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Shafqat R. Chaudhry Ilana S. Lendvai Sajjad Muhammad Philipp Westhofen Johannes Kruppenbacher Lukas Scheef Henning Boecker Dirk Scheele Rene Hurlemann Thomas M. Kinfe 《Brain stimulation》2019,12(3):643-651
Objective
To assay peripheral inter-ictal cytokine serum levels and possible relations with non-invasive vagus nerve stimulation (nVNS) responsiveness in migraineurs.Methods
This double-blinded, sham-controlled study enrolled 48 subjects and measured headache severity, frequency [headache days/month, number of total and mild/moderate/severe classified attacks/month], functional state [sleep, mood, body weight, migraine-associated disability] and serum levels of inflammatory markers [inter-ictal] using enzyme-linked immunoassays at baseline and after 2 months of adjunctive nVNS compared to sham stimulation and suitably matched controls.Results
No significant differences were observed at baseline and after 2 months for headache severity, total attacks/month, headache days/month and functional outcome [sleep, mood, disability] between verum and sham nVNS. However, the number of severe attacks/month significantly decreased in the verum nVNS group and circulating pro-inflammatory IL-1β was elevated significantly in the sham group compared to nVNS. Levels of anti-inflammatory IL-10 were significantly higher at baseline in both groups compared to healthy controls, but not at 2 months follow-up [p?<?0.05]. Concentrations of high-mobility group box-1 (HMGB-1), IL-6, tumor-necrosis factor-α (TNF-α), leptin, adiponectin, ghrelin remained unchanged [p?>?0.05]. No severe device-/stimulation-related adverse events occurred.Conclusion
2 months of adjunctive cervical nVNS significantly declined the number of severe attacks/month. Pro-inflammatory IL-1β plasma levels [inter-ictal] were higher in sham-treated migraine patients compared to verum nVNS. However, pro- [IL-6, HMGB-1, TNF-α, leptin] and anti-inflammatory [IL-10, adiponectin, ghrelin] mediators did not differ statistically. Profiling of neuroinflammatory circuits in migraine to predict nVNS responsiveness remains an experimental approach, which may be biased by pre-analytic variables warranting large-scale biobank-based systematic investigations [omics]. 相似文献106.
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《Journal of thoracic oncology》2021,16(10):1694-1704
IntroductionIn patients with NSCLC, the prognostic significance of the tumor microenvironment (TME) immune composition has been revealed using single- or dual-marker staining on sequential tissue sections. Although these studies reveal that relative abundance and localization of immune cells are important parameters, deeper analyses of the NSCLC TME are necessary to refine the potential application of these findings to clinical care. Currently, the complex spatial relationships between cells of the NSCLC TME and potential drivers contributing to its immunologic composition remain unknown.MethodsWe used multispectral quantitative imaging on the lung adenocarcinoma TME in 153 patients with resected tumors. On a single slide per patient, we evaluated the TME with markers for CD3, CD8, CD14, CD19, major histocompatibility complex II (MHCII), cytokeratin, and 4′,6-diamidino-2-phenylindole (DAPI). Image analysis, including tissue segmentation, phenotyping, and spatial localization, was performed.ResultsSpecimens wherein greater than or equal to 5% of lung cancer cells expressed MHCII (MHCIIhi TME) had increased levels of CD4+ and CD8+ T cells and CD14+ cell infiltration. In the MHCIIhi TME, the immune infiltrate was closer to cancer cells and expressed an activated phenotype. Morphologic image analysis revealed cancer cells in the MHCIIhi TME more frequently interfaced with CD4+ and CD8+ T cells. Patients with an MHCIIhi TME experienced improved overall survival (p = 0.046).ConclusionsLung cancer cell-specific expression of MHCII associates with levels of immune cell infiltration, spatial localization, and activation status within the TME. This suggests that cancer cell-specific expression of MHCII may represent a biomarker for the immune system’s recognition and activation against the tumor. 相似文献
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Toshiro Hara Rony Chanoch-Myers Nathan D. Mathewson Chad Myskiw Lyla Atta Lillian Bussema Stephen W. Eichhorn Alissa C. Greenwald Gabriela S. Kinker Christopher Rodman L. Nicolas Gonzalez Castro Hiroaki Wakimoto Orit Rozenblatt-Rosen Xiaowei Zhuang Jean Fan Tony Hunter Inder M. Verma Kai W. Wucherpfennig Itay Tirosh 《Cancer cell》2021,39(6):779-792.e11
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A typical time series in functional magnetic resonance imaging (fMRI) exhibits autocorrelation, that is, the samples of the time series are dependent. In addition, temporal filtering, one of the crucial steps in preprocessing of functional magnetic resonance images, induces its own autocorrelation. While performing connectivity analysis in fMRI, the impact of the autocorrelation is largely ignored. Recently, autocorrelation has been addressed by variance correction approaches, which are sensitive to the sampling rate. In this article, we aim to investigate the impact of the sampling rate on the variance correction approaches. Toward this end, we first derived a generalized expression for the variance of the sample Pearson correlation coefficient (SPCC) in terms of the sampling rate and the filter cutoff frequency, in addition to the autocorrelation and cross‐covariance functions of the time series. Through simulations, we illustrated the importance of the variance correction for a fixed sampling rate. Using the real resting state fMRI data sets, we demonstrated that the data sets with higher sampling rates were more prone to false positives, in agreement with the existing empirical reports. We further demonstrated with single subject results that for the data sets with higher sampling rates, the variance correction strategy restored the integrity of true connectivity. 相似文献
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目的:探讨3.0 T磁敏感加权成像(susceptibility weighted imaging,SWI)中"燕尾征"缺失在帕金森病(Parkinson's dis-ease,PD)的诊断价值并分析黑质小体-1 (nigrosome-1)可视化与PD患者临床资料的相关性.方法:收集2017年9月至2019年11月于重庆医科大学附属第一医院神经内科住院的50例PD患者及年龄、性别与之匹配的57例非PD患者.所有受试者均接受3.0 T头颅SWI检查.在获得的SWI图像上,由2名临床医师采用盲法独立对双侧"燕尾征"进行评估.一侧"燕尾征"缺失即判定为PD.计算"燕尾征"缺失诊断PD的灵敏度、特异度、预测值和准确度,并分析nigrosome-1可视化与PD患者临床资料的相关性.结果:以临床诊断作为金标准,45例PD患者判断正确,评估者之间的一致性很高(k=0.963,P=0.000)."燕尾征"缺失诊断PD的灵敏度为90.0%,特异度为91.2%,阳性预测值为90.0%,阴性预测值为91.2%,准确度为90.7%.44例PD患者临床症状不对称,其中32例患者nigrosome-1可视化不对称.PD患者nigrosome-1可视化偏侧和临床症状偏侧比较差异无统计学意义(x2=5.756,P=0.056).11例PD患者双侧nigrosome-1全部缺失,纳入全部缺失组,其余PD患者为非全部缺失组.全部缺失组和非全部缺失组患者的汉密尔顿抑郁量表评分差异有统计学意义(U=126.500,P=-0.038),而病程、帕金森病统一评定量表第Ⅲ部分、改良Hoehn-Yahr(H-Y)分级、简易智能状态量表和蒙特利尔认知评估量表评分差异均无统计学意义(P=0.768、0.140、0.839、0.054、0.067).结论:"燕尾征"缺失诊断PD的准确率较高,缺失程度可能与PD患者的抑郁程度有关,对PD的诊断有一定参考价值. 相似文献