A meta-analysis of contrast-enhanced spectral mammography versus MRI in the diagnosis of breast cancer.

BACKGROUND: To identify the performance of contrast-enhanced spectral mammography (CESM) and magnetic resonance imaging (MRI) for breast cancer diagnosis by pooling the open published data. METHODS: A systematic review of studies relevant to CESM and MRI in the diagnosis of breast cancer were screened in the electronic databases of Pubmed, EMBASE, the Cochrane Library, Web of Science, Google scholar and CNKI. The methodical quality of the included publications was evaluated by the quality assessment of diagnostic accuracy studies-2 (QUADAS-2). The diagnostic sensitivity, specificity and area under the ROC curve (AUC) were pooled and the true positive (TP), false positive (FP), false negative (FN) and true negative (TN) of the original studies were calculated. RESULTS: A total of 13 diagnostic publications were identified and included in the meta-analysis. Of those included, five were retrospective studies and the remaining eight were prospective work. The combined data indicating the pooled sensitivity and specificity of CESM and MRI were 0.97 (95% CI: 0.95-0.98), 0.66 (95% CI: 0.59-0.71), 0.97 (95% CI: 0.95-0.98),and 0.52 (95% CI: 0.46-0.58), respectively. The pooled +LR and -LR for CESM were 2.70 (95% CI: 1.57-4.65), 0.06 (95% CI: 0.04-0.09), and 2.01 (95% CI: 1.78-2.26), 0.08 (95% CI: 0.05-0.11) for MRI, respectively. For the diagnostic odds ratio (DOR), the pooled results of CESM and MRI were 60.15 (95% CI: 24.72-146.37) and 31.34 (95% CI: 19.61-50.08), respectively. The AUC of the symmetric receiver operating characteristic curve (SROC) was 0.9794 and 0.9157 for CESM and MRI, respectively, calculated using the Moses model in the diagnosis of breast cancer. CONCLUSIONS: Both CESM and MRI are effective methods for the detection of breast cancer with high diagnostic sensitivity. The diagnostic performance of CESM appears to be more effective than MRI.

Gain of CTCF-Anchored Chromatin Loops Marks the Exit from Naive Pluripotency.

The genome of pluripotent stem cells adopts a unique three-dimensional architecture featuring weakly condensed heterochromatin and large nucleosome-free regions. Yet, it is unknown whether structural loops and contact domains display characteristics that distinguish embryonic stem cells (ESCs) from differentiated cell types. We used genome-wide chromosome conformation capture and super-resolution imaging to determine nuclear organization in mouse ESC and neural stem cell (NSC) derivatives. We found that loss of pluripotency is accompanied by widespread gain of structural loops. This general architectural change correlates with enhanced binding of CTCF and cohesins and more pronounced insulation of contacts across chromatin boundaries in lineage-committed cells. Reprogramming NSCs to pluripotency restores the unique features of ESC domain topology. Domains defined by the anchors of loops established upon differentiation are enriched for developmental genes. Chromatin loop formation is a pervasive structural alteration to the genome that accompanies exit from pluripotency and delineates the spatial segregation of developmentally regulated genes.

Correlative live and super-resolution imaging reveals the dynamic structure of replication domains.

Chromosome organization in higher eukaryotes controls gene expression, DNA replication, and DNA repair. Genome mapping has revealed the functional units of chromatin at the submegabase scale as self-interacting regions called topologically associating domains (TADs) and showed they correspond to replication domains (RDs). A quantitative structural and dynamic description of RD behavior in the nucleus is, however, missing because visualization of dynamic subdiffraction-sized RDs remains challenging. Using fluorescence labeling of RDs combined with correlative live and super-resolution microscopy in situ, we determined biophysical parameters to characterize the internal organization, spacing, and mechanical coupling of RDs. We found that RDs are typically 150 nm in size and contain four co-replicating regions spaced 60 nm apart. Spatially neighboring RDs are spaced 300 nm apart and connected by highly flexible linker regions that couple their motion only <550 nm. Our pipeline allows a robust quantitative characterization of chromosome structure in situ and provides important biophysical parameters to understand general principles of chromatin organization.

Evaluation of Hepatic Tumors Using Intravoxel Incoherent Motion Diffusion-Weighted MRI.

BACKGROUND This study aimed to evaluate the diagnostic value of the D value, D* value, and f magnitude for identifying benign and malignant hepatic tumors using intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI). MATERIAL AND METHODS Data of 89 cases (123 lesions) with hepatic tumor confirmed by surgical pathology and postoperative follow-up were retrospectively collected. Among these cases, 40 cases were benign hepatic tumors (57 lesions) and 49 cases were malignant hepatic tumors (66 lesions). All subjects underwent conventional MRI with T1WI, T2WI, multi-b-value DWI, and dynamic enhanced LAVA scan. Diffusion-weighted images with 11 b values (0, 10, 20, 30, 50, 80, 100, 200, 400, 800, and 1000 s/mm2) were obtained to calculate true molecular diffusion (D), perfusion-related diffusion coefficient (D*), and perfusion fraction (f). The diagnostic performance in differentiating between malignant and benign hepatic lesions was analyzed. RESULTS Malignant lesions had a significantly lower D value ([1.04±0.34]×10-3 mm2/s) and D* value ([16.5±7.7]×10-3 mm2/s) compared to benign lesions (D value: [1.70±0.55]×10-3 mm2/s, P<0.01; D* value: [21.7±9.9]×10-3 mm2/s, P<0.01). There was no statistically significant difference in f values between malignant (23.3±9.5) and benign lesions (33.5±14.9, P=0.13). In addition, D exhibited a better diagnostic performance than D* in terms of the area under the curve, sensitivity, and specificity when identifying malignancies from benign lesions. CONCLUSIONS D and D* are significant parameters for diagnosing hepatic tumors. Moreover, the D value is a more reliable parameter in distinguishing benign and malignant hepatic tumors.

Live imaging and modeling of inner nuclear membrane targeting reveals its molecular requirements in mammalian cells.

Targeting of inner nuclear membrane (INM) proteins is essential for nuclear architecture and function, yet its mechanism remains poorly understood. Here, we established a new reporter that allows real-time imaging of membrane protein transport from the ER to the INM using Lamin B receptor and Lap2ß as model INM proteins. These reporters allowed us to characterize the kinetics of INM targeting and establish a mathematical model of this process and enabled us to probe its molecular requirements in an RNA interference screen of 96 candidate genes. Modeling of the phenotypes of genes involved in transport of these INM proteins predicted that it critically depended on the number and permeability of nuclear pores and the availability of nuclear binding sites, but was unaffected by depletion of most transport receptors. These predictions were confirmed with targeted validation experiments on the functional requirements of nucleoporins and nuclear lamins. Collectively, our data support a diffusion retention model of INM protein transport in mammalian cells.

Isoform-specific regulation of the inositol 1,4,5-trisphosphate receptor by O-linked glycosylation.

The inositol 1,4,5-trisphosphate receptor (InsP(3)R), an intracellular calcium channel, has three isoforms with >65% sequence homology, yet the isoforms differ in their function and regulation by post-translational modifications. We showed previously that InsP(3)R-1 is functionally modified by O-linked ß-N-acetylglucosamine glycosylation (O-GlcNAcylation) (Rengifo, J., Gibson, C. J., Winkler, E., Collin, T., and Ehrlich, B. E. (2007) J. Neurosci. 27, 13813-13821). We now report the effect of O-GlcNAcylation on InsP(3)R-2 and InsP(3)R-3. Analysis of AR4-2J cells, a rat pancreatoma cell line expressing predominantly InsP(3)R-2, showed no detectable O-GlcNAcylation of InsP(3)R-2 and no significant functional changes despite the presence of the enzymes for addition (O-ß-N-acetylglucosaminyltransferase) and removal (O-ß-N-acetylglucosaminidase) of the monosaccharide. In contrast, InsP(3)R-3 in Mz-ChA-1 cells, a human cholangiocarcinoma cell line expressing predominantly InsP(3)R-3, was functionally modified by O-GlcNAcylation. Interestingly, the functional impact of O-GlcNAcylation on the InsP(3)R-3 channel was opposite the effect measured with InsP(3)R-1. Addition of O-GlcNAc by O-ß-N-acetylglucosaminyltransferase increased InsP(3)R-3 single channel open probability. Incubation of Mz-ChA-1 cells in hyperglycemic medium caused an increase in the InsP(3)-dependent calcium release from the endoplasmic reticulum. The dynamic and inducible nature of O-GlcNAcylation and the InsP(3)R isoform specificity suggest that this form of modification of InsP(3)R and subsequent changes in intracellular calcium transients are important in physiological and pathophysiological processes.