Repeatability of IVIM biomarkers from diffusion-weighted MRI in head and neck:Bayesian probability versus neural network

Purpose: The intravoxel incoherent motion (IVIM) model for DWI might provide useful biomarkers for disease management in head and neck cancer. This study compared the repeatability of three IVIM fitting methods to the conventional nonlinear least-squares regression: Bayesian probability estimation, a recently introduced neural network approach, IVIM-NET, and a version of the neural network modified to increase consistency, IVIM-NETmod. Methods: Ten healthy volunteers underwent two imaging sessions of the neck, two weeks apart, with two DWI acquisitions per session. Model parameters (ADC, diffusion coefficient (Formula presented.), perfusion fraction (Formula presented.), and pseudo-diffusion coefficient (Formula presented.)) from each fit method were determined in the tonsils and in the pterygoid muscles. Within-subject coefficients of variation (wCV) were calculated to assess repeatability. Training of the neural network was repeated 100 times with random initialization to investigate consistency, quantified by the coefficient of variance. Results: The Bayesian and neural network approaches outperformed nonlinear regression in terms of wCV. Intersession wCV of (Formula presented.) in the tonsils was 23.4% for nonlinear regression, 9.7% for Bayesian estimation, 9.4% for IVIM-NET, and 11.2% for IVIM-NETmod. However, results from repeated training of the neural network on the same data set showed differences in parameter estimates: The coefficient of variances over the 100 repetitions for IVIM-NET were 15% for both (Formula presented.) and (Formula presented.), and 94% for (Formula presented.); for IVIM-NETmod, these values improved to 5%, 9%, and 62%, respectively. Conclusion: Repeatabilities from the Bayesian and neural network approaches are superior to that of nonlinear regression for estimating IVIM parameters in the head and neck

An integrated multi-omic analysis of iPSC-derived motor neurons from C9ORF72 ALS patients

Neurodegenerative diseases are challenging for systems biology because of the lack of reliable animal models or patient samples at early disease stages. Induced pluripotent stem cells (iPSCs) could address these challenges. We investigated DNA, RNA, epigenetics, and proteins in iPSC-derived motor neurons from patients with ALS carrying hexanucleotide expansions in C9ORF72. Using integrative computational methods combining all omics datasets, we identified novel and known dysregulated pathways. We used a C9ORF72 Drosophila model to distinguish pathways contributing to disease phenotypes from compensatory ones and confirmed alterations in some pathways in postmortem spinal cord tissue of patients with ALS. A different differentiation protocol was used to derive a separate set of C9ORF72 and control motor neurons. Many individual -omics differed by protocol, but some core dysregulated pathways were consistent. This strategy of analyzing patient-specific neurons provides disease-related outcomes with small numbers of heterogeneous lines and reduces variation from single-omics to elucidate network-based signatures.Genetics of disease, diagnosis and treatmen

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

An integrated multi-omic analysis of iPSC-derived motor neurons from C9ORF72 ALS patients

Neurodegenerative diseases are challenging for systems biology because of the lack of reliable animal models or patient samples at early disease stages. Induced pluripotent stem cells (iPSCs) could address these challenges. We investigated DNA, RNA, epigenetics, and proteins in iPSC-derived motor neurons from patients with ALS carrying hexanucleotide expansions in C9ORF72. Using integrative computational methods combining all omics datasets, we identified novel and known dysregulated pathways. We used a C9ORF72 Drosophila model to distinguish pathways contributing to disease phenotypes from compensatory ones and confirmed alterations in some pathways in postmortem spinal cord tissue of patients with ALS. A different differentiation protocol was used to derive a separate set of C9ORF72 and control motor neurons. Many individual -omics differed by protocol, but some core dysregulated pathways were consistent. This strategy of analyzing patient-specific neurons provides disease-related outcomes with small numbers of heterogeneous lines and reduces variation from single-omics to elucidate network-based signatures

Predicting Non-Residential Building Fire Risk using geospatial information and Convolutional Neural Networks

Building fire risk prediction is crucial for allocation of building inspection resources and prevention of fire incidents. Existing research of building fire prediction makes use of data relating to local demography, crime, building use and physical building characteristics, yet few studies have analysed the relative importance of predictive features. Furthermore, image features relating to buildings, such as aerial imagery and digital surface models (DSM), have not been explored. This research presents a multi-modal hybrid neural network for the prediction of fire risk at the building level using the London Fire Brigade dataset. The inclusion of traditional and novel image features is assessed using Shapley values and an ablation study. The ablation study found that while building use is the most effective contributor of classification performance, demographic features, apart from social class, are detrimental. Moreover, while the DSM did not lead to any notable improvement in classification performance, the inclusion of the aerial imagery feature lead to a 4% increase in median validation ROC AUC. The final model presented achieved an ROC AUC of 0.8195 on the test set

A Fast Characterization Method for Semi-invasive Fault Injection Attacks

Semi-invasive fault injection attacks are powerful techniques well-known by attackers and secure embedded system designers. When performing such attacks, the selection of the fault injection parameters is of utmost importance and usually based on the experience of the attacker. Surprisingly, there exists no formal and general approach to characterize the target behavior under attack. In this work, we present a novel methodology to perform a fast characterization of the fault injection impact on a target, depending on the possible attack parameters. We experimentally show our methodology to be a successful one when targeting different algorithms such as DES and AES encryption and then extend to the full characterization with the help of deep learning. Finally, we show how the characterization results are transferable between different targets.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Cyber Securit

Proteomics, post-translational modifications, and integrative analyses reveal molecular heterogeneity within medulloblastoma subgroups

There is a pressing need to identify therapeutic targets in tumors with low mutation rates such as the malignant pediatric brain tumor medulloblastoma. To address this challenge, we quantitatively profiled global proteomes and phospho-proteomes of 45 medulloblastoma samples. Integrated analyses revealed that tumors with similar RNA expression vary extensively at the post-transcriptional and post-translational levels. We identified distinct pathways associated with two subsets of SHH tumors, and found post-translational modifications of MYC that are associated with poor outcomes in group 3 tumors. We found kinases associated with subtypes and showed that inhibiting PRKDC sensitizes MYC-driven cells to radiation. Our study shows that proteomics enables a more comprehensive, functional readout, providing a foundation for future therapeutic strategies

Proteomics, Post-translational Modifications, and Integrative Analyses Reveal Molecular Heterogeneity within Medulloblastoma Subgroups

There is a pressing need to identify therapeutic targets in tumors with low mutation rates such as the malignant pediatric brain tumor medulloblastoma. To address this challenge, we quantitatively profiled global proteomes and phospho-proteomes of 45 medulloblastoma samples. Integrated analyses revealed that tumors with similar RNA expression vary extensively at the post-transcriptional and post-translational levels. We identified distinct pathways associated with two subsets of SHH tumors, and found post-translational modifications of MYC that are associated with poor outcomes in group 3 tumors. We found kinases associated with subtypes and showed that inhibiting PRKDC sensitizes MYC-driven cells to radiation. Our study shows that proteomics enables a more comprehensive, functional readout, providing a foundation for future therapeutic strategies