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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 OSTI2022

Proteomic and phosphoproteomic measurements enhance ability to predict ex vivo drug response in AML

Acute Myeloid Leukemia (AML) affects 20,000 patients in the US annually with a five-year survival rate of approximately 25%. One reason for the low survival rate is the high prevalence of clonal evolution that gives rise to heterogeneous sub-populations of leukemic cells with diverse mutation spectra, which eventually leads to disease relapse. This genetic heterogeneity drives the activation of complex signaling pathways that is reflected at the protein level. This diversity makes it difficult to treat AML with targeted therapy, requiring custom patient treatment protocols tailored to each individual’s leukemia. Toward this end, the Beat AML research program prospectively collected genomic and transcriptomic data from over 1000 AML patients and carried out ex vivo drug sensitivity assays to identify genomic signatures that could predict patient-specific drug responses. However, there are inherent weaknesses in using only genetic and transcriptomic measurements as surrogates of drug response, particularly the absence of direct information about phosphorylation-mediated signal transduction. As a member of the Clinical Proteomic Tumor Analysis Consortium, we have extended the molecular characterization of this cohort by collecting proteomic and phosphoproteomic measurements from a subset of these patient samples (38 in total) to evaluate the hypothesis that proteomic signatures can improve the ability to predict response to 26 drugs in AML ex vivo samples. In this work we describe our systematic, multi-omic approach to evaluate proteomic signatures of drug response and compare protein levels to other markers of drug response such as mutational patterns. We explore the nuances of this approach using two drugs that target key pathways activated in AML: quizartinib (FLT3) and trametinib (Ras/MEK), and show how patient-derived signatures can be interpreted biologically and validated in cell lines. In conclusion, this pilot study demonstrates strong promise for proteomics-based patient stratification to assess drug sensitivity in AML.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Overcoming Resilience Challenges on the Outer Banks of North Carolina

In 2021, the Town of Nags Head, located in the Outer Banks region of North Carolina, was among the first cohort of coastal and island communities to participate in the U.S. Department of Energy's Energy Transitions Initiative Partnership Project (ETIPP), which offers technical assistance and cash awards to competitively selected coastal, remote, and island communities seeking to transform their energy systems and increase their energy resilience. As a barrier island separated from mainland North Carolina, Nags Head experiences impacts from extreme weather events, including power outages, especially during hurricane season. To address challenges, the Nags Head ETIPP team sought to improve the town's disaster resilience by ensuring that critical facilities can remain powered during and after extreme events. With support from experts at Sandia National Laboratories, the National Renewable Energy Laboratory, and the Coastal Studies Institute, the community team identified the following goals for its participation in ETIPP: 1. Identify and prioritize critical facilities that, when powered during disruptions, support the town's resilience. 2. Analyze the potential for on-site solar photovoltaic (PV) and storage systems at 2-4 prioritized critical facilities owned and/or operated by the town. 3. Analyze the potential for interconnecting solar PV and storage systems at a cluster of public and privately owned facilities into a resilient microgrid. 4. Explore finance options and utility interconnection requirements and compensation mechanisms. 5. Summarize outcomes and next steps for town leadership.

25 ENERGY STORAGE↗
NASA NTRS1985

Gravity, Body Mass and Composition, and Metabolic Rate

Metabolic rate and body composition as a function of sex and age were defined in 5 species of common laboratory mammals, the mouse, hamster, rat, guinea pig and rabbit. Oxygen consumption and carbon dioxide production rates were measured individually in 6 male and 6 female animals for each of 8 age cohorts ranging from 1 month to 2 years, and for each of the species. From the results it is evident that among these small mammals there is no indication of scaling of muscularity to body size, despite the 100-fold difference in body mass represented by the skeletal musculature seems to reach a pronounced peak value at age 2 to 3 months and then declines, the fraction of the fat-free body represented by other body components in older animals must increase complementarily. Under normal gravity conditions muscularity in small laboratory mammals displays large, systematic variation as a function both of species and age. This variation must be considered when such animals are subjects of experiments to study the effects of altered gravitational loading on the skeletal musculature of the mammal.

Nello Pace↗
DOE OSTI2025

Assessment of diagenesis in archaeological human second metacarpal bones using the intensity of the small angle X-ray scattering D -period peak

Bone consists mainly of carbonated apatite (cAp) nanoplatelets embedded in a matrix of collagen fibrils. Earlier, high-energy small angle X-ray scattering (SAXS) studies of archaeological adult human second metacarpal bones (mc2) found collagen D-period peaks with high-intensity I D in specimens in which microcomputed tomography (microCT) showed little diagenesis and I D ~ 0 for specimens where microCT revealed severe diagenesis (Park et al. 2022 Int. J. Osteoarchaeol. 32, 170–181 (doi:10.1002/oa.3053); Stock et al. 2022 Int. J. Osteoarchaeol. 32, 120–131 (doi:10.1002/oa.3049)). Here, the present paper uses SAXS at beamline 1-ID, Advanced Photon Source, Argonne National Laboratory and other techniques to study a set of 10 mc2 from an early Medieval cemetery at Greding, Germany. We hypothesized that non-invasive measurement of I D would provide an accurate and rapid (approx. 6 min/specimen) assessment of diagenesis in archaeological mc2. Results of Raman spectroscopy, laboratory microCT and backscattered electron, reflected light and polarized transmitted light microscopies confirmed the SAXS determinations, but lattice parameter values from X-ray diffraction were uncorrelated with I D value. Age-at-death estimates placed the 10 mc2 in three age categories (young adult, middle adult, old adult): lattice parameters from X-ray diffraction were uncorrelated with age at death. Cross-sectional bone area fraction from microCT dropped noticeably for the older age cohort.

Raman spectroscopy↗
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 OSTI2021

Radium Dial Workers: Back to the Future

This report reviews the history of the radium dial workers in the United States, summarizes the scientific progress made since the last evaluation in the early 1990s, and discusses current progress in updating the epidemiologic cohort and applying new dosimetric models for radiation risk assessment. The discoveries of radiation and radioactivity led quickly to medical and commercial applications at the turn of the 20th century, including the development of radioluminescent paint, made by combining radium with phosphorescent material and adhesive. Workers involved with the painting of dials and instruments included painters, handlers, ancillary workers, and chemists who fabricated the paint. Dial painters were primarily women and, prior to the mid to late 1920s, would use their lips to give the brush a fine point, resulting in high intakes of radium. The tragic experience of the dial painters had a significant impact on industrial safety standards, including protection measures taken during the Manhattan Project. The dial workers study has formed the basis for radiation protection standards for intakes of radionuclides by workers and the public. The mortality experience of 3,276 radium dial painters and handlers employed between 1913-1949 is being determined through 2019. The last epidemiologic follow-up was 30 years ago when most of these workers were still alive. Nearly 65% were born before 1920, 37.5% were teenagers when first hired, and nearly 50% were hired before 1930 when the habit of placing brushes in mouths essentially stopped. Comprehensive dose reconstruction techniques are being applied to estimate organ doses for each worker related to the intake of 226Ra, 228Ra, and associated photon exposures. Time dependent dose-response analyses will estimate lifetime risks for specific causes of death. The study of radium dial workers is part of the Million Person Study of low-dose health effects that is designed to evaluate radiation risks among healthy American workers and veterans. Despite being one of the most important and influential radiation effects studies ever conducted, shifting programmatic responsibilities and declining funding led to the termination of the radium program of studies in the early 1990s. Renewed interest and opportunity have arisen. With scientific progress made in dosimetric methodology and models, the ability to perform a study over the entire life span, and the potential applicability to other scenarios such as medicine, environmental contamination and space exploration, the radium dial workers have once again come to the forefront.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2022

Prognostic importance of the preoperative New‐Naples prognostic score for patients with gastric cancer

Abstract Background The wide applicability of the Naples prognostic score (NPS) is still worthy of further study in gastric cancer (GC). This study aimed to construct a New‐NPS based on the differences in immunity and nutrition in patients with upper and lower gastrointestinal tumors to help obtain an individualized prediction of prognosis. Methods This study retrospectively analyzed patients who underwent radical gastrectomy from April 2014 to September 2016. The cutoff values of the preoperative neutrophil‐to‐lymphocyte ratio (NLR), lymphocyte‐to‐monocyte ratio (LMR), serum albumin (Alb), and total cholesterol (TC) were calculated by ROC curve analysis. ROC and t‐ROC were used to evaluate the accuracy of the prognostic markers. The Kaplan–Meier method and log‐rank test were used to analyze the overall survival probability. Univariate and multivariate analyses based on Cox risk regression were used to show the independent predictors. The nomogram was made by R studio. The predictive accuracy of nomogram was assessed using a calibration plot, concordance index (C‐index), and decision curve. Results A total of 737 patients were included in training cohort, 411 patients were included in validation cohort. ROC showed that the New‐NPS was more suitable for predicting the prognosis of GC patients. NPS = 2 indicated a poor prognosis. Multivariate analysis showed that CEA ( P = 0.026), Borrmann type ( P = 0.001), pTNM ( P < 0.001), New‐NPS ( P < 0.001), and nerve infiltration ( P = 0.035) were independent risk factors for prognosis. Conclusion The New‐NPS based on the cutoff values of NLR, LMR, Alb, and TC is not only suitable for predicting prognosis but can also be combined with clinicopathological characteristics to construct a nomogram model for GC patients.

Wang, Hao↗
DOE OSTI2022

Acute Copper Toxicity Displays a Nonmonotonic Relationship with Age Across the Medaka ( Oryzias latipes ) Life Span

The ability of an organism to cope with environmental stressors varies across the life span because of developmental stage–specific responses and age-related functional declines. In the present study, we examined the effect of age on acute copper toxicity in Japanese medaka (Oryzias latipes). We first determined the median lethal concentration (LC50) at 96 h for embryos, 7-day-old fry, and 6-month-old medaka. Embryos were exposed to 0, 15, 30, 60, 125, 250, and 500 ppb CuSO 4 through hatching. Fry were exposed to 0, 20, 50, 75, 100, 150, 250, and 500 ppb CuSO 4 for 96 h. Adult fish were exposed to 0, 100, 150, 200, 250, and 300 ppb CuSO 4 for 96 h. The 96-h LC50 was 804 ppb for embryos, 262 ppb for embryonically exposed larvae, 60.3 ppb for 7-day-old fry, and 226 ppb for adults. We then challenged cohorts of fish aged 2, 3, 5, 6, 7, 8, 9, 10, 11, 13, 14, 15, and 16 months with a 225-ppb CuSO 4 exposure to determine the acute toxicity across the life span. The fish exhibited a bimodal tolerance to copper, with tolerance peaking in 2- and 3-month-old fish and again at 10 and 11 months of age. Our data demonstrate that copper sensitivity is dynamic throughout the medaka life span and may be influenced by trade-offs with reproduction. Environ Toxicol Chem 2022;41:2999–3006. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

Proteogenomic insights suggest druggable pathways in endometrial carcinoma

We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity. PIK3R1 in-frame indels are associated with elevated AKT phosphorylation and increased sensitivity to AKT inhibitors. CTNNB1 hotspot mutations are concentrated near phosphorylation sites mediating pS45-induced degradation of β-catenin, which may render Wnt-FZD antagonists ineffective. Deep learning accurately predicts EC subtypes and mutations from histopathology images, which may be useful for rapid diagnosis. Overall, this study identified molecular and imaging markers that can be further investigated to guide patient stratification for more precise treatment of EC.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2007

Development of Sub-optimal Airway Protocols for the International Space Station (ISS) by the Medical Operation Support Team (MOST)

Airway management techniques are necessary to establish and maintain a patent airway while treating a patient undergoing respiratory distress. There are situations where such settings are suboptimal, thus causing the caregiver to adapt to these suboptimal conditions. Such occurrences are no exception aboard the International Space Station (ISS). As a result, the NASA flight surgeon (FS) and NASA astronaut cohorts must be ready to adapt their optimal airway management techniques for suboptimal situations. Based on previous work conducted by the Medical Operation Support Team (MOST) and other investigators, the MOST had members of both the FS and astronaut cohorts evaluate two oral airway insertion techniques for the Intubating Laryngeal Mask Airway (ILMA) to determine whether either technique is sufficient to perform in suboptimal conditions within a microgravity environment. Methods All experiments were conducted in a simulated microgravity environment provided by parabolic flight aboard DC-9 aircraft. Each participant acted as a caregiver and was directed to attempt both suboptimal ILMA insertion techniques following a preflight instruction session on the day of the flight and a demonstration of the technique by an anesthesiologist physician in the simulated microgravity environment aboard the aircraft. Results Fourteen participants conducted 46 trials of the suboptimal ILMA insertion techniques. Overall, 43 of 46 trials (94%) conducted were properly performed based on criteria developed by the MOST and other investigators. Discussion The study demonstrated the use of airway management techniques in suboptimal conditions relating to space flight. Use of these techniques will provide a crew with options for using the ILMA to manage airway issues aboard the ISS. Although it is understood that the optimal method for patient care during space flight is to have both patient and caregiver restrained, these techniques provide a needed backup should conditions not present themselves in an ideal manner.

Polk, James D.↗
DOE OSTI2023

Virulence factors and antimicrobial resistance profiles of Campylobacter isolates recovered from consecutively reused broiler litter

ABSTRACT Campylobacterinfections are a leading cause of bacterial diarrhea in humans globally. Infections are due to consumption of contaminated food products and are highly associated with chicken meat, with chickens being an important reservoir forCampylobacter. Here, we characterized the genetic diversity ofCampylobacter jejuni(C. jejuni) andCampylobacter coli(C. coli) detected in broiler chicken litter over three consecutive flocks and determined their antimicrobial resistance (ARM) and virulence factor (VF) profiles.Campylobacterwas detected in 9.38% (27/288) of litter samples collected. Antimicrobial susceptibility testing and whole genome sequencing were performed onC. jejuni(n= 39) andC. coli(n= 5) isolates.Campylobactervirulence factors differed within and across broiler houses but were explained by the broiler flock cohort raised on litter,Campylobacterspecies andCampylobactermultilocus sequence type (MLST). Virulence factors involved in the ability to invade and colonize host tissues and evade host defenses were present inC. jejuniisolates (ST-464) from flock cohorts 1 and 2 but absent inC. jejuniisolates (ST-48) from flock cohort 3.C. jejuniisolates from house three harbored a significantly higher proportion of virulence genes with functions related to glycosylation and immune evasion thanC. jejuniisolates from houses 1 and 2 (P< 0.01). AllC. jejuniisolates were susceptible to all antibiotics tested whileC. coli(n= 4) were resistant to tetracycline and harbored the tetracycline resistant ribosomal protection protein (TetO). Our results suggest that house environment and broiler management practices imposed selective pressures on virulence factors and antimicrobial resistance genes ofCampylobacter. IMPORTANCE Campylobacteris a leading cause of foodborne illness in the United States due to consumption of contaminated or mishandled food products, often associated with chicken meat.Campylobacteris common in the microbiota of avian and mammalian gut; however, acquisition of antimicrobial resistance genes (ARGs) and virulence factors (VFs) may result in strains that pose significant threat to public health. Although there are studies investigating the genetic diversity ofCampylobacterstrains isolated from post-harvest chicken samples, there are limited data on the genome characteristics of isolates recovered from preharvest broiler production. Here, we show thatCampylobacter jejuniandCampylobacter colidiffer in their carriage of antimicrobial resistance and virulence factors may also differ in their ability to persist in litter during consecutive grow-out of broiler flocks. We found that presence/absence of virulence factors needed for evasion of host defense mechanisms and gut colonization played an integral role in differentiatingCampylobacterstrains.

Microbiology↗
NASA NTRSDate not supplied

Long-term Engagement in Authentic Research with NASA (LEARN): Innovative Practices Suggested by a New Model for Teacher Research Experiences

NASA's LEARN Project is an innovative program that provides long-term immersion in the practice of atmospheric science for middle and high school in-service teachers. Working alongside NASA scientists and using authentic NASA Science Mission Directorate research data, teachers develop individual research topics of interest during two weeks in the summer while on-site at NASA Langley. With continued, intensive mentoring by NASA scientists, the teachers further develop their research throughout the academic year through virtual group meetings and data team meetings mirroring scientific collaborations. At the end of the first year, LEARN teachers present scientific posters. The LEARN experience has had such an impact that multiple teachers from the first two cohorts have elected to continue their research. The LEARN project evaluation has provided insights into particularly effective elements of this new approach. Findings indicate that teachers? perceptions of the scientific enterprise have changed, and that LEARN provided substantial resources to help them take real-world research to their students. This presentation will focus on key factors from LEARN?s implementation that inform best practices for the incorporation of authentic scientific research into teacher professional development experiences. We suggest that these factors should be considered in the development of other such experiences, including: (1) The involvement of a single scientist as both the project leader/manager and the project scientist, to ensure that the project can meet teachers? needs. (2) An emphasis on framing and approaching scientific research questions, so that teachers can learn to evaluate the feasibility of studies based on scope, scale, and availability of data. (3) Long term, ongoing relationships where teachers and scientists work as collaborators, beyond the workshop ?mold.? (4) A focus on meeting the needs of individual teachers, whether their needs relate to elements of research and analysis, or to their tight professional schedules. (5) Above all, flexibility and patience. LEARN builds relationships with teachers slowly, over a long period of time. In the middle, life often intervenes. LEARN has emphasized that teachers? success is more important than deadlines or following a rigid protocol.

M Pippin↗
DOE OSTI2020

A nomogram for prediction of stage III/IV gastric cancer outcome after surgery: A multicenter population‐based study

Abstract Most patients with gastric cancer (GC) are first diagnosed at stage III‐IV and surgery resection remains the primary therapeutic modality for these patients. However, clinical staging used for prediction of those patients provides limited information. We collected clinicopathological data and disease‐progression information from 508 patients with stage III‐IV GC at three Chinese hospitals and 1298 patients from the Surveillance, Epidemiology, and End Results database. Based on the stepwise multivariate regression model, we constructed a novel nomogram to predict overall survival (OS). The performance of discrimination for this model was measured using Harrell's concordance index (C‐index) and receiver‐operating characteristic curve (ROC), and was validated using calibration plots. Multivariate Cox regression analyses showed that tumor size, age at diagnosis, N stage, tumor grade, and distant metastases were outstanding independent prognostic factors of stage III‐IV GC. We developed a nomogram based on these five prognostic predictors. In the training set, the C‐index of the nomogram was 0.645 (95% CI: 0.611‐0.679), which was higher than that of the American Joint Committee on Cancer TNM system alone (sixth TNM: 0.544; seventh TNM: 0.575; eighth TNM: 0.568). Similar results were observed in validation cohort. Moreover, calibration blots demonstrated good consistency between the actual and predicted OS probabilities. According to the nomogram, GC individuals could be classified into three groups (low‐, middle‐, and high‐risk) ( P < .001). Our nomogram complements the current staging system for prediction of individual prognosis with stage III‐IV GC, and may be helpful for making individualized treatment decisions.

Gao, Zhiying↗
DOE OSTI2022

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

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

Orthopedics↗
DOE OSTI2023

Characterization of the antispike IgG immune response to COVID-19 vaccines in people with a wide variety of immunodeficiencies

Research on coronavirus disease 2019 vaccination in immune-deficient/disordered people (IDP) has focused on cancer and organ transplantation populations. In a prospective cohort of 195 IDP and 35 healthy volunteers (HV), antispike immunoglobulin G (IgG) was detected in 88% of IDP after dose 2, increasing to 93% by 6 months after dose 3. Despite high seroconversion, median IgG levels for IDP never surpassed one-third that of HV. IgG binding to Omicron BA.1 was lowest among variants. Angiotensin-converting enzyme 2 pseudo-neutralization only modestly correlated with antispike IgG concentration. IgG levels were not significantly altered by receipt of different messenger RNA–based vaccines, immunomodulating treatments, and prior severe acute respiratory syndrome coronavirus 2 infections. While our data show that three doses of coronavirus disease 2019 vaccinations induce antispike IgG in most IDP, additional doses are needed to increase protection. Because of the notably reduced IgG response to Omicron BA.1, the efficacy of additional vaccinations, including bivalent vaccines, should be studied in this population.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2016

Clinical Outcome Metrics for Optimization of Robust Training

Introduction: The emphasis of this research is on the Human Research Program (HRP) Exploration Medical Capability's (ExMC) "Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-Flight Medical Capabilities." Specifically, this project aims to contribute to the closure of gap ExMC 2.02: We do not know how the inclusion of a physician crew medical officer quantitatively impacts clinical outcomes during exploration missions. The experiments are specifically designed to address clinical outcome differences between physician and non-physician cohorts in both near-term and longer-term (mission impacting) outcomes. Methods: Medical simulations will systematically compare success of individual diagnostic and therapeutic procedure simulations performed by physician and non-physician crew medical officer (CMO) analogs using clearly defined short-term (individual procedure) outcome metrics. In the subsequent step of the project, the procedure simulation outcomes will be used as input to a modified version of the NASA Integrated Medical Model (IMM) to analyze the effect of the outcome (degree of success) of individual procedures (including successful, imperfectly performed, and failed procedures) on overall long-term clinical outcomes and the consequent mission impacts. The procedures to be simulated are endotracheal intubation, fundoscopic examination, kidney/urinary ultrasound, ultrasound-guided intravenous catheter insertion, and a differential diagnosis exercise. Multiple assessment techniques will be used, centered on medical procedure simulation studies occurring at 3, 6, and 12 months after initial training (as depicted in the following flow diagram of the experiment design). Discussion: Analysis of procedure outcomes in the physician and non-physician groups and their subsets (tested at different elapsed times post training) will allow the team to 1) define differences between physician and non-physician CMOs in terms of both procedure performance (pre-IMM analysis) and overall mitigation of the mission medical impact (IMM analysis); 2) refine the procedure outcome and clinical outcome metrics themselves; 3) refine or develop innovative medical training products and solutions to maximize CMO performance; and 4) validate the methods and products of this experiment for operational use in the planning, execution, and quality assurance of the CMO training process The team has finalized training protocols and developed a software training/testing tool in collaboration with Butler Graphics (Detroit, MI). In addition to the "hands on" medical procedure modules, the software includes a differential diagnosis exercise (limited clinical decision support tool) to evaluate the diagnostic skills of participants. Human subject testing will occur over the next year.

Ebert, D.↗
DOE OSTI2024

Transcriptomic and Proteomic Insights into Host Immune Responses in Pediatric Severe Malarial Anemia: Dysregulation in HSP60-70-TLR2/4 Signaling and Altered Glutamine Metabolism

Severe malarial anemia (SMA, Hb < 6.0 g/dL) is a leading cause of childhood morbidity and mortality in holoendemic Plasmodium falciparum transmission zones. This study explored the entire expressed human transcriptome in whole blood from 66 Kenyan children with non-SMA (Hb ≥ 6.0 g/dL, n = 41) and SMA (n = 25), focusing on host immune response networks. RNA-seq analysis revealed 6862 differentially expressed genes, with equally distributed up-and down-regulated genes, indicating a complex host immune response. Deconvolution analyses uncovered leukocytic immune profiles indicative of a diminished antigenic response, reduced immune priming, and polarization toward cellular repair in SMA. Weighted gene co-expression network analysis revealed that immune-regulated processes are central molecular distinctions between non-SMA and SMA. A top dysregulated immune response signaling network in SMA was the HSP60-HSP70-TLR2/4 signaling pathway, indicating altered pathogen recognition, innate immune activation, stress responses, and antigen recognition. Validation with high-throughput gene expression from a separate cohort of Kenyan children (n = 50) with varying severities of malarial anemia (n = 38 non-SMA and n = 12 SMA) confirmed the RNA-seq findings. Proteomic analyses in 35 children with matched transcript and protein abundance (n = 19 non-SMA and n = 16 SMA) confirmed dysregulation in the HSP60-HSP70-TLR2/4 signaling pathway. Additionally, glutamine transporter and glutamine synthetase genes were differentially expressed, indicating altered glutamine metabolism in SMA. This comprehensive analysis underscores complex immune dysregulation and novel pathogenic features in SMA.

Microbiology↗
DOE OSTI2023

Drivers of stability and transience in composition-functioning links during serial propagation of litter-decomposing microbial communities

ABSTRACT Biotic factors that influence the temporal stability of microbial community functioning are an emerging research focus for the control of natural and engineered systems. The discovery of common features within community ensembles that differ in functional stability over time is a starting point to explore biotic factors. We serially propagated a suite of soil microbial communities through five generations of 28-day microcosm incubations to examine microbial community compositional and functional stability during plant litter decomposition. Using dissolved organic carbon (DOC) abundance as a target function, we hypothesized that microbial diversity, compositional stability, and associated changes in interactions would explain the relative stability of the ecosystem function between generations. Communities with initially high DOC abundance tended to converge towards a “low DOC” phenotype within two generations, but across all microcosms, functional stability between generations was highly variable. By splitting communities into two cohorts based on their relative DOC functional stability, we found that compositional shifts, diversity, and interaction network complexity were associated with the stability of DOC abundance between generations. Further, our results showed that legacy effects were important in determining compositional and functional outcomes, and we identified taxa associated with high DOC abundance. In the context of litter decomposition, achieving functionally stable communities is required to utilize soil microbiomes to increase DOC abundance and long-term terrestrial DOC sequestration as one solution to reduce atmospheric carbon dioxide concentrations. Identifying factors that stabilize function for a community of interest may improve the success of microbiome engineering applications. IMPORTANCE Microbial community functioning can be highly dynamic over time. Identifying and understanding biotic factors that control functional stability is of significant interest for natural and engineered communities alike. Using plant litter–decomposing communities as a model system, this study examined the stability of ecosystem function over time following repeated community transfers. By identifying microbial community features that are associated with stable ecosystem functions, microbial communities can be manipulated in ways that promote the consistency and reliability of the desired function, improving outcomes and increasing the utility of microorganisms.

59 BASIC BIOLOGICAL SCIENCES↗