%的消费者曾感到"购买巴氏杀菌乳不方便";54.85%的消费者认为本地品牌"更新鲜、更健康"。结果启示:本地乳企应该充分利用在当地的良好品牌信誉度和牧场资源,尽早布局低温奶市场,通过研发高品质低温乳制品、普及科学饮奶理念、改善冷链物流能力、完善购物体验和精细化服务能力等手段,提高生产竞争力,抵御进口乳制品和常温乳对当地乳品市场的冲击,占领区域低温奶消费市场。 相似文献