Multikernel linear mixed model with adaptive lasso for complex phenotype prediction

Linear mixed models (LMMs) and their extensions have been widely used for high-dimensional genomic data analyses. While LMMs hold great promise for risk prediction research, the high dimensionality of the data and different effect sizes of genomic regions bring great analytical and computational challenges. In this work, we present a multikernel linear mixed model with adaptive lasso (KLMM-AL) to predict phenotypes using high-dimensional genomic data. We develop two algorithms for estimating parameters from our model and also establish the asymptotic properties of LMM with adaptive lasso when only one dependent observation is available. The proposed KLMM-AL can account for heterogeneous effect sizes from different genomic regions, capture both additive and nonadditive genetic effects, and adaptively and efficiently select predictive genomic regions and their corresponding effects. Through simulation studies, we demonstrate that KLMM-AL outperforms most of existing methods. Moreover, KLMM-AL achieves high sensitivity and specificity of selecting predictive genomic regions. KLMM-AL is further illustrated by an application to the sequencing dataset obtained from the Alzheimer's disease neuroimaging initiative.     

基于TCGA数据挖掘筛选肺鳞癌预后相关lncRNA分子标签

目的：通过对TCGA数据库的挖掘,筛选与肺鳞癌预后相关的lncRNA。方法：提取TCGA数据库中肺鳞癌患者临床数据以及肺鳞癌和癌旁组织中的lncRNA表达数据,采用LASSO Cox回归筛选肺鳞癌预后相关的lncRNA,并构建lncRNA分子标签。采用Cox模型研究该分子标签的表达水平对肺鳞癌患者预后的影响。结果：首先筛选出322个在癌和癌旁组织中差异表达的lncRNA。经LASSO Cox回归分析从中筛选出6个与肺鳞癌预后相关的lncRNA,分别为KTN1-AS1、FAM83A-AS1、AF131217.1、RP11-108M12.3、CTD-2555C10.3和AC068831.16。根据这6个lncRNA构建的分子标签表达水平中位数-0.09将肺鳞癌病人分为高表达组和低表达组,高表达组病人死亡风险是低表达组的2.14倍（HR=2.14,95%CI：1.50~3.04,P < 0.01）。预测模型的Harrell's C统计量为0.69（95%CI：0.64~0.75）。结论：通过对TCGA数据库的挖掘,发现KTN1-AS1、FAM83A-AS1、AF131217.1、RP11-108M12.3、CTD-2555C10.3和AC068831.16对肺鳞癌的预后有影响,且构建的lncRNA分子标签表达水平与肺鳞癌病人的预后有显著性关联。     

Computed tomography-guided percutaneous microwave ablation of hepatocellular carcinoma in challenging locations: safety and efficacy of high-power microwave platforms

Objective: To evaluate the clinical efficacy/safety of CT-guided percutaneous microwave ablation for HCC in challenging locations using high-power microwave platforms.

Materials and methods: A retrospective review was conducted in 26 patients with 36 HCC tumours in challenging locations (hepatic dome, subcapsular, close to the heart/diaphragm/hepatic hilum, exophytic) undergoing CT-guided percutaneous microwave ablation in a single centre since January 2011. Two different microwave platforms were used both operating at 2.45?GHz: AMICA and Acculis MWA System. Patient demographics including age, sex, tumour size and location, as well as technical details were recorded. Technical success, treatment response, patients survival and complication rate were evaluated.

Results: Treated tumours were located in the hepatic dome (n?=?14), subcapsularly (n?=?16), in proximity to the heart (n?=?2) or liver hilum (n?=?2), while two were exophytic tumours at segment VI (n?=?2). Mean tumour diameter was 3.30?cm (range 1.4–5?cm). In 3/26 patients (diameter?>4?cm), an additional session of DEB-TACE was performed due to tumour size. Technical success rate was 100%; complete response rate was recorded in 33/36 tumours (91.6%). According to Kaplan–Meier analysis, survival rate was 92.3% and 72.11% at 24- and 60-month follow-up, respectively. There were no major complications; two cases of minor pneumothorax and two cases of small subcapsular haematoma were resolved only with observation requiring no further treatment.

Conclusion: CT-guided percutaneous microwave ablation for hepatocellular carcinoma tumours in challenging locations and up to 5?cm in diameter can be performed with high efficacy and safety rates.     

Utility of Maximum Standard Uptake Value as a Predictor for Differentiating the Invasiveness of T1 Stage Pulmonary Adenocarcinoma

Background

The present study was performed to investigate the maximum standardized uptake value (SUVmax) in 2-[fluorine-18]-fluoro-2-deoxy-d-glucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) to preoperatively distinguish invasive from less-invasive pulmonary adenocarcinoma.

A New Wall Stress Equation for Aneurysm-Rupture Prediction

Aneurysms, especially in the abdominal aorta (AAA), are prone to rupture, and hence a reliable and easy-to-use predictor is most desirable. Based on clinical observations and numerical analyses, a semi-empirical equation for the peak AAA-wall stress has been developed. It can be readily used for AAA-rupture predictions or can be integrated into more elaborate AAA-assessment models.     

Antibody responses against B-cell epitopes of the hypervariable region 1 of hepatitis C virus in self-limiting and chronic human hepatitis C followed-up using consensus peptides.

A rare collection of serum samples from patients with hepatitis C virus (HCV) infection followed up from the onset of clinical symptoms was acquired. RNA corresponding to the hypervariable region 1 (HVR1) of E2 protein of HCV isolated from nine patients was reverse-transcribed, amplified, sequenced, and HVR1 amino acid sequences were deduced. These sequences and a selection of HVR1 amino acid sequences of matching HCV genotypes from protein and translated DNA sequence databanks were used to create the HVR1 amino acid consensus. The degenerated peptides mimicking N- and C-termini of the consensus were synthesized. Most (76%) of 17 patients followed up for the period from 1 week to a minimum of 7 months from the onset of acute symptoms developed antibodies reacting with peptides representing N- and/or C- termini of HVR1. Antibody recognition of the consensus HVR1 peptides indicates that the variability of HVR1 sequence on the protein level is limited with certain conserved structure(s) being untouched. A tendency was observed for a slower development of anti-HVR1 antibody response in patients developing chronic HCV, as compared to those with self-limiting HCV infection.     

Searching for Interactive Effects in the Etiology of Early-Onset Substance Use

This study sought to expand the modest literature investigating gene × environment interactions in the prediction of substance use. Our sample consisted of 591 male twins from the Minnesota Twin Family Study. Their relative genetic risk was estimated from their parents' substance-related diagnoses and their environmental risk from their affiliations at age 11 with social groups likely to either encourage or discourage substance use. At age 14, the boys' own substance use was assessed. We hypothesized both main effects and an interaction between our genetic- and environmental-risk variables in the prediction of substance use by this young age. We further theorized that the boys' inherited risk might take the form of temperament, specifically externalizing tendencies. Using regression analyses and biometrical modeling, we corroborated earlier research by finding evidence for a significant interactive effect in the etiology of substance use. Our results suggest that low levels of environmental risk may buffer against the potentially unfavorable effects of high familial risk; however, when environmental risk is high, the degree of familial risk is consequential. We were not able to support our second hypothesis; rather, temperament predicted substance use only through shared environmental factors.     

Prediction of an unfavourable course of low back pain in general practice: comparison of four instruments

BACKGROUND: Several instruments can be used to identify patients with an unfavourable course of low back pain in general practice. However, it is unclear which instrument is the predictor of outcome. AIM: To compare the predictive performance (that is, calibration and discrimination) of risk estimation by GPs with assessments using the Orebro Musculoskeletal Pain Screening Questionnaire, the Low Back Pain Perception Scale (LBPPS), and a prediction rule developed for this purpose. Design of study: A prospective cohort study with 1-year follow-up. SETTING: General practice in The Netherlands. METHOD: The outcome 'unfavourable course of low back pain' was defined as having no clinically important improvement at minimally 50% of the measurements at 6, 13, 26, and 52 weeks. Logistic regression analyses were used to study associations between potential predictors and outcome. RESULTS: In total, 60 GPs recruited 314 patients to the study (16 patients were excluded from analysis due to missing data on the course of low back pain). Over a third of patients (112/298) showed an unfavourable course of low back pain on follow-up. Risk estimation by GPs, the Orebro questionnaire, the LBPPS, and the prediction rule had discriminative ability (area under the curve) of 0.59 (95% CI [confidence intervals] = 0.52 to 0.66); 0.61 (95% CI = 0.54 to 0.67); 0.59 (95% CI = 0.52 to 0.66); and 0.75 (95% CI = 0.69 to 0.81) respectively. The prediction rule included history of low back pain, self-perceived risk to develop chronic low back pain, no solicitous responses of the patient's partner (as reported by the patient), frequent walking at work, and 'pain catastrophising'. CONCLUSION: Although the prediction rule performed best with regard to calibration and discrimination, it needs to be externally validated. Risk estimation by GPs performs as well as other instruments and, at present, seems to be the best available option.