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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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All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Cross‐Cultural Validation of the Binge Eating Disorder Screener‐7 ( BEDS ‐7) Across 42 Countries

ABSTRACT Objective This study aimed to evaluate the reliability and validity of the Binge Eating Disorder Screener‐7 (BEDS‐7) across 42 countries and 26 languages, assessing its reliability and validity as a screening tool for binge‐eating disorder (BED) in diverse cultural contexts. Specifically, it sought to enhance early recognition of BED symptoms in primary care settings globally, contributing to a standardized framework for assessing BED. Method The International Sex Survey, a cross‐sectional online study, was conducted in 42 countries and 26 languages. A diverse community sample of 82,243 participants, aged 18 years or older, completed the BEDS‐7 and measures of sexuality, mental health, substance use, and sociodemographic characteristics. Confirmatory factor analyses and tests of measurement invariance were employed to evaluate the reliability and validity of the BEDS‐7 across languages, countries, genders, and sexual orientations. Results The BEDS‐7 demonstrated scalar factorial invariance across languages and countries, indicating consistent factor loadings and item intercepts. In contrast, the screener showed residual invariance across gender and sexual orientation groups, supporting its robustness across these demographics. Kruskal–Wallis tests revealed significant differences in BED symptoms across languages, countries, genders, and sexual orientations, with the highest BED scores observed among queer, pansexual, and gender‐diverse individuals. The BEDS‐7 also demonstrated adequate reliability (Cronbach's alpha > 0.80) and moderate criterion validity. Discussion The findings provide further evidence of the reliability and validity of the BEDS‐7 as a potential screening tool for identifying probable cases of BED globally, facilitating early intervention in primary care settings.

Gewirtz‐Meydan, Ateret [School of Social Work, Fac↗
DOE OSTI2022

Development of radiopharmaceuticals for targeted alpha therapy: Where do we stand?

Targeted alpha therapy is an oncological treatment, where cytotoxic doses of alpha radiation are locally delivered to tumor cells, while the surrounding healthy tissue is minimally affected. This therapeutic strategy relies on radiopharmaceuticals made of medically relevant radionuclides chelated by ligands, and conjugated to targeting vectors, which promote the drug accumulation in tumor sites. This review discusses the state-of-the-art in the development of radiopharmaceuticals for targeted alpha therapy, breaking down their key structural components, such as radioisotope, targeting vector, and delivery formulation, and analyzing their pros and cons. Moreover, we discuss current drawbacks that are holding back targeted alpha therapy in the clinic, and identify ongoing strategies in field to overcome those issues, including radioisotope encapsulation in nanoformulations to prevent the release of the daughters. Lastly, we critically discuss potential opportunities the field holds, which may contribute to targeted alpha therapy becoming a gold standard treatment in oncology in the future.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2025

Effect of bisphosphonate treatment on the oim mouse middle ear ossicles' structure, composition and hearing

Hearing loss is common in people with osteogenesis imperfecta (OI or brittle bone disease). Bisphosphonates are commonly used to treat long bone fragility in children with OI. However, its impact on the bone quality of the middle ear ossicles and hearing remains unknown. This study determines whether bisphosphonates treatment itself may contribute to hearing loss in OI by evaluating its effects in the oim/oim mouse model of severe OI having normal auditory function. Specifically, this study reports the effects of alendronate (ALN), a nitrogen-containing bisphosphonate, on ossicle morphology, porosity, and elemental composition in 14-week-old oim/oim mice treated weekly, starting at 2 weeks of age. The ossicles were examined using synchrotron microtomography and X-ray fluorescence microscopy (XFM). Hearing was assessed longitudinally until 26 weeks of age by determining auditory brainstem response (ABR) thresholds in another group of mice also treated weekly starting at 2 weeks of age. ALN treatment further reduces in size the already small oim/oim ossicles, specifically in female mice. Porosity, bone composition, and hearing function, however, were generally not affected by the ALN treatment. Furthermore, ALN does not prevent joint fusions, excessive bone formations, or enlarged joint spaces in WT or oim/oim experimental groups. One ALN-treated oim/oim mouse with a bone formation in the interior of the footplate, and one ALN-treated WT mouse with a fixed footplate had frequency-specific hearing loss. Since footplate abnormalities are not observed in PBS-treated mice in this study, it remains unclear whether ALN fails to prevent these changes or contributes to their development. Future studies should investigate the mechanisms of ossicular abnormalities and bisphosphonates modulatory role in the ossicles.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Network-medicine framework for studying disease trajectories in U.S. veterans

A better understanding of the sequential and temporal aspects in which diseases occur in patient’s lives is essential for developing improved intervention strategies that reduce burden and increase the quality of health services. Here we present a network-based framework to study disease relationships using Electronic Health Records from > 9 million patients in the United States Veterans Health Administration (VHA) system. We create the Temporal Disease Network, which maps the sequential aspects of disease co-occurrence among patients and demonstrate that network properties reflect clinical aspects of the respective diseases. We use the Temporal Disease Network to identify disease groups that reflect patterns of disease co-occurrence and the flow of patients among diagnoses. Finally, we define a strategy for the identification of trajectories that lead from one disease to another. The framework presented here has the potential to offer new insights for disease treatment and prevention in large health care systems.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Reflection on the Challenges, Accomplishments, and New Frontiers of Gene Drives

Ongoing pest and disease outbreaks pose a serious threat to human, crop, and animal lives, emphasizing the need for constant genetic discoveries that could serve as mitigation strategies. Gene drives are genetic engineering approaches discovered decades ago that may allow quick, super-Mendelian dissemination of genetic modifications in wild populations, offering hopes for medicine, agriculture, and ecology in combating diseases. Following its first discovery, several naturally occurring selfish genetic elements were identified and several gene drive mechanisms that could attain relatively high threshold population replacement have been proposed. This review provides a comprehensive overview of the recent advances in gene drive research with a particular emphasis on CRISPR-Cas gene drives, the technology that has revolutionized the process of genome engineering. Herein, we discuss the benefits and caveats of this technology and place it within the context of natural gene drives discovered to date and various synthetic drives engineered. Later, we elaborate on the strategies for designing synthetic drive systems to address resistance issues and prevent them from altering the entire wild populations. Lastly, we highlight the major applications of synthetic CRISPR-based gene drives in different living organisms, including plants, animals, and microorganisms.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Inhibition of the eukaryotic initiation factor-2α kinase PERK decreases risk of autoimmune diabetes in mice

Preventing the onset of autoimmune type 1 diabetes (T1D) is feasible through pharmacological interventions that target molecular stress–responsive mechanisms. Cellular stresses, such as nutrient deficiency, viral infection, or unfolded proteins, trigger the integrated stress response (ISR), which curtails protein synthesis by phosphorylating eukaryotic translation initiation factor-2α (eIF2α). In T1D, maladaptive unfolded protein response (UPR) in insulin-producing β cells renders these cells susceptible to autoimmunity. We found that inhibition of the eIF2α kinase PKR-like ER kinase (PERK), a common component of the UPR and ISR, reversed the mRNA translation block in stressed human islets and delayed the onset of diabetes, reduced islet inflammation, and preserved β cell mass in T1D-susceptible mice. Single-cell RNA-Seq of islets from PERK-inhibited mice showed reductions in the UPR and PERK signaling pathways and alterations in antigen-processing and presentation pathways in β cells. Spatial proteomics of islets from these mice showed an increase in the immune checkpoint protein programmed death-ligand 1 (PD-L1) in β cells. Golgi membrane protein 1, whose levels increased following PERK inhibition in human islets and EndoC-βH1 human β cells, interacted with and stabilized PD-L1. Collectively, our studies show that PERK activity enhances β cell immunogenicity and that inhibition of PERK may offer a strategy for preventing or delaying the development of T1D.

Research & Experimental Medicine↗
DOE OSTI2021

Phase 3 Randomized Trial of Topical Steroid Versus Placebo for Prevention of Radiation Dermatitis in Patients With Head and Neck Cancer Receiving Chemoradiation

Radiation dermatitis is one of the most common acute toxicities induced by chemoradiation therapy (CRT) for head and neck cancer (HNC). The benefit of topical steroids in the management of radiation dermatitis is still unclear. This phase 3, multi-institutional, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of topical steroids for radiation dermatitis in patients with locally advanced HNC receiving CRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

The Oral CXCR4 Inhibitor X4-136 Improves Tumor Control and Reduces Toxicity in Cervical Cancer Treated With Radiation Therapy and Concurrent Chemotherapy

Cervical cancer is a global health problem. Despite the growth of prevention programs, there is an important need to improve the effectiveness of treatment for patients with invasive, locally advanced disease. In this study we examined (1) the efficacy of radiation therapy (RT) with cisplatin (RTCT) and an orally administered CXCR4 inhibitor suitable for clinical use, X4-136; (2) biomarkers of response to RTCT and X4-136; and (3) intestinal toxicity from RTCT and X4-136.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Challenges in Clinical Trial Implementation: Results from a Survey of the National Accreditation Program of Breast Centers (NAPBC)

Background: Although the results of clinical trials often guide best practices, changing clinical practice based on clinical trial results can be challenging. The objective of this study was to examine provider-reported barriers to adopting best clinical practices according to clinical trial data. Methods: A cross-sectional survey was conducted of providers from the National Accreditation Program for Breast Centers about barriers that prevent the incorporation of trial findings. Descriptive analyses and multivariable analyses were performed to determine provider characteristics that were significantly associated with reported barriers. Results: Overall, 383 institutions participated (63.5% response rate), with a total of 1226 physicians responding to the survey (80% response rate). Providers identified national guidelines and meetings as the most compelling way to receive practice-changing information. They reported the following internal barriers to trial implementation: patient preference (45%), strongly held beliefs by partners/colleagues (37%), and insufficient time to discuss new practices (30%). External barriers preventing trial implementation included a lack of agreement from multidisciplinary tumor boards (32%), fear of reimbursement loss (23%), and resistance from clinical staff (20%). Reported barriers differed by provider specialty, with plastic surgeons and radiation oncologists reporting that strongly held beliefs by partners/colleagues and disagreement from multidisciplinary tumor boards were the most significant factors preventing clinical trial implementation. Conclusions: Physician beliefs and patient preferences are the most frequently reported barriers to clinical trial implementation. Tactics to better educate providers about how to explain new clinical trial data to their patients and colleagues are needed.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2024

Towards maintaining canine training aid integrity: Effects of environmental factors and operational use on the triacetone triperoxide polymer odor capture‐and‐release system

Abstract There are many factors that may affect the longevity of or guide the use of canine training aids. Literature to date has mainly focused on identifying the headspace volatiles associated with training aids or odors and only minimal research exists into how different variables may alter those volatiles. The current study examines several factors affecting canine training aids: humidity, air flow, transportation, and operational deployment, using the triacetone triperoxide polymer odor capture‐and‐release canine training aid (TATP POCR) as the target. The TATP POCR is an absorption‐based canine training aid developed to be used to safely train canines to detect the odor of the explosive TATP in operational settings. Comparisons of the TATP POCR to neat TATP are made throughout the manuscript. First, humidity increased the background components of the POCR matrix, as well as the amount of TATP recovered was above the POCR. Humidity thus affected the amount of TATP detected but did not prevent detection. Second, air flow lessened the lifetime of the TATP POCR. Third, the practice of using primary and secondary containment successfully prevented contamination, cross‐contamination, and significant target loss, thereby maintaining kit integrity. Finally, the absorption of background odors from training environments was not observed. TATP headspace concentrations between a Deployed and Control POCR kit were not significantly different at time 0 (i.e., upon opening), which suggests that the operational use does not affect the function of the TATP POCR system. This information provides pivotal evidence for explosives detection canine handlers or trainers who utilize the TATP POCR.

Legal Medicine↗
DOE OSTI2025

Bayesian estimation of HIV acquisition dates for prevention trials

Accurate timing estimates of when participants acquire HIV in HIV prevention trials are necessary for determining antibody levels at acquisition. The Antibody-Mediated Prevention (AMP) Studies showed that a passively administered broadly neutralizing antibody can prevent the acquisition of HIV from a neutralization-sensitive virus. We developed a pipeline for estimating the date of detectable HIV acquisition (DDA) in AMP Study participants using diagnostic and viral sequence data. Using a Bayesian strategy that combines three streams of data (REN [rev/vpu/env/Δnef] sequence, GP [gag/Δpol] sequence, and diagnostic) where their 95% credible intervals overlap based on pre-specified criteria and decision rules. We evaluated the performance of our AMP pipeline using PacBio viral sequence data from 41 participants across two prospective acute HIV acquisition cohort studies, FRESH and RV217, with twice-weekly sampling. These cohort studies enrolled young women in South Africa and men and women in Kenya and Thailand, respectively, with a high likelihood of HIV acquisition. In evaluating performance, “true DDA” was the center of bounds between last-negative and first-positive RNA diagnostic tests (median time 4 days, range 2–7 days); bias was the mean difference between estimated and true DDA. Using diagnostic data alone yielded timing estimates with a bias of 2.4 days and root mean square error (RMSE) of 7.9 days. These results were improved using sequence + diagnostic data (bias 1.5 days, RMSE 6.9 days), as well as by restricting sequence-based estimation to samples from ≤5 weeks post-DDA (bias 0.2 days, RMSE 7.8 days).

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Involved-Field Radiation Therapy Prevents Recurrences in the Early Stages of Hodgkin Lymphoma in PET-Negative Patients After ABVD Chemotherapy: Relapse Analysis of GHSG Phase 3 HD16 Trial

The HD16 trial of the German Hodgkin Study Group (NCT00736320) demonstrated that radiation therapy in early-stage Hodgkin lymphoma without risk factors cannot be safely omitted, and therefore combined modality therapy (CMT) remains the standard treatment. To demonstrate the local effect of consolidating involved-field radiation therapy (IF-RT), we performed an analysis of the recurrence pattern of positron emission tomography (PET)-negative HD16 patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2023

Immunotherapy-induced neutralizing antibodies disrupt allergen binding and sustain allergen tolerance in peanut allergy

In IgE-mediated food allergies, exposure to the allergen activates systemic allergic responses. Oral immunotherapy (OIT) treats food allergies through incremental increases in oral allergen exposure. However, OIT only induces sustained clinical tolerance and decreased basophil sensitivity in a subset of individuals despite increases in circulating allergen-specific IgG in all treated individuals. Therefore, we examined the allergen-specific antibodies from 2 OIT cohorts of patients with sustained and transient responses. Here, we compared antibodies from individuals with sustained or transient responses and discovered specific tolerance-associated conformational epitopes of the immunodominant allergen Ara h 2 recognized by neutralizing antibodies. First, we identified what we believe to be previously unknown conformational, intrahelical epitopes using x-ray crystallography with recombinant antibodies. We then identified epitopes only recognized in sustained tolerance. Finally, antibodies recognizing tolerance-associated epitopes effectively neutralized allergen to suppress IgE-mediated effector cell activation. Our results demonstrate the molecular basis of antibody-mediated protection in IgE-mediated food allergy, by defining how these antibodies disrupt IgE-allergen interactions to prevent allergic reactions. Our approach to studying the structural and functional basis for neutralizing antibodies demonstrates the clinical relevance of specific antibody clones in antibody-mediated tolerance. We anticipate that our findings will form the foundation for treatments of peanut allergy using neutralizing antibodies and hypoallergens.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Optimization of a Lethal, Combat-Relevant Model of Sterile Inflammation in Mice for Drug Candidate Screening

ABSTRACT Introduction Extensive trauma, commonly seen in wounded military Service Members, often leads to a severe sterile inflammation termed systemic inflammatory response syndrome (SIRS), which can progress to multiple organ dysfunction syndrome (MODS) and death. MODS is a serious threat to wounded Service Members, historically causing 10% of all deaths in trauma admissions at a forward deployed combat hospital. The importance of this problem will be exacerbated in large-scale combat operations, in which evacuation will be delayed and care of complex injuries at lower echelons of care may be prolonged. The main goal of this study was to optimize an existing mouse model of lethal SIRS/MODS as a therapeutic screening platform for the evaluation of immunomodulatory drugs. Materials and Methods Male C57BL/6 mice were euthanized, and the bones and muscles were collected and blended into a paste termed tissue–bone matrix (TBX). The TBX at 12.5%–20% relative to body weight of each recipient mouse was implanted into subcutaneous pouches created on the dorsum of anesthetized animals. Mice were observed for clinical scores for up to 48 hours postimplantation and euthanized at the preset point of moribundity. To test effects of anesthetics on TBX-induced mortality, animals received isoflurane or ketamine/xylazine (K/X). In a separate set of studies, mice received TBX followed by intraperitoneal injection with 20 mg/kg or 40 mg/kg Eritoran or a placebo carrier. All Eritoran studies were performed in a blinded fashion. Results We observed that K/X anesthesia significantly increased the lethality of the implanted TBX in comparison to inhaled anesthetics. Although all the mice anesthetized with isoflurane and implanted with 12.5% TBX survived for 24 hours, 60% of mice anesthetized with K/X were moribund by 24 hours postimplantation. To mimic more closely the timing of lethal SIRS/MODS following polytrauma in human patients, we extended observation to 48 hours. We performed TBX dose–response studies and found that as low as 15%, 17.5%, and 20% TBX caused moribundity/mortality in 50%, 80%, and 100% mice, respectively, over a 48-hour time period. With 17.5% TBX, we tested if moribundity/mortality could be rescued by anti-inflammatory drug Eritoran, a toll-like receptor 4 antagonist. Neither 20 mg/kg nor 40 mg/kg doses of Eritoran were found to be effective in this model. Conclusions We optimized a TBX mouse model of SIRS/MODS for the purpose of evaluating novel therapeutic interventions to prevent trauma-related pathophysiologies in wounded Service Members. Negative effects of K/X on lethality of TBX should be further evaluated, particularly in the light of widespread use of ketamine in treatment of pain. By mimicking muscle crush, bone fracture, and necrosis, the TBX model has pleiotropic effects on physiology and immunology that make it uniquely valuable as a screening tool for the evaluation of novel therapeutics against trauma-induced SIRS/MODS.

General & Internal Medicine↗
DOE OSTI2024

Physiologically based modeling reveals different risk of respiratory depression after fentanyl overdose between adults and children

Despite a rapid increase in pediatric mortality rate from prescription and illicit opioids, there is limited research on the dose-dependent impact of opioids on respiratory depression in children, the leading cause of opioid-associated death. In this article, we extend a previously developed translational model to cover pediatric populations by incorporating age-dependent pharmacokinetic, pharmacodynamic, and physiological changes compared to adults. Our model reproduced previous perioperative clinical findings that adults and children have similar risk of respiratory depression at the same plasma fentanyl concentration when specific endpoints (minute ventilation, CO 2 tension in the blood) were used. However, our model points to a potential caveat that, in a perioperative setting, routine use of mechanical ventilation and supplemental oxygen maintained the blood and tissue oxygen partial pressures in patients and prevented the use of oxygen-related endpoints to evaluate the consequences of respiratory depression. In a community setting when such oxygenation procedures are not immediately available, our model suggests that the higher oxygen demand and reduced cerebrovascular reactivity could make children more susceptible to severe hypoxemia and brain hypoxia, even with the same plasma fentanyl concentration as adults. Our work indicates that when developing intervention strategies to protect children from opioid overdose in a community setting, these pediatric-specific factors may need to be considered.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Dietary Methionine Supplementation Exacerbates Gastrointestinal Toxicity in a Mouse Model of Abdominal Irradiation

Identification of appropriate dietary strategies for prevention of weight and muscle loss in cancer patients is crucial for successful treatment and prolonged patient survival. High-protein oral nutritional supplements decrease mortality and improve indices of nutritional status in cancer patients; however, high-protein diets are often rich in methionine, and experimental evidence indicates that a methionine-supplemented diet (MSD) exacerbates gastrointestinal toxicity after total body irradiation. Here, we sought to investigate whether MSD can exacerbate gastrointestinal toxicity after local abdominal irradiation, an exposure regimen more relevant to clinical settings.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Fostering Radiation Oncology Physician Scientist Trainees Within a Diverse Workforce: The Radiation Oncology Research Scholar Track

There is a need to foster future generations of radiation oncology physician scientists, but the number of radiation oncologists with sufficient education, training, and funding to make transformative discoveries is relatively small. A large number of MD/PhD graduates have entered he field of radiation oncology over the past 2 decades, but this has not led to a significant cohort of externally funded physician scientists. Because radiation oncologists leading independent research labs have the potential to make transformative discoveries that advance our field and positively affect patients with cancer, we created the Duke Radiation Oncology Research Scholar (RORS) Program. In crafting this program, we sought to eliminate barriers preventing radiation oncology trainees from becoming independent physician scientists. The RORS program integrates the existing American Board of Radiology Holman Pathway with a 2-year post-graduate medical education instructor position with 80% research effort at the same institution. We use a separate match for RORS and traditional residency pathways, which we hope will increase the diversity of our residency program. Since the inception of the RORS program, we have matched 2 trainees into our program. We encourage other radiation oncology residency programs at peer institutions to consider this training pathway as a means to foster the development of independent physician scientists and a diverse workforce in radiation oncology.

62 RADIOLOGY AND NUCLEAR MEDICINE↗