Primary cilia are microtubule-based organelles that play important roles in development and tissue homeostasis. Tau-tubulin kinase-2 (TTBK2) is genetically linked to spinocerebellar ataxia type 11, and its kinase activity is crucial for ciliogenesis. Although it has been shown that TTBK2 is recruited to the centriole by distal appendage protein CEP164, little is known about TTBK2 substrates associated with its role in ciliogenesis. Here, we perform superresolution microscopy and discover that serum starvation results in TTBK2 redistribution from the periphery toward the root of distal appendages. Our biochemical analyses uncover CEP83 as a bona fide TTBK2 substrate with four phosphorylation sites characterized. We also demonstrate that CEP164-dependent TTBK2 recruitment to distal appendages is required for subsequent CEP83 phosphorylation. Specifically, TTBK2-dependent CEP83 phosphorylation is important for early ciliogenesis steps, including ciliary vesicle docking and CP110 removal. In summary, our results reveal a molecular mechanism of kinase regulation in ciliogenesis and identify CEP83 as a key substrate of TTBK2 during cilia initiation.

We discuss a bent-ray ultrasound tomography algorithm with total-variation (TV) regularization.We have applied this algorithm to 61 in vivo breast datasets collected with our in-house clinical prototype for imaging sound-speed distributions in the breast. Our analysis showed that TV regularization could preserve sharper lesion edges than the classic Tikhonov regularization.Furthermore, the image quality of our TV bent-ray sound-speed tomograms was superior to that of the straight-ray counterparts for all types of breasts within BI-RADS density categories 1-4.For all four breast types from fatty to dense, the improvements for average sharpness (in the unit of (m· s) -1) of lesion edges in our TV bent-ray tomograms are between 2.1 to 3.4 fold compared to the straight ray tomograms. Reconstructed sound-speed tomograms illustrated that our algorithm could successfully image fatty and glandular tissues within the breast. We calculated the mean sound-speed values for fatty tissue and breast parenchyma as 1422 ± 9 ml s (mean± SD) and1487 ± 21 ml s, respectively. Based on 32 lesions in a cohort of 61 patients, we also found that the mean sound-speed for malignant breast lesions (1548±17 mls) was higher, on average, than that of benign ones (1513±27 mls) (one-sided p

We report the effectiveness of low-concentration n-butyl-2-cyanoacrylate (NBCA)-Lipiodol-tungsten mixture (10-15 %) in the management of patients with aggressive or recurrent complex cavernous dural arteriovenous fistulae (CSDAVF). We treated five patients with complex CSDAVF with a low concentration of an NBCA-Lipiodol-tungsten mixture after catheterisation of the feeding arteries arising from the external carotid artery. Three had a recurrent CSDAVF after transarterial particulate embolisation. Three refused transvenous treatment or could not be treated in this way; two patients had also feeding dural branches of the internal carotid artery. All patients had complete resolution of symptoms and signs within a month of the procedure. No definite neurological complication was found during follow-up ranging from 12 to 36 months. Transarterial embolisation with low-concentration cyanoacrylate appears to be an effective alternative management of aggressive or recurrent CSDAVF.

TCCS, combining B-mode imaging for SN echogenicity and trancranial Doppler for intracranial hemodynamics, is a useful diagnostic tool in the differentiation between IPD and VP. These findings also suggest that multiple subcortical vascular lesions may damage the basal ganglia and thalamocortical circuit and result in parkinsonism features in VP patients.

AbstractResearch has failed to resolve the dilemma experienced by localized prostate cancer patients who must choose between radical prostatectomy (RP) and external beam radiotherapy (RT). Because the Charlson Comorbidity Index (CCI) is a measurable factor that affects survival events, this research seeks to validate the potential of the CCI to improve the accuracy of various prediction models. Thus, we employed the Cox proportional hazard model and machine learning methods, including random forest (RF) and support vector machine (SVM), to model the data of medical records in the National Health Insurance Research Database (NHIRD). In total, 8581 individuals were enrolled, of whom 4879 had received RP and 3702 had received RT. Patients in the RT group were older and exhibited higher CCI scores and higher incidences of some CCI items. Moderate-to-severe liver disease, dementia, congestive heart failure, chronic pulmonary disease, and cerebrovascular disease all increase the risk of overall death in the Cox hazard model. The CCI-reinforced SVM and RF models are 85.18% and 81.76% accurate, respectively, whereas the SVM and RF models without the use of the CCI are relatively less accurate, at 75.81% and 74.83%, respectively. Therefore, CCI and some of its items are useful predictors of overall and prostate-cancer-specific survival and could constitute valuable features for machine-learning modeling.