Arthropods transmit diverse infectious agents; however, the ways microbes influence their vector to enhance colonization are poorly understood.Ixodes scapularisticks harbor numerous human pathogens, includingAnaplasma phagocytophilum,the agent of human granulocytic anaplasmosis. We now demonstrate thatA. phagocytophilummodifies theI. scapularismicrobiota to more efficiently infect the tick.A. phagocytophiluminduces ticks to expressIxodes scapularisantifreeze glycoprotein (iafgp), which encodes a protein with several properties, including the ability to alter bacterial biofilm formation. IAFGP thereby perturbs the tick gut microbiota, which influences the integrity of the peritrophic matrix and gut barrier—critical obstacles forAnaplasmacolonization. Mechanistically, IAFGP binds the terminald-alanine residue of the pentapeptide chain of bacterial peptidoglycan, resulting in altered permeability and the capacity of bacteria to form biofilms. These data elucidate the molecular mechanisms by which a human pathogen appropriates an arthropod antibacterial protein to alter the gut microbiota and more effectively colonize the vector.

Purpose: To determine if mosaic tuberous sclerosis complex (TSC) can be stratified into subtypes that correspond with prognosis and extent of disease. Methods: Next-generation sequencing of skin tumor and other samples was used to identify patients with mosaic pathogenic variants in TSC1 or TSC2 . Extent of disease, onset age, and family history of TSC were determined through retrospective analysis of patient records. Results: The median number of disease findings and age at penetrance differed between mosaic patients with asymmetrically distributed facial angiofibromas (4 findings, 24y, n=7), mosaic patients with bilaterally symmetric facial angiofibromas (8 findings, 10y, n=12), and germline TSC patients (10 findings, 4y, n=29). Cutaneous and internal organ involvement positively correlated in mosaic (R=0.62, p=0.005), but not germline (R=−0.24, p=0.24) TSC. Variant allele fraction (VAF) in the blood (range: 0-19%) positively correlated with the number of major features (R=0.55, p=0.028). Five had a TSC2 variant identified in the skin that was below detection in the blood. One of 12 children from a mosaic parent had TSC. Conclusion: The phenotype of mosaic TSC ranged from mild to indistinguishable from germline disease. Patients with mosaicism and asymmetric facial angiofibromas exhibited fewer findings, later onset, and lower VAF in the blood.

Image segmentation is a fundamental problem in medical image analysis. In recent years, deep neural networks achieve impressive performances on many medical image segmentation tasks by supervised learning on large manually annotated data. However, expert annotations on big medical datasets are tedious, expensive or sometimes unavailable. Weakly supervised learning could reduce the effort for annotation but still required certain amounts of expertise. Recently, deep learning shows a potential to produce more accurate predictions than the original erroneous labels. Inspired by this, we introduce a very weakly supervised learning method, for cystic lesion detection and segmentation in lung CT images, without any manual annotation. Our method works in a self-learning manner, where segmentation generated in previous steps (first by unsupervised segmentation then by neural networks) is used as ground truth for the next level of network learning. Experiments on a cystic lung lesion dataset show that the deep learning could perform better than the initial unsupervised annotation, and progressively improve itself after self-learning.

BACKGROUND Secondary peritonitis continues to carry a high mortality rate despite aggressive use of imaging, drainage and antibiotics. Although host factors and microbial burden contribute to the outcome of peritonitis, here we propose a role bacterial virulence as a determinant of outcome from peritonitis. Bacterial virulence is an inducible trait that is activated in response to specific local “cues” that we have previously shown to be present in the mouse gut exposed to surgical stress and injury. METHODS Pseudomonas aeruginosa was harvested following its intestinal inoculation into the cecum of mice subjected to surgical injury (30% hepatectomy) or sham surgery (controls). Harvested strains were then injected into the peritoneum of non-injured (naïve) mice and mortality determined. RESULTS P. aeruginosa harvested from the intestines of surgically injured mice caused 100% mortality whereas strains harvested from control mice caused no mortality. Among recovered strains a distinct P. aeruginosa morphotype (wrinked shape) was demonstrated to cause lethal peritonitis compared to smooth shaped strains which were non-lethal. Wrinked strains were associated with a tendency to elicit a more pro inflammatory response in mice compared to smooth shaped strains. CONCLUSIONS Surgical injury transforms the morphotype of intestinal P. aeruginosa to express a hypervirulent response in the peritoneum of mice. Enhanced virulence of intestinal pathogens in response to surgical injury may play an important role in predicting the outcome of peritonitis.

BACKGROUND:In lymphangioleiomyomatosis (LAM), infiltration of the lungs with smooth muscle-like LAM cells results in cystic destruction and decline in lung function, effects stabilized by sirolimus therapy. LAM lung disease is followed, in part, by high-resolution CT scans. To obtain further information from these scans, we quantified changes in lung parenchyma by analyzing image "texture."METHODS: Twenty-six texture properties were quantified by analyzing the distribution and intensity of pixels with a computer-aided system. Both cross-sectional and longitudinal studies were performed to examine the relationships between texture properties, cyst score (percentage of lung occupied by cysts), FEV 1 , and diffusion capacity for carbon monoxide (DLCO), and to determine the effect of sirolimus treatment. RESULTS:In the cross-sectional study, 18 texture properties showed significant positive correlations with cyst score. Cyst score and 13 of the 18 texture properties showed significant differences in rates of change after sirolimus treatment; 11 also significantly predicted FEV 1 and DLCO.CONCLUSIONS: Increased cyst score was associated with increased texture degradation near cysts. Sirolimus treatment improved lung texture surrounding cysts and stabilized cyst score. Eleven texture properties were associated with FEV 1 , DLCO, cyst score, and response to sirolimus. Texture analysis may be valuable in evaluating LAM severity and treatment response.

We present a solution to meet an unmet clinical need of an in‐situ “close look” at a pulmonary nodule or at the margins of a pulmonary cyst revealed by a primary (screening) chest CT while the patient is still in the scanner. We first evaluated options available on current whole‐body CT scanners for high resolution screening scans, including ROI reconstruction of the primary scan data and HRCT, but found them to have insufficient SNR in lung tissue or discontinuous slice coverage. Within the capabilities of current clinical CT systems, we opted for the solution of a secondary, volume‐of‐interest (VOI) protocol where the radiation dose is focused into a short‐beam axial scan at the z position of interest, combined with a small‐FOV reconstruction at the xy position of interest. The objective of this work was to design a VOI protocol that is optimized for targeted lung imaging in a clinical whole‐body CT system. Using a chest phantom containing a lung‐mimicking foam insert with a simulated cyst, we identified the appropriate scan mode and optimized both the scan and recon parameters. The VOI protocol yielded 3.2 times the texture amplitude‐to‐noise ratio in the lung‐mimicking foam when compared to the standard chest CT, and 8.4 times the texture difference between the lung mimicking and reference foams. It improved details of the wall of the simulated cyst and better resolution in a line‐pair insert. The Effective Dose of the secondary VOI protocol was 42% on average and up to 100% in the worst‐case scenario of VOI positioning relative to the standard chest CT. The optimized protocol will be used to obtain detailed CT textures of pulmonary lesions, which are biomarkers for the type and stage of lung diseases.

BACKGROUND: Given the rising utilization of medical imaging and the risks of radiation, there is increased interest in reducing radiation exposure. The objective of this study was to evaluate, as a proof of principle, CT scans performed at radiation doses equivalent to that of a posteroanterior and lateral chest radiograph series in the cystic lung disease lymphangioleiomyomatosis (LAM). METHODS: From November 2016 to May 2018, 105 consecutive subjects with LAM received chest CT scans at standard and ultra-low radiation doses. Standard and ultra-low-dose images, respectively, were reconstructed with routine iterative and newer model-based iterative reconstruction. LAM severity can be quantified as cyst score (percentage of lung occupied by cysts), an ideal benchmark for validating CT scans performed at a reduced dose compared with a standard dose. Cyst scores were quantified using semi-automated software and evaluated by linear correlation and Bland-Altman analysis. RESULTS: Overall, ultra-low-dose CT scans represented a 96% dose reduction, with a median dose equivalent to 1 vs 22 posteroanterior and lateral chest radiograph series (0.14 mSv; 5th-95th percentile, 0.10-0.20 vs standard dose 3.4 mSv; 5th-95th percentile, 1.5-7.4; P < .0001). The mean difference in cyst scores between ultra-low-and standard-dose CT scans was 1.1% AE 2.0%, with a relative difference in cyst score of 11%. Linear correlation coefficient was excellent at 0.97 (P < .0001). CONCLUSIONS: In LAM chest CT scan at substantial radiation reduction to doses equivalent to that of a posteroanterior and lateral chest radiograph series provides cyst score quantification similar to that of standard-dose CT scan.

Future work will involve more comprehensive representation of host factors, and especially the ability of those host factors to activate virulence potential in the microbes involved.