Pathway-based analyses of gene expression profiles at low doses of ionizing radiation.

Radiation exposure poses a significant threat to human health. Emerging research indicates that even low-dose radiation once believed to be safe, may have harmful effects. This perception has spurred a growing interest in investigating the potential risks associated with low-dose radiation exposure across various scenarios. To comprehensively explore the health consequences of low-dose radiation, our study employs a robust statistical framework that examines whether specific groups of genes, belonging to known pathways, exhibit coordinated expression patterns that align with the radiation levels. Notably, our findings reveal the existence of intricate yet consistent signatures that reflect the molecular response to radiation exposure, distinguishing between low-dose and high-dose radiation. Moreover, we leverage a pathway-constrained variational autoencoder to capture the nonlinear interactions within gene expression data. By comparing these two analytical approaches, our study aims to gain valuable insights into the impact of low-dose radiation on gene expression patterns, identify pathways that are differentially affected, and harness the potential of machine learning to uncover hidden activity within biological networks. This comparative analysis contributes to a deeper understanding of the molecular consequences of low-dose radiation exposure.

Location-based electrotactile feedback localizes hitting point in virtual-reality table tennis game.

Learning new motor skills is often challenged by sensory mismatches. For reliable sensory information, people have actively employed sensory intervention methods. Visual assistance is the most popular method to provide sensory information, which is equivalent to the knowledge of performance (KP) in motor tasks. However, its efficacy is questionable because of visual-proprioceptive mismatch as well as heavy intrinsic visual and cognitive engagement in motor tasks. Electrotactile intervention is a promising technique to address the current limitations, as it provides KP using tactile feedback that has a close neurophysiological association with proprioception. To test its efficacy, we compared the effects of visual and electrotactile assistance on hitting point localization of the table-tennis racket during virtual-reality table-tennis game. Experimental results suggest that location-based electrotactile feedback outperforms visual assistance in localizing the hitting point on a table-tennis racket during virtual-reality table-tennis game. Our study showed the potential of electrotactile intervention for improving the efficacy of new motor skill training.

Entropy removal of medical diagnostics.

Shannon entropy is a core concept in machine learning and information theory, particularly in decision tree modeling. To date, no studies have extensively and quantitatively applied Shannon entropy in a systematic way to quantify the entropy of clinical situations using diagnostic variables (true and false positives and negatives, respectively). Decision tree representations of medical decision-making tools can be generated using diagnostic variables found in literature and entropy removal can be calculated for these tools. This concept of clinical entropy removal has significant potential for further use to bring forth healthcare innovation, such as quantifying the impact of clinical guidelines and value of care and applications to Emergency Medicine scenarios where diagnostic accuracy in a limited time window is paramount. This analysis was done for 623 diagnostic tools and provided unique insights into their utility. For studies that provided detailed data on medical decision-making algorithms, bootstrapped datasets were generated from source data to perform comprehensive machine learning analysis on these algorithms and their constituent steps, which revealed a novel and thorough evaluation of medical diagnostic algorithms.

Routine Ureteral Stenting in Kidney Transplant Reduces Postoperative Hydronephrosis and Percutaneous Ureteral Interventions: A Single-Center Experience.

OBJECTIVES: The effect of routine ureteral stenting on postoperative hydronephrosis and percutaneous ureteral intervention in kidney transplant remains unknown. This study aimed to evaluate the effects of routine ureteral stenting on hydronephrosis and percutaneous ureteral intervention and the cost benefit of ureteral stenting in kidney transplant. MATERIALS AND METHODS: We retrospectively analyzed patients who underwent kidney transplant at a tertiary institution between 2005 and 2021. We adopted a ureteral stentingprotocol in2017, anda comparisonwas performed with previous patients without stents. RESULTS: In total, 539 patients underwent kidney transplant(271 with stents [51.3%], 268 without stents [49.7%]). Hydronephrosis was detected in 16 cases (5.9%) and 30 cases (11.2%) of groups with and without stents,respectively (P = .041). Among patients with hydronephrosis, the number of patients who underwent percutaneous ureteral intervention was significantly lower in the stent group than in the nostent group (1 [6.25%] vs 10 [33.33%]; P= .014).Twenty patients (3.71%) experienced major urologic complications (19 [7.1%] in the no-stent group, and 1 [0.4%] in the stent group; P = .001). No significant differences between the groups were shown in the incidence of urinary tract infections within 3 months of transplant (24 [8.9%] vs 22 [8.2%]; P = .846). No differences were shown between the groups in ureterovesical anastomosis time (24.4 vs 24.03 min; P = .699) or 1-year graft survival (97% vs 97.8%; P = .803). The healthcare cost was significantly lower in the stent group than in the no-stent group by $1702.05 ($15000.89 vs $16702.95; P < .001). CONCLUSIONS: Routine ureteral stenting in kidney transplant significantly decreased the incidence of postoperative hydronephrosis and percutaneous ureteral intervention. Stenting did notlead to increased urinary tract infections and was cost-effective.

Knowledge-driven learning, optimization, and experimental design under uncertainty for materials discovery.

Significant acceleration of the future discovery of novel functional materials requires a fundamental shift from the current materials discovery practice, which is heavily dependent on trial-and-error campaigns and high-throughput screening, to one that builds on knowledge-driven advanced informatics techniques enabled by the latest advances in signal processing and machine learning. In this review, we discuss the major research issues that need to be addressed to expedite this transformation along with the salient challenges involved. We especially focus on Bayesian signal processing and machine learning schemes that are uncertainty aware and physics informed for knowledge-driven learning, robust optimization, and efficient objective-driven experimental design.

Optimal decision-making in high-throughput virtual screening pipelines.

The need for efficient computational screening of molecular candidates that possess desired properties frequently arises in various scientific and engineering problems, including drug discovery and materials design. However, the enormous search space containing the candidates and the substantial computational cost of high-fidelity property prediction models make screening practically challenging. In this work, we propose a general framework for constructing and optimizing a high-throughput virtual screening (HTVS) pipeline that consists of multi-fidelity models. The central idea is to optimally allocate the computational resources to models with varying costs and accuracy to optimize the return on computational investment. Based on both simulated and real-world data, we demonstrate that the proposed optimal HTVS framework can significantly accelerate virtual screening without any degradation in terms of accuracy. Furthermore, it enables an adaptive operational strategy for HTVS, where one can trade accuracy for efficiency.

Autism Spectrum Disorder: A Neuro-Immunometabolic Hypothesis of the Developmental Origins.

Fetal neuroinflammation and prenatal stress (PS) may contribute to lifelong neurological disabilities. Astrocytes and microglia, among the brain's non-neuronal "glia" cell populations, play a pivotal role in neurodevelopment and predisposition to and initiation of disease throughout lifespan. One of the most common neurodevelopmental disorders manifesting between 1-4 years of age is the autism spectrum disorder (ASD). A pathological glial-neuronal interplay is thought to increase the risk for clinical manifestation of ASD in at-risk children, but the mechanisms remain poorly understood, and integrative, multi-scale models are needed. We propose a model that integrates the data across the scales of physiological organization, from genome to phenotype, and provides a foundation to explain the disparate findings on the genomic level. We hypothesize that via gene-environment interactions, fetal neuroinflammation and PS may reprogram glial immunometabolic phenotypes that impact neurodevelopment and neurobehavior. Drawing on genomic data from the recently published series of ovine and rodent glial transcriptome analyses with fetuses exposed to neuroinflammation or PS, we conducted an analysis on the Simons Foundation Autism Research Initiative (SFARI) Gene database. We confirmed 21 gene hits. Using unsupervised statistical network analysis, we then identified six clusters of probable protein-protein interactions mapping onto the immunometabolic and stress response networks and epigenetic memory. These findings support our hypothesis. We discuss the implications for ASD etiology, early detection, and novel therapeutic approaches. We conclude with delineation of the next steps to verify our model on the individual gene level in an assumption-free manner. The proposed model is of interest for the multidisciplinary community of stakeholders engaged in ASD research, the development of novel pharmacological and non-pharmacological treatments, early prevention, and detection as well as for policy makers.

Network Analysis of Academic Medical Center Websites in the United States.

Healthcare resources are published annually in repositories such as the AHA Annual Survey DatabaseTM. However, these data repositories are created via manual surveying techniques which are cumbersome in collection and not updated as frequently as website information of the respective hospital systems represented. Also, this resource is not widely available to patients in an easy-to-use format. Network analysis techniques have the potential to create topological maps which serve to aid in pathfinding for patients in their search for healthcare services. This study explores the topological structure of forty United States academic health center websites. Network analysis is utilized to analyze and visualize 48,686 webpages. Several elements of network structure are examined including basic network properties, and centrality measures distributions. The Louvain community detection algorithm is used to examine the extent to which these techniques allow identification of healthcare resources within networks. The results indicate that websites with related healthcare services tend to form observable clusters useful in mapping key resources within a hospital system.

Sensitivity Analysis of Genome-Scale Metabolic Flux Prediction.

TRIMER, Transcription Regulation Integrated with MEtabolic Regulation, is a genome-scale modeling pipeline targeting at metabolic engineering applications. Using TRIMER, regulated metabolic reactions can be effectively predicted by integrative modeling of metabolic reactions with a transcription factor-gene regulatory network (TRN), which is modeled through a Bayesian network (BN). In this article, we focus on sensitivity analysis of metabolic flux prediction for uncertainty quantification of BN structures for TRN modeling in TRIMER. We propose a computational strategy to construct the uncertainty class of TRN models based on the inferred regulatory order uncertainty given transcriptomic expression data. With that, we analyze the prediction sensitivity of the TRIMER pipeline for the metabolite yields of interest. The obtained sensitivity analyses can guide optimal experimental design (OED) to help acquire new data that can enhance TRN modeling and achieve specific metabolic engineering objectives, including metabolite yield alterations. We have performed small- and large-scale simulated experiments, demonstrating the effectiveness of our developed sensitivity analysis strategy for BN structure learning to quantify the edge importance in terms of metabolic flux prediction uncertainty reduction and its potential to effectively guide OED.

Network-Based Structural Alignment of RNA Sequences Using TOPAS.

TOPAS (TOPological network-based Alignment of Structural RNAs) is a network-based alignment algorithm that predicts structurally sound pairwise alignment of RNAs. In order to take advantage of recent advances in comparative network analysis for efficient structurally sound RNA alignment, TOPAS constructs topological network representations for RNAs, which consist of sequential edges connecting nucleotide bases as well as structural edges reflecting the underlying folding structure. Structural edges are weighted by the estimated base-pairing probabilities. Next, the constructed networks are aligned using probabilistic network alignment techniques, which yield a structurally sound RNA alignment that considers both the sequence similarity and the structural similarity between the given RNAs. Compared to traditional Sankoff-style algorithms, this network-based alignment scheme leads to a significant reduction in the overall computational cost while yielding favorable alignment results. Another important benefit is its capability to handle arbitrary folding structures, which can potentially lead to more accurate alignment for RNAs with pseudoknots.

Optimal high-throughput virtual screening pipeline for efficient selection of redox-active organic materials.

As global interest in renewable energy continues to increase, there has been a pressing need for developing novel energy storage devices based on organic electrode materials that can overcome the shortcomings of the current lithium-ion batteries. One critical challenge for this quest is to find materials whose redox potential (RP) meets specific design targets. In this study, we propose a computational framework for addressing this challenge through the effective design and optimal operation of a high-throughput virtual screening (HTVS) pipeline that enables rapid screening of organic materials that satisfy the desired criteria. Starting from a high-fidelity model for estimating the RP of a given material, we show how a set of surrogate models with different accuracy and complexity may be designed to construct a highly accurate and efficient HTVS pipeline. We demonstrate that the proposed HTVS pipeline construction and operation strategies substantially enhance the overall screening throughput.

Looking back on forward-looking COVID models.

Covid Act Now (CAN) developed an epidemiological model that takes various non-pharmaceutical interventions (NPIs) into account and predicts viral spread and subsequent health outcomes. In this study, the projections of the model developed by CAN were back-tested against real-world data, and it was found that the model consistently overestimated hospitalizations and deaths by 25%-100% and 70%-170%, respectively, due in part to an underestimation of the efficacy of NPIs. Other COVID models were also back-tested against historical data, and it was found that all models generally captured the potential magnitude and directionality of the pandemic in the short term. There are limitations to epidemiological models, but understanding these limitations enables these models to be utilized as tools for data-driven decision-making in viral outbreaks. Further, it can be valuable to have multiple, independently developed models to mitigate the inaccuracies of or to correct for the incorrect assumptions made by a particular model.

Robust importance sampling for error estimation in the context of optimal Bayesian transfer learning.

Classification has been a major task for building intelligent systems because it enables decision-making under uncertainty. Classifier design aims at building models from training data for representing feature-label distributions-either explicitly or implicitly. In many scientific or clinical settings, training data are typically limited, which impedes the design and evaluation of accurate classifiers. Atlhough transfer learning can improve the learning in target domains by incorporating data from relevant source domains, it has received little attention for performance assessment, notably in error estimation. Here, we investigate knowledge transferability in the context of classification error estimation within a Bayesian paradigm. We introduce a class of Bayesian minimum mean-square error estimators for optimal Bayesian transfer learning, which enables rigorous evaluation of classification error under uncertainty in small-sample settings. Using Monte Carlo importance sampling, we illustrate the outstanding performance of the proposed estimator for a broad family of classifiers that span diverse learning capabilities.

Synthetic data for design and evaluation of binary classifiers in the context of Bayesian transfer learning.

Transfer learning (TL) techniques can enable effective learning in data scarce domains by allowing one to re-purpose data or scientific knowledge available in relevant source domains for predictive tasks in a target domain of interest. In this Data in Brief article, we present a synthetic dataset for binary classification in the context of Bayesian transfer learning, which can be used for the design and evaluation of TL-based classifiers. For this purpose, we consider numerous combinations of classification settings, based on which we simulate a diverse set of feature-label distributions with varying learning complexity. For each set of model parameters, we provide a pair of target and source datasets that have been jointly sampled from the underlying feature-label distributions in the target and source domains, respectively. For both target and source domains, the data in a given class and domain are normally distributed, where the distributions across domains are related to each other through a joint prior. To ensure the consistency of the classification complexity across the provided datasets, we have controlled the Bayes error such that it is maintained within a range of predefined values that mimic realistic classification scenarios across different relatedness levels. The provided datasets may serve as useful resources for designing and benchmarking transfer learning schemes for binary classification as well as the estimation of classification error.

AI-enabled, implantable, multichannel wireless telemetry for photodynamic therapy.

Photodynamic therapy (PDT) offers several advantages for treating cancers, but its efficacy is highly dependent on light delivery to activate a photosensitizer. Advances in wireless technologies enable remote delivery of light to tumors, but suffer from key limitations, including low levels of tissue penetration and photosensitizer activation. Here, we introduce DeepLabCut (DLC)-informed low-power wireless telemetry with an integrated thermal/light simulation platform that overcomes the above constraints. The simulator produces an optimized combination of wavelengths and light sources, and DLC-assisted wireless telemetry uses the parameters from the simulator to enable adequate illumination of tumors through high-throughput (<20 mice) and multi-wavelength operation. Together, they establish a range of guidelines for effective PDT regimen design. In vivo Hypericin and Foscan mediated PDT, using cancer xenograft models, demonstrates substantial suppression of tumor growth, warranting further investigation in research and/or clinical settings.

Protocol for condition-dependent metabolite yield prediction using the TRIMER pipeline.

This protocol explains the pipeline for condition-dependent metabolite yield prediction using Transcription Regulation Integrated with MEtabolic Regulation (TRIMER). TRIMER targets metabolic engineering applications via a hybrid model integrating transcription factor (TF)-gene regulatory network (TRN) with a Bayesian network (BN) inferred from transcriptomic expression data to effectively regulate metabolic reactions. For E. coli and yeast, TRIMER achieves reliable knockout phenotype and flux predictions from the deletion of one or more TFs at the genome scale. For complete details on the use and execution of this protocol, please refer to Niu et al. (2021).

Deep graph representations embed network information for robust disease marker identification.

MOTIVATION: Accurate disease diagnosis and prognosis based on omics data rely on the effective identification of robust prognostic and diagnostic markers that reflect the states of the biological processes underlying the disease pathogenesis and progression. In this article, we present GCNCC, a Graph Convolutional Network-based approach for Clustering and Classification, that can identify highly effective and robust network-based disease markers. Based on a geometric deep learning framework, GCNCC learns deep network representations by integrating gene expression data with protein interaction data to identify highly reproducible markers with consistently accurate prediction performance across independent datasets possibly from different platforms. GCNCC identifies these markers by clustering the nodes in the protein interaction network based on latent similarity measures learned by the deep architecture of a graph convolutional network, followed by a supervised feature selection procedure that extracts clusters that are highly predictive of the disease state. RESULTS: By benchmarking GCNCC based on independent datasets from different diseases (psychiatric disorder and cancer) and different platforms (microarray and RNA-seq), we show that GCNCC outperforms other state-of-the-art methods in terms of accuracy and reproducibility. AVAILABILITY AND IMPLEMENTATION: https://github.com/omarmaddouri/GCNCC. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

TRIMER: Transcription Regulation Integrated with Metabolic Regulation.

There has been extensive research in predictive modeling of genome-scale metabolic reaction networks. Living systems involve complex stochastic processes arising from interactions among different biomolecules. For more accurate and robust prediction of target metabolic behavior under different conditions, not only metabolic reactions but also the genetic regulatory relationships involving transcription factors (TFs) affecting these metabolic reactions should be modeled. We have developed a modeling and simulation pipeline enabling the analysis of Transcription Regulation Integrated with Metabolic Regulation: TRIMER. TRIMER utilizes a Bayesian network (BN) inferred from transcriptomes to model the transcription factor regulatory network. TRIMER then infers the probabilities of the gene states relevant to the metabolism of interest, and predicts the metabolic fluxes and their changes that result from the deletion of one or more transcription factors at the genome scale. We demonstrate TRIMER's applicability to both simulated and experimental data and provide performance comparison with other existing approaches.

Effects of probiotics on bowel function restoration following ileostomy closure in rectal cancer patients: a randomized controlled trial.

AIM: The aim was to determine the efficacy of probiotics in restoring bowel function following ileostomy reversal in patients with rectal cancer. METHOD: This was a pilot, randomized, double-blind, placebo-controlled trial. The probiotic used in this study, Lactobacillus plantarum CJLP243, was derived from kimchi. Patients were randomly allocated to a probiotic or placebo group and medication was taken once daily from preoperative day 1 to day 21. Primary outcomes were the Memorial Sloan Kettering Cancer Centre Bowel Function Index (MSKCC BFI) instrument and the low anterior resection syndrome score. The secondary outcomes were the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and CR29 questionnaire responses. RESULTS: Forty patients were enrolled, and 36 patients (probiotics, n = 17; placebo, n = 19) completed the primary outcomes. Total scores for the MSKCC questionnaire (56.2 ± 12.0 vs. 55.0 ± 10.7, P = 0.356) and low anterior resection syndrome scores (33.3 ± 7.6 vs. 36.0 ± 5.3, P = 0.257) were not significantly different between the probiotic and placebo groups, respectively. In the MSKCC BFI, the postoperative dietary scale score at week 1 was significantly higher in the probiotic group (13.1 ± 3.8 vs. 9.0 ± 3.0, P < 0.001). There were no other significant differences between the two groups for any other questionnaire scores. CONCLUSION: There were no significant effects supporting the use of a probiotic for improved bowel function in patients following ileostomy reversal. Nevertheless, the administration of probiotics showed trends toward improvements in some subscale bowel function measures, suggesting further studies may be warranted.