•We propose a pretext task, namely Rubik's cube+, consisting of three sub-tasks, i.e., cube ordering, cube orientation and masking identification.•Experiments on the two target tasks, i.e., cerebral ...hemorrhage classification and brain tumor segmentation, are conducted to demonstrate the effectiveness of our Rubik’s cube+.•Comprehensive discussions on the limitation and potential applications of our study are included.
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Due to the development of deep learning, an increasing number of research works have been proposed to establish automated analysis systems for 3D volumetric medical data to improve the quality of patient care. However, it is challenging to obtain a large number of annotated 3D medical data needed to train a neural network well, as such manual annotation by physicians is time consuming and laborious. Self-supervised learning is one of the potential solutions to mitigate the strong requirement of data annotation by deeply exploiting raw data information. In this paper, we propose a novel self-supervised learning framework for volumetric medical data. Specifically, we propose a pretext task, i.e., Rubik’s cube+, to pre-train 3D neural networks. The pretext task involves three operations, namely cube ordering, cube rotating and cube masking, forcing networks to learn translation and rotation invariant features from the original 3D medical data, and tolerate the noise of the data at the same time. Compared to the strategy of training from scratch, fine-tuning from the Rubik’s cube+ pre-trained weights can remarkablely boost the accuracy of 3D neural networks on various tasks, such as cerebral hemorrhage classification and brain tumor segmentation, without the use of extra data.
Identifying differentially expressed genes (DEG) is a fundamental step in studies that perform genome wide expression profiling. Typically, DEG are identified by univariate approaches such as ...Significance Analysis of Microarrays (SAM) or Linear Models for Microarray Data (LIMMA) for processing cDNA microarrays, and differential gene expression analysis based on the negative binomial distribution (DESeq) or Empirical analysis of Digital Gene Expression data in R (edgeR) for RNA-seq profiling.
Here we present a new geometrical multivariate approach to identify DEG called the Characteristic Direction. We demonstrate that the Characteristic Direction method is significantly more sensitive than existing methods for identifying DEG in the context of transcription factor (TF) and drug perturbation responses over a large number of microarray experiments. We also benchmarked the Characteristic Direction method using synthetic data, as well as RNA-Seq data. A large collection of microarray expression data from TF perturbations (73 experiments) and drug perturbations (130 experiments) extracted from the Gene Expression Omnibus (GEO), as well as an RNA-Seq study that profiled genome-wide gene expression and STAT3 DNA binding in two subtypes of diffuse large B-cell Lymphoma, were used for benchmarking the method using real data. ChIP-Seq data identifying DNA binding sites of the perturbed TFs, as well as known drug targets of the perturbing drugs, were used as prior knowledge silver-standard for validation. In all cases the Characteristic Direction DEG calling method outperformed other methods. We find that when drugs are applied to cells in various contexts, the proteins that interact with the drug-targets are differentially expressed and more of the corresponding genes are discovered by the Characteristic Direction method. In addition, we show that the Characteristic Direction conceptualization can be used to perform improved gene set enrichment analyses when compared with the gene-set enrichment analysis (GSEA) and the hypergeometric test.
The application of the Characteristic Direction method may shed new light on relevant biological mechanisms that would have remained undiscovered by the current state-of-the-art DEG methods. The method is freely accessible via various open source code implementations using four popular programming languages: R, Python, MATLAB and Mathematica, all available at: http://www.maayanlab.net/CD.
There is clinical evidence that suppressing the bone structures in Chest X-rays (CXRs) improves diagnostic value, either for radiologists or computer-aided diagnosis. However, bone-free CXRs are not ...always accessible. We hereby propose a coarse-to-fine CXR bone suppression approach by using structural priors derived from unpaired computed tomography (CT) images. In the low-resolution stage, we use the digitally reconstructed radiograph (DRR) image that is computed from CT as a bridge to connect CT and CXR. We then perform CXR bone decomposition by leveraging the DRR bone decomposition model learned from unpaired CTs and domain adaptation between CXR and DRR. To further mitigate the domain differences between CXRs and DRRs and speed up the learning convergence, we perform all the aboved operations in Laplacian of Gaussian (LoG) domain. After obtaining the bone decomposition result in DRR, we upsample it to a high resolution, based on which the bone region in the original high-resolution CXR is cropped and processed to produce a high-resolution bone decomposition result. Finally, such a produced bone image is subtracted from the original high-resolution CXR to obtain the bone suppression result. We conduct experiments and clinical evaluations based on two benchmarking CXR databases to show that (i) the proposed method outperforms the state-of-the-art unsupervised CXR bone suppression approaches; (ii) the CXRs with bone suppression are instrumental to radiologists for reducing their false-negative rate of lung diseases from 15% to 8%; and (iii) state-of-the-art disease classification performances are achieved by learning a deep network that takes the original CXR and its bone-suppressed image as inputs.
A wide spectrum of clinical manifestations has become a hallmark of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic, although the immunological underpinnings of ...diverse disease outcomes remain to be defined. We performed detailed characterization of B cell responses through high-dimensional flow cytometry to reveal substantial heterogeneity in both effector and immature populations. More notably, critically ill patients displayed hallmarks of extrafollicular B cell activation and shared B cell repertoire features previously described in autoimmune settings. Extrafollicular activation correlated strongly with large antibody-secreting cell expansion and early production of high concentrations of SARS-CoV-2-specific neutralizing antibodies. Yet, these patients had severe disease with elevated inflammatory biomarkers, multiorgan failure and death. Overall, these findings strongly suggest a pathogenic role for immune activation in subsets of patients with COVID-19. Our study provides further evidence that targeted immunomodulatory therapy may be beneficial in specific patient subpopulations and can be informed by careful immune profiling.
Multi-modal tumor segmentation exploits complementary information from different modalities to help recognize tumor regions. Known multi-modal segmentation methods mainly have deficiencies in two ...aspects: First, the adopted multi-modal fusion strategies are built upon well-aligned input images, which are vulnerable to spatial misalignment between modalities (caused by respiratory motions, different scanning parameters, registration errors, etc). Second, the performance of known methods remains subject to the uncertainty of segmentation, which is particularly acute in tumor boundary regions. To tackle these issues, in this paper, we propose a novel multi-modal tumor segmentation method with deformable feature fusion and uncertain region refinement. Concretely, we introduce a deformable aggregation module, which integrates feature alignment and feature aggregation in an ensemble, to reduce inter-modality misalignment and make full use of cross-modal information. Moreover, we devise an uncertain region inpainting module to refine uncertain pixels using neighboring discriminative features. Experiments on two clinical multi-modal tumor datasets demonstrate that our method achieves promising tumor segmentation results and outperforms state-of-the-art methods.
Semi-supervised learning (SSL) methods show their powerful performance to deal with the issue of data shortage in the field of medical image segmentation. However, existing SSL methods still suffer ...from the problem of unreliable predictions on unannotated data due to the lack of manual annotations for them. In this paper, we propose an unreliability-diluted consistency training (UDiCT) mechanism to dilute the unreliability in SSL by assembling reliable annotated data into unreliable unannotated data. Specifically, we first propose an uncertainty-based data pairing module to pair annotated data with unannotated data based on a complementary uncertainty pairing rule, which avoids two hard samples being paired off. Secondly, we develop SwapMix, a mixed sample data augmentation method, to integrate annotated data into unannotated data for training our model in a low-unreliability manner. Finally, UDiCT is trained by minimizing a supervised loss and an unreliability-diluted consistency loss, which makes our model robust to diverse backgrounds. Extensive experiments on three chest CT datasets show the effectiveness of our method for semi-supervised CT lesion segmentation.
Among patients with coronavirus disease (COVID-19), IgM levels increased early after symptom onset for those with mild and severe disease, but IgG levels increased early only in those with severe ...disease. A similar pattern was observed in a separate serosurveillance cohort. Mild COVID-19 should be investigated separately from severe COVID-19.
Identification of differentially expressed genes is an important step in extracting knowledge from gene expression profiling studies. The raw expression data from microarray and other high-throughput ...technologies is deposited into the Gene Expression Omnibus (GEO) and served as Simple Omnibus Format in Text (SOFT) files. However, to extract and analyze differentially expressed genes from GEO requires significant computational skills.
Here we introduce GEO2Enrichr, a browser extension for extracting differentially expressed gene sets from GEO and analyzing those sets with Enrichr, an independent gene set enrichment analysis tool containing over 70 000 annotated gene sets organized into 75 gene-set libraries. GEO2Enrichr adds JavaScript code to GEO web-pages; this code scrapes user selected accession numbers and metadata, and then, with one click, users can submit this information to a web-server application that downloads the SOFT files, parses, cleans and normalizes the data, identifies the differentially expressed genes, and then pipes the resulting gene lists to Enrichr for downstream functional analysis. GEO2Enrichr opens a new avenue for adding functionality to major bioinformatics resources such GEO by integrating tools and resources without the need for a plug-in architecture. Importantly, GEO2Enrichr helps researchers to quickly explore hypotheses with little technical overhead, lowering the barrier of entry for biologists by automating data processing steps needed for knowledge extraction from the major repository GEO.
GEO2Enrichr is an open source tool, freely available for installation as browser extensions at the Chrome Web Store and FireFox Add-ons. Documentation and a browser independent web application can be found at http://amp.pharm.mssm.edu/g2e/.
avi.maayan@mssm.edu.
Purpose:
Pelvic bone segmentation in CT has always been an essential step in clinical diagnosis and surgery planning of pelvic bone diseases. Existing methods for pelvic bone segmentation are either ...hand-crafted or semi-automatic and achieve limited accuracy when dealing with image appearance variations due to the multi-site domain shift, the presence of contrasted vessels, coprolith and chyme, bone fractures, low dose, metal artifacts, etc. Due to the lack of a large-scale pelvic CT dataset with annotations, deep learning methods are not fully explored.
Methods:
In this paper, we aim to bridge the data gap by curating a large pelvic CT dataset pooled from multiple sources, including 1184 CT volumes with a variety of appearance variations. Then, we propose for the first time, to the best of our knowledge, to learn a deep multi-class network for segmenting lumbar spine, sacrum, left hip, and right hip, from multiple-domain images simultaneously to obtain more effective and robust feature representations. Finally, we introduce a post-processor based on the signed distance function (SDF).
Results:
Extensive experiments on our dataset demonstrate the effectiveness of our automatic method, achieving an average Dice of 0.987 for a metal-free volume. SDF post-processor yields a decrease of 15.1% in Hausdorff distance compared with traditional post-processor.
Conclusion:
We believe this large-scale dataset will promote the development of the whole community and open source the images, annotations, codes, and trained baseline models at
https://github.com/ICT-MIRACLE-lab/CTPelvic1K
.
Rates of arteriovenous fistula maturation failure are still high, especially when suboptimal size veins are used. During successful maturation, the vein undergoes lumen dilatation and medial ...thickening, adapting to the increased hemodynamic forces. The vascular extracellular matrix plays an important role in regulating these adaptive changes and may be a target for promoting fistula maturation. In this study, we tested whether a device-enabled photochemical treatment of the vein prior to fistula creation facilitates maturation. Sheep cephalic veins were treated using a balloon catheter coated by a photoactivatable molecule (10-8-10 Dimer) and carrying an internal light fiber. As a result of the photochemical reaction, new covalent bonds were created during light activation among oxidizable amino acids of the vein wall matrix proteins. The treated vein lumen diameter and media area became significantly larger than the contralateral control fistula vein at 1 week (
= 0.035 and
= 0.034, respectively). There was also a higher percentage of proliferating smooth muscle cells in the treated veins than in the control veins (
= 0.029), without noticeable intimal hyperplasia. To prepare for the clinical testing of this treatment, we performed balloon over-dilatation of isolated human veins and found that veins can tolerate up to 66% overstretch without notable histological damage.
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