Imaging pulmonary fissures by CT provides useful information on diagnosis of pulmonary diseases. Automatic segmentation of fissures is a challenging task due to the variable appearance of fissures,... Show moreImaging pulmonary fissures by CT provides useful information on diagnosis of pulmonary diseases. Automatic segmentation of fissures is a challenging task due to the variable appearance of fissures, such as inhomogeneous intensities, pathological deformation and imaging noise. To overcome these challenges, we propose an anisotropic differential operator called directional derivative of plate (DDoP) filter to probe the presence of fissure objects in 3D space by modeling the profile of a fissure patch with three parallel plates. To reduce the huge computation burden of dense matching with rotated DDoP kernels, a family of spherical harmonics are particularly utilized for acceleration. Additionally, a two-stage post-processing scheme is introduced to segment fissures. The performance of our method was verified in experiments using 55 scans from the publicly available LOLA11 dataset and 50 low-dose CT scans of lung cancer patients from the VIA-ELCAP database. Our method showed superior performance compared to the derivative of sticks (DoS) method and the Hessian-based method in terms of median and mean F-1 - score. The median F-1 - score for DDoP, DoS-based and Hessian-based methods on the LOLA11 dataset was 0.899, 0.848 and 0.843, respectively, and the mean F-1 - score was 0.858 +/- 0.103, 0.781 +/- 0.165 and 0.747 +/- 0.239, respectively. (C) 2020 Elsevier B.V. All rights reserved. Show less
Multiomic profiling of several cohorts of patients treated with immune checkpoint blockade highlights the presence and potential role of B cells and tertiary lymphoid structures in promoting... Show moreMultiomic profiling of several cohorts of patients treated with immune checkpoint blockade highlights the presence and potential role of B cells and tertiary lymphoid structures in promoting therapy response.Treatment with immune checkpoint blockade (ICB) has revolutionized cancer therapy. Until now, predictive biomarkers(1-10) and strategies to augment clinical response have largely focused on the T cell compartment. However, other immune subsets may also contribute to anti-tumour immunity(11-15), although these have been less well-studied in ICB treatment(16). A previously conducted neoadjuvant ICB trial in patients with melanoma showed via targeted expression profiling(17) that B cell signatures were enriched in the tumours of patients who respond to treatment versus non-responding patients. To build on this, here we performed bulk RNA sequencing and found that B cell markers were the most differentially expressed genes in the tumours of responders versus non-responders. Our findings were corroborated using a computational method (MCP-counter(18)) to estimate the immune and stromal composition in this and two other ICB-treated cohorts (patients with melanoma and renal cell carcinoma). Histological evaluation highlighted the localization of B cells within tertiary lymphoid structures. We assessed the potential functional contributions of B cells via bulk and single-cell RNA sequencing, which demonstrate clonal expansion and unique functional states of B cells in responders. Mass cytometry showed that switched memory B cells were enriched in the tumours of responders. Together, these data provide insights into the potential role of B cells and tertiary lymphoid structures in the response to ICB treatment, with implications for the development of biomarkers and therapeutic targets. Show less
The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and... Show moreThe risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations. Show less
