Primary central nervous system lymphoma and glioblastoma differentiation based on conventional magnetic resonance imaging by high-throughput SIFT features

Purpose of the study: Due to the totally different therapeutic regimens needed for primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM), accurate differentiation of the two diseases by noninvasive imaging techniques is important for clinical decision-making.

Materials and methods: Thirty cases of PCNSL and 66 cases of GBM with conventional T1-contrast magnetic resonance imaging (MRI) were analyzed in this study. Convolutional neural networks was used to segment tumor automatically. A modified scale invariant feature transform (SIFT) method was utilized to extract three-dimensional local voxel arrangement information from segmented tumors. Fisher vector was proposed to normalize the dimension of SIFT features. An improved genetic algorithm (GA) was used to extract SIFT features with PCNSL and GBM discrimination ability. The data-set was divided into a cross-validation cohort and an independent validation cohort by the ratio of 2:1. Support vector machine with the leave-one-out cross-validation based on 20 cases of PCNSL and 44 cases of GBM was employed to build and validate the differentiation model.

Results: Among 16,384 high-throughput features, 1356 features show significant differences between PCNSL and GBM with p < 0.05 and 420 features with p < 0.001. A total of 496 features were finally chosen by improved GA algorithm. The proposed method produces PCNSL vs. GBM differentiation with an area under the curve (AUC) curve of 99.1% (98.2%), accuracy 95.3% (90.6%), sensitivity 85.0% (80.0%) and specificity 100% (95.5%) on the cross-validation cohort (and independent validation cohort).

Conclusions: Since the local voxel arrangement characterization provided by SIFT features, proposed method produced more competitive PCNSL and GBM differentiation performance by using conventional MRI than methods based on advanced MRI.     

Wireless Capsule Endoscopy Video Reduction Based on Camera Motion Estimation

Wireless capsule endoscopy (WCE) is a novel technology aiming for investigating the diseases and abnormalities in small intestine. The major drawback of WCE examination is that it takes a long time to examine the whole WCE video. In this paper, we present a new reduction scheme for WCE video to reduce the examination time. To achieve this task, a WCE video motion model is proposed. Under this motion model, the WCE imaging motion is estimated in two stages (the coarse level and the fine level). In the coarse level, the WCE camera motion is estimated with a combination of Bee Algorithm and Mutual Information. In the fine level, the local gastrointestinal tract motion is estimated with SIFT flow. Based on the result of WCE imaging motion estimation, the reduction scheme preserves key images in WCE video with scene changes. From experimental results, we notice that the proposed motion model is suitable for the motion estimation in successive WCE images. Through the comparison with APRS and FCM-NMF scheme, our scheme can produce an acceptable reduction sequence for browsing and examination.     

Non-neutral nonsynonymous single nucleotide polymorphisms in human ABC transporters: the first comparison of six prediction methods

Nonsynonymous single nucleotide polymorphisms (nsSNPs) in coding regions that can lead to amino acid changes may cause alteration of protein function and account for susceptibility to disease and altered drug/xenobiotic response. Abundant nsSNPs have been found in genes coding for human ATP-binding cassette (ABC) transporters, but there is little known about the relationship between the genotype and phenotype of nsSNPs in these membrane proteins. In addition, it is unknown which prediction method is better suited for the prediction of non-neutral nsSNPs of ABC transporters. We have identified 2,172 validated nsSNPs in 49 human ABC transporter genes from the Ensembl genome database and the NCBI SNP database. Using six different algorithms, 41 to 52% of nsSNPs in ABC transporter genes were predicted to have functional impacts on protein function. Predictions largely agreed with the available experimental annotations. Overall, 78.5% of non-neutral nsSNPs were predicted correctly as damaging by SNAP, which together with SIFT and PolyPhen, was superior to the prediction methods Pmut, PhD-SNP, and Panther. This study also identified any amino acids that were likely to be functionally critical but have not yet been studied experimentally. There was significant concordance between the predicted results of SIFT and PolyPhen. Evolutionarily non-neutral (destabilizing) amino acid substitutions are predicted to be the basis for the pathogenic alteration of ABC transporter activity that is associated with disease susceptibility and altered drug/xenobiotic response.     

Ammonia release from heated 'street' cannabis leaf and its potential toxic effects on cannabis users

Aims To use selected ion flow tube mass spectrometry (SIFT‐MS) to analyse the molecular species emitted by heated ‘street’ cannabis plant material, especially targeting ammonia. Materials and methods Samples of ‘street’ cannabis leaf, held under a UK Home Office licence, were prepared by finely chopping and mixing the material. The samples were then heated in commercially available devices. The air containing the released gaseous compounds was sampled into the SIFT‐MS instrument for analysis. Smoke from standard 3% National Institute on Drug Abuse (NIDA) cannabis cigarettes was also analysed. Findings For ‘street’ cannabis, ammonia was present in the air samples from the devices at levels approaching 200 parts per million (p.p.m.). This is compared with peak levels of 10 p.p.m. using NIDA samples of known provenance and tetrahydrocannabinol content (3%). Several other compounds were present at lower levels, including acetaldehyde, methanol, acetone, acetic acid and uncharacterized terpenes. Conclusions Awareness of the risks of inhaling the smoke directly from burning cannabis has led to the development of a number of alternative methods of delivery, which are claimed to be safer than direct smoking. Ammonia at toxic levels is produced from heating ‘street’ cannabis in these commercially available devices. Thus, the use of these devices to deliver ‘street’ cannabis is now open to question and further research is needed to investigate their safety.     

Pathogenicity of MSH2 missense mutations is typically associated with impaired repair capability of the mutated protein

BACKGROUND & AIMS: Inherited deleterious mutations in mismatch repair genes MLH1, MSH2, and MSH6 predispose to hereditary nonpolyposis colorectal cancer. A major diagnostic challenge is the difficulty in evaluating the pathogenicity of missense mutations. Previously we showed that most missense variants in MSH6 do not impair MMR capability and are associated with no or low cancer susceptibility, whereas in MLH1, functional studies distinguished nontruncating mutations with severe defects from those not or slightly impaired in protein expression or function. The present study was undertaken to evaluate the pathogenicity of inherited missense mutations in MSH2. METHODS: Fifteen mutated MSH2 proteins including 14 amino acid substitutions and one in-frame deletion were tested for expression/stability, MSH2/MSH6 interaction, and repair efficiency. The genetic and biochemical data were correlated with the clinical data. Comparative sequence analysis was performed to assess the value of sequence homology as a tool for predicting functional results. RESULTS: None of the studied MSH2 mutations destroyed the protein or abolished MSH2/MSH6 interaction, whereas 12 mutations impaired the repair capability of the protein. Comparative sequence analysis correctly predicted functional studies for 13 of 14 amino acid substitutions. CONCLUSIONS: Interpretation was pathogenic for 12, nonpathogenic for 2, and contradictory for 1 mutation. The pathogenicity could not be distinguished unambiguously by phenotypic characteristics, although correlation between the absence of staining for MSH2 and pathogenicity of the missense mutation was notable. Unlike in MSH6 and MLH1, the pathogenicity of missense mutations in MSH2 was always associated with impaired repair capability of the mutated protein.     

Variants in the UBR1 gene are not associated with chronic pancreatitis in Japan

Background/objectivesThe UBR1 gene encodes the enzyme ubiquitin-protein ligase E3 component n-recognin 1. Loss-of-function mutations in the UBR1 gene cause Johanson-Blizzard syndrome, which involves pancreatic exocrine insufficiency. No previous studies have examined an association of UBR1 variants with pancreatitis, in part due to the large size of the gene. This study aimed to clarify whether UBR1 variants are associated with chronic pancreatitis (CP) by the application of targeted next generation sequencing.MethodsExon sequences of the UBR1 gene from 389 Japanese patients with CP (188 idiopathic, 172 alcoholic, 20 hereditary, 9 familial) were captured by the HaloPlex target enrichment technology and subjected to next generation sequencing.ResultsNinety nine point two % of the coding regions of the UBR1 gene could be sequenced by ≥ 20 reads with a mean read depth of 595 and a median depth of 399. Fifteen non-synonymous variants including three novel ones [c.4514T > C (p.I1505T), c.4828C > G (p.H1610D) and c.4856A > T (p.D1619V)] and two synonymous variants were identified in the exonic regions. The frequency of any non-synonymous or synonymous variants was not different between the patients with CP and controls.ConclusionsVariants in the UBR1 gene were not associated with CP in Japan.     

基于SUKF与SIFT特征的红外目标跟踪算法研究

针对复杂红外背景下单一跟踪算法难以准确定位运动目标的问题,提出了基于尺度无迹卡尔曼滤波(SUKF,scale unscented Kalman filter)与尺度不变特征变换(SIFT,scale invariant featuretransform)相结合的红外运动目标跟踪方法。首先,通过SUKF算法对状态空间进行滤波估计,确定运动目标的初步位置,并以此建立局部SIFT特征检测域。其次,SIFT算法在该局部检测域内对运动目标进行特征提取与匹配,最终实现对目标的准确定位;同时,利用定位结果更新并校正SUKF的状态模型。实验结果表明,本文提出的基于SUKF-SIFT的跟踪策略与相关算法相比,体现出较好的跟踪效果与实时性能。