Phase 1/2 clinical trial of COVID-19 vaccine in Japanese participants: A report of interim findings

We initiated a randomized, placebo-controlled, phase 1/2 trial to evaluate the safety and immunogenicity of the S-268019-b recombinant protein vaccine, scheduled as 2 intramuscular injections given 21 days apart, in 60 randomized healthy Japanese adults. We evaluated 2 regimens of the S-910823 antigen (5 μg [n = 24] and 10 μg [n = 24]) with an oil-in-water emulsion formulation and compared against placebo (n = 12). Reactogenicity was mild in most participants. No serious adverse events were noted. For both regimens, vaccination resulted in robust IgG and neutralizing antibody production at days 36 and 50 and predominant T-helper 1-mediated immune reaction, as evident through antigen-specific polyfunctional CD4+ T-cell responses with IFN-γ, IL-2, and IL-4 production on spike protein peptides stimulation. Based on the interim analysis, the S-268019-b vaccine is safe, produces neutralizing antibodies titer comparable with that in convalescent serum from COVID-19-recovered patients. However, further evaluation of the vaccine in a large clinical trial is warranted.     

Cancer Stem Cells and Circulatory Tumor Cells Promote Breast Cancer Metastasis

Breast cancer (BC) is a highly metastatic, pathological cancer that significantly affects women worldwide. The mortality rate of BC is related to its heterogeneity, aggressive phenotype, and metastasis. Recent studies have highlighted that the tumor microenvironment (TME) is critical for the interplay between metastasis mediators in BC. BC stem cells, tumor-derived exosomes, circulatory tumor cells (CTCs), and signaling pathways dynamically remodel the TME and promote metastasis. This review examines the cellular and molecular mechanisms governing the epithelial to mesenchymal transition (EMT) that facilitate metastasis. This review also discusses the role of cancer stem cells (CSCs), tumor-derived exosomes, and CTs in promoting BC metastasis. Furthermore, the review emphasizes major signaling pathways that mediate metastasis in BC. Finally, the interplay among CSCs, exosomes, and CTCs in mediating metastasis have been highlighted. Therefore, understanding the molecular cues that mediate the association of CSCs, exosomes, and CTCs in TME helps to optimize systemic therapy to target metastatic BC.     

Inflamación y adecuación de la hemodiálisis: ¿están los niveles de proteína C reactiva influidos por la dosis de diálisis recibida?

IntroductionChronic inflammation and the underlying cardiovascular comorbidity are still current problems in chronic hemodialysis patients. There are few studies comparing the “dialysis dose” (Kt/V) with the degree of inflammation in the patient. Our main objective was to determine whether there is a relationship between serum C-reactive protein (CRP) levels and the Kt/V using ionic dialysance.MethodsMulticenter cross-sectional study. A total of 536 prevalent chronic hemodialysis patients were included. CRP levels, neutrophil-lymphocyte ratio and platelet-lymphocyte ratio were collected. Kt was obtained by ionic dialysance and urea distribution volume was calculated from the Watson's formula. The sample was divided into 2 groups, taking the median CRP as the cut-off point. Dialysis adequacy obtained in each group was compared. Finally, a logistic regression model was carried out to determine the variables with the greatest influence.ResultsMedian CRP was 4.10 mg/L (q25-q75: 1.67-10) and mean Kt/V was 1.48 ± 0.308. Kt/V was lower in the patients included in the high inflammation group (P = .01). In the multivariate logistic regression, the “high” levels of CRP were directly correlated with the Log neutrophil-lymphocyte ratio (P < .001) and inversely proportional with serum albumin values (P = .014), Kt/V (P = .037) and serum iron (P < .001).ConclusionThe poorer adequacy in terms of dialysis doses (lower Kt/V values) may contribute to a higher degree of inflammation in chronic hemodialysis patients.     

Assessment of a novel deep learning-based marker-less motion capture system for gait study

BackgroundMarker-less systems based on digital video cameras and deep learning for gait analysis could have a deep impact in clinical routine. A recently developed system has shown promising results in terms of joint center position but has not been yet evaluated in terms of gait outcomes.Research questionHow does this novel marker-less system compare to a marker-based reference system in terms of clinically relevant gait parameters?MethodsThe deep learning method behind the developed marker-less system was trained on a dedicated dataset consisting of forty-one asymptomatic and pathological subjects each performing ten walking trials. The system could estimate the three-dimensional position of seventeen joint centers or keypoints (e.g., neck, shoulders, hip, knee, and ankles). We evaluated the marker-less system against a marker-based system in terms of differences in joint position (Euclidean distance), detection of gait events (e.g., heel strike and toe-off), spatiotemporal parameters (e.g., step length, time), kinematic parameters (e.g., hip and knee extension-flexion), and inter-trial reliability for kinematic parameters.ResultsThe marker-less system was able to estimate the three-dimensional position of joint centers with a mean difference of 13.1 mm (SD = 10.2 mm). 99% of the estimated gait events were estimated within 10 ms of the corresponding reference values. Estimated spatiotemporal parameters showed zero bias. The mean and standard deviation of the differences of the estimated kinematic parameters varied by parameter (for example, the mean and standard deviation for knee extension flexion angle were −3.0° and 2.7°). Inter-trial reliability of the measured parameters was similar to that of the marker-based references.SignificanceThe developed marker-less system can measure the spatiotemporal parameters within the range of the minimum detectable changes obtained using the marker-based reference system. Moreover, except for hip extension flexion, the system showed promising results in terms of several kinematic parameters.     

Multiscale quantification of morphological heterogeneity with creation of a predictor of longer survival in glioblastoma

Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered.     

胶质瘤复发与放射性脑损伤的MRI鉴别诊断探讨

目的:讨论胶质瘤复发与放射性脑损伤的MRI鉴别诊断。方法:回顾性分析2018年1月~2020年2月本院收治的68例胶质瘤术后患者,对所有患者进行MRI平扫、增强以及灌注加权成像(PWI)扫描,记录影像学特征,对脑血容量中位数最大值(rCBV_max)、表观扩散系数(ADC_mean、ADC_min)指标进行对比。结果:有15例患者复发,其胶质瘤复发率为22.06%,其放射性脑损伤的发生率为8.82%(6例);胶质瘤复发与放射性脑损伤患者rCBV_max、ADC_min值有明显差异(P<0.05),ADC_mean比较无明显差异(P>0.05)。结论:进行MRI检查临床效果较好,可准确鉴别胶质瘤复发与反射性脑损伤。     

外周血单个核细胞内人类免疫缺陷病毒DNA和RNA定量对病毒转录活性的区分

目的基于人类免疫缺陷病毒Ⅰ型(HIV-1)感染者外周血单个核细胞(PBMCs)中HIV-1总DNA和RNA定量检测结果对感染细胞内病毒的转录活性进行区分。方法采集2017年10月至2018年12月于哈尔滨医科大学附属第四医院感染科就诊的HIV-1感染者血液样本,分离PBMCs细胞,采用PCR荧光探针法对PBMCs细胞内HIV-1总DNA和RNA进行定量检测,并计算两者比值(Ratio)。根据Ratio值筛选出HIV-1转录活跃组样本和相对非活跃组样本,另外选择健康人PBMCs样本作为对照组。对3组样本进行基因转录组表达谱检测以及人口特征差异性检验,并对基因表达谱检测结果进行主成分分析以验证对3组样本病毒转录活性区分的准确性。结果从60例感染HIV-1患者的PBMCs样本中筛选出HIV-1转录活跃组样本(10例)和相对非活跃组样本(11例),另外选择6例健康人PBMCs样本作为对照组。其中转录活跃组样本Ratio值为165.2~738.93,平均为(339.27±189.68);相对非活跃组Ratio值为4.67~42.39,平均为(17.65±11.78)。转录活跃组和相对非活跃组样本间的CD4+T细胞计数(P=0.049)和Ratio值(P<0.001)差异均具有统计学意义;3组样本年龄(P=0.989)和性别(P=0.650)分布差异无统计学意义。对3组样本的PBMCs基因表达谱主成分分析结果显示:对照组与HIV-1感染者(包括转录活跃组和相对非活跃组)间区分明显。转录活跃组和相对非活跃组间有部分样本重合,同时结果也显示当HIV-1感染者的CD4+T淋巴细胞计数与健康人无显著差异时,其细胞内的基因表达与健康人接近。结论基于HIV-1总DNA和RNA定量检测结果及两者间比值可以较好地区分PBMCs内病毒转录活性。HIV-1感染细胞内部病毒的不同转录激活状况可导致其基因表达谱的异质性。     

乙肝相关性肝癌临床病理学特征与高敏C反应蛋白和溶血磷脂酸表达的相关性

目的探讨乙肝相关性肝癌临床病理学特征与溶血磷脂酸(LPA)和高敏C反应蛋白(hs-CRP)表达的相关性。方法选取2019年1月至2020年1月间河南省驻马店市中心医院收治的198例乙肝相关性肝癌患者作为乙肝组,198例酒精相关性肝癌患者作为酒精组。两组患者都进行血清hs-CRP和LPA表达检测,调查患者的病理学特征并进行相关性分析。结果乙肝组患者血清hs-CRP和LPA含量均高于酒精组,差异均有统计学意义(均P <0.05)。两组患者血清ALP、AFP、ALT、AST和GGT含量比较,差异均无统计学意义(P> 0.05)。乙肝组不同临床分期和组织学分化患者的血清hs-CRP和LPA含量比较,差异均有统计学意义(均P <0.05)。乙肝组患者的临床分期和组织学分化与血清hs-CRP和LPA表达均存在相关性,差异均有统计学意义(均P <0.05)。患者的临床分期和组织学分化均为影响hs-CRP和LPA表达的重要因素,差异均有统计学意义(均P <0.05)。结论相对于酒精相关性肝癌,乙肝相关性肝癌的血清hs-CRP和LPA呈现高表达,与患者的临床病理学特征存在相关性。