Automated classification of depression from structural brain measures across two independent community‐based cohorts

Major depressive disorder (MDD) has been the subject of many neuroimaging case–control classification studies. Although some studies report accuracies ≥80%, most have investigated relatively small samples of clinically‐ascertained, currently symptomatic cases, and did not attempt replication in larger samples. We here first aimed to replicate previously reported classification accuracies in a small, well‐phenotyped community‐based group of current MDD cases with clinical interview‐based diagnoses (from STratifying Resilience and Depression Longitudinally cohort, ‘STRADL’). We performed a set of exploratory predictive classification analyses with measures related to brain morphometry and white matter integrity. We applied three classifier types—SVM, penalised logistic regression or decision tree—either with or without optimisation, and with or without feature selection. We then determined whether similar accuracies could be replicated in a larger independent population‐based sample with self‐reported current depression (UK Biobank cohort). Additional analyses extended to lifetime MDD diagnoses—remitted MDD in STRADL, and lifetime‐experienced MDD in UK Biobank. The highest cross‐validation accuracy (75%) was achieved in the initial current MDD sample with a decision tree classifier and cortical surface area features. The most frequently selected decision tree split variables included surface areas of bilateral caudal anterior cingulate, left lingual gyrus, left superior frontal, right precentral and paracentral regions. High accuracy was not achieved in the larger samples with self‐reported current depression (53.73%), with remitted MDD (57.48%), or with lifetime‐experienced MDD (52.68–60.29%). Our results indicate that high predictive classification accuracies may not immediately translate to larger samples with broader criteria for depression, and may not be robust across different classification approaches.     

肿瘤免疫治疗时代的多重免疫组织化学/免疫荧光技术

常规免疫组织化学(immunohistochemistry,IHC)是组织病理学中广泛应用的诊断技术.但该技术存在诸多局限性,包括观察者间的变异性高,每张组织切片仅能标记一个标志物.本文详细描述了各种多重检测技术,这些技术克服了上述局限性,可在单张切片上同时检测多个标志物,可对细胞组成、细胞功能和细胞间相互作用进行整合...     

Swine as a principal reservoir of hepatitis E virus that infects humans in eastern China

BACKGROUND AND METHODS: Genotype IV hepatitis E virus (HEV) has been isolated from humans and swine. To study the relationship between the human and swine reservoirs, we estimated their respective viral burden, analyzed the genetic makeup of the virus populations, and assessed the risk of infection associated with swine farming. RESULTS: In 2 swine-farming districts of eastern China, 9.6% of swine and 0.3% of healthy human subjects excreted HEV in stool, as did 68.8% of patients with confirmed HEV infection. The virus population circulating in humans consisted of genotype I and at least 4 phylogenetically distinct subgroups of genotype IV viruses, 2 of which concurrently circulated among swine. Persons engaged in occupations related to swine farming were found to have a 74% higher risk of infection than those engaged in other occupations, and persons living in communities downstream of the swine farms were found to have a 29% higher risk of infection than persons living in communities upstream. CONCLUSIONS: Genotype IV HEV is freely transmitted between humans and swine. Because the size of the swine population and its viral burden are much larger than those of humans, transmission of the virus most likely is directed from swine to humans. Infection can be acquired through contact with swine and their waste.     

金银花药材中抗呼吸道病毒感染的咖啡酰奎宁酸类成分的定量研究

目的:寻找金银花中的抗呼吸道病毒感染的成分,并进行定量研究。方法:采用各种柱层析和制备薄层层析等方法分离、细胞病变法进行抗病毒作用的研究,采用RP-HPLC方法进行定量方法的研究。结果:分离得到了13种咖啡酰奎宁酸类化合物和咖啡酸、咖啡酸甲酯,确认咖啡酰奎宁酸类成分具有较强的抗呼吸道病毒作用,并采用HPLC方法测定了金银花中的 6种咖啡酰奎宁酸类成分和咖啡酸的含量。结论:咖啡酰奎宁酸类成分为金银花中的有效成分,定量方法准确、重复性好。     

Laparoscopic-assisted versus open resection of right-sided colonic cancer—a prospective randomized controlled trial

Purposes  

This study aims to compare the perioperative outcomes and survival between laparoscopic-assisted right hemicolectomy (LARH) and open right hemicolectomy (ORH) for right-sided colon cancer.     

Pure endoscopic resection versus laparoscopic assisted procedure for upper gastrointestinal stromal tumors: Perspective from a surgical endoscopist

Management of upper gastrointestinal (UGI) tract gastrointestinal stromal tumor (GIST) has evolved significantly over the past two decades. For GIST size smaller than 5 cm, laparoscopic resection has become the current standard. To avoid postoperative gastric deformity and preserve gastric function, laparoscopic endoscopic cooperative surgery (LECS) was developed and various modifications have been reported and utilized successfully. Pure endoscopic resection techniques have also been reported at a similar period of time, which further push the boundary of incisionless surgery in managing these lesions. Both tunneling and nontunneling exposed type endoscopic full thickness resection are well described procedures for resection of small UGI GIST. In this review, a summary of these procedures is provided, and the pros and cons of each technique from the perspective of a surgical endoscopist are discussed in detail. LECS and endoscopic resection are complementary to each other. The choice of technique should be tailored to the location, morphology, and size of the target lesions, taking into account the experience of the laparoscopic surgeons and endoscopists.     

LABRADOR—A Computational Workflow for Virus Detection in High-Throughput Sequencing Data

High-throughput sequencing (HTS) allows detection of known and unknown viruses in samples of broad origin. This makes HTS a perfect technology to determine whether or not the biological products, such as vaccines are free from the adventitious agents, which could support or replace extensive testing using various in vitro and in vivo assays. Due to bioinformatics complexities, there is a need for standardized and reliable methods to manage HTS generated data in this field. Thus, we developed LABRADOR—an analysis pipeline for adventitious virus detection. The pipeline consists of several third-party programs and is divided into two major parts: (i) direct reads classification based on the comparison of characteristic profiles between reads and sequences deposited in the database supported with alignment of to the best matching reference sequence and (ii) de novo assembly of contigs and their classification on nucleotide and amino acid levels. To meet the requirements published in guidelines for biologicals’ safety we generated a custom nucleotide database with viral sequences. We tested our pipeline on publicly available HTS datasets and showed that LABRADOR can reliably detect viruses in mixtures of model viruses, vaccines and clinical samples.     

HIV-1-specific cytolytic T-lymphocyte activity correlates with lower viral load, higher CD4 count, and CD8+CD38-DR- phenotype: comparison of statistical methods for measurement.

OBJECTIVES: The objective of this study was to use novel statistical methods to determine the correlation between HIV-1-specific cytolytic T-lymphocyte (CTL) activity and HIV-1 plasma viral load, in a blinded study of HIV-infected patients at various stages of clinical disease. METHODS: Peripheral blood mononuclear cells (PBMC) were collected and stored at enrollment and 2 weeks later, from 15 HIV-infected individuals who were receiving stable antiretroviral therapy for the previous 6 weeks and during the study period. HIV-1-specific CTL activity was measured using an antigen-specific PBMC in vitro stimulation method. Measurements of plasma viral load, as well as CD4+ and CD8+ T lymphocytes expressing T-cell activation markers (DR and CD38) were also performed at each time point. CTL activity was quantified using three separate statistical methods: area under the net HIV-specific lysis curve (AUC), lytic units (LU20), and linear regression (LR) of net HIV-specific lysis. RESULTS: HIV-1 nef-, pol- and gag-specific CTL activity (AUC method) was significantly higher in subjects with a plasma viral load < or = 30,000 RNA copies/ml, than in those with viral load >30,000 RNA copies/ml. When plasma viral load was analyzed as a continuous variable, there was a strong correlation between higher CTL activity and lower viral load for nef (r2 = .77; p < .001), pol (r2 = .63; p < .001) and gag (r2 = 0.75; p < .001) targets by the AUC, but not for the LU20 analysis. Using the LR analysis, which is less dependent on in vitro PBMC growth than the AUC analysis, an independent association was demonstrated between nef- and gag-specific CTL activity and lower viral load. Measurement of CTL activity was also significantly correlated with a higher percentage of circulating CD8+DR-CD38- T lymphocytes. CONCLUSIONS: In this blinded study using an in vitro stimulation of frozen PBMC, higher HIV-1 nef-, pol-, and gag-specific CTL activity correlated with lower plasma viral load, particularly in patients with a CD4 count <500 cells/mm3. Two new statistical methods for estimating CTL activity, AUC and LR analyses, were superior to the standard lytic unit (LU20) method for demonstrating this correlation. These data also demonstrated that higher circulating CD8+ T lymphocytes with a DR-CD38-phenotype, correlate with a lower plasma viral and load and higher HIV-specific CTL activity. This suggests that lymphocytes with this double-negative phenotype may include circulating HIV-specific CD8+ CTL.