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All sourcesNASA NTRSDOE OSTI
DOE OSTI2026

Aligning NASA Earth Science Data Stewardship with FAIR Principles: Outcomes, Recommendations, and Future Directions

The FAIR Principles—Findable, Accessible, Interoperable, and Reusable—offer a widely accepted framework for improving the sharing and reuse of digital scientific data by both human and machine users. Following these principles is critical for effective scientific data stewardship, broader scientific collaboration, and compliance with federal and agency data policies. This paper, based on the work of NASA’s Open, Free, and FAIR Working Group (O’FAIR WG) under the Earth Science Data Systems Program, presents an overview of how FAIR is being applied within NASA’s Earth science data landscape. It highlights ongoing progress and challenges, identifies FAIR-enabling resources, and offers recommendations and strategic actions to enhance the FAIRness of NASA-funded open and free Earth science data products. The FAIR-enabling resources identified underscore the vital role of NASA's existing enterprise processes, standards, tools, and infrastructures in supporting FAIR implementation. Our findings show strong performance in making NASA Earth science data more findable and accessible. However, further work is needed—especially in enhancing interoperability, so that different systems and tools can better understand and exchange data. This is especially important for enabling machine-driven discovery and analysis. We emphasize the importance of a balanced strategy that combines a centralized, top-down approach—focused on building enterprise-level capabilities and processes—with a decentralized, bottom-up approach driven by discipline-specific needs and community practices. We advocate for coordinated efforts to enhance (meta)data interoperability to facilitate seamless data and information sharing and exchange of Earth science data both within NASA and across other agencies managing Earth science data.

Data Product↗
DOE OSTI2025

Work In Progress: Using Internships as Means for Indirect Assessment of ABET Criteria 3 "1-7" Student Outcomes

PSU operates the Power Engineering Internship program with funding from two U.S. Department of Energy grants. The program is operated in partnership with the lead organizations of these grants, an investor-owned utility, Portland General Electric (PGE), and the Confederated Tribes of the Warm Springs (CTWS). One of the programmatic goals of the PEI is to create and sustain a clean energy engineering workforce pipeline on behalf of these lead organizations. Both grants support internships at PGE, which is also a partner on the CTWS grant. The PEI provides engineering students with year-long internships, spanning both the academic year and the summer. The interns work at PGE facilities located throughout the Portland metropolitan area. Interns are employed full-time during summers and part-time during the academic year. Proximity of the worksites to the PSU campus enables the interns to participate in the program while attending school full-time. During the academic year, students average fifteen hours per week, adjusting their work schedule according to their academic workload. The interns are allocated 930 hours per year, 480 in the summer and 450 during the academic year, which they can plan as they see fit. The internships provide meaningful financial support for the students, who can earn up to $21k if they use all of their allocated hours. Such funding is particularly important for the typical student who attends a minority serving institutions,

99 GENERAL AND MISCELLANEOUS↗
DOE OSTI2025

Geospatial analysis of preterm and small-for-gestational age births in Washington D.C.

Background: This study is based on the recognition that adverse pregnancy outcomes significantly affect maternal and infant health, leading to increased morbidity and mortality. These outcomes are shaped by a complex interplay of individual-level factors—like maternal age and education—and community-level influences, including socio-economic status and access to healthcare. Understanding these determinants is crucial for developing effective public health strategies, especially for marginalized populations, by identifying high-risk areas and informing targeted interventions that address both individual and structural barriers. Methods: We utilized geospatial analysis to explore the association between individual- and community-level factors and adverse pregnancy outcomes, specifically preterm birth (PTB) and small-for-gestational-age (SGA) birthweight in Washington, D.C. We used Empirical Bayes smoothing methods to calculate rates of adverse birth outcomes from 2010 to 2018 at the U.S. Census tract–level. Spatial scan statistics were used to investigate if adverse birth outcomes clustered in specific areas. ANOVA tests were conducted for individual- and community-level factors within identified clusters. Results: Spatial analysis identified significant high-risk clusters for PTB and SGA infants primarily in southeastern Washington, D.C., particularly in Wards 7 and 8. Individuals residing within these clusters experienced a 47% increased risk of PTB (RR = 1.467) and a 56% increased risk of SGA (RR = 1.560) compared to those outside clusters. Space–time analysis revealed temporal variation, with PTB clusters persisting from 2011 to 2014 and SGA clusters extending through 2017. Compared to low-risk clusters, high-risk clusters had younger birthing individuals (mean age ~26.5 vs. ~33 years), lower maternal college degree attainment (~20% vs. ~80%), higher rates of late or no prenatal care (~16% vs. 11%), and increased prevalence of smoking and hypertension (all P < 0.001). Community-level indicators showed lower median household incomes ($\$40,000$ vs. ~$\$105,000$), greater poverty (~16% vs. ~7% below $\$10,000$/year), higher public assistance use (~32% vs. ~5%), and reduced healthcare access (greater distances to emergency and specialty care) in high-risk areas (all P < 0.001). Neighborhood deprivation indices were significantly elevated, commutes were longer, and population density was lower in these clusters. These findings highlight that adverse birth outcomes cluster in neighborhoods with pronounced socioeconomic and health disparities. Conclusion: High-risk birth clusters highlight intertwined factors: individual, socio-economic, and geographic. Addressing these requires comprehensive interventions focusing on social and structural determinants of health.

Birth outcomes↗
DOE OSTI2025

Low Peripheral Blood Counts and Elevated Proinflammatory Cytokines Signal a Poor CD19 Chimeric Antigen Receptor T-cell Response in Acute Lymphoblastic Leukemia

CD19 chimeric antigen receptor T-cell (CAR-T) therapy has significantly improved outcomes for patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). However, approximately 20% of patients fail to achieve a complete remission (CR), and some develop severe, life-threatening toxicities. Understanding the biological mechanisms underlying both dysfunctional responses and severe toxicity is essential for optimizing patient management and improving therapeutic efficacy. This study aimed to (1) characterize cytokine profiles associated with dysfunctional responses and severe toxicity following CAR-T infusion, (2) examine the timing and trajectory of cytokine changes in relation to treatment outcomes, and evaluate potential strategies for mitigating toxicity and treatment failure. We conducted a comprehensive analysis of serum cytokine profiles in 86 adult and pediatric patients undergoing autologous CD19 CAR-T therapy for B-ALL. Patients were categorized into three groups: (1) Dysfunctional response—Patients who failed to achieve a minimal residual disease-negative CR (MRD-CR) by Day 63 or who experienced recurrence of CD19+ disease in the setting ongoing CAR-T cell detection before Day 63. (2) Functional response with severe cytokine release syndrome (CRS) and/or neurotoxicity (NTX)—Patients with best response of MRD-CR by Day 63 who experienced grade 3 or higher CRS or NTX. (3) Functional response without severe CRS or NTX—Patients with best response of MRD-CR by Day 63 who did not experience grade =3 CRS or NTX. Cytokine levels were measured during the first-week postinfusion and correlated with treatment efficacy, toxicity outcomes, complete blood counts, and CAR-T expansion dynamics. This analysis aimed to better understand how cytokine profiles relate to patient outcomes and immune responses in CAR-T therapy. Patients with dysfunctional response exhibited decreased neutrophils, platelets, and levels of granulocytic cytokines (suggestive of low bone marrow reserve) alongside elevated pro-inflammatory cytokines by Day 1. Functional response with severe toxicity patients showed a progressive rise in proinflammatory cytokines, reaching similar levels to dysfunctional response patients by Day 7. We observed that high cytokines at both the Day 1 and Day 7 time points were associated with poor survival. These findings remained significant when adjusting for high disease burden, a known predictor of severe inflammatory toxicity and lack of response. Early post-CAR-T infusion inflammation is associated with both dysfunctional response and severe toxicity—even after adjusting for disease burden. This suggests that inflammation, in addition to disease burden, plays a role in determining patient outcome. Therefore, strategies aimed at reducing the pro-inflammatory state prior to or early after CAR-T cell infusion may improve outcomes for R/R B-ALL patients.

Serum cytokines↗
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 OSTI2025

Pivotal trial characteristics and types of endpoints used to support Food and Drug Administration rare disease drug approvals between 2013 and 2022

Background/aims Rare disease drug development faces unique challenges, such as genotypic and phenotypic heterogeneity within small patient populations and a lack of established outcome measures for conditions without previously successful drug development programs. These challenges complicate the process of selecting the appropriate trial endpoints and conducting clinical trials in rare diseases. In this descriptive study, we examined novel drug approvals for non-oncologic rare diseases by the U.S. Food and Drug Administration’s Center for Drug Evaluation and Research over the past decade and characterized key regulatory and trial design elements with a focus on the primary efficacy endpoint utilized as the basis of approval. Methods Using the Food and Drug Administration’s Data Analysis Search Host database, we identified novel new drug applications and biologics license applications with orphan drug designation that were approved between 2013 and 2022 for non-oncologic indications. From Food and Drug Administration review documents and other external databases, we examined characteristics of pivotal trials for the included drugs, such as therapeutic area, trial design, and type of primary efficacy endpoints. Differences in trial design elements associated with primary efficacy endpoint type were assessed such as randomization and blinding. Then, we summarized the primary efficacy endpoint types utilized in pivotal trials by therapeutic area, approval pathway, and whether the disease etiology is well defined. Results One hundred and seven drugs that met our inclusion criteria were approved between 2013 and 2022. Assessment of the 107 drug development programs identified 150 pivotal trials that were subsequently analyzed. The pivotal trials were mostly randomized (80%) and blinded (69.3%). Biomarkers (41.1%) and clinical outcomes (42.1%) were commonly utilized as primary efficacy endpoints. Analysis of the use of clinical trial design elements across trials that utilized biomarkers, clinical outcomes, or composite endpoints did not reveal statistically significant differences. The choice of primary efficacy endpoint varied by the drug’s therapeutic area, approval pathway, and whether the indicated disease etiology was well defined. For example, biomarkers were commonly selected as primary efficacy endpoints in hematology drug approvals (70.6%), whereas clinical outcomes were commonly selected in neurology drug approvals (69.6%). Further, if the disease etiology was well defined, biomarkers were more commonly used as primary efficacy endpoints in pivotal trials (44.7%) than if the disease etiology was not well defined (27.3%). Discussion In the past 10 years, numerous novel drugs have been approved to treat non-oncologic rare diseases in various therapeutic areas. To demonstrate their efficacy for regulatory approval, biomarkers and clinical outcomes were commonly utilized as primary efficacy endpoints. Biomarkers were not only frequently used as surrogate efficacy endpoints in accelerated approvals, but also in traditionally approved rare disease drugs. The choice of primary efficacy endpoints varied by therapeutic area, approval pathway, and understanding of disease etiology.

Hong, Kyungwan [Rare Diseases Team, Office of New ↗
DOE OSTI2024

Customer enrollment and participation in building demand management programs: A review of key factors

Increasing the efficiency and flexibility of electricity demand is necessary for ensuring a cost-effective and reliable transition to zero-carbon electricity systems. Such demand-side management (DSM) resources have been procured by utilities for decades via energy efficiency and demand response programs; however, the key drivers of program enrollment and customer participation levels remain poorly understood — even as governments and grid planners seek to scale up the deployment of DSM assets to meet climate targets. Here we systematically review the evidence on multiple factors that may influence customer enrollment and participation in building DSM programs, focusing primarily on residential and commercial buildings. We examine the contexts in which relationships between DSM factors and outcomes are most often explored and with which methods; we also score the strength, direction, and internal consistency of each factor's reported impact on the enrollment and participation outcomes. We find that studies most commonly assess the effects of economic incentives for load flexibility on program participation levels, often using simulation-based methods in lieu of measured data. Few studies focus on program enrollment outcomes or regulatory drivers of either enrollment or participation, and gaps are also evident in the coverage of emerging DSM opportunities like load electrification. Removal of structural barriers (e.g., the lack of controls infrastructure) and the use of third party services (e.g., load aggregators) are the factors with the largest positive impacts on DSM outcomes, but no single factor emerges as clearly most impactful. For a given factor, the range of reported impacts typically varies widely across the relevant studies reviewed. Our findings provide a snapshot of the state of knowledge about building DSM and customer decision-making, and they expose key gaps in understanding that must be filled if building DSM is to expand as a critical resource for operating clean power grids.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2024

The interplay of DNA repair context with target sequence predictably biases Cas9-generated mutations

Abstract Repair of double-stranded breaks generated by CRISPR/Cas9 is highly dependent on the flanking DNA sequence. To learn about interactions between DNA repair and target sequence, we measure frequencies of over 236,000 distinct Cas9-generated mutational outcomes at over 2800 synthetic target sequences in 18 DNA repair deficient mouse embryonic stem cells lines. We classify the outcomes in an unbiased way, finding a specialised role forPrkdc(DNA-PKcs protein) andPolmin creating 1 bp insertions matching the nucleotide on the protospacer-adjacent motif side of the break, a variable involvement ofNbnandPolqin the creation of different deletion outcomes, and uni-directional deletions dependent on both end-protection and end-resection. Using our dataset, we build predictive models of the mutagenic outcomes of Cas9 scission that outperform the current standards. This work improves our understanding of DNA repair gene function, and provides avenues for more precise modulation of Cas9-generated mutations.

Science & Technology - Other Topics↗
DOE OSTI2024

Quantum Information Encoding and Decoding for Quantum Sensi

This two-year theory project focused on theoretical investigations of novel paradigms for quantum sensing, building on information encoding and techniques from quantum error correction, quantum computing and other quantum information domains. The outcomes facilitate quantum information technology development, especially at the interface of quantum computing and quantum sensing. The results of the project show new use cases and new paradigms for quantum sensing beyond what has so far been considered. One outcome shows how quantum sensing opens new opportunities for fundamental physics such as the capability of single graviton detection. Another outcome reveals a new application of NISQ quantum computers with error correction for metrology, building on recent advances in practical quantum error correction implementation. The third outcome of the project creates new paradigms of back-action-evading sensing inspired by collective quantum information encoding, which achieves quantum sensing beyond the quantum limit without the use of entanglement.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2025

Quantitative Risk Assessment for Fuel Cell Electric Bus Hydrogen Storage and Refueling Facility

It is necessary to understand the safety implications and risk mitigation options for fuel cell electric bus fleet deployment, especially for related facilities responsible for operations such as production, storage, compression, and dispensing of hydrogen for use by the buses. In this report, we present a quantitative risk assessment for a potential fuel cell electric bus fleet that was motivated by efforts to improve resilience at the Portland International Airport but can be applicable to a range of hydrogen case studies and use cases. We estimated risk for a facility that produces, stores, compresses, and dispenses hydrogen for the fleet of buses, with a focus on individual risk to people in terms of annual frequency of fatality. We considered the frequency of hydrogen leaks that could result in harmful physical outcomes like jet fires or explosions, and the consequences of those outcomes for people. We created customized fault trees to calculate the frequencies of different sizes of leaks and event sequence diagrams to calculate ignition probabilities for the various leak sizes. We also leveraged the HyRAM+ toolkit to use these inputs to calculate overall risk for the facility, which we separated into one section responsible for producing, storing, and compressing hydrogen, and one section responsible for dispensing the hydrogen to the buses. We found that the dispensing area seemed to have a higher risk than the production/storage/compression area of the facility, largely because of the inclusion of a component with a high leak frequency (the heat exchanger used to cool the hydrogen before entering the vehicle, to prevent overheating and expansion of hydrogen in the onboard tank). For the example production and refueling facility we evaluated and the data we used for the analysis, the leak frequency had a larger impact on the risk differences between the two sections on the facility, compared to the physical outcome consequence, which was slightly different due to the varying fuel conditions, but not substantially different. Actions can be taken to prevent these hazards (e.g., lowering leak frequencies in system components) or to mitigate the consequences if they do occur (e.g., installing barriers to protect people if ignition events occur). The choice of which actions to take depends not only on safety considerations but also on space, time, staffing, feasibility, and financial constraints. Therefore, the quantitative risk assessment approach can help understand relative risk contributions from different components, leak sizes, consequences, and human actions, to prioritize risk reduction strategies and balance these parameters. The outcomes of this report may be useful for a variety of stakeholders working in the hydrogen, transportation, vehicle, and aviation sector, including those responsible for aspects like facility design, operations, and regulations. There is not a single value of risk that determines whether a hypothetical system is “safe” or not. The insights about risk mitigations may be leveraged, and the quantitative risk assessment approach can be applied to other case studies to understand risk priorities and contributions specific to different FCEB and hydrogen facility uses.

08 HYDROGEN↗
DOE OSTI2025

The relationship between below average cognitive ability at age 5 years and the child’s experience of school at age 9

Background At age 5, while only embarking on their educational journey, substantial differences in children’s cognitive ability will already exist. The aim of this study was to examine the causal association between below average cognitive ability at age 5 years and child-reported experience of school and self-concept, and teacher-reported class engagement and emotional-behavioural function at age 9 years. Methods This longitudinal cohort study used data from 7,392 children in the Growing Up in Ireland Infant Cohort, who had completed the Picture Similarities and Naming Vocabulary subtests of the British Abilities Scales at age 5. Principal components analysis was used to produce a composite general cognitive ability score for each child. Children with a general cognitive ability score more than 1 standard deviation (SD) below the mean at age 5 were categorised as ‘Below Average Cognitive Ability’ (BACA), and those scoring above this as ‘Typical Cognitive Development’ (TCD). The outcomes of interest, measured at age 9, were child-reported experience of school, child’s self-concept, teacher-reported class engagement, and teacher-reported emotional behavioural function. Binary and multinomial logistic regression models were used to examine the association between BACA and these outcomes. Results Compared to those with TCD, those with BACA had significantly higher odds of never liking school [Adjusted odds ratio (AOR) 1.82, 95% CI 1.37–2.43, p < 0.001], of being picked on (AOR 1.27, 95% CI 1.09–1.48) and of picking on others (AOR 1.53, 95% CI 1.27–1.84). They had significantly higher odds of experiencing low self-concept (AOR 1.20, 95% CI 1.02–1.42) and emotional-behavioural difficulties (AOR 1.34, 95% CI 1.10–1.63, p = 0.003). Compared to those with TCD, children with BACA had significantly higher odds of hardly ever or never being interested, motivated and excited to learn (AOR 2.29, 95% CI 1.70–3.10). Conclusion Children with BACA at school-entry had significantly higher odds of reporting a negative school experience and low self-concept at age 9. They had significantly higher odds of having teacher-reported poor class engagement and problematic emotional-behavioural function at age 9. The findings of this study suggest BACA has a causal role in these adverse outcomes. Early childhood policy and intervention design should be cognisant of the important role of cognitive ability in school and childhood outcomes.

Bowe, Andrea K.↗
DOE OSTI2025

The Evolution of Randomized Clinical Trial Designs to Assess Therapeutics in Alzheimer Disease

Importance The success of recent randomized clinical trials (RCTs) for Alzheimer disease (AD), particularly those focusing on anti-amyloid therapies, has been discussed at length. However, the evolution of RCT design features for AD that preceded this success remain underexplored. Objective To describe temporal changes in the features of RCT design for interventions in AD. Evidence Review PubMed, Scopus, and Web of Science databases were searched in January 2025 for phase 2 and 3 AD RCTs published between January 1992 and December 2024. RCTs that investigated an intervention for AD, with a placebo or standard-of-care control group, were included. Four assessors independently reviewed full-text articles to capture study characteristics. Main Outcomes and Measures The number of participants and the duration of RCTs as well as the target population, outcomes, and funding were extracted from published reports. These features were analyzed with respect to time using linear regression and χ 2 analyses. Results The study included 203 RCTs with 79 589 participants testing interventions in AD. From 1992 to 2024, the mean sample size increased by 464% for phase 2 RCTs (from 42 to 237), and 50% for phase 3 RCTs (from 632 to 951), while the mean trial duration increased by 188% (from 16 to 46 weeks) for phase 2, and 256% (from 20 to 71 weeks) for phase 3 RCTs. This longer duration of RCTs may be partially attributed by a greater share of disease-modifying rather than symptomatic treatments. Similarly, more recent trials required AD biomarker evidence for enrollment (from 1 of 36 [2.7%] before 2006 to 40 of 76 [52.6%] since 2019). A substantial difference in the type of therapeutics researched was observed, with anti-amyloid and anti-tau RCTs being more likely to be funded by the pharmaceutical industry compared with neurotransmitter or other RCTs (anti-amyloid or anti-tau, 68 of 71 [95.8%]; neurotransmitter, 52 of 69 [77.6%]; other, 33 of 52 [63.5%]). RCT transparency improved, with more frequent data accessibility statements, registered reports, and better reporting on race and ethnicity. Conclusions and Relevance This methodology research of AD RCTs highlights substantial changes in key features of AD clinical trials from 1992 to 2024. AD RCTs have become larger and longer, such that they are powered to detect smaller clinical differences. The increased sample sizes and duration should enable the detection of smaller and more slowly occurring outcomes, which may lead to successful RCTs of therapies with slower and more subtle efficacy.

General & Internal Medicine↗
DOE OSTI2025

The health and indoor environmental quality impacts of residential building envelope retrofits: A literature review

Retrofitting existing buildings to improve energy efficiency is an important strategy to meet increasingly stringent energy efficiency targets. While the primary objective of energy efficiency retrofits is to reduce energy consumption and greenhouse gas emissions, retrofits can also result in non-energy impacts (NEIs), which contribute to decision-making processes and overall value of the retrofit. NEIs have been studied extensively in retrofitted residential buildings; however, these studies have historically grouped passive (i.e., building envelope) and active (i.e., heating, ventilation, and air conditioning (HVAC) and energy system) upgrades, making it difficult to identify the underlying mechanism(s) of action for each NEI and developing effective retrofit strategies, based on occupant need. The purpose of this study was to better account for NEIs, based on a literature review, summarizing the current state of knowledge on NEIs associated with residential building envelope retrofits. We limited our search to health- and indoor environmental quality-related NEIs. The review identified strong evidence that building envelope retrofits improve acoustic comfort, wintertime thermal comfort, and respiratory and cardiovascular health outcomes. IAQ outcomes were mixed, with studies reporting both increases and decreases to indoor contaminant concentrations following retrofits. The strength of the effect was generally governed by pre-retrofit contaminant concentrations and whether indoor concentrations were dominated by indoor or outdoor sources. Most studies evaluating summertime thermal comfort identified increased incidence of summertime overheating; however, none of these studies linked the change in thermal conditions to health outcomes. Recommendations for future work include expanding studies to include more market rate housing and the health impacts of summertime overheating in retrofitted buildings.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2026

Identification of drug repurposing candidates for amyotrophic lateral sclerosis using electronic health records: a retrospective cohort study

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with a life expectancy of only 3–5 years and few approved treatments. To identify drug repurposing candidates for the treatment of ALS, we analysed the electronic health records (EHRs) of a large cohort of military veterans with ALS. We analysed the EHRs of individuals in the US Veterans Health Administration (VHA) database who were diagnosed with ALS between Jan 1, 2009 and Dec 31, 2019 to assess medication effects. Individuals without recorded prescriptions after the date of diagnosis were excluded. Two sets of criteria were applied to ascertain exposure. Exposure criteria A were met if the dispense date or the end date of the medication was within 12 months of ALS diagnosis and the end date was at least 6 months after the dispense date. Exposure criteria B were met if there were at least two dispenses within 6 months before diagnosis and 12 months after diagnosis. Propensity score-matched control groups were generated on the basis of confounders included in the EHR, with methodology of potential outcomes used to infer treatment effects. The primary outcome was death. A standard Cox proportional hazards analysis was done to assess association with survival. Survival was defined as the time from diagnosis date recorded in the EHR to death reported in the Department for Veterans Affairs Vital Status File. Follow-up survival time was censored on Dec 31, 2020, for those alive on this date. Downstream protein targets of drugs with clinically significant effects were analysed using the protein–protein interaction networks-based algorithm PathFX. The EHRs of 11 003 individuals with ALS in the VHA database were appropriate for analysis. 162 medications with treatment groups of 30 or more individuals were identified. Among these 162 medications, 27 were associated with statistically significant changes (≥0·1) in the hazard ratio (HR) for death. 18 of the medications were associated with a reduced HR for death (prolonged survival), and nine were associated with an increased HR for death (reduced survival). Drugs associated with reduced HR included HMG-CoA reductase inhibitors (simvastatin, pravastatin, lovastatin, and atorvastatin), PDE5 inhibitors (vardenafil and sildenafil), and α-adrenergic antagonists (tamsulosin and terazosin). The medications associated with an increased HR were drugs used either in the management of clinical features of ALS associated with poor outcomes or in end-of-life care. PathFx analysis identified a complex of proteins interacting with several of the identified drugs. To our knowledge, this analysis is the largest EHR-based study for identifying drug repurposing candidates for ALS. We identified several drugs that warrant further assessment as therapeutic options in ALS, as well as a protein network complex that might serve as a therapeutic target for ALS.

Reimer, Richard J. [Stanford Univ., CA (United Sta↗
DOE OSTI2025

Evaluating the factors influencing accuracy, interpretability, and reproducibility in the use of machine learning classifiers in biology to enable standardization

The complexity and variability of biological data has promoted the increased use of machine learning methods to understand processes and predict outcomes. These same features complicate reliable, reproducible, interpretable, and responsible use of such methods, resulting in questionable relevance of the derived. outcomes. Here we systematically explore challenges associated with applying machine learning to predict and understand biological processes using a well- characterized in vitro experimental system. We evaluated factors that vary while applying machine learning classifers: (1) type of biochemical signature (transcripts vs. proteins), (2) data curation methods (pre- and post-processing), and (3) choice of machine learning classifier. Using accuracy, generalizability, interpretability, and reproducibility as metrics, we found that the above factors significantly mod- ulate outcomes even within a simple model system. Our results caution against the unregulated use of machine learning methods in the biological sciences, and strongly advocate the need for data standards and validation tool-kits for such studies.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Neutrino heating in 1D, 2D, and 3D core-collapse supernovae: characterizing the explosion of high-compactness stars

Massive stars can end their lives with a successful supernova explosion (leaving behind a neutron star or, more rarely, a black hole), or a failed explosion that leaves behind a black hole. The density structure of the pre-collapse progenitor star already encodes much of the information regarding the outcome and properties of the explosion. However, the complexity of the collapse and subsequent shock expansion phases prevents drawing a straightforward connection between the pre-collapse and post-explosion properties. In order to derive such a connection several explodability studies have been performed in recent years. However, different studies can predict different explosion outcomes. In this article, we show how compactness, which is related to the average density of the star’s core, has an important role in determining the efficiency of neutrino heating, and therefore the outcome of the explosion. Commonly, high-compactness progenitors are assumed to yield failed explosions, due to their large mass accretion rates, preventing the shock from expanding. We show by analysing ~150 2D flash and F ornax simulations and 20 3D F ornax simulations that this is not the case. Instead, due to the rapid increase of neutrino heating with compactness, high-compactness progenitors lead to successful shock revival. We also show that 1D+ simulations that include v-driven convection using a mixing-length theory approach correctly reproduce this trend. Finally, we compare 1D+ models, which we show can reproduce some aspects of multi-D simulations with reasonable accuracy, with other widely used 1D models in the literature.

neutrinos↗