A Structured Tumor-Immune Microenvironment in Triple Negative Breast Cancer Revealed by Multiplexed Ion Beam Imaging.

The immune system is critical in modulating cancer progression, but knowledge of immune composition, phenotype, and interactions with tumor is limited. We used multiplexed ion beam imaging by time-of-flight (MIBI-TOF) to simultaneously quantify in situ expression of 36 proteins covering identity, function, and immune regulation at sub-cellular resolution in 41 triple-negative breast cancer patients. Multi-step processing, including deep-learning-based segmentation, revealed variability in the composition of tumor-immune populations across individuals, reconciled by overall immune infiltration and enriched co-occurrence of immune subpopulations and checkpoint expression. Spatial enrichment analysis showed immune mixed and compartmentalized tumors, coinciding with expression of PD1, PD-L1, and IDO in a cell-type- and location-specific manner. Ordered immune structures along the tumor-immune border were associated with compartmentalization and linked to survival. These data demonstrate organization in the tumor-immune microenvironment that is structured in cellular composition, spatial arrangement, and regulatory-protein expression and provide a framework to apply multiplexed imaging to immune oncology.

CoInNet: A Convolution-Involution Network With a Novel Statistical Attention for Automatic Polyp Segmentation.

Polyps are very common abnormalities in human gastrointestinal regions. Their early diagnosis may help in reducing the risk of colorectal cancer. Vision-based computer-aided diagnostic systems automatically identify polyp regions to assist surgeons in their removal. Due to their varying shape, color, size, texture, and unclear boundaries, polyp segmentation in images is a challenging problem. Existing deep learning segmentation models mostly rely on convolutional neural networks that have certain limitations in learning the diversity in visual patterns at different spatial locations. Further, they fail to capture inter-feature dependencies. Vision transformer models have also been deployed for polyp segmentation due to their powerful global feature extraction capabilities. But they too are supplemented by convolution layers for learning contextual local information. In the present paper, a polyp segmentation model CoInNet is proposed with a novel feature extraction mechanism that leverages the strengths of convolution and involution operations and learns to highlight polyp regions in images by considering the relationship between different feature maps through a statistical feature attention unit. To further aid the network in learning polyp boundaries, an anomaly boundary approximation module is introduced that uses recursively fed feature fusion to refine segmentation results. It is indeed remarkable that even tiny-sized polyps with only 0.01% of an image area can be precisely segmented by CoInNet. It is crucial for clinical applications, as small polyps can be easily overlooked even in the manual examination due to the voluminous size of wireless capsule endoscopy videos. CoInNet outperforms thirteen state-of-the-art methods on five benchmark polyp segmentation datasets.

A deep CNN model for anomaly detection and localization in wireless capsule endoscopy images.

Wireless capsule endoscopy (WCE) is one of the most efficient methods for the examination of gastrointestinal tracts. Computer-aided intelligent diagnostic tools alleviate the challenges faced during manual inspection of long WCE videos. Several approaches have been proposed in the literature for the automatic detection and localization of anomalies in WCE images. Some of them focus on specific anomalies such as bleeding, polyp, lesion, etc. However, relatively fewer generic methods have been proposed to detect all those common anomalies simultaneously. In this paper, a deep convolutional neural network (CNN) based model 'WCENet' is proposed for anomaly detection and localization in WCE images. The model works in two phases. In the first phase, a simple and efficient attention-based CNN classifies an image into one of the four categories: polyp, vascular, inflammatory, or normal. If the image is classified in one of the abnormal categories, it is processed in the second phase for the anomaly localization. Fusion of Grad-CAM++ and a custom SegNet is used for anomalous region segmentation in the abnormal image. WCENet classifier attains accuracy and area under receiver operating characteristic of 98% and 99%. The WCENet segmentation model obtains a frequency weighted intersection over union of 81%, and an average dice score of 56% on the KID dataset. WCENet outperforms nine different state-of-the-art conventional machine learning and deep learning models on the KID dataset. The proposed model demonstrates potential for clinical applications.

Deaf intermarriage has limited effect on the prevalence of recessive deafness and no effect on underlying allelic frequency.

The idea that deaf intermarriage increases the prevalence of deafness was forcefully pushed in the late 19th century by Alexander Graham Bell, in proceedings published by the National Academy of Science. Bell's hypothesis was not supported by a 19th century study by Edward Allen Fay, which was funded by Bell's own organization, the Volta Bureau. The Fay study showed through an analysis of 4,471 deaf marriages that the chances of having deaf children did not increase significantly when both parents were deaf. In light of an apparent increase in non-complementary pairings when a modern dataset of Gallaudet alumni was compared with the 19th century Fay dataset, Bell's argument has been resurrected. This hypothesis is that residential schools for the deaf, which concentrate signing deaf individuals together, have promoted assortative mating, which in turn has increased the prevalence of recessive deafness and also the commonest underlying deafness allele. Because this hypothesis persists, even though it contradicts classical models of assortative mating, it is critically important that it be thoroughly investigated. In this study, we used an established forward-time genetics simulator with parameters and measurements collected from the published literature. Compared to mathematical equations, simulations allowed for more complex modeling, operated without assumptions of parametricity, and captured ending distributions and variances. Our simulation results affirm predictions from classical equations and show that intense assortative mating only modestly increases the prevalence of deafness, with this effect mostly completed by the third generation. More importantly, our data show that even intense assortative mating does not affect the frequency of the underlying alleles under reported conditions. These results are not locus-specific and are generalizable to other forms of recessive deafness. We explain the higher rate of non-complementary pairings measured in the contemporary Gallaudet alumni sample as compared to the Fay dataset.

Detection of abnormality in wireless capsule endoscopy images using fractal features.

One of the most recent non-invasive technologies to examine the gastrointestinal tract is wireless capsule endoscopy (WCE). As there are thousands of endoscopic images in an 8-15 h long video, an evaluator has to pay constant attention for a relatively long time (60-120 min). Therefore the possibility of the presence of pathological findings in a few images (displayed for evaluation for a few seconds only) brings a significant risk of missing the pathology with all negative consequences for the patient. Hence, manually reviewing a video to identify abnormal images is not only a tedious and time consuming task that overwhelms human attention but also is error prone. In this paper, a method is proposed for the automatic detection of abnormal WCE images. The differential box counting method is used for the extraction of fractal dimension (FD) of WCE images and the random forest based ensemble classifier is used for the identification of abnormal frames. The FD is a well-known technique for extraction of features related to texture, smoothness, and roughness. In this paper, FDs are extracted from pixel-blocks of WCE images and are fed to the classifier for identification of images with abnormalities. To determine a suitable pixel block size for FD feature extraction, various sizes of blocks are considered and are fed into six frequently used classifiers separately, and the block size of 7×7 giving the best performance is empirically determined. Further, the selection of the random forest ensemble classifier is also done using the same empirical study. Performance of the proposed method is evaluated on two datasets containing WCE frames. Results demonstrate that the proposed method outperforms some of the state-of-the-art methods with AUC of 85% and 99% on Dataset-I and Dataset-II respectively.