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At least 199 records · Page 11

Enhancing the Operational Resilience of Advanced Reactors with Digital Twins by Recurrent Neural Networks

Because of a lack of operational data and uncertainty in evaluation model for abnormal and accident scenarios, the established operating procedures can be biased in characterizing the reactor states and ensuring operational resilience. To reduce uncertainty associated with actual plant conditions, digital twin (DT) technology is suggested to support operator’s decision-making by effectively extracting and using knowledge of the current and future plant states from the knowledge base. This study first builds a knowledge base based on the characterization of issue space and the simulation tool. Next, this study discusses diagnosis and prognosis DTs for enhancing operational resilience by recovering the complete states of reactors and by predicting the future reactor behaviors. Finally, the decision-making module of the control system can determine the optimal control strategy that meets operational goals during loss-of-flow scenarios. To demonstrate and evaluate the DTs capability for supporting the operations of nuclear reactors, this study develops and assesses both the diagnosis and prognosis DTs in a nearly autonomous management and control system for an Experimental Breeder Reactor-II simulator during different loss-of-flow scenarios.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Accuracy of Tau Positron Emission Tomography as a Prognostic Marker in Preclinical and Prodromal Alzheimer Disease: A Head-to-Head Comparison Against Amyloid Positron Emission Tomography and Magnetic Resonance Imaging

Importance: Tau positron emission tomography (PET) tracers have proven useful for the differential diagnosis of dementia, but their utility for predicting cognitive change is unclear. Objective: To examine the prognostic accuracy of baseline fluorine 18 ( 18 F)-flortaucipir and [18F]RO948 (tau) PET in individuals across the Alzheimer disease (AD) clinical spectrum and to perform a head-to-head comparison against established magnetic resonance imaging (MRI) and amyloid PET markers. Design, setting, and participants: This prognostic study collected data from 8 cohorts in South Korea, Sweden, and the US from June 1, 2014, to February 28, 2021, with a mean (SD) follow-up of 1.9 (0.8) years. A total of 1431 participants were recruited from memory clinics, clinical trials, or cohort studies; 673 were cognitively unimpaired (CU group; 253 [37.6%] positive for amyloid-β [Aβ]), 443 had mild cognitive impairment (MCI group; 271 [61.2%] positive for Aβ), and 315 had a clinical diagnosis of AD dementia (315 [100%] positive for Aβ). Exposures: [ 18 F]Flortaucipir PET in the discovery cohort (n = 1135) or [ 18 F]RO948 PET in the replication cohort (n = 296), T1-weighted MRI (n = 1431), and amyloid PET (n = 1329) at baseline and repeated Mini-Mental State Examination (MMSE) evaluation. Main outcomes and measures: Baseline [ 18 F]flortaucipir/[ 18 F]RO948 PET retention within a temporal region of interest, MRI-based AD-signature cortical thickness, and amyloid PET Centiloids were used to predict changes in MMSE using linear mixed-effects models adjusted for age, sex, education, and cohort. Mediation/interaction analyses tested whether associations between baseline tau PET and cognitive change were mediated by baseline MRI measures and whether age, sex, and APOE genotype modified these associations. Results: Among 1431 participants, the mean (SD) age was 71.2 (8.8) years; 751 (52.5%) were male. Findings for [ 18 F]flortaucipir PET predicted longitudinal changes in MMSE, and effect sizes were stronger than for AD-signature cortical thickness and amyloid PET across all participants (R 2 , 0.35 [tau PET] vs 0.24 [MRI] vs 0.17 [amyloid PET]; P < .001, bootstrapped for difference) in the Aβ-positive MCI group (R2, 0.25 [tau PET] vs 0.15 [MRI] vs 0.07 [amyloid PET]; P < .001, bootstrapped for difference) and in the Aβ-positive CU group (R 2 , 0.16 [tau PET] vs 0.08 [MRI] vs 0.08 [amyloid PET]; P < .001, bootstrapped for difference). These findings were replicated in the [ 18 F]RO948 PET cohort. MRI mediated the association between [ 18 F]flortaucipir PET and MMSE in the groups with AD dementia (33.4% [95% CI, 15.5%-60.0%] of the total effect) and Aβ-positive MCI (13.6% [95% CI, 0.0%-28.0%] of the total effect), but not the Aβ-positive CU group (3.7% [95% CI, -17.5% to 39.0%]; P = .71). Age (t = -2.28; P = .02), but not sex (t = 0.92; P = .36) or APOE genotype (t = 1.06; P = .29) modified the association between baseline [ 18 F]flortaucipir PET and cognitive change, such that older individuals showed faster cognitive decline at similar tau PET levels. Conclusions and relevance: The findings of this prognostic study suggest that tau PET is a promising tool for predicting cognitive change that is superior to amyloid PET and MRI and may support the prognostic process in preclinical and prodromal stages of AD.

59 BASIC BIOLOGICAL SCIENCES↗

Tau Positron Emission Tomography for Predicting Dementia in Individuals With Mild Cognitive Impairment

An accurate prognosis is especially pertinent in mild cognitive impairment (MCI), when individuals experience considerable uncertainty about future progression. To evaluate the prognostic value of tau positron emission tomography (PET) to predict clinical progression from MCI to dementia. This was a multicenter cohort study with external validation and a mean (SD) follow-up of 2.0 (1.1) years. Data were collected from centers in South Korea, Sweden, the US, and Switzerland from June 2014 to January 2024. Participant data were retrospectively collected and inclusion criteria were a baseline clinical diagnosis of MCI; longitudinal clinical follow-up; a Mini-Mental State Examination (MMSE) score greater than 22; and available tau PET, amyloid-β (Aβ) PET, and magnetic resonance imaging (MRI) scan less than 1 year from diagnosis. A total of 448 eligible individuals with MCI were included (331 in the discovery cohort and 117 in the validation cohort). None of these participants were excluded over the course of the study. Exposures included Tau PET, Aβ PET, and MRI. Positive results on tau PET (temporal meta–region of interest), Aβ PET (global; expressed in the standardized metric Centiloids), and MRI (Alzheimer disease [AD] signature region) was assessed using quantitative thresholds and visual reads. Clinical progression from MCI to all-cause dementia (regardless of suspected etiology) or to AD dementia (AD as suspected etiology) served as the primary outcomes. The primary analyses were receiver operating characteristics. In the discovery cohort, the mean (SD) age was 70.9 (8.5) years, 191 (58%) were male, the mean (SD) MMSE score was 27.1 (1.9), and 110 individuals with MCI (33%) converted to dementia (71 to AD dementia). Only the model with tau PET predicted all-cause dementia (area under the receiver operating characteristic curve [AUC], 0.75; 95% CI, 0.70-0.80) better than a base model including age, sex, education, and MMSE score (AUC, 0.71; 95% CI, 0.65-0.77; P = .02), while the models assessing the other neuroimaging markers did not improve prediction. In the validation cohort, tau PET replicated in predicting all-cause dementia. Compared to the base model (AUC, 0.75; 95% CI, 0.69-0.82), prediction of AD dementia in the discovery cohort was significantly improved by including tau PET (AUC, 0.84; 95% CI, 0.79-0.89; P < .001), tau PET visual read (AUC, 0.83; 95% CI, 0.78-0.88; P = .001), and Aβ PET Centiloids (AUC, 0.83; 95% CI, 0.78-0.88; P = .03). In the validation cohort, only the tau PET and the tau PET visual reads replicated in predicting AD dementia. In this study, tau-PET showed the best performance as a stand-alone marker to predict progression to dementia among individuals with MCI. This suggests that, for prognostic purposes in MCI, a tau PET scan may be the best currently available neuroimaging marker.

59 BASIC BIOLOGICAL SCIENCES↗

Evaluation of a visual interpretation method for tau-PET with 18 F-flortaucipir

Introduction: Positron emission tomography targeting tau (tau-PET) is a promising diagnostic tool for the identification of Alzheimer's disease (AD). Currently available data rely on quantitative measures, and a visual interpretation method, critical for clinical translation, is needed. Methods: In this work, we developed a visual interpretation method for 18 F-flortaucipir tau-PET and tested it on 274 individuals (cognitively normal controls, patients with mild cognitive impairment [MCI], AD dementia, and non-AD diagnoses). Two readers interpreted 18 F-flortaucipir PET using two complementary indices: a global visual score and a visual distribution pattern. Results: Global visual scores were reliable, correlated with global cortical 18 F-flortaucipir standardized uptake value ratio (SUVR) and were associated with clinical diagnosis and amyloid status. The AD-like 18 F-flortaucipir pattern had good sensitivity and specificity to identify amyloid-positive patients with AD dementia or MCI. Discussion: This 18 F-flortaucipir visual rating scheme is associated with SUVR quantification, clinical diagnosis, and amyloid status, and constitutes a promising approach to tau measurement in clinical settings.

59 BASIC BIOLOGICAL SCIENCES↗

Establishment of time‐resolved fluoroimmunoassay of IgG4 based on magnetic microspheres

Abstract Background The abnormal increase in serum IgG4 level is an important clinical symptom of IgG4‐related disease (IgG4‐RD), and the detection of serum IgG4 level is a powerful tool for the diagnosis of IgG4‐RD. This study was conducted to establish a simple and rapid immunoassay for the determination of human serum IgG4 levels. Methods Based on the competition method, a novel immunoassay was established for the determination of human serum IgG4 using a combination of time‐resolved fluoroimmunoassay (TRFIA) and magnetic microspheres. IgG4 was coupled with magnetic microspheres and competed with IgG4 in the samples to bind the Eu 3+ ‐labeled anti‐IgG4 antibody. The immunocomplex was separated and washed in a magnetic field, and the fluorescence counts were measured according to the number of dissociated europium ions. Results The analytical sensitivity of IgG4‐TRFIA based on magnetic microspheres was 0.006 g/L, and the detection range was 0.006–20 g/L under optimal conditions. The precision, recovery, and specificity of this immunoassay were demonstrated to be acceptable. The clinical application of IgG4‐TRFIA based on magnetic microspheres was evaluated and compared with that of immunonephelometry. The results showed that the two detection methods had a good correlation, with a correlation coefficient of .9871. Conclusion IgG4‐TRFIA based on magnetic microspheres has the advantages of high sensitivity, wide detection range, and short analysis time and has the potential to become a useful tool for the diagnosis of IgG4‐RD.

Wu, Qingqing↗

Post-Combat-Injury Opioid Prescription and Alcohol Use Disorder in the Military

Previous studies have identified combat exposure and combat traumatic experience as problematic drinking risk factors. Increasing evidence suggests that opioid use increases the risk of alcohol use disorder. This study investigated the association between opioid prescription use after injury and (1) alcohol use disorder and (2) severity of alcohol use disorder among deployed military servicemembers. Deidentified health records data of 9,029 deployed servicemembers from a retrospective cohort study were analyzed. Data were randomly selected from the Department of Defense Trauma Registry and included servicemembers with combat injuries during deployment in Iraq or Afghanistan (2002–2016). Pharmacy records and International Classification of Diseases, Ninth and Tenth Revision diagnosis codes were used. Three groups were identified (no opioid prescription use, nonpersistent opioid prescription use, and persistent opioid prescription use) and were compared on the basis of alcohol use disorder risk using Cox proportional hazard models. Data analyses were performed in 2021. Of the 9,029 servicemembers with combat injury, 2,262 developed alcohol use disorder (1,322 developed severe alcohol use disorder). Compared with no opioid prescription use, increased alcohol use disorder risk was associated with persistent opioid prescription use, with a hazard ratio of 1.13 (95% CI=1.02, 1.26). After covariate adjustment, increased risk remained statistically significant (hazards ratio=1.24; 95% CI=1.10, 1.39). There was no significant difference in alcohol use disorder risk between no opioid prescription use and nonpersistent opioid prescription use. The risk of severe alcohol use disorder did not vary by opioid use among servicemembers with alcohol use disorder diagnosis. Furthermore, the findings of the study suggest that the incidence of alcohol use disorder was higher among injured servicemembers with persistent opioid prescription use than among those without opioid use. If replicated in prospective studies, the findings highlight the need for clinicians to consider the current and history of alcohol use of patients in initiating treatment involving opioids.

60 APPLIED LIFE SCIENCES↗

Pre-trained network-based transfer learning: A small-sample machine learning approach to nuclear power plant classification problem

Some research topics belonging to classification problems in the nuclear industry, such as fault diagnosis and accident identification, can be solved by feature extraction and subsequent application of statistical machine learning classifiers. Recently, deep neural network-based methods with automatic feature extraction and high accuracy have gained wide attention. They usually require large-scale training data, however, plant fault or accident data are scarce or difficult to obtain. Here this paper proposes a convolutional network (CNN)-based transfer learning method to solve this problem. The network's shallow layer is derived from a pre-trained CNN based on the ImageNet database to automatically extract features, and the deep layer is customized to match the classification problem. Data in non-image formats are converted to image formats and subsequently used to train the network. Case studies of rotating machines fault diagnosis show that the proposed method requires only limited training data to achieve high accuracy.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

How much information on precipitation is contained in satellite infrared imagery?

Satellite infrared (IR) brightness temperature providing information on the characteristics of cloud tops is one of the primary input data used for estimating precipitation from satellites. Thus, the natural questions to ask are: Does IR imagery contain more information about precipitation in some regions more than others? What are the factors that lead to such differences? Should we expect the amount of information provided by IR imagery to change with respect to temporal or spatial aggregation? Comprehensive analysis of the accuracy of satellite-based precipitation estimates obtained from any given algorithm may provide qualitative answers to the above questions. However, such an approach only offers conclusions within the limited context of the algorithm used to obtain precipitation estimates; that is, patterns caused by the inherent information content of IR imagery are inextricable from those induced by assumptions embedded in the precipitation estimation algorithm. Here, we address the abovementioned questions from a different perspective using an information-theoretic measure, free of structural assumptions and general to a wide range of relationships, to characterize the average and seasonal dependence between IR imagery provided by satellite sensors in the spectral range (10.7–11.5 μm) and precipitation rates in the contiguous United States (CONUS) across distinct temporal and spatial scales. We analyze a total of more than 1.3 billion pairs of IR and precipitation observations over CONUS, and we observe interesting patterns. First, we show that there is a strong inverse relationship (ρ = - 0.73) between the information content of IR data and the number of no-rain observations; however, its robustness varies regionally and seasonally with less significant correlation during the warm season. Second, we demonstrate that the intuitive relationship of increasing dependence between IR and precipitation as a result of temporal or spatial aggregation exhibits a diminishing returns behavior. For instance, temporal aggregation from 1 to 3 h increases the dependence approximately 7 times as much as temporal aggregation from 12 to 24 h. Furthermore, we quantitatively examine and re-confirm several statements previously reported in the literature such as the strong association between IR and precipitation in convective storms and the low association in orographic rainfall. Finally, we conclude by illustrating the potential of the analysis in diagnosis of operational algorithms for estimating precipitation from IR brightness temperature. The findings of this study pinpoint spatial domains and time scales at which IR is not an adequate proxy for estimating precipitation. Thus, they can potentially guide the development of operational algorithms that utilize satellite Infrared imagery for estimating, downscaling and data fusion of precipitation. Finally, the analysis presented here opens up the possibility of developing new methodologies for diagnosis of satellite-based precipitation estimation algorithms.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

The importance of cycle-by-cycle data in performing rapid battery technology development and validation

Lithium-ion battery (LiB) technology is playing a crucial role in transforming the predominantly fossil fuel-based transportation and stationary storage sectors to achieve a low-carbon economy. Rapid innovation in the LiB materials to electrode to cell design is happening to satisfy the performance, life, and safety metrics required by those myriads of applications. Lately, advanced analytics, such as machine-learning or artificial intelligence (ML/AI) techniques, are being used more frequently to aid in expedited LiB technology development, performance validation, and life prediction. The success of these techniques often relies on a large volume of well-defined and high-quality battery test data. On the other hand, most battery developers and research and development (R&D) communities are still following a classical approach to develop batteries, which is running calendar- and/or cycle-aging tests, performing reference performance tests (RPTs), and conducting post-mortem analyses periodically without paying attention to the wealth of data often not collected during the calendar or cycle life aging tests. This sparse data collection approach is time- and resource-intensive, requiring data capture and evaluation of months to years of RPT data to diagnose accurate battery state of performance, health, and safety. Even so, the underlying aging modes and mechanisms can be missed. If collected properly, battery test data during cycling or calendaring can be efficiently combined with ML/AI techniques to create powerful tools in the rapid diagnosis of battery state of performance, health, and safety along with insights into underlying aging modes and mechanisms. In this report, we discuss the importance of effective cycle-by-cycle (CBC) data collection with example case studies. Within a reasonable timeframe, RPT data are often inadequate in capturing many of the crucial battery aging dynamics, which often predominantly show up in CBC test data. Finally, we also show examples of ML/AI techniques that use CBC data in rapid diagnosis and projection of LiB state of health (SOH) to motivate the scientific community in collecting and using CBC data to facilitate expeditious technology development and validation.

25 ENERGY STORAGE↗

Persistent urinary metabolic signatures in children with type 1 diabetes

There are an estimated 3.7 million people with undiagnosed type 1 diabetes (T1D), living primarily in poor areas of the globe. Therefore, there is a need for non-invasive, affordable tests to provide accurate diagnosis despite the time post-disease onset and fasting state. Here, we studied persistent urinary T1D biomarkers that can be used to develop such tests. Here, we analyzed the urine metabolomes of three independent cohorts of samples collected within 48 h (from Indiana University), and 1 year (from University of Colorado) and 1–10 years (6 years in average) (from Children’s National Medical Center) post-diagnosis. Samples were submitted to gas chromatography-mass spectrometry and machine learning an0alyses to determine diagnostic metabolite panels. The data were also mapped into a metabolic pathway to understand persistently regulated processes in T1D. Seven metabolites showed consistent increases in all three cohorts: d-glucose, d-mannose, myo-inositol, 3-hydroxyisobutyric acid, gluconolactone, d-gluconic acid, and d-glucuronic acid. A combination of machine learning analysis and metabolite ratios as biomarker candidates diagnosed T1D with high sensitivity and specificity across different cohorts and times. Mapping the regulated metabolites into a pathway showed impairment in glycolysis and overflow of glucose towards other pathways in subjects with T1D that was persistent over time. We identified and cross-validated highly specific and sensitive urinary biomarkers. This opens opportunities to develop affordable, robust, and non-invasive tests. The results also show that most of the biomarkers were signatures of dysregulated glucose metabolism.

Type 1 diabetes↗

A Telomerase-Activated Magnetic Resonance Imaging Probe for Consecutively Monitoring Tumor Growth Kinetics and In Situ Screening Inhibitors

Telomerase has long been considered as a biomarker for cancer diagnosis and a therapeutic target for drug discovery. Detecting telomerase activity in vivo could provide more direct information of tumor progression and response to drug treatment, which, however, is hampered by the lack of an effective probe that can generate an output signal without a tissue penetration depth limit. Here in this study, using the principle of distance-dependent magnetic resonance tuning, we constructed a telomerase-activated magnetic resonance imaging probe (TAMP) by connecting superparamagnetic ferroferric oxide nanoparticles (SPFONs) and paramagnetic Gd-DOTA (Gd(III) 1,4,7,10- tetraazacyclododecane-1,4,7,10-tetraazacyclododecane-1,4,7,10-tet-raacetic acid) complexes via telomerase-responsive DNA motifs. Upon telomerase-catalyzed extension of the primer in TAMP, Gd-DOTA-conjugated oligonucleotides can be liberated from the surface of SPFONs through a DNA strand displacement reaction, restoring the T 1 signal of the Gd-DOTA for a direct readout of the telomerase activity. Here we show that, by tracking telomerase activity, this probe provides consistent monitoring of tumor growth kinetics during progression and in response to drug treatment and enables in situ screening of telomerase inhibitors in whole-animal models. This study provides an alternative toolkit for cancer diagnosis, treatment response assessment, and anticancer drug screening.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DDxNet: a deep learning model for automatic interpretation of electronic health records, electrocardiograms and electroencephalograms

Effective patient care mandates rapid, yet accurate, diagnosis. With the abundance of non-invasive diagnostic measurements and electronic health records (EHR), manual interpretation for differential diagnosis has become time-consuming and challenging. This has led to wide-spread adoption of AI-powered tools, in pursuit of improving accuracy and efficiency of this process. While the unique challenges presented by each modality and clinical task demand customized tools, the cumbersome process of making problem-specific choices has triggered the critical need for a generic solution to enable rapid development of models in practice. In this spirit, we develop DDxNet, a deep architecture for time-varying clinical data, which we demonstrate to be well-suited for diagnostic tasks involving different modalities (ECG/EEG/EHR), required level of characterization (abnormality detection/phenotyping) and data fidelity (single-lead ECG/22-channel EEG). Using multiple benchmark problems, we show that DDxNet produces high-fidelity predictive models, and sometimes even provides significant performance gains over problem-specific solutions.

60 APPLIED LIFE SCIENCES↗

A Population-Level Summary of Health Care Utilization for the Management of Patellar Tendinopathy in the Military Health System

Abstract Patellar tendinopathy (PT) is a common nontraumatic orthopaedic disorder of the knee suffered by many service members. Understanding the make-up of usual care for PT at the system level can better frame current clinical gaps and areas that need improvement. Exercise therapy is recommended as a core treatment for PT, but it is unclear how often it is used as a part of usual care for PT within the Military Health System (MHS). The purpose of the study was to identify interventions used in the management of PT and the timing of these interventions. A secondary purpose was to determine if exercise therapy use was associated with reduced recurrence of knee pain. In total, 4,719 individuals aged 17 to 50 years in the MHS diagnosed with PT between 2010 and 2011 were included. Pharmacological and nonpharmacological interventions, visits to specialty providers, and imaging services were captured. Descriptive statistics were used to report the findings. Interventions were further categorized as being part of initial care (within the first 7 days), the initial episode of care (within the first 60 days), or the 2-year time period after diagnosis. Linear regression assessed the relationship between the number of exercise therapy visits in the initial episode of care and recurrences of knee pain. In total, 50.6% of this cohort had no more than one medical visit total for PT. Exercise therapy (18.2%) and nonsteroidal anti-inflammatory drugs (4.3%) were the two most used interventions in the initial episode of care. Radiographs were ordered for 23.1% of the cohort in the initial episode of care. The number of exercise therapy visits a patient received during the initial episode of care was not associated with recurrences of knee pain. Half of the individuals received no further care beyond an initial visit for the diagnosis of PT. Exercise therapy was the most common intervention used during the initial episode of care, but exercise therapy did not influence the recurrence of knee pain.

Orthopedics↗

Analysis of limited coverage effects on areal density measurements in inertial confinement fusion implosions

Accurate diagnosis of areal density ($\textit{ρR}$) is critical for the inference of performance metrics in inertial confinement fusion implosions. One potential source of error in this diagnosis is the existence of low mode perturbations in the imploding target, which lead to asymmetries in the inference of the $\textit{ρR}$ from different lines of sight. Here, the error accrued as a result of limited coverage of the sphere due to a finite number of detectors is quantified, and the development of a forward scatter measurement from the OMEGA neutron time-of-flight detectors is motivated. In this work, a method by which the 1D-equivalent 4 π-averaged $\langleρR\rangle$ can be reconstructed, if accurate mode information can be diagnosed by other means, is validated.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Exploring extreme magnetization phenomena in directly driven imploding cylindrical targets

Abstract This paper uses extended-magnetohydrodynamics (MHD) simulations to explore an extreme magnetized plasma regime realizable by cylindrical implosions on the OMEGA laser facility. This regime is characterized by highly compressed magnetic fields (greater than 10 kT across the fuel), which contain a significant proportion of the implosion energy and induce large electrical currents in the plasma. Parameters governing the different magnetization processes such as Ohmic dissipation and suppression of instabilities by magnetic tension are presented, allowing for optimization of experiments to study specific phenomena. For instance, a dopant added to the target gas-fill can enhance magnetic flux compression while enabling spectroscopic diagnosis of the imploding core. In particular, the use of Ar K-shell spectroscopy is investigated by performing detailed non-LTE atomic kinetics and radiative transfer calculations on the MHD data. Direct measurement of the core electron density and temperature would be possible, allowing for both the impact of magnetization on the final temperature and thermal pressure to be obtained. By assuming the magnetic field is frozen into the plasma motion, which is shown to be a good approximation for highly magnetized implosions, spectroscopic diagnosis could be used to estimate which magnetization processes are ruling the implosion dynamics; for example, a relation is given for inferring whether thermally driven or current-driven transport is dominating.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

miss-SNF: a multimodal patient similarity network integration approach to handle completely missing data sources

Abstract Motivation Precision medicine leverages patient-specific multimodal data to improve prevention, diagnosis, prognosis, and treatment of diseases. Advancing precision medicine requires the non-trivial integration of complex, heterogeneous, and potentially high-dimensional data sources, such as multi-omics and clinical data. In the literature, several approaches have been proposed to manage missing data, but are usually limited to the recovery of subsets of features for a subset of patients. A largely overlooked problem is the integration of multiple sources of data when one or more of them are completely missing for a subset of patients, a relatively common condition in clinical practice. Results We propose miss-Similarity Network Fusion (miss-SNF), a novel general-purpose data integration approach designed to manage completely missing data in the context of patient similarity networks. miss-SNF integrates incomplete unimodal patient similarity networks by leveraging a non-linear message-passing strategy borrowed from the SNF algorithm. miss-SNF is able to recover missing patient similarities and is “task agnostic”, in the sense that can integrate partial data for both unsupervised and supervised prediction tasks. Experimental analyses on nine cancer datasets from The Cancer Genome Atlas (TCGA) demonstrate that miss-SNF achieves state-of-the-art results in recovering similarities and in identifying patients subgroups enriched in clinically relevant variables and having differential survival. Moreover, amputation experiments show that miss-SNF supervised prediction of cancer clinical outcomes and Alzheimer’s disease diagnosis with completely missing data achieves results comparable to those obtained when all the data are available. Availability and implementation miss-SNF code, implemented in R, is available at https://github.com/AnacletoLAB/missSNF.

Biochemistry & Molecular Biology↗

Mondo: integrating disease terminology across communities

Precision medicine aims to enhance diagnosis, treatment, and prognosis by integrating multimodal data at the point of care. However, challenges arise due to the vast number of diseases, differing methods of classification, and conflicting terminological coding systems and practices used to represent molecular definitions of disease. This lack of interoperability artificially constrains the potential for diagnosis, clinical decision support, care outcome analysis, as well as data linkage across research domains to support the development or repurposing of therapeutics. There is a clear and pressing need for a unified system for managing disease entities⁠—including identifiers, synonyms, and definitions. To address these issues, we created the Mondo disease ontology—a community-driven, open-source, unified disease classification system that harmonizes diverse terminologies into a consistent, computable framework. Mondo integrates key medical and biomedical terminologies, including Online Mendelian Inheritance in Man (OMIM), Orphanet, Medical Subject Headings (MeSH), National Cancer Institute Thesaurus (NCIt), and more, to provide a comprehensive and accurate representation of disease concepts with fully provenanced and attributed links back to the sources. Mondo can be used as the handle for curation of gene–disease associations utilized in diagnostic applications, research applications such as computational phenotyping, and in clinical coding systems in clinical decision support by pointing the clinician to the numerous knowledge resources linked to the Mondo identifier. Mondo's community-centric approach, stewarded by the Monarch Initiative's expertise in ontologies, ensures that the ontology remains adaptable to the evolving needs of biomedical research and clinical communities, as well as the knowledge providers.

biomedical informatics↗

In with the old, in with the new: machine learning for time to event biomedical research

The predictive modeling literature for biomedical applications is dominated by biostatistical methods for survival analysis, and more recently some out of the box machine learning approaches. In this article, we show a presentation of a machine learning method appropriate for time-to-event modeling in the area of prostate cancer long-term disease progression. Using XGBoost adapted to long-term disease progression, we developed a predictive model for 118 788 patients with localized prostate cancer at diagnosis from the Department of Veterans Affairs (VA). Our model accounted for patient censoring. Harrell’s c-index for our model using only features available at the time of diagnosis was 0.757 95% confidence interval [0.756, 0.757]. Our results show that machine learning methods like XGBoost can be adapted to use accelerated failure time (AFT) with censoring to model long-term risk of disease progression. Furthermore, the long median survival justifies and requires censoring. Overall, we show that an existing machine learning approach can be used for AFT outcome modeling in prostate cancer, and more generally for other chronic diseases with long observation times.

96 KNOWLEDGE MANAGEMENT AND PRESERVATION↗