Single-dose replicating poxvirus vector-based RBD vaccine drives robust humoral and T cell immune response against SARS-CoV-2 infection

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Multiomic analysis reveals conservation of cancer-associated fibroblast phenotypes across species and tissue of origin

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基于生物信息学的肥厚型心肌病易感基因TNNC1单核苷酸多态性致病表型分析

肥厚型心肌病(HCM)是一种常见的遗传性心脏病,是青少年及年轻运动员心源性猝死的最主要原因之一,其分子遗传学基础为基因突变。TNNC1是HCM的重要致病基因之一,目前仅发现其少量非同义单核苷酸多态性(nsSNPs)位点与HCM发病相关,但该基因其他nsSNPs数量较多,结合临床进行实验遗传检测其基因型与表型的关系,工作量巨大,尚不可行。因此,采用生物信息学方法,从dbSNP数据库中筛选出TNNC1基因全部的nsSNPs,联合4款(Mutation Taster、PolyPhen-2、PhD-SNP和MutPred)专业软件,进行有害性分级筛选和致病关联预测,最后进行突变蛋白三维结构建模及可视化分析。结果显示,首次从TNNC1基因102个nsSNPs位点中预测出疾病相关的18个(G159D、S69R、P52R、D149G、D3V、G140E、N51K、D151V、M47R、G110C、A23D、G140R、K158N、C35Y、R147C、L48P、F74C和V44G)高风险nsSNPs。基于生物信息学方法,以TNNC1基因的nsSNPs为示范,分析其nsSNPs与疾病表型的关系,这为其他遗传疾病致病基因nsSNPs的关联分析打下理论研究基础,具有重要的参考价值。     

Defining the dimensions of circulating tumor cells in a large series of breast,prostate, colon,and bladder cancer patients

Circulating tumor cells (CTCs) in the blood of cancer patients are of high clinical relevance. Since detection and isolation of CTCs often rely on cell dimensions, knowledge of their size is key. We analyzed the median CTC size in a large cohort of breast (BC), prostate (PC), colorectal (CRC), and bladder (BLC) cancer patients. Images of patient‐derived CTCs acquired on cartridges of the FDA‐cleared CellSearch^® method were retrospectively collected and automatically re‐analyzed using the accept software package. The median CTC diameter (μm) was computed per tumor type. The size differences between the different tumor types and references (tumor cell lines and leukocytes) were nonparametrically tested. A total of 1962 CellSearch^® cartridges containing 71 612 CTCs were included. In BC, the median computed diameter (CD) of patient‐derived CTCs was 12.4 μm vs 18.4 μm for cultured cell line cells. For PC, CDs were 10.3 μm for CTCs vs 20.7 μm for cultured cell line cells. CDs for CTCs of CRC and BLC were 7.5 μm and 8.6 μm, respectively. Finally, leukocytes were 9.4 μm. CTC size differed statistically significantly between the four tumor types and between CTCs and the reference data. CTC size differences between tumor types are striking and CTCs are smaller than cell line tumor cells, whose size is often used as reference when developing CTC analysis methods. Based on our data, we suggest that the size of CTCs matters and should be kept in mind when designing and optimizing size‐based isolation methods.

Abbreviations

ACCEPT

Automated CTC Classification, Enumeration, and PhenoTyping software

BC

breast cancer

BLC

bladder cancer

CD

computed diameter

CEL

cultured tumor cell (cell line)

CK

cytokeratin

CRC

colorectal cancer

CTC‐L

circulating tumor cells derived from cerebrospinal fluid (liquor)

CTCs

circulating tumor cells

DAPI

4′6‐diamidino‐2‐phenylindole

EMT

epithelial–mesenchymal transition

EpCAM

epithelial cell adhesion molecule

IQR

interquartile range

KW test

Kruskal–Wallis test

MWU test

Mann–Whitney U test

NCR

nucleus/cytoplasm ratio

P2A

perimeter to area

PC

prostate cancer

TIF

tagged Image Format files

TXT

text file

μm

micrometer

µm²

square micrometers

     

Motor dysfunction in mild cognitive impairment as tested by kinematic analysis and transcranial magnetic stimulation

ObjectivePrevious studies have demonstrated voluntary movement alterations as well as motor cortex excitability and plasticity changes in patients with mild cognitive impairment (MCI). To investigate the pathophysiology of movement abnormalities in MCI, we tested possible relationships between movement abnormalities and primary motor cortex alterations in patients.MethodsFourteen amnestic MCI (aMCI) patients and 16 healthy controls were studied. Cognitive assessment was performed using clinical scales. Finger tapping was recorded by a motion analysis system. Transcranial magnetic stimulation was used to test the input/output curve of motor evoked potentials, intracortical inhibition, and short-latency afferent inhibition. Primary motor cortex plasticity was probed by theta burst stimulation. We investigated correlations between movement abnormalities, clinical scores, and cortical neurophysiological parameters.ResultsMCI patients showed less rhythmic movement but no other movement abnormalities. Cortical excitability measures were normal in patients, whereas plasticity was reduced. Movement rhythm abnormalities correlated with frontal dysfunction scores.ConclusionOur study in MCI patients demonstrated abnormal voluntary movement and plasticity changes, with no correlation between the two. Altered rhythm correlated with frontal dysfunction.SignificanceOur results contribute to the understanding of pathophysiological mechanisms of motor impairment in MCI.     

Reduced nontarget embolization and increased targeted delivery with a reflux-control microcatheter in a swine model

PurposeTo evaluate the potential differences in non-target embolization and vessel microsphere filling of a reflux-control microcatheter (RCM) compared to a standard end-hole microcatheter (SEHM) in a swine model.Materials and methodsRadiopaque microspheres were injected with both RCM and SEHM (2.4-Fr and 2.7-Fr) in the kidneys of a preclinical swine model. Transarterial renal embolization procedures with RCM or SEHM were performed in both kidneys of 14 pigs. Renal arteries were selectively embolized with an automated injection protocol of radio-opaque microspheres. Ex-vivo X-ray microtomography images of the kidneys were utilized to evaluate the embolization by quantification of the deposition of injected microspheres in the target vs. the non-target area of injection. X-ray microtomography images were blindly analyzed by five interventional radiologists. The degree of vessel filling and the non-target embolization were quantified using a scale from 1 to 5 for each parameter. An analysis of variance was used to compare the paired scores.ResultsTotal volumes of radio-opaque microspheres injected were similar for RCM (11.5 ± 3.6 [SD] mL; range: 6–17 mL) and SEHM (10.6 ± 5.2 [SD] mL; range: 4–19 mL) (P = 0.38). The voxels enhanced ratio in the target (T) vs. non-target (NT) areas was greater with RCM (T = 98.3% vs. NT = 1.7%) than with SEHM (T = 89% vs. NT = 11%) but the difference was not significant (P = 0.30). The total score blindly given by the five interventional radiologists was significantly different between RCM (12.3 ± 2.1 [SD]; range: 6–15) and the standard catheter (11.3 ± 2.5 [SD]; range: 4–15) (P = 0.0073), with a significant decrease of non-target embolization for RCM (3.8 ± 1.3 [SD]; range: 3.5–4.2) compared to SEHM (3.2 ± 1.5 [SD]; range: 2.9–3.5) (P = 0.014).ConclusionIn an animal model, RCM microcatheters reduce the risk of non-target embolization from 11% to 1.7%, increasing the delivery of microspheres of 98% to the target vessels, compared to SEHM microcatheters.     

CT引导下经皮穿刺二次活检诊断肺部病变的可行性及安全性

目的 评价CT引导下经皮二次穿刺活检用于明确诊断肺部病变的可行性及安全性。方法 回顾性分析40例接受2次肺穿刺活检患者的临床、影像学及随访资料,根据最终诊断结果,比较2次活检的诊断准确率,分析并发症及初次活检误诊的危险因素。结果 40例中,17例初次活检诊断结果与最终诊断一致(确诊组)、23例诊断不一致(误诊组),诊断准确率为42.50%(17/40),并发症发生率为27.50%(11/40);39例二次活检诊断结果与最终诊断一致,诊断准确率为97.50%(39/40),并发症发生率为25.00%(10/40)。二次活检诊断准确率明显提高,并发症发生率与初次活检差异无统计学意义(P＞0.05)。组间病灶性质和气胸发生率差异均有统计学意义(P均＜0.05)。结论 CT引导下经皮二次穿刺活检用于明确诊断肺部病变安全、可行。