Surgical navigation is a well-established tool in endoscopic skull base surgery. However, navigational and endoscopic views are usually displayed on separate monitors, forcing the surgeon to focus on ...one or the other. Aiming to provide real-time integration of endoscopic and diagnostic imaging information, we present a new navigation technique based on augmented reality with fusion of intraoperative cone beam computed tomography (CBCT) on the endoscopic view. The aim of this study was to evaluate the accuracy of the method.
An augmented reality surgical navigation system (ARSN) with 3D CBCT capability was used. The navigation system incorporates an optical tracking system (OTS) with four video cameras embedded in the flat detector of the motorized C-arm. Intra-operative CBCT images were fused with the view of the surgical field obtained by the endoscope's camera. Accuracy of CBCT image co-registration was tested using a custom-made grid with incorporated 3D spheres.
Co-registration of the CBCT image on the endoscopic view was performed. Accuracy of the overlay, measured as mean target registration error (TRE), was 0.55 mm with a standard deviation of 0.24 mm and with a median value of 0.51mm and interquartile range of 0.39--0.68 mm.
We present a novel augmented reality surgical navigation system, with fusion of intraoperative CBCT on the endoscopic view. The system shows sub-millimeter accuracy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Fluoropyrimidine treatment can result in severe toxicity in up to 30% of patients and is often the result of reduced activity of the key metabolic enzyme dihydropyrimidine dehydrogenase (DPD), mostly ...caused by genetic variants in the gene encoding DPD (DPYD). We assessed the effect of prospective screening for the four most relevant DPYD variants (DPYD*2A rs3918290, c.1905+1G>A, IVS14+1G>A, c.2846A>T rs67376798, D949V, c.1679T>G rs55886062, DPYD*13, I560S, and c.1236G>A rs56038477, E412E, in haplotype B3) on patient safety and subsequent DPYD genotype-guided dose individualisation in daily clinical care.
In this prospective, multicentre, safety analysis in 17 hospitals in the Netherlands, the study population consisted of adult patients (≥18 years) with cancer who were intended to start on a fluoropyrimidine-based anticancer therapy (capecitabine or fluorouracil as single agent or in combination with other chemotherapeutic agents or radiotherapy). Patients with all tumour types for which fluoropyrimidine-based therapy was considered in their best interest were eligible. We did prospective genotyping for DPYD*2A, c.2846A>T, c.1679T>G, and c.1236G>A. Heterozygous DPYD variant allele carriers received an initial dose reduction of 25% (c.2846A>T and c.1236G>A) or 50% (DPYD*2A and c.1679T>G), and DPYD wild-type patients were treated according to the current standard of care. The primary endpoint of the study was the frequency of severe (National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 grade ≥3) overall fluoropyrimidine-related toxicity across the entire treatment duration. We compared toxicity incidence between DPYD variant allele carriers and DPYD wild-type patients on an intention-to-treat basis, and relative risks (RRs) for severe toxicity were compared between the current study and a historical cohort of DPYD variant allele carriers treated with full dose fluoropyrimidine-based therapy (derived from a previously published meta-analysis). This trial is registered with ClinicalTrials.gov, number NCT02324452, and is complete.
Between April 30, 2015, and Dec 21, 2017, we enrolled 1181 patients. 78 patients were considered non-evaluable, because they were retrospectively identified as not meeting inclusion criteria, did not start fluoropyrimidine-based treatment, or were homozygous or compound heterozygous DPYD variant allele carriers. Of 1103 evaluable patients, 85 (8%) were heterozygous DPYD variant allele carriers, and 1018 (92%) were DPYD wild-type patients. Overall, fluoropyrimidine-related severe toxicity was higher in DPYD variant carriers (33 39% of 85 patients) than in wild-type patients (231 23% of 1018 patients; p=0·0013). The RR for severe fluoropyrimidine-related toxicity was 1·31 (95% CI 0·63–2·73) for genotype-guided dosing compared with 2·87 (2·14–3·86) in the historical cohort for DPYD*2A carriers, no toxicity compared with 4·30 (2·10–8·80) in c.1679T>G carriers, 2·00 (1·19–3·34) compared with 3·11 (2·25–4·28) for c.2846A>T carriers, and 1·69 (1·18–2·42) compared with 1·72 (1·22–2·42) for c.1236G>A carriers.
Prospective DPYD genotyping was feasible in routine clinical practice, and DPYD genotype-based dose reductions improved patient safety of fluoropyrimidine treatment. For DPYD*2A and c.1679T>G carriers, a 50% initial dose reduction was adequate. For c.1236G>A and c.2846A>T carriers, a larger dose reduction of 50% (instead of 25%) requires investigation. Since fluoropyrimidines are among the most commonly used anticancer agents, these findings suggest that implementation of DPYD genotype-guided individualised dosing should be a new standard of care.
Dutch Cancer Society.
Remote Sensing Image Retrieval remains a challenging topic due to the special nature of Remote Sensing imagery. Such images contain various different semantic objects, which clearly complicates the ...retrieval task. In this paper, we present an image retrieval pipeline that uses attentive, local convolutional features and aggregates them using the Vector of Locally Aggregated Descriptors (VLAD) to produce a global descriptor. We study various system parameters such as the multiplicative and additive attention mechanisms and descriptor dimensionality. We propose a query expansion method that requires no external inputs. Experiments demonstrate that even without training, the local convolutional features and global representation outperform other systems. After system tuning, we can achieve state-of-the-art or competitive results. Furthermore, we observe that our query expansion method increases overall system performance by about 3%, using only the top-three retrieved images. Finally, we show how dimensionality reduction produces compact descriptors with increased retrieval performance and fast retrieval computation times, e.g., 50% faster than the current systems.
This paper presents a camera-based vessel-speed enforcement system based on two cameras. The proposed system detects and tracks vessels per camera view and employs a re-identification (re-ID) ...function for linking vessels between the two cameras based on multiple bounding-box images per vessel. Newly detected vessels in one camera (query) are compared to the gallery set of all vessels detected by the other camera. To train and evaluate the proposed detection and re-ID system, a new Vessel-reID dataset is introduced. This extensive dataset has captured a total of 2474 different vessels covered in multiple images, resulting in a total of 136,888 vessel bounding-box images. Multiple CNN detector architectures are evaluated in-depth. The SSD512 detector performs best with respect to its speed (85.0% Recall@95Precision at 20.1 frames per second). For the re-ID of vessels, a large portion of the total trajectory can be covered by the successful detections of the SSD model. The re-ID experiments start with a baseline single-image evaluation obtaining a score of 55.9% Rank-1 (49.7% mAP) for the existing TriNet network, while the available MGN model obtains 68.9% Rank-1 (62.6% mAP). The performance significantly increases with 5.6% Rank-1 (5.7% mAP) for MGN by applying matching with multiple images from a single vessel. When emphasizing more fine details by selecting only the largest bounding-box images, another 2.0% Rank-1 (1.4% mAP) is added. Application-specific optimizations such as travel-time selection and applying a cross-camera matching constraint further enhance the results, leading to a final 88.9% Rank-1 and 83.5% mAP performance.
Error-free repair of DNA double-strand breaks (DSBs) is achieved by homologous recombination (HR), and BRCA1 is an important factor for this repair pathway. In the absence of BRCA1-mediated HR, the ...administration of PARP inhibitors induces synthetic lethality of tumour cells of patients with breast or ovarian cancers. Despite the benefit of this tailored therapy, drug resistance can occur by HR restoration. Genetic reversion of BRCA1-inactivating mutations can be the underlying mechanism of drug resistance, but this does not explain resistance in all cases. In particular, little is known about BRCA1-independent restoration of HR. Here we show that loss of REV7 (also known as MAD2L2) in mouse and human cell lines re-establishes CTIP-dependent end resection of DSBs in BRCA1-deficient cells, leading to HR restoration and PARP inhibitor resistance, which is reversed by ATM kinase inhibition. REV7 is recruited to DSBs in a manner dependent on the H2AX-MDC1-RNF8-RNF168-53BP1 chromatin pathway, and seems to block HR and promote end joining in addition to its regulatory role in DNA damage tolerance. Finally, we establish that REV7 blocks DSB resection to promote non-homologous end-joining during immunoglobulin class switch recombination. Our results reveal an unexpected crucial function of REV7 downstream of 53BP1 in coordinating pathological DSB repair pathway choices in BRCA1-deficient cells.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Several genome-wide association studies have been performed on warfarin. For acencoumarol, the most frequently used coumarin in many countries worldwide, pharmcodynamic influences are expected to be ...comparable. Pharmacokinetics however might differ. We aimed to confirm known or identify new genetic variants contributing to interindividual variation on stabilized acenocoumarol dosage by a GWAS. The index population consisted of 1451 Caucasian subjects from the Rotterdam study and results were replicated in 287 subjects from the Rotterdam study extended cohort. Both cohorts were genotyped on the Illumina 550K Human Map SNP array. From polymorphisms tested for association with acenocoumarol dosage, 35 single nucleotide polymorphisms (SNPs) on chromosome 16 and 18 SNPs on chromosome 10 reached genome-wide significance. The SNP with the lowest P-value was rs10871454 on chromosome 16 linked to SNPs within the vitamin K epoxide reductase complex subunit 1 (VKORC1) (P = 2.0 × 10−123). The lowest P-value on chromosome 10 was obtained by rs4086116 within cytochrome P450 2C9 (CYP2C9) (P = 3.3 × 10−24). After adjustment for these SNPs, the rs2108622 polymorphism within cytochrome P450 4F2 (CYP4F2) gene on chromosome 19 reached genome-wide significance (P = 2.0 × 10−8). On chromosome 10, we further identified genetic variation in the cytochrome P450 2C18 (CYP2C18) gene contributing to variance of acenocoumarol dosage. Thus we confirmed earlier findings that acenocoumarol dosage mainly depends on polymorphisms in the VKORC1 and CYP2C9 genes. Besides age, gender, body mass index and target INR, one polymorphism within each of the VKORC1, CYP2C9, CYP4F2 and CYP2C18 genes could explain 48.8% of acencoumarol dosage variation.
The mechanism of cobalt(II)−porphyrin-mediated cyclopropanation of olefins with diazoesters was studied. The first stepreaction of cobalt(II)−porphyrin with ethyl diazoacetate (EDA)was examined ...using EPR and ESI-MS techniques. EDA reacts with cobalt(II)−porphyrin to form a 1:1 Co(por)(CHCOOEt) adduct that exists as two isomers: the ‘bridging carbene’ C′ in which the ‘carbene’ is bound to the metal and the pyrrolic nitrogen of the porphyrin that has a d7 configuration on the metal, and the ‘terminal carbene’ C in which the ‘carbene’ behaves as a redox noninnocent ligand having a d6 cobalt center and the unpaired electron residing on the ‘carbene’ carbon atom. The subsequent reactivities of the thus formed ‘cobalt carbene radical’ with propene, styrene, and methyl acrylate were studied using DFT calculations. The calculations suggest that the formation of the carbene is the rate-limiting step for the unfunctionalized CoII(por) and that the cyclopropane ring formation proceeds via a stepwise radical process: Radical addition of the ‘carbene radical’ C to the CC double bonds of the olefins results in formation of the γ-alkyl radical intermediates D. Species D then easily collapse in almost barrierless ring-closure reactions (TS3) to form the cyclopropanes. This radical mechanism readily explains the high activity of CoII(por) species in the cyclopropanation of electron-deficient olefins such as methyl acrylate.
Purpose
Vestibular schwannomas (VSs) are uncommon benign brain tumors, generally treated using Gamma Knife radiosurgery (GKRS). However, due to the possible adverse effect of transient tumor ...enlargement (TTE), large VS tumors are often surgically removed instead of treated radiosurgically. Since microsurgery is highly invasive and results in a significant increased risk of complications, GKRS is generally preferred. Therefore, prediction of TTE for large VS tumors can improve overall VS treatment and enable physicians to select the most optimal treatment strategy on an individual basis. Currently, there are no clinical factors known to be predictive for TTE. In this research, we aim at predicting TTE following GKRS using texture features extracted from MRI scans.
Methods
We analyzed clinical data of patients with VSs treated at our Gamma Knife center. The data was collected prospectively and included patient‐ and treatment‐related characteristics and MRI scans obtained at day of treatment and at follow‐up visits, 6, 12, 24 and 36 months after treatment. The correlations of the patient‐ and treatment‐related characteristics to TTE were investigated using statistical tests. From the treatment scans, we extracted the following MRI image features: first‐order statistics, Minkowski functionals (MFs), and three‐dimensional gray‐level co‐occurrence matrices (GLCMs). These features were applied in a machine learning environment for classification of TTE, using support vector machines.
Results
In a clinical data set, containing 61 patients presenting obvious non‐TTE and 38 patients presenting obvious TTE, we determined that patient‐ and treatment‐related characteristics do not show any correlation to TTE. Furthermore, first‐order statistical MRI features and MFs did not significantly show prognostic values using support vector machine classification. However, utilizing a set of 4 GLCM features, we achieved a sensitivity of 0.82 and a specificity of 0.69, showing their prognostic value of TTE. Moreover, these results increased for larger tumor volumes obtaining a sensitivity of 0.77 and a specificity of 0.89 for tumors larger than 6 cm3.
Conclusions
The results found in this research clearly show that MRI tumor texture provides information that can be employed for predicting TTE. This can form a basis for individual VS treatment selection, further improving overall treatment results. Particularly in patients with large VSs, where the phenomenon of TTE is most relevant and our predictive model performs best, these findings can be implemented in a clinical workflow such that for each patient, the most optimal treatment strategy can be determined.
Optical biopsy in Barrett's oesophagus (BE) using endocytoscopy (EC) could optimize endoscopic screening. However, the identification of dysplasia is challenging due to the complex interpretation of ...the highly detailed images. Therefore, we assessed whether using artificial intelligence (AI) as second assessor could help gastroenterologists in interpreting endocytoscopic BE images. First, we prospectively videotaped 52 BE patients with EC. Then we trained and tested the AI pm distinct datasets drawn from 83,277 frames, developed an endocytoscopic BE classification system, and designed online training and testing modules. We invited two successive cohorts for these online modules: 10 endoscopists to validate the classification system and 12 gastroenterologists to evaluate AI as second assessor by providing six of them with the option to request AI assistance. Training the endoscopists in the classification system established an improved sensitivity of 90.0% (+32.67%,
< 0.001) and an accuracy of 77.67% (+13.0%,
= 0.020) compared with the baseline. However, these values deteriorated at follow-up (-16.67%,
< 0.001 and -8.0%,
= 0.009). Contrastingly, AI-assisted gastroenterologists maintained high sensitivity and accuracy at follow-up, subsequently outperforming the unassisted gastroenterologists (+20.0%,
= 0.025 and +12.22%,
= 0.05). Thus, best diagnostic scores for the identification of dysplasia emerged through human-machine collaboration between trained gastroenterologists with AI as the second assessor. Therefore, AI could support clinical implementation of optical biopsies through EC.
The primary treatment for malignant brain tumors is surgical resection. While gross total resection improves the prognosis, a supratotal resection may result in neurological deficits. On the other ...hand, accurate intraoperative identification of the tumor boundaries may be very difficult, resulting in subtotal resections. Histological examination of biopsies can be used repeatedly to help achieve gross total resection but this is not practically feasible due to the turn-around time of the tissue analysis. Therefore, intraoperative techniques to recognize tissue types are investigated to expedite the clinical workflow for tumor resection and improve outcome by aiding in the identification and removal of the malignant lesion. Hyperspectral imaging (HSI) is an optical imaging technique with the power of extracting additional information from the imaged tissue. Because HSI images cannot be visually assessed by human observers, we instead exploit artificial intelligence techniques and leverage a Convolutional Neural Network (CNN) to investigate the potential of HSI in twelve in vivo specimens. The proposed framework consists of a 3D-2D hybrid CNN-based approach to create a joint extraction of spectral and spatial information from hyperspectral images. A comparison study was conducted exploiting a 2D CNN, a 1D DNN and two conventional classification methods (SVM, and the SVM classifier combined with the 3D-2D hybrid CNN) to validate the proposed network. An overall accuracy of 80% was found when tumor, healthy tissue and blood vessels were classified, clearly outperforming the state-of-the-art approaches. These results can serve as a basis for brain tumor classification using HSI, and may open future avenues for image-guided neurosurgical applications.
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