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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 343 records · Page 19
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

A device for volatile organic compound (VOC) analysis from skin using heated dynamic headspace sampling

Abstract Human skin is an important source of volatile organic compounds (VOCs) offering noninvasive methods to gain clinical metabolite information. This work was focused on the development of a skin sampling device based on a dynamic headspace sampling method with the addition of temperature to increase VOC metabolite recovery. The device preconcentrates skin VOC emissions onto a sorbent substrate, which can either be preserved for offline analysis or attached to a real time sensor downstream. In this work, skin VOC samples were analyzed offline using thermal desorption-gas chromatography-mass spectrometry. A list of 10 common skin VOCs was pre-selected to optimize parameters of sampling time, sampling temperature, and sorbent selection. Overall, this study highlights an effective skin VOC sampling technology with a heating dimension (40 °C, rather than 30 °C or no heating) with a sampling time of 15 min (rather than 5 or 30 mins) and onto Tenax TA sorbent (rather than PDMS), which collectively increases the recovery of compounds with lower vapor pressure and decreases the observed variability in skin VOC measurements. Finally, a list of 79 skin VOC compounds were detected and identified within a cohort of 20 young, healthy volunteers.

Biochemistry & Molecular Biology↗
DOE OSTI2023

Use of Longitudinal Serum Analysis and Machine Learning to Develop a Classifier for Cancer Early Detection

Early detection of solid tumors through a simple screening process, such as the proteomic analysis of biofluids, has the potential to significantly alter the management and outcomes of cancers. The application of advanced targeted proteomics measurements and data analysis strategies to uniformly collected serum or plasma samples would enable longitudinal studies of cancer risk, progression, and response to therapy that have the potential to significantly reduce cancer burden in general. In this article, we describe a generalizable workflow combining robust, multiplexed targeted proteomics measurements applied to longitudinal samples from the Department of Defense Serum Repository with a Random Forest machine learning method for developing and initially evaluating the performance of candidate biomarker panels for early detection of cancers. The effectiveness of this approach was demonstrated in a cohort of 175 head and neck squamous cell carcinoma patients. The outlined protocols include methods for sample preparation, instrument analysis, and data analysis and interpretation using this workflow.

Longitudinal analysis, machine learning, cancer, e↗
DOE OSTI2025

Do Piperonyl Butoxide Long-Lasting Insecticide Treated Nets Provide Additional Protection Against Malaria Infections Compared with Conventional Nets in an Operational Setting in Western Kenya?

Malaria control in sub-Saharan Africa has stagnated despite widespread adoption of control measures such as long-lasting insecticidal nets (LLINs). Progress has stalled, in part, because of pyrethroid insecticide resistance, driving the need for retooling to increase the effectiveness of bed nets. Consequently, LLINs have been treated with the chemical synergist piperonyl butoxide (PBO). Piperonyl butoxide LLINs have been shown to be efficacious in controlled settings; however, their effectiveness in real-world settings warrants investigation. In Bungoma County, Western Kenya, a cohort of 768 participants was followed from June 2017 to December 2023 via active and passive surveillance. Household visits were conducted monthly, during which LLIN use for nets distributed in 2017 and 2021 was recorded, and symptomatic malaria cases were identified using rapid diagnostic tests (RDTs). The comparative effectiveness of PBO versus conventional LLINs was assessed in terms of malaria infections. A multilevel logistic regression model was fit with monthly RDT results as the dependent variable. The study results indicate that PBO LLINs provide greater protection against malaria at the individual level than conventional LLINs (odds ratio: 0.70; 95% CI: 0.47–1.03), although the findings were not statistically significant. The added protection against malaria infections provided by PBO LLINs compared with conventional LLINs observed in the current study aligns with findings from most previous studies, although this finding was not statistically significant. In areas with documented pyrethroid resistance, the use of LLINs with an added synergist, such as PBO, can provide additional protection against malaria infections (compared with pyrethroid-only LLINs) and should be considered for scaled-up scenarios despite the additional cost.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2017

Zoledronate Prevents Simulated Weightlessness-Induced Bone Loss in the Cancellous Compartment While Blunting the Efficacy of a Mechanical Loading Countermeasure

Astronauts using high-force resistance training while weightless show a high-turnover remodeling state within the skeletal system, with resorption and formation biomarkers being elevated. One countermeasure for the skeletal health of astronauts includes an antiresorptive of the bisphosphonate (BP) drug class. We asked, does the combination of an anti-resorptive and high-force exercise during weightlessness have negative effects on bone remodeling and strength? In this study, we developed an integrated model to mimic the mechanical strain of exercise via cyclical loading (CL) in mice treated with the BP Zoledronate (ZOL) combined with hind limb unloading (HU) to simulate weightlessness. We hypothesized that ZOL prevents structural degradation from simulated weightlessness and that CL and ZOL interact to render CL less effective. Thirty-two C57BL/6 mice (male, 16 weeks old, n=8/group) were exposed to 3 weeks of either HU or normal ambulation (NA). Cohorts of mice received one subcutaneous injection of ZOL (45μg/kg), or saline vehicle (VEH), prior to the start of HU. The right tibia was axially compressed in vivo 60x/day to 9N (+1200μstrain on the periosteal surface) and repeated 3x/week during HU. Left tibiae served as a within subject, non-compressed control. Ex vivo μCT was performed on all subjects to determine cancellous and cortical architectural parameters. Static and dynamic histomorphometry were carried out for the left and right tibiae to determine osteoclast- and osteoblast relevant surfaces. Further, micro damage was assessed in select groups by basic-fuchsin staining to test whether CL had an effect. For all assays, a multivariate (2x2x2) ANCOVA model was used to account for body weight changes. Additionally, for the tibiae, we incorporated a random effect for the subject (hence, a mixed model) to account for observations of both left and right tibiae within each subject. P < 0.05 was considered significant. In the cancellous compartment of the proximal tibial metaphysis, we observed a main effect from each independent variable, as determined by structural and histomorphometric assays. Specifically, as expected, ZOL showed an increase in the cancellous bone volume to total volume fraction (BV/TV, +32%) and trabecular number (+18%) compared to the VEH. As expected, ZOL decreased osteoclast surface (OC/BS) by -45% compared to VEH. Surprisingly, ZOL reduced mineralizing surface (MS/BS) and bone formation rate (BFR), indicators of osteoblast activity, by -40% and -54%, respectively, compared to VEH. Altogether, ZOL-treated mice displayed a low turnover state of remodeling in the metaphysis. In the context of skeletal aging, we speculate that ZOL prevented age-related cancellous strut loss during the experiment. As a main effect, as expected, HU decreased BV/TV by - 31% via reductions in both trabecular thickness (-11%) and number (-22%) compared to NA controls. Additionally, HU decreased MS/BS by -38% and bone formation rate (BFR) by -50% compared to NA controls. Altogether, these data are consistent with structural degradation resulting from imbalanced remodeling that favors resorption. As a main effect, CL increased BV/TV by +15% via increased trabecular thickness (+12%) compared to the noncompressed limb. As expected, CL increased MS/BS (+20%) and BFR (+24%), indicating osteoblast mineralization contributed to bone gains. These data show that CL provided an anabolic stimulus to the cancellous tissue. We observed unique interactions in ZOL*CL and HU*CL. First, ZOL prevented CL-induced increases in BV/TV and trabecular number, as compared to VEH. In the context of skeletal aging, these data suggest no added benefit from CL in the ZOL-treated mice. Interestingly, no microdamage was observed in mice that were unloaded and treated with ZOL (independent of CL). Secondly, HU prevented CL-induced increases in BFR, as compared to NA controls. These data suggest that either exercise is less effective or the kinetics of formation are slower during simulated weightlessness. Osteoclast surface was unchanged by either treatment. Thus, in contrast to exercising astronauts, these data do not suggest a high-turnover state in the metaphysis. To assess mechanical properties as a function of HU or ZOL, we tested the left femur in three-point bending ex vivo. As expected, HU decreased stiffness (-30%) compared to NA, and ZOL increased stiffness compared to VEH (+28%). Interestingly, HU increased the post-yield displacement, related to collagenous tensile loading, compared to NA (+20%). ZOL increased yield force (+11%) and ultimate force (+17%), which seems to explain the significant effect of ZOL increasing total energy (work-to-fracture, +15%), while not affecting the post yield displacement. Taken together, ZOL did not have detrimental affect on mechanical properties. Our integrated model simulates the combination of weightlessness, exercise-induced mechanical strain, and anti-resorptive treatment that astronauts experience during space missions. We conclude that Zoledronate was an effective countermeasure against weightlessness-induced bone loss, though zoledronate, as well as weightlessness, rendered exercise-related mechanical loading less effective.

bone↗
DOE OSTI2022

Identifying intragenic functional modules of genomic variations associated with cancer phenotypes by learning representation of association networks

Background Genome-wide Association Studies (GWAS) aims to uncover the link between genomic variation and phenotype. They have been actively applied in cancer biology to investigate associations between variations and cancer phenotypes, such as susceptibility to certain types of cancer and predisposed responsiveness to specific treatments. Since GWAS primarily focuses on finding associations between individual genomic variations and cancer phenotypes, there are limitations in understanding the mechanisms by which cancer phenotypes are cooperatively affected by more than one genomic variation. Results This paper proposes a network representation learning approach to learn associations among genomic variations using a prostate cancer cohort. The learned associations are encoded into representations that can be used to identify functional modules of genomic variations within genes associated with early- and late-onset prostate cancer. The proposed method was applied to a prostate cancer cohort provided by the Veterans Administration’s Million Veteran Program to identify candidates for functional modules associated with early-onset prostate cancer. The cohort included 33,159 prostate cancer patients, 3181 early-onset patients, and 29,978 late-onset patients. The reproducibility of the proposed approach clearly showed that the proposed approach can improve the model performance in terms of robustness. Conclusions To our knowledge, this is the first attempt to use a network representation learning approach to learn associations among genomic variations within genes. Associations learned in this way can lead to an understanding of the underlying mechanisms of how genomic variations cooperatively affect each cancer phenotype. This method can reveal unknown knowledge in the field of cancer biology and can be utilized to design more advanced cancer-targeted therapies.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Optimal Stopping Ages for Colorectal Cancer Screening

Importance Prior studies have shown that the benefits, harms, and costs of colorectal cancer (CRC) screening at older ages are associated with a patient’s sex, health, and screening history. However, these studies were hypothetical exercises and not directly informed by data on CRC risk. Objective To identify the optimal stopping ages for CRC screening by sex, comorbidity, and screening history from a cost-effectiveness perspective. Design, Setting, and Participants This economic evaluation first validated the MISCAN-Colon (Microsimulation Screening Analysis–Colon) model against community-based CRC incidence and mortality rates for 2 subcohorts of the PRECISE (Optimizing Colorectal Cancer Screening Precision and Outcomes in Community-Based Populations) cohort. Subsequently, different CRC screening scenarios were simulated in older individuals. Cohorts of US adults aged 76 to 90 years varied by sex and comorbidity status (none, low, moderate, or severe). Statistical and sensitivity analyses were performed from March 2023 to May 2024. Exposures CRC screening histories including fecal immunochemical test (FIT) or colonoscopy, such as a negative colonoscopy result from 10, 15, 20, 25, or 30 years before the index age; 1 to 5 negative FIT results within 5 years of the index age, with different patterns of recency; or a combination of negative colonoscopy and negative FIT results. Main Outcomes and Measures The main outcomes included estimated lifetime clinical outcomes, incremental costs, and quality-adjusted life-years gained (QALYG) associated with 1 additional FIT or colonoscopy. Optimal stopping age for screening, defined as the oldest age for which the incremental cost-effectiveness ratio was still below the willingness-to-pay threshold of $\$$100 000 per QALYG, was evaluated. Results The first of the 2 PRECISE subcohorts used in validating the simulation model included 25 974 adults (15 060 females [58.0%]; 54.7% aged 76 to 80 years) with a negative colonoscopy result 10 years before the index date. The second subcohort consisted of 118 269 adults (67 058 females [56.7%]; 90.5% aged 76 to 80 years) with a negative FIT result 1 year before the index date. Older age, male sex, higher comorbidity levels, and recent CRC screenings were associated with reduced incremental benefit and cost-effectiveness of additional screening. For the reference cohort of 76-year-old females without comorbidities and a negative colonoscopy result 10 years before the index age, 1 additional colonoscopy cost $\$$38 226 per QALYG. For cohorts with otherwise equivalent characteristics, associated costs increased to $\$$1 689 945 per QALYG for females at age 90 years without comorbidities and a negative colonoscopy results 10 years before the index age, $\$$51 604 per QALYG for males at age 76 years without comorbidities and a negative colonoscopy result 10 years before the index age, and $\$$108 480 per QALYG for females at age 76 years with severe comorbidities and a negative colonoscopy result 10 years before the index age and decreased to $\$$16 870 per QALYG for females without comorbidities and a negative colonoscopy result 30 years before the index age. The optimal stopping ages across different cohorts ranged from younger than 76 to 86 years for colonoscopy and younger than 76 to 88 years for FIT. Conclusions and Relevance In this economic evaluation, age, sex, screening history, comorbidity, and future screening modality were associated with the clinical outcomes, cost-effectiveness, and optimal stopping age for CRC screening. These results can inform guideline development and patient-directed informed decision-making.

Harlass, Matthias [Erasmus Erasmus University Medi↗
DOE OSTI2023

Acquisition of Rickettsia rickettsii (Rickettsiales: Rickettsiaceae) by Haemaphysalis longicornis (Acari: Ixodidae) through co-feeding with infected Dermacentor variabilis (Acari: Ixodidae) in the laboratory

Abstract Haemaphysalis longicornis (Neumann) is an invasive ixodid tick originating from eastern Asia which recently has become established in the United States. In its native range, this tick can transmit several pathogens to animals and humans, but little is known about its ability to acquire and transmit pathogens native to the United States. Geographic overlap with ticks such as Dermacentor variabilis (Say), a known vector of Rickettsia rickettsii, makes investigation into the interactions between H. longicornis and D. variabilis of interest to the public health community. Previous studies have shown that H. longicornis can serve as a competent vector of R. rickettsii under laboratory settings, but there is little information on its ability to acquire this pathogen via other biologically relevant routes, such as co-feeding. Here, we assess the ability of H. longicornis nymphs to acquire R. rickettsii through co-feeding with infected D. variabilis adults on a vertebrate animal model under laboratory conditions. The median infection prevalence in engorged H. longicornis nymphs across 8 cohorts was 0% with an interquartile range (IQR) of 4.13%. Following transstadial transmission, the median infection prevalence in flat females was 0.7% (IQR = 2.4%). Our results show that co-feeding transmission occurs at low levels in the laboratory between these 2 species. However, based on the relatively low transmission rates, this may not be a likely mechanism of R. rickettsii introduction to H. longicornis.

Entomology↗
DOE OSTI2024

Analyses of GWAS signal using GRIN identify additional genes contributing to suicidal behavior

Genome-wide association studies (GWAS) identify genetic variants underlying complex traits but are limited by stringent genome-wide significance thresholds. We present GRIN (Gene set Refinement through Interacting Networks), which increases confidence in the expanded gene set by retaining genes strongly connected by biological networks when GWAS thresholds are relaxed. GRIN was validated on both simulated interrelated gene sets as well as multiple GWAS traits. From multiple GWAS summary statistics of suicide attempt, a complex phenotype, GRIN identified additional genes that replicated across independent cohorts and retained biologically interrelated genes despite a relaxed significance threshold. We present a conceptual model of how these retained genes interact through neurobiological pathways that may influence suicidal behavior, and identify existing drugs associated with these pathways that would not have been identified under traditional GWAS thresholds. We demonstrate GRIN’s utility in boosting GWAS results by increasing the number of true positive genes identified from GWAS results.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2019

Using DNA Damage to Investigate the Individual Variability of Human Sensitivity to Ionizing Radiation

High-LET ionizing radiation is a major occupational health hazard for astronauts, but risk assessment remains elusive due to limited epidemiological data. Identifying genetic factors modulating the individual radiation response may be the most effective strategy to provide individualized risk management for long-duration high-radiation missions. We have started tackling the challenge of predicting individual risks by identifying human genetic loci associated with various radiation sensitivity phenotypes in primary blood mononuclear cells from a relatively large healthy human cohort. To date, we have performed the isolation of PBMCs from 768 subjects of the same ethnicity, and irradiated PBMCs from 576 subjects with 1 and 3 particles/100µm2 of 600 MeV/n 56Fe, 350 MeV/n 40Ar and 350 MeV/n 28Si ions. The phenotypes of interest were: number of radiation-induced foci (or RIFs), CellROX oxidative stress responses and cell death, at 4h and 24h following irradiation. We have observed a significant inter-individual variability at 0 Gy between the 576 studied subjects, with a mean fold difference between the 10% lowest and highest responders of 5.6 of RIFs/cell, 7.9 in mean CellRox intensity, and 9.3 in percentage of dead cells. In order to better assess genetic factors influencing DNA repair, we used a metric previously introduced by our group to sort out radiation sensitivity phenotypes in mice: i.e. the ratio of the first to the second slope of RIFs/cell (between 0 and 1, and between 1 and 3 particle/100µm2). Preliminary data on 192 individuals showed a distribution of low-dose responders (ratio > 1) to high-dose responders (ratio < 1) at 4h of 12%, 55% and 52% respectively for Fe, Ar and Si. The average value for the first and the second slopes was very similar for the two lowest LET (0.10 [-0.26;0.58] and 0.09 [-0.45;0.41] for Ar, 0.07 [-0.27;0.38] and 0.08 [-0.19;0.42] for Si), indicating a linear dose response across both fluence. Fe showed clear saturation for the highest dose with a slope of -0.09 [-0.86;1.51] against 0.68 [-2.21;2.20] for the low dose range, which probably reflects that many PBMCs are beyond repair at the high dose. Note that other significances were found for additional factors such as BMI and age whereas none were found for sex. GWAS will be performed on all phenotypes upon completion of measurements.

Pariset, E.↗
NASA NTRS2019

Using DNA Damage to Investigate the Individual Variability of Human Sensitivity to Ionizing Radiation

High-LET ionizing radiation is a major occupational health hazard for astronauts, but risk assessment remains elusive due to limited epidemiological data. Identifying genetic factors modulating the individual radiation response may be the most effective strategy to provide individualized risk management for long-duration high-radiation missions. We have started tackling the challenge of predicting individual risks by identifying human genetic loci associated with various radiation sensitivity phenotypes in primary blood mononuclear cells from a relatively large healthy human cohort. To date, we have performed the isolation of PBMCs from 768 subjects of the same ethnicity, and irradiated PBMCs from 576 subjects with 1 and 3 particles/100µm2 of 600 MeV/n 56Fe, 350 MeV/n 40Ar and 350 MeV/n 28Si ions. The phenotypes of interest were: number of radiation-induced foci (or RIFs), CellROX oxidative stress responses and cell death, at 4h and 24h following irradiation. We have observed a significant inter-individual variability at 0 Gy between the 576 studied subjects, with a mean fold difference between the 10% lowest and highest responders of 5.6 of RIFs/cell, 7.9 in mean CellRox intensity, and 9.3 in percentage of dead cells. In order to better assess genetic factors influencing DNA repair, we used a metric previously introduced by our group to sort out radiation sensitivity phenotypes in mice: i.e. the ratio of the first to the second slope of RIFs/cell (between 0 and 1, and between 1 and 3 particle/100µm2). Preliminary data on 192 individuals showed a distribution of ?low-dose responders? (ratio > 1) to ?high-dose responders? (ratio < 1) at 4h of 12%, 55% and 52% respectively for Fe, Ar and Si. The average value for the first and the second slopes was very similar for the two lowest LET (0.10 [-0.26;0.58] and 0.09 [-0.45;0.41] for Ar, 0.07 [-0.27;0.38] and 0.08 [-0.19;0.42] for Si), indicating a linear dose response across both fluence. Fe showed clear saturation for the highest dose with a slope of -0.09 [-0.86;1.51] against 0.68 [-2.21;2.20] for the low dose range, which probably reflects that many PBMCs are beyond repair at the high dose. Note that other significances were found for additional factors ? such as BMI and age ? whereas none were found for sex. GWAS will be performed on all phenotypes upon completion of measurements.

Pariset, E.↗
DOE OSTI2021

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Suicide is a leading cause of death worldwide, and non-fatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium. The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via mtCOJO, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders and other known risk factors. Results: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with non-psychiatric traits remained largely unchanged. Conclusions: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Advanced Transmission Technologies – GETs and HPCs Session 2: Advanced Power Flow Control and Transmission Topology Optimization

The INL TADA GETs Cohort Session 2, held on November 7, 2025, conducted in collaboration with ScottMadden, focused on two core Advanced Transmission Technologies (ATTs): Advanced Power Flow Control (APFC) and Transmission Topology Optimization (TTO). These technologies are pivotal in enhancing grid flexibility, reliability, and cybersecurity resilience. APFC, particularly through modular FACTS devices like Modular Static Synchronous Series Compensators (M-SSSCs), enables dynamic voltage injection to reroute power flows. The session highlighted the deployment benefits of APFC, such as rapid installation, minimal civil works, and re-deployability. Regulatory drivers like FERC Order 2023 mandate the inclusion of Grid-Enhancing Technologies (GETs) in interconnection studies. Case studies from Central Hudson, CAISO, and National Grid (UK) demonstrated APFC’s effectiveness in congestion relief and cost savings. The session also addressed cybersecurity concerns, including firmware vulnerabilities, SCADA integration risks, and supply chain dependencies. Participants engaged in interactive exercises to rank cybersecurity and supply chain risks, emphasizing the need for robust digital assurance strategies. TTO involves software-based reconfiguration of transmission networks to optimize power flow without new infrastructure. The session showcased its operational value, with examples from SPP, PJM, and MISO showing significant congestion cost reductions. Cybersecurity vulnerabilities were discussed, particularly in API security and software supply chains, referencing incidents like SolarWinds and attacks on Danish utilities. Digital assurance exercises explored worst-case scenarios, attack paths, and mitigation responsibilities between vendors and utilities. Reliability challenges such as algorithm stability, vendor dependency, and operator trust were also examined. Cross-cutting themes emphasized the importance of digital assurance tools, including Software Bills of Materials (SBOMs) and hardware-in-loop testing. Human performance, training, and operational confidence were identified as critical enablers of technology adoption. The session concluded with a preview of Session 3, which will focus on High Performance Conductors (HPCs) and risk-based cybersecurity tools. Session 2 of 3.

24 - POWER TRANSMISSION AND DISTRIBUTION↗
DOE OSTI2022

Comparison of Machine Learning and Deep Learning for View Identification from Cardiac Magnetic Resonance Images

Background: Artificial intelligence is increasingly utilized to aid in the interpretation of cardiac magnetic resonance (CMR) studies. One of the first steps is the identification of the imaging plane depicted, which can be achieved by both deep learning (DL) and classical machine learning (ML) techniques without user input. We aimed to compare the accuracy of ML and DL for CMR view classification and to identify potential pitfalls during training and testing of the algorithms. Methods: To train our DL and ML algorithms, we first established datasets by retrospectively selecting 200 CMR cases. The models were trained using two different cohorts (passively and actively curated) and applied data augmentation to enhance training. Once trained, the models were validated on an external dataset, consisting of 20 cases acquired at another center. We then compared accuracy metrics and applied class activation mapping (CAM) to visualize DL model performance. Results: The DL and ML models trained with the passively-curated CMR cohort were 99.1% and 99.3% accurate on the validation set, respectively. However, when tested on the CMR cases with complex anatomy, both models performed poorly. After training and testing our models again on all 200 cases (active cohort), validation on the external dataset resulted in 95% and 90% accuracy, respectively. The CAM analysis depicted heat maps that demonstrated the importance of carefully curating the datasets to be used for training. Conclusions: Both DL and ML models can accurately classify CMR images, but DL outperformed ML when classifying images with complex heart anatomy.

artificial intelligence↗
DOE OSTI2025

Specific Bacterial Taxa and Their Metabolite, DHPS, May Be Linked to Gut Dyshomeostasis in Patients with Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis

Background: Neurodegenerative diseases (NDDs) are multifactorial disorders frequently associated with gut dysbiosis, oxidative stress, and inflammation; however, the pathophysiological mechanisms remain poorly understood. Methods: Using untargeted mass spectrometry-based metabolomics and 16S sequencing of human stool, we investigated bacterial and metabolic dyshomeostasis in the gut microbiome associated with early disease stages across three NDDs—amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), Parkinson’s disease (PD)—and healthy controls (HC). Results: We discovered a previously unrecognized link between a microbial-derived metabolite with an unknown role in human physiology, 2,3-dihydroxypropane-1-sulfonate (DHPS), and gut dysbiosis in NDDs. DHPS was downregulated in AD, ALS, and PD, while bacteria involved in DHPS metabolism, Eubacterium and Desulfovibrio, were increased in all disease cohorts. Additionally, select taxa within the Clostridia class had strong negative correlations to DHPS, suggesting a potential role in DHPS metabolism. A catabolic product of DHPS is hydrogen sulfide, and when in excess, it is known to promote inflammation, oxidative stress, mitochondrial damage, and gut dysbiosis, known hallmarks of NDDs. Conclusions: These findings suggest that cryptic sulfur metabolism via DHPS is a potential missing link in our current understanding of gut dysbiosis associated with NDD onset and progression. As this was a hypothesis generating study, more work is needed to elucidate the role of DHPS in gut dysbiosis and neurodegenerative diseases.

Nutrition & Dietetics↗
DOE OSTI2021

Sclerostin Depletion Induces Inflammation in the Bone Marrow of Mice

Romosozumab, a humanized monoclonal antibody specific for sclerostin (SOST), has been approved for treatment of postmenopausal women with osteoporosis at a high risk for fracture. Previous work in sclerostin global knockout (Sost-/- ) mice indicated alterations in immune cell development in the bone marrow (BM), which could be a possible side effect in romosozumab-treated patients. Here, we examined the effects of short-term sclerostin depletion in the BM on hematopoiesis in young mice receiving sclerostin antibody (Scl-Ab) treatment for 6 weeks, and the effects of long-term Sost deficiency on wild-type (WT) long-term hematopoietic stem cells transplanted into older cohorts of Sost-/- mice. Our analyses revealed an increased frequency of granulocytes in the BM of Scl-Ab-treated mice and WT→Sost -/- chimeras, indicating myeloid-biased differentiation in Sost-deficient BM microenvironments. This myeloid bias extended to extramedullary hematopoiesis in the spleen and was correlated with an increase in inflammatory cytokines TNFα, IL-1α, and MCP-1 in Sost-/- BM serum. Additionally, we observed alterations in erythrocyte differentiation in the BM and spleen of Sost-/- mice. Taken together, our current study indicates novel roles for Sost in the regulation of myelopoiesis and control of inflammation in the BM.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Influence of the broadly neutralizing antibody VRC01 on HIV breakthrough virus populations in antibody-mediated prevention trials

In the antibody mediated prevention (AMP) trials, the broadly neutralizing antibody (bNAb) VRC01 demonstrated protective efficacy against susceptible HIV strains. To understand how VRC01 shaped breakthrough infections, deep sequencing was performed on 172 participants (>100,000 gag-Δpol and rev-env-Δnef sequences), at diagnosis and over time, in the placebo and treatment arms of the African (HVTN703/HPTN081; NCT02568215) and Americas/Europe (HVTN704/HPTN085; NCT02716675) cohorts. A high frequency of multilineage infections was detected (38%), including co-infection with both VRC01 sensitive and resistant viruses. This high frequency is largely accounted for by low-abundance lineages. Although VRC01 does not significantly affect the genetic transmission bottleneck compared to placebo, higher VRC01 doses trend towards greater VRC01 neutralization differences among co-infecting lineages. Two-thirds of multilineage infections showed evidence of recombination at the diagnostic timepoint. In the treatment group there is evidence of recombinant viruses preferentially inheriting resistance-associated mutations. This study provides critical insights into viral genetic and antigenic diversity that needs to be targeted to achieve protection, and highlights the role of recombination in facilitating escape.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Forest carbon sequestration on the west coast, USA: Role of species, productivity, and stockability

Forest ecosystems store large amounts of carbon and can be important sources, or sinks, of the atmospheric carbon dioxide that is contributing to global warming. Understanding the carbon storage potential of different forests and their response to management and disturbance events are fundamental to developing policies and scenarios to partially offset greenhouse gas emissions. Projections of live tree carbon accumulation are handled differently in different models, with inconsistent results. We developed growth-and-yield style models to predict stand-level live tree carbon density as a function of stand age in all vegetation types of the coastal Pacific region, US (California, Oregon, and Washington), from 7,523 national forest inventory plots. We incorporated site productivity and stockability within the Chapman-Richards equation and tested whether intensively managed private forests behaved differently from less managed public forests. We found that the best models incorporated stockability in the equation term controlling stand carrying capacity, and site productivity in the equation terms controlling the growth rate and shape of the curve. RMSEs ranged from 10 to 137 Mg C/ha for different vegetation types. There was not a significant effect of ownership over the standard industrial rotation length (~50 yrs) for the productive Douglas-fir/western hemlock zone, indicating that differences in stockability and productivity captured much of the variation attributed to management intensity. Our models suggest that doubling the rotation length on these intensively managed lands from 35 to 70 years would result in 2.35 times more live tree carbon stored on the landscape. These findings are at odds with some studies that have projected higher carbon densities with stand age for the same vegetation types, and have not found an increase in yields (on an annual basis) with longer rotations. We suspect that differences are primarily due to the application of yield curves developed from fully-stocked, undisturbed, single-species, “normal” stands without accounting for the substantial proportion of forests that don’t meet those assumptions. The carbon accumulation curves developed here can be applied directly in growth-and-yield style projection models, and used to validate the predictions of ecophysiological, cohort, or single-tree style models being used to project carbon futures for forests in the region. Our approach may prove useful for developing robust models in other forest types.

Chisholm, Paul J. (ORCID:0000000238784707)↗
DOE OSTI2023

Prevalence of Self-Reported Voice Concerns and Associated Risk Markers in a Nonclinical Sample of Military Service Members

Introduction: Difficult communication environments are common in military settings, and effective voice use can be critical to mission success. This study aimed to estimate the prevalence of self-reported voice disorders among U.S. military service members and to identify factors that contribute to their voice concerns. Method: A nonclinical sample of 4,123 active-duty service members was recruited across Department of Defense hearing conservation clinics. During their required annual hearing evaluation, volunteers provided responses to voice-related questions including a slightly adapted version of the Voice Handicap Index-10 (VHI-10) as part of a larger survey about communication issues. Changepoint detection was applied to age and years of service to explore cohort effects in the reporting of voice concerns. Logistic regression analyses examined multiple available factors related to communication to identify factors associated with abnormal results on the VHI-10. Results: Among the respondents, 41% reported experiencing vocal hoarseness or fatigue at least several times per year, and 8.2% ( n = 336) scored above the recommended abnormal cut-point value of 11 on the VHI-10. Factors independently associated with the greatest risk for self-reported voice concerns were sex (female), cadmium exposure, vocal demands (the need for a strong, clear voice), and auditory health measures (frequency of experiencing temporary threshold shifts; self-reported hearing difficulties). Conclusions: Based on self-reported voice concerns and false negative rates reported in the literature, the prevalence of dysphonia in a large sample of active-duty service members is estimated to be 11.7%, which is higher than that in the general population. Certain predictors for voice concerns were expected based on previous literature, like female sex and voice use, but frequency of temporary threshold shifts and exposure to cadmium were surprising. The strong link between voice and auditory problems has particular implications regarding the need for effective communication in high-noise military and other occupational environments.

Audiology & Speech-Language Pathology↗