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While new studies emphasize that patients with a CAC greater than or equal to 1000 be considered a distinct patient group, a CAC of 0 has additionally emerged to be a reliable negative risk factor, identifying patients at low risk of both CVD and non-CVD mortality. © RSNA, 2020.

To implement, validate, and apply a self-gated free-running whole-heart five-dimensional (5D) flow MRI framework to evaluate respiration-driven effects on three-dimensional (3D) hemodynamics in a clinical setting.

In this prospective study, a free-running five-dimensional (5D) flow sequence was implemented with 3D radial sampling, self-gating, and a compressed-sensing reconstruction. The 5D flow was evaluated in a pulsatile phantom and adult participants with aortic and/or valvular disease who were enrolled between May and August 2019. Conventional twofold-accelerated four-dimensional (4D) flow of the thoracic aorta with navigator gating was performed as a reference comparison. Continuous parameters were evaluated for parameter normality and were compared between conventional 4D flow and 5D flow using a signed-rank or two-tailed paired

test. Differences between respiratory states were evaluated using a repeated-measure analysis of variance or a nonparametric Friedman test.

A total of 20 adult particimics in less than 8 minutes.

© RSNA, 2020.

A free-running 5D flow MRI framework consistently captured cardiac and respiratory motion-resolved 3D hemodynamics in less than 8 minutes. Supplemental material is available for this article. © RSNA, 2020.Cell division cycle 25 (CDC25) dual specificity phosphatases positively regulate the cell cycle by activating cyclin-dependent kinase/cyclin complexes. Here, we demonstrate that in addition to its role in cell cycle regulation, CDC25B functions as a regulator of protein phosphatase 2A (PP2A), a major cellular Ser/Thr phosphatase, through its direct interaction with PP2A catalytic subunit. Importantly, CDC25B alters the regulation of AMP-activated protein kinase signaling (AMPK) by PP2A, increasing AMPK activity by inhibiting PP2A to dephosphorylate AMPK. CDC25B depletion leads to metformin resistance by inhibiting metformin-induced AMPK activation. Furthermore, dual inhibition of CDC25B and PP2A further inhibits growth of 3D organoids isolated from patient derived xenograft model of breast cancer compared to CDC25B inhibition alone. Our study identifies CDC25B as a regulator of PP2A, and uncovers a mechanism of controlling the activity of a key energy metabolism marker, AMPK.TP53 deficiency in cancer is associated with poor patient outcomes and resistance to DNA damaging therapies. However, the mechanisms underlying treatment resistance in p53-deficient cells remain poorly characterized. Using live cell imaging of DNA double-strand breaks (DSBs) and cell cycle state transitions, we show that p53-deficient cells exhibit accelerated repair of radiomimetic-induced DSBs arising in S phase. Low-dose DNA-dependent protein kinase (DNA-PK) inhibition increases the S-phase DSB burden in p53-deficient cells, resulting in elevated rates of mitotic catastrophe. However, a subset of p53-deficient cells exhibits intrinsic resistance to radiomimetic-induced DSBs despite DNA-PK inhibition. We show that p53-deficient cells under DNA-PK inhibition utilize DNA polymerase theta (Pol θ)-mediated end joining repair to promote their viability in response to therapy-induced DSBs. Pol θ inhibition selectively increases S-phase DSB burden after radiomimetic therapy and promotes prolonged G2 arrest. Dual inhibition of DNA-PK and Pol θ restores radiation sensitivity in p53-deficient cells as well as in p53-mutant breast cancer cell lines. Thus, combination targeting of DNA-PK- and Pol θ-dependent end joining repair represents a promising strategy for overcoming resistance to DNA damaging therapies in p53-deficient cancers.

To evaluate the combination of tumor volume and sound speed as a potential imaging marker for assessing neoadjuvant chemotherapy (NAC) response.

This study was carried out under an IRB-approved protocol (written consent required). Fourteen patients undergoing NAC for invasive breast cancer were examined with ultrasound tomography (UST) throughout their treatment. Selleck MEK inhibitor The volume (V) and the volume-averaged sound speed (VASS) of the tumors and their changes were measured for each patient. Time-dependent response curves of V and VASS were constructed individually for each patient and then as averages for the complete versus partial response groups in order to characterize differences between the two groups. Differences in group means were assessed for statistical significance using

-tests. Differences in shapes of group curves were evaluated with Kolmogorov-Smirnoff tests.

On average, tumor volume and sound speed in the partial response group showed a gradual decline in the first 60 days of treatment, while the complete response group showed a much steeper decline (

< 0.05). The shapes of the response curves of the two groups, corresponding to the entire treatment period, were also found to be significantly different (

< 0.05). Furthermore, large simultaneous drops in volume and sound speed in the first 3 weeks of treatment were characteristic only of the complete responders (

< 0.05).

This study demonstrates the feasibility of using UST to monitor NAC response, warranting future studies to better define the potential of UST for noninvasive, rapid identification of partial versus complete responders in women undergoing NAC.

This study demonstrates the feasibility of using UST to monitor NAC response, warranting future studies to better define the potential of UST for noninvasive, rapid identification of partial versus complete responders in women undergoing NAC.The feasibility of Optical Coherence Tomography (OCT) for in-line monitoring of pharmaceutical film coating processes has recently been demonstrated. OCT enables real-time acquisition of high-resolution cross-sectional images of coating layers and computation of coating thickness. In addition, coating quality attributes can be computed based on in-line data. This study assesses the in-line applicability of OCT to various coating functionalities and formulations. Several types of commercial film-coated tablets containing the most common ingredients were investigated. To that end, the tablets were placed into a miniaturized perforated drum. An in-line OCT system was used to monitor the tablet bed. This set-up resembles the final stage of an industrial pan coating process. All investigated coatings were measured, and the coating thickness, homogeneity and roughness were computed. The rotation rate was varied in a range comparable to large-scale coating operations, and no influence on the outcome was observed. The results indicate that OCT can be used to determine end-point and establish in-process control for a wide range of coating formulations.