This paper addresses the problem of detecting possible serious bacterial infection (pSBI) of infancy, i.e. a clinical presentation consistent with bacterial sepsis in newborn infants using cranial ultrasound (cUS) images. The captured image set for each patient enables multi-view imagery: coronal and sagittal, with geometric overlap. To exploit this geometric relation, we develop a new learning framework, called the intersection-guided Cross-view Local- and Image-level Fusion Network (CLIF-Net). Our technique employs two distinct convolutional neural network branches to extract features from coronal and sagittal images with newly developed multi-level fusion blocks. Specifically, we leverage the spatial position of these images to locate the intersecting region. We then identify and enhance the semantic features from this region across multiple levels using cross-attention modules, facilitating the acquisition of mutually beneficial and more representative features from both views. The final enhanced features from the two views are then integrated and projected through the image-level fusion layer, outputting pSBI and non-pSBI class probabilities. We contend that our method of exploiting multi-view cUS images enables a first of its kind, robust 3D representation tailored for pSBI detection. When evaluated on a dataset of 302 cUS scans from Mbale Regional Referral Hospital in Uganda, CLIF-Net demonstrates substantially enhanced performance, surpassing the prevailing state-of-the-art infection detection techniques.

MOTIVATION: In recent years, significant strides have been made in the field of genomics, with the commencement of large-scale studies aimed at collecting host mutational profiles and microbiome data. The amalgamation of host gene mutational profiles in both healthy and diseased subjects with microbial abundance data holds immense promise in providing insights into several crucial research questions, including the development and progression of diseases, as well as individual responses to therapeutic interventions. With the advent of sequencing methods such as 16s ribosomal RNA (rRNA) sequencing and whole genome sequencing, there is increasing evidence of interplay of human genetics and microbial communities. Quantitative trait loci associated with microbial abundance (mbQTLs), are genetic variants that influence the abundance of microbial populations within the host. RESULTS: Here, we introduce mbQTL, the first R package integrating 16S ribosomal RNA (rRNA) sequencing and single-nucleotide variation (SNV) and single-nucleotide polymorphism (SNP) data. We describe various statistical methods implemented for the identification of microbe-SNV pairs, relevant statistical measures, and plot functionality for interpretation. AVAILABILITY AND IMPLEMENTATION: mbQTL is available on bioconductor at https://bioconductor.org/packages/mbQTL/.

High resolution Magnetic Resonance (MR) images are desired for accurate diagnostics. In practice, image resolution is restricted by factors like hardware and processing constraints. Recently, deep learning methods have been shown to produce compelling state-of-the-art results for image enhancement/super-resolution. Paying particular attention to desired hi-resolution MR image structure, we propose a new regularized network that exploits image priors, namely a low-rank structure and a sharpness prior to enhance deep MR image super-resolution (SR). Our contributions are then incorporating these priors in an analytically tractable fashion as well as towards a novel prior guided network architecture that accomplishes the super-resolution task. This is particularly challenging for the low rank prior since the rank is not a differentiable function of the image matrix (and hence the network parameters), an issue we address by pursuing differentiable approximations of the rank. Sharpness is emphasized by the variance of the Laplacian which we show can be implemented by a fixed feedback layer at the output of the network. As a key extension, we modify the fixed feedback (Laplacian) layer by learning a new set of training data driven filters that are optimized for enhanced sharpness. Experiments performed on publicly available MR brain image databases and comparisons against existing state-of-the-art methods show that the proposed prior guided network offers significant practical gains in terms of improved SNR/image quality measures. Because our priors are on output images, the proposed method is versatile and can be combined with a wide variety of existing network architectures to further enhance their performance.

High resolution magnetic resonance (MR) images are desired for accurate diagnostics. In practice, image resolution is restricted by factors like hardware, cost and processing constraints. Recently, deep learning methods have been shown to produce compelling state of the art results for image super-resolution. Paying particular attention to desired hi-resolution MR image structure, we propose a new regularized network that exploits image priors, namely a low-rank structure and a sharpness prior to enhance deep MR image superresolution. Our contributions are then incorporating these priors in an analytically tractable fashion in the learning of a convolutional neural network (CNN) that accomplishes the super-resolution task. This is particularly challenging for the low rank prior, since the rank is not a differentiable function of the image matrix (and hence the network parameters), an issue we address by pursuing differentiable approximations of the rank. Sharpness is emphasized by the variance of the Laplacian which we show can be implemented by a fixed feedback layer at the output of the network. Experiments performed on two publicly available MR brain image databases exhibit promising results particularly when training imagery is limited.

Cell volume changes are ubiquitous in normal and pathological activity of the brain. Nevertheless, we know little of how cell volume affects neuronal dynamics. We here performed the first detailed study of the effects of cell volume on neuronal dynamics. By incorporating cell swelling together with dynamic ion concentrations and oxygen supply into Hodgkin-Huxley type spiking dynamics, we demonstrate the spontaneous transition between epileptic seizure and spreading depression states as the cell swells and contracts in response to changes in osmotic pressure. Our use of volume as an order parameter further revealed a dynamical definition for the experimentally described physiological ceiling that separates seizure from spreading depression, as well as predicted a second ceiling that demarcates spreading depression from anoxic depolarization. Our model highlights the neuroprotective role of glial K buffering against seizures and spreading depression, and provides novel insights into anoxic depolarization and the relevant cell swelling during ischemia. We argue that the dynamics of seizures, spreading depression, and anoxic depolarization lie along a continuum of the repertoire of the neuron membrane that can be understood only when the dynamic ion concentrations, oxygen homeostasis,and cell swelling in response to osmotic pressure are taken into consideration. Our results demonstrate the feasibility of a unified framework for a wide range of neuronal behaviors that may be of substantial importance in the understanding of and potentially developing universal intervention strategies for these pathological states.

Data assimilation is a valuable tool in the study of any complex system, where measurements are incomplete, uncertain, or both. It enables the user to take advantage of all available information including experimental measurements and short-term model forecasts of a system. Although data assimilation has been used to study other biological systems, the study of the sleep-wake regulatory network has yet to benefit from this toolset. We present a data assimilation framework based on the unscented Kalman filter (UKF) for combining sparse measurements together with a relatively high-dimensional nonlinear computational model to estimate the state of a model of the sleep-wake regulatory system. We demonstrate with simulation studies that a few noisy variables can be used to accurately reconstruct the remaining hidden variables. We introduce a metric for ranking relative partial observability of computational models, within the UKF framework, that allows us to choose the optimal variables for measurement and also provides a methodology for optimizing framework parameters such as UKF covariance inflation. In addition, we demonstrate a parameter estimation method that allows us to track non-stationary model parameters and accommodate slow dynamics not included in the UKF filter model. Finally, we show that we can even use observed discretized sleep-state, which is not one of the model variables, to reconstruct model state and estimate unknown parameters. Sleep is implicated in many neurological disorders from epilepsy to schizophrenia, but simultaneous observation of the many brain components that regulate this behavior is difficult. We anticipate that this data assimilation framework will enable better understanding of the detailed interactions governing sleep and wake behavior and provide for better, more targeted, therapies.

Observability of a dynamical system requires an understanding of its state-the collective values of its variables. However, existing techniques are too limited to measure all but a small fraction of the physical variables and parameters of neuronal networks. We constructed models of the biophysical properties of neuronal membrane, synaptic, and microenvironment dynamics, and incorporated them into a model-based predictor-controller framework from modern control theory. We demonstrate that it is now possible to meaningfully estimate the dynamics of small neuronal networks using as few as a single measured variable. Specifically, we assimilate noisy membrane potential measurements from individual hippocampal neurons to reconstruct the dynamics of networks of these cells, their extracellular microenvironment, and the activities of different neuronal types during seizures. We use reconstruction to account for unmeasured parts of the neuronal system, relating micro-domain metabolic processes to cellular excitability, and validate the reconstruction of cellular dynamical interactions against actual measurements. Data assimilation, the fusing of measurement with computational models, has significant potential to improve the way we observe and understand brain dynamics.