Changing clinical and therapeutic trends in tentorial dural arteriovenous fistulas: a systematic review

BACKGROUND AND PURPOSE: Tentorial dural arteriovenous fistulas are characterized by a high hemorrhagic risk. We evaluated trends in outcomes and management of tentorial dural arteriovenous fistulas and performed a meta-analysis evaluating clinical and angiographic outcomes by treatment technique. MATERIALS AND METHODS: We performed a comprehensive literature search for studies on surgical and endovascular treatment of tentorial dural arteriovenous fistulas. We compared the proportion of patients undergoing endovascular, surgical, and combined endovascular/surgical management; the proportion of patients presenting with ruptured tentorial dural arteriovenous fistulas; and proportion of patients with good neurologic outcome across 3 time periods: 1980-1995, 1996-2005, and 2006-2014. We performed a random-effects meta-analysis, evaluating the rates of occlusion, long-term good neurologic outcome, perioperative morbidity, and resolution of symptoms for the 3 treatment modalities. RESULTS: Twenty-nine studies with 274 patients were included. The proportion of patients treated with surgical treatment alone decreased from 38.7% to 20.4% between 1980-1995 and 2006-2014. The proportion of patients treated with endovascular therapy alone increased from 16.1% to 48.0%. The proportion of patients presenting with ruptured tentorial dural arteriovenous fistulas decreased from 64.4% to 43.6%. The rate of good neurologic outcome increased from 80.7% to 92.9%. Complete occlusion rates were highest for patients receiving multimodality treatment (84.0%; 95% CI, 72.0%-91.0%) and lowest for endovascular treatment (71.0%; 95% CI, 56.0%-83.0%; P < .01). Long-term good neurologic outcome was highest in the endovascular group (89.0%; 95% CI, 80.0%-95.0%) and lowest for the surgical group (73.0%; 95% CI, 51.0%-87.0%; P < .03). CONCLUSIONS: Patients with tentorial dural arteriovenous fistulas are increasingly presenting with unruptured lesions, being treated endovascularly, and experiencing higher rates of good neurologic outcomes. Endovascular treatment was associated with superior neurologic outcomes but lower occlusion rate

A Novel Transformer-Based IMU Self-Calibration Approach through On-Board RGB Camera for UAV Flight Stabilization

During flight, unmanned aerial vehicles (UAVs) need several sensors to follow a predefined path and reach a specific destination. To this aim, they generally exploit an inertial measurement unit (IMU) for pose estimation. Usually, in the UAV context, an IMU entails a three-axis accelerometer and a three-axis gyroscope. However, as happens for many physical devices, they can present some misalignment between the real value and the registered one. These systematic or occasional errors can derive from different sources and could be related to the sensor itself or to external noise due to the place where it is located. Hardware calibration requires special equipment, which is not always available. In any case, even if possible, it can be used to solve the physical problem and sometimes requires removing the sensor from its location, which is not always feasible. At the same time, solving the problem of external noise usually requires software procedures. Moreover, as reported in the literature, even two IMUs from the same brand and the same production chain could produce different measurements under identical conditions. This paper proposes a soft calibration procedure to reduce the misalignment created by systematic errors and noise based on the grayscale or RGB camera built-in on the drone. Based on the transformer neural network architecture trained in a supervised learning fashion on pairs of short videos shot by the UAV’s camera and the correspondent UAV measurements, the strategy does not require any special equipment. It is easily reproducible and could be used to increase the trajectory accuracy of the UAV during the flight

The restoring of interhemispheric brain connectivity following carotid endarterectomy: an exploratory observational study

This study aimed to evaluate the differences of brain connectivity between healthy subjects (HS) and patients with extracranial internal carotid artery (eICA) stenosis before and after carotid endarterectomy (CEA). An exploratory prospective study was designed. The study population consisted of a patient group (PG) of 20 patients with eICA stenosis eligible for CEA, and a control group (CG) of 20 HS, matched for age and sex. The subjects of the PG group underwent Magnetic Resonance Imaging (MRI) for resting-state functional connectivity MRI (rs-fc MRI) analysis within one week from the CEA (pre-CEA) and 12&nbsp;months following CEA (post-CEA). The CG underwent a single MRI with the same protocol utilized for the PG. Three region-of-interest to region-of-interest (ROI-to-ROI) rs-fc MRI analyses were conducted: analysis 1 to compare pre-CEA PG and CG; analysis 2 to compare pre-CEA PG and post-CEA PG; analysis 3 to compare post-CEA PG and CG. The Functional Network Connectivity multivariate parametric technique was used for statistical analysis, adopting a p-uncorrected (p-unc) &lt; 0.05 as connection threshold, and a cluster level False Discovery Rate corrected p (p-FDR) &lt; 0.05 as cluster threshold. The clusters were defined by using a data-driven hierarchical clustering procedure. Analysis 1 revealed two clusters of reduced interhemispheric connectivity of pre-CEA PG when compared to CG. Analysis 2 and 3 showed no statistically significant differences. Our exploratory analysis suggests that patients with eICA stenosis have reduced interhemispheric connectivity when compared to a matched control group, and this difference was not evident anymore following endarterectomy

The estrogen receptor alpha:insulin receptor substrate 1 complex in breast cancer: structure-function relationships

Background: Insulin receptor substrate 1 (IRS-1) is a signaling molecule that exerts a key role in mediating cross talk between estrogen receptor a (ERa) and insulin-like growth factor 1 (IGF-1) in breast cancer cells. Previously, we demonstrated that a fraction of IRS-1 binds ERa, translocates to the nucleus, and modulates ERa-dependent transcription at estrogen response elements (ERE). Here, we studied structure–function relationships of the ERa:IRS-1 complex under IGF-1 and/or estradiol (E2) stimulation. Materials and methods: ERa and IRS-1 deletion mutants were used to analyze structural and functional ERa/IRS-1 interactions. IRS-1 binding to ERE and IRS-1 role in ERa-dependent ERE transcription was examined by chromatin immunoprecipitation and gene reporter analysis, respectively. The requirement for IRS-1 in ERa function was tested with RNAi technology. Results: Nuclear translocation of IRS-1 was induced by E2, IGF-1, and a combination of both stimuli. ERa/IRS-1 binding was direct and involved the activation function-1 (AF-1)/DNA binding domain (DBD) region of ERa and two discrete regions of IRS-1 (the N-terminal pleckstrin homology domain and a region within the C-terminus). IRS-1 knock down abrogated IGF-1-dependent transcriptional activity of unliganded ERa, but induced the activity of liganded ERa. Conclusions: ERa/IRS-1 interactions are direct and involve the ERa AF-1/DBD domain and IRS-1 domains mapping within N- and C-terminus. IRS-1 may act as a repressor of liganded ERa and coactivator of unliganded ERa

A Novel GAN-Based Anomaly Detection and Localization Method for Aerial Video Surveillance at Low Altitude

The last two decades have seen an incessant growth in the use of Unmanned Aerial Vehicles (UAVs) equipped with HD cameras for developing aerial vision-based systems to support civilian and military tasks, including land monitoring, change detection, and object classification. To perform most of these tasks, the artificial intelligence algorithms usually need to know, a priori, what to look for, identify. or recognize. Actually, in most operational scenarios, such as war zones or post-disaster situations, areas and objects of interest are not decidable a priori since their shape and visual features may have been altered by events or even intentionally disguised (e.g., improvised explosive devices (IEDs)). For these reasons, in recent years, more and more research groups are investigating the design of original anomaly detection methods, which, in short, are focused on detecting samples that differ from the others in terms of visual appearance and occurrences with respect to a given environment. In this paper, we present a novel two-branch Generative Adversarial Network (GAN)-based method for low-altitude RGB aerial video surveillance to detect and localize anomalies. We have chosen to focus on the low-altitude sequences as we are interested in complex operational scenarios where even a small object or device can represent a reason for danger or attention. The proposed model was tested on the UAV Mosaicking and Change Detection (UMCD) dataset, a one-of-a-kind collection of challenging videos whose sequences were acquired between 6 and 15 m above sea level on three types of ground (i.e., urban, dirt, and countryside). Results demonstrated the effectiveness of the model in terms of Area Under the Receiving Operating Curve (AUROC) and Structural Similarity Index (SSIM), achieving an average of 97.2% and 95.7%, respectively, thus suggesting that the system can be deployed in real-world applications

FoxO3a as a positive prognostic marker and a therapeutic target in Tamoxifen-resistant breast cancer

Background: Resistance to endocrine treatments is a major clinical challenge in the management of estrogen receptor positive breast cancers. Although multiple mechanisms leading to endocrine resistance have been proposed, the poor outcome of this subgroup of patients demands additional studies. Methods: FoxO3a involvement in the acquisition and reversion of tamoxifen resistance was assessed in vitro in three parental ER+ breast cancer cells, MCF-7, T47D and ZR-75-1, in the deriving Tamoxifen resistant models (TamR) and in Tet-inducible TamR/FoxO3a stable cell lines, by growth curves, PLA, siRNA, RT-PCR, Western blot, Immunofluorescence, Transmission Electron Microscopy, TUNEL, cell cycle, proteomics analyses and animal models. FoxO3a clinical relevance was validated in silico by Kaplan−Meier survival curves. Results: Here, we show that tamoxifen resistant breast cancer cells (TamR) express low FoxO3a levels. The hyperactive growth factors signaling, characterizing these cells, leads to FoxO3a hyper-phosphorylation and subsequent proteasomal degradation. FoxO3a re-expression by using TamR tetracycline inducible cells or by treating TamR with the anticonvulsant lamotrigine (LTG), restored the sensitivity to the antiestrogen and strongly reduced tumor mass in TamR-derived mouse xenografts. Proteomics data unveiled novel potential mediators of FoxO3a anti-proliferative and pro-apoptotic activity, while the Kaplan−Meier analysis showed that FoxO3a is predictive of a positive response to tamoxifen therapy in Luminal A breast cancer patients. Conclusions: Altogether, our data indicate that FoxO3a is a key target to be exploited in endocrine-resistant tumors. In this context, LTG, being able to induce FoxO3a, might represent a valid candidate in combination therapy to prevent resistance to tamoxifen in patients at risk

po 154 progesterone through progesterone receptor b inhibits invasion of human breast cancer cells by targeting cytoplasmic cyclin d1

Introduction Progesterone Receptor (PR) positivity is associated with a good prognosis and better response to breast cancer treatment. Conversely, cyclin D1 (CD1) is retained a marker of poor outcome since it has been associated with breast cancer metastasis in clinical studies. Material and methods 17-Hydroxyprogesterone (OHPg) was from Sigma-Aldrich. Antibodies and Protein A/GPLUS-Agarose were from Santa Cruz Biotechnology. T47-D, MCF-7 and MDA-MB-231 human breast cancer cells from the American Type Culture Collection; Total real-time RT-PCR assay; Western blotting and immunoprecipitation; Transfections and luciferase assays; Lipid-Mediated Transfection of siRNA Duplexes; Chromatin immunoprecipitation (ChIP) assays and realtime ChIP; Wound-healing assays; Transmigration assays; Cell invasion assay; Phalloidin staining. Results and discussions Herein we provide evidences that OHPg through PR-B isoform, reduces motility and invasion of T47-D and MCF-7 breast cancer cells, by targeting the cytoplasmic CD1. Specifically, OHPg reduces CD1 expression through a transcriptional mechanism due to the occupancy of CD1 promoter at a canonical half progesterone responsive element by PR-B. This allows the recruitment of HDAC1 influencing a less permissive chromatin conformation for gene transcription and the release of RNA Pol II. CD1 has an active role in the control of cell migration and metastasis through the interaction with key components of focal adhesion such as Paxillin (Pxn). In untreated T47-D and MCF-7 cells a specific co-immunoprecipitation of endogenous cytoplasmic CD1 with Pxn was detected. Interestingly, OHPg exposure reduced the interaction between these proteins although total Pxn expression was substantially unaffected. Moreover a concomitant reduction of p-Pxn levels was observed and these effects were required for OHPg/PR-B dependent delay in cell invasion, as evidenced by assays carried out with the phoshomimetic mutants of Pxn. Conclusion Collectively these findings support the importance of PR-B expression in breast cancer cells behaviour, suggesting potentiating of PR-B signalling as a prospective useful strategy to restrict breast tumour cells invasion and metastasis

Treatment of Cavernous Sinus Aneurysms with Flow Diversion: Results in 44 Patients

ABSTRACT BACKGROUND AND PURPOSE: Aneurysms of the cavernous segment of the ICA are difficult to treat with standard endovascular techniques, and ICA sacrifice achieves a high rate of occlusion but carries an elevated level of surgical complications and risk of de novo aneurysm formation. We report rates of occlusion and treatment-related data in 44 patients with cavernous sinus aneurysms treated with flow diversion

po 058 unravelling the protective role of androgens androgen receptorin breast cancer when bad goes good

Introduction Androgen receptor (AR) expression in breast cancer growth and progression appears to be clinically relevant and disease context specific. In oestrogen receptor (ER)α-positive primary breast cancers, AR positivity correlates with lower tumour grade and a better clinical outcome. These clinical-pathological findings mirror the capability of androgens to counteract ERα-dependent proliferation in both normal mammary epithelium and ERα-positive breast cancer preclinical models in which androgen/AR-dependent pro-apoptotic effects have been also evidenced. Here we report a novel additional mechanism underlining the protective, anti-proliferative role exerted by AR signalling. This mechanism involves modulation of the expression, cellular distribution and function of BAD, a pro-apoptotic member of the Bcl-2 family proteins, whose expression is related to a significantly better disease free survival in (ER)α-positive human breast cancers. Material and methods MCF-7, TD47D, ZR-75 breast cancer cells; qReal Time PCR; western blotting (WB); immunofluorescence analysis (IF); immunoprecipitation assay (IP); DNA affinity precipitation assay; Chromatin Immunoprecipitation Assay. Results and discussions The expression of a panel of pro/anti-apoptotic proteins was investigated in cellular protein lysates from ERα/AR-positive MCF-7 cells cultured for 1, 3 and 6 days under androgen treatment. The expression of the anti-apoptotic Bcl-2 protein, or the pro-apoptotic BID and BAX remained unchanged, while a sustained increase in the expression of the pro-apoptotic BAD could be observed, reducing the Bcl-2/BAD ratio and, thus, shifting the delicate balance between inhibitors and inducers of cell death. Interestingly, androgens induced a marked BAD levels increase into the nuclear compartment in ERα/AR-positive MCF-7, T47D and ZR-75 as well as in ERα negative/AR-positive SKBR3 cells. The androgen-regulated intracellular localization of BAD involved an AR/BAD physical interaction, suggesting a nuclear role for BAD upon androgen stimulation. Indeed, androgens induced both AR and BAD recruitment at a AP-1 and at a ARE site within the cyclin D1 promoter region, contributing to explain the anti-proliferative effect of androgens in breast cancer cells. Conclusion We defined a novel mechanism by which androgens modulate BAD expression and force its ability to act as a cell cycle inhibitor through modulation of cyclin D1 gene transcriptional activity, strengthening the protective role of androgen signalling in estrogen-responsive breast cancer