Signatures of selection in core and accessory genomes indicate different ecological drivers of diversification among Bacillus cereus clades.

Bacterial clades are often ecologically distinct, despite extensive horizontal gene transfer (HGT). How selection works on different parts of bacterial pan-genomes to drive and maintain the emergence of clades is unclear. Focusing on the three largest clades in the diverse and well-studied Bacillus cereus sensu lato group, we identified clade-specific core genes (present in all clade members) and then used clade-specific allelic diversity to identify genes under purifying and diversifying selection. Clade-specific accessory genes (present in a subset of strains within a clade) were characterized as being under selection using presence/absence in specific clades. Gene ontology analyses of genes under selection revealed that different gene functions were enriched in different clades. Furthermore, some gene functions were enriched only amongst clade-specific core or accessory genomes. Genes under purifying selection were often clade-specific, while genes under diversifying selection showed signs of frequent HGT. These patterns are consistent with different selection pressures acting on both the core and the accessory genomes of different clades and can lead to ecological divergence in both cases. Examining variation in allelic diversity allows us to uncover genes under clade-specific selection, allowing ready identification of strains and their ecological niche.

Restriction Spectrum Imaging-Magnetic Resonance Imaging to Improve Prostate Cancer Imaging in Men on Active Surveillance.

PURPOSE: Restriction spectrum imaging-magnetic resonance imaging is a short duration enhanced diffusion-weighted technique that seeks to standardize sequences and predict upgrading. We test this technology for active surveillance biopsies. Our objective is to investigate the utility of restriction spectrum imaging-magnetic resonance imaging to improve upgrading detection in a prostate cancer active surveillance cohort. MATERIALS AND METHODS: We prospectively enrolled men on active surveillance undergoing repeat biopsy from January 2016 to June 2019. Subjects underwent prostate multiparametric magnetic resonance imaging and restriction spectrum imaging-magnetic resonance imaging reviewed by a urological radiologist for PI-RADS® scored lesions, followed by magnetic resonance imaging-guided prostate biopsy by a urologist. Restriction spectrum imaging-magnetic resonance imaging analysis with proprietary research software (CorTechs Labs, San Diego, California) generated a restricted signal map. We compared the restricted signal map and apparent diffusion coefficient values using T-test, ANOVA, and logistic regression analyses for prediction of upgrading. RESULTS: Of 123 enrolled men we identified 74 restriction spectrum imaging-magnetic resonance imaging regions of interest (targeted lesions) in 110 subjects, with 105 subjects completing biopsy. The restricted signal map was significant per PI-RADS score for true-positive lesion detection (mean difference 28, SD 0.7, p=0.001), and better than apparent diffusion coefficient (mean difference -15, SD 55, p=0.6). Restriction spectrum imaging generated restricted signal map values >50 improved sensitivity, specificity, positive predictive value and negative predictive value (81.0%, 81.8%, 54.2% and 94.2%) over PI-RADS ≥3 (71.4%, 38.9%, 23.7% and 83.7%, respectively) for Gleason upgrading. Overall restriction spectrum imaging is able to improve the AUC of 0.70 (95% CI 0.49-0.92, p=0.03) to 0.90 (95% CI 0.82-0.98, p <0.001). CONCLUSIONS: Restriction spectrum imaging-magnetic resonance imaging enhances the standard PI-RADS system by providing a noninvasive radiological biomarker to predict upgrading in active surveillance.

C3HeB/FeJ Mice mimic many aspects of gene expression and pathobiological features of human hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) remains a deadly cancer, underscoring the need for relevant preclinical models. Male C3HeB/FeJ mice model spontaneous HCC with some hepatocarcinogenesis susceptibility loci corresponding to syntenic regions of human chromosomes altered in HCC. We tested other properties of C3HeB/FeJ tumors for similarity to human HCC. C3HeB/FeJ tumors were grossly visible at 4 months of age, with prevalence and size increasing until about 11 months of age. Histologic features shared with human HCC include hepatosteatosis, tumor progression from dysplasia to poorly differentiated, vascular invasion, and trabecular, oncocytic, vacuolar, and clear cell variants. More tumor cells displayed cytoplasmic APE1 staining versus normal liver. Ultrasound effectively detected and monitored tumors, with 85.7% sensitivity. Over 5000 genes were differentially expressed based on the GSE62232 and GSE63898 human HCC datasets. Of these, 158 and 198 genes, respectively, were also differentially expressed in C3HeB/FeJ. Common cancer pathways, cell cycle, p53 signaling and other molecular aspects, were shared between human and mouse differentially expressed genes. We established eigengenes that distinguish HCC from normal liver in the C3HeB/FeJ model and a subset of human HCC. These features extend the relevance and improve the utility of the C3HeB/FeJ line for HCC studies.

Trailblazing: the historical development of the posterior lumbar interbody fusion (PLIF).

Today, the posterior lumbar interbody fusion (PLIF), and related methods of fusion, represent the gold standard in spinal arthrodesis. However, despite the PLIF being first performed in the 1940s, its reputation was marked by animosity for the next fifty years. Only due to the extraordinary talent and perseverance from a small group of pioneers, was the operation eventually appreciated to be an ideal fusion technique. This process of popularization has assisted the surgical community to better recognize the complexities of spinal biomechanics and has encouraged the momentum of success in modern spinal surgery. Neither the complete origins of the technique, nor the remarkable story of its propagation, have previously been reported.

Divergence in environmental adaptation between terrestrial clades of the Bacillus cereus group.

The Bacillus cereus group encompasses beneficial and harmful species in diverse niches and has a much debated taxonomy. Investigating whether selection has led to ecological divergence between phylogenetic clades can help understand the basis of speciation, and has implications for predicting biological safety across this group. Using three most terrestrial species in this group (B. cereus, Bacillus thuringiensis and Bacillus mycoides) we charactererized ecological specialization in terms of resource use, thermal adaptation and fitness in different environmental conditions and tested whether taxonomic species or phylogenetic clade best explained phenotypic variation. All isolates grew vigorously in protein rich media and insect cadavers, but exploitation of soil or plant derived nutrients was similarly weak for all. For B. thuringiensis and B. mycoides, clade and taxonomic species were important predictors of relative fitness in insect infections. Fully psychrotolerant isolates could outcompete B. thuringiensis in insects at low temperature, although psychrotolerance predicted growth in artificial media better than clade. In contrast to predictions, isolates in the Bacillus anthracis clade had sub-optimal growth at 37°C. The common ecological niche in these terrestrial B. cereus species is the ability to exploit protein rich resources such as cadavers. However, selection has led to different phylogenetic groups developing different strategies for accessing this resource. Thus, clades, as well as traditional taxonomic phenotypes, predict biologically important traits.

Validation of 3D volumetric-based renal function prediction calculator for nephron sparing surgery.

OBJECTIVE: To evaluate a recently published volume-based renal function prediction calculator intended to be used in small renal mass surgical counseling. METHODS: Retrospective data collection included three-dimensional calculation of renal mass and parenchyma of patients who have undergone extirpative therapy. The predicted glomerular filtration rate (GFR) was calculated using the online calculator. The predicted GFR was compared with the actual 6-month GFR. The Pearson correlation coefficient, paired t test and root-mean-square error (RMSE) are utilized for statistical analysis. RESULTS: After institutional review board approval, three institutions provided data for analysis. After patients with renal mass size >300 cc, renal size >400 cc or preoperative CKD ≥stage 3 had been excluded, we retrospectively analyzed data from 136 patients. The median mass volume was 22.2 cc (IQR 7-49). In multiple linear regression analysis, the most significant variables predicting postoperative GFR were partial versus radical nephrectomy and preoperative GFR with an overall R2 of .68 (F = 26.13, P < .001). The predicted GFR was 75.4 mL/min/1.73 m2 compared to an actual GFR of 70.7 mL/min/1.73 m2 (P < .001, paired t test). The predicted GFR was highly correlated with the actual postoperative GFR at 6 months (Pearson correlation, r = .65, P < .001). RMSE of the validation cohort was 16.87. CONCLUSIONS: The predictive tool to determine renal function benefit of nephron sparing surgery compared to radical nephrectomy online calculator effectively predicts GFR and could potentially be used to help urologists and patients discuss renal function prior to extirpative renal surgery.

Transcolonic Migration of Retained Epicardial Pacing Wires.

Temporary epicardial pacing wires are associated with rare complications. Most of these occur in the chest. Even rarer are complications that occur within the abdomen. We report a case of migrating epicardial pacing wires entering the abdomen and penetrating the transverse colon found incidentally on colonoscopy in an asymptomatic patient.

Evaluation of coronary artery image quality with knowledge-based iterative model reconstruction.

RATIONALE AND OBJECTIVES: To evaluate knowledge-based iterative model reconstruction (IMR) to improve image quality and reduce radiation dose in coronary computed tomography angiography (cCTA). MATERIALS AND METHODS: We evaluated 45 consecutive cCTA studies, including 25 studies performed with an 80% systolic dose reduction using tube current modulation (TCM). Each study was reconstructed with filtered back projection (FBP), hybrid iterative reconstruction (iDose(4)), and IMR in a diastolic phase. Additional systolic phase reconstructions were obtained for TCM studies. Mean pixel attenuation value and standard deviation (SD) were measured in the left ventricle and left main coronary artery. Subjective scores were obtained by two independent reviewers on a 5-point scale for definitions of contours of small coronary arteries (<3 mm), coronary calcifications, noncalcified plaque, and overall diagnostic confidence for the presence/absence of stenosis. RESULTS: There was no significant difference in pixel intensity among FBP, iDose(4), and IMR (P > .8). For diastolic phase images, noise amplitude in the left main coronary artery was reduced by a factor of 1.3 from FBP to iDose(4) (SD = 99 vs. 74; P = .005) and by a factor of 2.6 from iDose(4) to IMR (SD = 74 vs. 28; P < .001). For systolic phase TCM images, noise amplitude in the left main coronary artery was reduced by a factor of 2.3 from FBP to iDose(4) (SD = 322 vs. 142; P < .001) and by a factor of 3.0 from iDose(4) to IMR (SD = 142 vs. 48; P < .001). All four subjective image quality scores were significantly better with IMR compared to iDose(4) and FBP (P < .001). The reduction in image noise amplitude and improvement in image quality scores were greatest among obese patients. CONCLUSIONS: IMR reduces intravascular noise on cCTA by 86%-88% compared to FBP, and improves image quality at radiation exposure levels 80% below our standard technique.