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

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At least 145 records · Page 8
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Brown Dog Tick (Rhipicephalus sanguineus Sensu Lato) Infection with Endosymbiont and Human Pathogenic Rickettsia spp., in Northeastern México

Of the documented tick-borne diseases infecting humans in México, Rocky Mountain spotted fever (RMSF), caused by the Gram-negative bacterium Rickettsia rickettsii, is responsible for most fatalities. Given recent evidence of brown dog tick, Rhipicephalus sanguineus s.l., as an emerging vector of human RMSF, we aimed to evaluate dogs and their ticks for rickettsiae infections as an initial step in assessing the establishment of this pathosystem in a poorly studied region of northeastern México while evaluating the use of dogs as sentinels for transmission/human disease risk. We sampled owned dogs living in six disadvantaged neighborhoods of Reynosa, northeastern México to collect whole blood and ticks. Of 168 dogs assessed, tick infestation prevalence was 53%, composed of exclusively Rh. sanguineus s. l. (n = 2170 ticks). Using PCR and sequencing, we identified an overall rickettsiae infection prevalence of 4.1% (n = 12/292) in ticks, in which eight dogs harbored at least one infected tick. Rickettsiae infections included Rickettsia amblyommatis and Rickettsia parkeri, both of which are emerging human pathogens, as well as Candidatus Rickettsia andeanae. This is the first documentation of pathogenic Rickettsia species in Rh. sanguineus s.l. collected from dogs from northeastern México. Domestic dog infestation with Rickettsia-infected ticks indicates ongoing transmission; thus, humans are at risk for exposure, and this underscores the importance of public and veterinary health surveillance for these pathogens.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Anatomy of an agricultural antagonist: Feeding complex structure and function of three xylem sap‐feeding insects illuminated with synchrotron‐based 3D imaging

Abstract Many insects feed on xylem or phloem sap of vascular plants. Although physical damage to the plant is minimal, the process of insect feeding can transmit lethal viruses and bacterial pathogens. Disparities between insect‐mediated pathogen transmission efficiency have been identified among xylem sap‐feeding insects; however, the mechanistic drivers of these trends are unclear. Identifying and understanding the structural factors and associated integrated functional components that may ultimately determine these disparities are critical for managing plant diseases. Here, we applied synchrotron‐based X‐ray microcomputed tomography to digitally reconstruct the morphology of three xylem sap‐feeding insect vectors of plant pathogens: Graphocephala atropunctata (blue‐green sharpshooter; Hemiptera, Cicadellidae) and Homalodisca vitripennis (glassy‐winged sharpshooter; Hemiptera, Cicadellidae), and the spittlebug Philaenus spumarius (meadow spittlebug; Hemiptera, Aphrophoridae). The application of this technique revealed previously undescribed anatomical features of these organisms, such as key components of the salivary complex. The visualization of the 3D structure of the precibarial valve led to new insights into the mechanism of how this structure functions. Morphological disparities with functional implications between taxa were highlighted as well, including the morphology and volume of the cibarial dilator musculature responsible for extracting xylem sap, which has implications for force application capabilities. These morphological insights will be used to target analyses illuminating functional differences in feeding behavior.

3D imaging↗
DOE OSTI2023

Phylogeography of the blacklegged tick ( Ixodes scapularis ) throughout the USA identifies candidate loci for differences in vectorial capacity

Abstract The blacklegged tick ( Ixodes scapularis ( Journal of the Academy of Natural Sciences of Philadelphia , 1821, 2 , 59)) is a vector of Borrelia burgdorferi sensu stricto ( s.s .) ( International Journal of Systematic Bacteriology , 1984, 34 , 496), the causative bacterial agent of Lyme disease, part of a slow‐moving epidemic of Lyme borreliosis spreading across the northern hemisphere. Well‐known geographical differences in the vectorial capacity of these ticks are associated with genetic variation. Despite the need for detailed genetic information in this disease system, previous phylogeographical studies of these ticks have been restricted to relatively few populations or few genetic loci. Here we present the most comprehensive phylogeographical study of genome‐wide markers in I. scapularis , conducted by using 3RAD (triple‐enzyme restriction‐site associated sequencing) and surveying 353 ticks from 33 counties throughout the species' range. We found limited genetic variation among populations from the Northeast and Upper Midwest, where Lyme disease is most common, and higher genetic variation among populations from the South. We identify five spatially associated genetic clusters of I. scapularis . In regions where Lyme disease is increasing in frequency, the I. scapularis populations genetically group with ticks from historically highly Lyme‐endemic regions. Finally, we identify 10 variable DNA sites that contribute the most to population differentiation. These variable sites cluster on one of the chromosome‐scale scaffolds for I. scapularis and are within identified genes. Our findings illuminate the need for additional research to identify loci causing variation in the vectorial capacity of I. scapularis and where additional tick sampling would be most valuable to further understand disease trends caused by pathogens transmitted by I. scapularis .

3RAD↗
DOE OSTI2023

Evaluation of DNA Vaccine Candidates against Foot-and-Mouth Disease Virus in Cattle

We evaluated four DNA vaccine candidates for their ability to produce virus-like particles (VLPs) and elicit a protective immune response against Foot-and-mouth disease virus (FMDV) in cattle. Two traditional DNA plasmids and two DNA minicircle constructs were evaluated. Both the pTarget O1P1-3C plasmid and O1P1-3C minicircle encoded a wild-type FMDV 3C protease to process the P1-2A polypeptide, whereas the O1P1-HIV-3CT minicircle used an HIV-1 ribosomal frameshift to down-regulate expression of a mutant 3C protease. A modified pTarget plasmid with a reduced backbone size, mpTarget O1P1-3C LT , used a 3C protease containing two mutations reported to enhance expression. All constructs produced mature FMDV P1 cleavage products in transfected cells, as seen by western blot analysis. Three constructs, O1P1-3C minicircles, pTarget O1P1-3C, and mpTarget O1P1-3C LT plasmids, produced intracellular VLP crystalline arrays detected by electron microscopy. Despite VLP formation in vitro, none of the DNA vaccine candidates elicited protection from clinical disease when administered independently. Administration of pTarget O1P1-3C plasmid enhanced neutralizing antibody titers when used as a priming dose prior to administration of a conditionally licensed adenovirus-vectored FMD vaccine. Further work is needed to develop these DNA plasmid-based constructs into standalone FMD vaccines in cattle.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2023

Racoons ( Procyon Lotor ) Show Higher Trypanosoma Cruzi Detection Rates than Virginia Opossums ( Didelphis Virginiana ) in South Carolina, USA

Chagas disease, a significant public health concern in the Americas, is caused by a protozoan parasite, Trypanosoma cruzi. The life cycle of T. cruzi involves kissing bugs (Triatoma spp.) functioning as vectors and mammalian species serving as hosts. Raccoons (Procyon lotor) and opossums (Didelphis virginiana) have been identified as important reservoir species in the life cycle of T. cruzi, but prevalence in both species in the southeastern US is currently understudied. We quantified T. cruzi prevalence in these two key reservoir species across our study area in South Carolina, US, and identified factors that may influence parasite detection. We collected whole blood from 183 raccoons and 126 opossums and used PCR to detect the presence of T. cruzi. We then used generalized linear models with parasite detection status as a binary response variable and predictor variables of land cover, distance to water, sex, season, and species. Our analysis indicated that raccoons experienced significantly higher parasite detection rates than Virginia opossums, with T. cruzi prevalence found to be 26.5% (95% confidence interval [CI], 20.0–33.8) in raccoons and 10.5% (95% CI, 5.51–17.5) in opossums. Altogether, our results concur with previous studies, in that T. cruzi is established in reservoir host populations in natural areas of the southeastern US.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Scoping review of Culex mosquito life history trait heterogeneity in response to temperature

Abstract Background Mosquitoes in the genus Culex are primary vectors in the US for West Nile virus (WNV) and other arboviruses. Climatic drivers such as temperature have differential effects on species-specific changes in mosquito range, distribution, and abundance, posing challenges for population modeling, disease forecasting, and subsequent public health decisions. Understanding these differences in underlying biological dynamics is crucial in the face of climate change. Methods We collected empirical data on thermal response for immature development rate, egg viability, oviposition, survival to adulthood, and adult lifespan for Culex pipiens, Cx. quinquefasciatus, Cx. tarsalis , and Cx. restuans from existing literature according to the PRISMA scoping review guidelines. Results We observed linear relationships with temperature for development rate and lifespan, and nonlinear relationships for survival and egg viability, with underlying variation between species. Optimal ranges and critical minima and maxima also appeared varied. To illustrate how model output can change with experimental input data from individual Culex species, we applied a modified equation for temperature-dependent mosquito type reproduction number for endemic spread of WNV among mosquitoes and observed different effects. Conclusions Current models often input theoretical parameters estimated from a single vector species; we show the need to implement the real-world heterogeneity in thermal response between species and present a useful data resource for researchers working toward that goal. Graphical Abstract

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1999

Adenovirus-mediated gene delivery to hypothalamic magnocellular neurons in mice

Vasopressin is synthesized by magnocellular neurons in supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei and released by their axon terminals in the neurohypophysis (NH). With its actions as an antidiuretic hormone and vasoactive agent, vasopressin plays a pivotal role in the control of body fluids and cardiovascular homeostasis. Because of its well-defined neurobiology and functional importance, the SON/PVN-NH system is ideal to establish methods for gene transfer of genetic material into specific pathways in the mouse central nervous system. In these studies, we compared the efficiency of transferring the gene lacZ, encoding for beta-galactosidase (beta-gal), versus a gene encoding for green fluorescent protein by using replication-deficient adenovirus (Ad) vectors in adult mice. Transfection with viral concentrations up to 2 x 10(7) plaque-forming units per coverslip of NH, PVN, and SON in dissociated, cultured cells caused efficient transfection without cytotoxicity. However, over an extended period of time, higher levels (50% to 75% of the cells) of beta-gal expression were detected in comparison with green fluorescent protein (5% to 50% of the cells). With the use of a stereotaxic approach, the pituitary glands of mice were injected with Ad (4 x 10(6) plaque-forming units). In material from these animals, we were able to visualize the expression of the beta-gal gene in the NH and in magnocellular neurons of both the PVN and SON. The results of these experiments indicate that Ad-Rous sarcoma virus promoter-beta-gal is taken up by nerve terminals at the injection site (NH) and retrogradely transported to the soma of the neurons projecting to the NH. We conclude that the application of these experimental approaches will provide powerful tools for physiological studies and potential approaches to deliver therapeutic genes to treat diseases.

Non-NASA Center↗
NASA NTRS2020

Emerging and Re-Emerging Leishmaniases in the Mediterranean Area: What Can Be Learned from a Retrospective Review Analysis of the Situation in Morocco during 1990 to 2010?

In Morocco, cutaneous and visceral leishmaniases represent a public health concern. In this opinion paper, we propose to highlight chosen elements that have governed the drastic increase in the incidence of leishmaniases recorded in Morocco during the period between 1990 to 2010 in order to guide the prediction of the expansion of diseases and epidemic events. We highlight that the dispersion of the zoonotic cutaneous leishmaniasis (ZCL) form, caused by the Leishmania major parasite, appears to be closely related to that of its arthropod vector density, which is sensitive to changes in climate. The dissemination of anthroponotic cutaneous leishmaniasis (ACL) was related to an increase in human travel and local tourism during the studied decades. These are linked to economic expansion and infrastructure development. Interestingly, the main ACL foci are spatially aligned with the highways, and their occurrence was synchronized with the building of transportation infrastructure. During the above-mentioned decades, the zoonotic visceral leishmaniasis (ZVL)caused by Leishmania infantum has expanded from its historical northern territories, dispersing outwards in all directions. This spread follows the emergence of hamlets and villages connecting with major cities.

leishmaniases↗
DOE OSTI2023

A New Repellent for Redbay Ambrosia Beetle (Coleoptera: Curculionidae: Scolytinae), Primary Vector of the Mycopathogen That Causes Laurel Wilt

The redbay ambrosia beetle, Xyleborus glabratus, was detected in Georgia, USA, in 2002 and has since spread to 11 additional states. This wood-boring weevil carries a symbiotic fungus, Harringtonia lauricola, that causes laurel wilt, a lethal disease of trees in the Lauraceae family. Native ambrosia beetles that breed in infected trees can acquire H. lauricola and contribute to the spread of laurel wilt. Since 2002, laurel wilt has devastated native Persea species in coastal forests and has killed an estimated 200,000 avocado trees in Florida. Since laurel wilt is difficult to manage once it has entered a susceptible agrosystem, this study evaluated piperitone as a candidate repellent to deter attacks by X. glabratus and other ambrosia beetles. Additionally, piperitone was compared to the known repellent verbenone as a potential cost-effective alternative. The repellent efficacy was determined by comparing captures in traps baited with commercial beetle lures containing α-copaene versus captures in traps baited with lures plus a repellent. In parallel 10-week field tests, the addition of piperitone reduced the captures of X. glabratus in α-copaene-baited traps by 90%; however, there was no significant reduction in the captures of native ambrosia beetles in ethanol-baited traps. In two replicate 10-week comparative tests, piperitone and verbenone both reduced X. glabratus captures by 68–90%, with longevity over the full 10 weeks. This study identifies piperitone as a new X. glabratus repellent with potential for pest management.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Advancing the central role of non-model biorepositories in predictive modeling of emerging pathogens

The COVID-19 pandemic demonstrated the insufficiency of a reactive approach to emerging zoonotic pathogens. With spillover increasing in frequency as environments change and the human footprint continues to grow, pandemic prevention will require predictive models that can identify (i) potential zoonoses with a high likelihood of emergence and (ii) environmental or other features that may trigger a shift in host, vector, or pathogen baselines associated with emergence and/or spillover. Artificial intelligence (AI), and particularly its machine learning and deep learning branches, holds enormous potential for detecting shifts in large-scale biodiversity and disease datasets (genomic, ecological, geospatial, etc.). Such algorithms can be trained to identify subtle patterns in large volumes of data to yield insights into complex phenomena for which we have limited knowledge of the true cause(s) or predictor(s), as is the case for emerging infectious diseases.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Effect of Foot-and-Mouth Disease Virus 2B Viroporin on Expression and Extraction of Mammalian Cell Culture Produced Foot-and-Mouth Disease Virus-like Particles

To improve the production of foot-and-mouth disease (FMD) molecular vaccines, we sought to understand the effects of the FMD virus (FMDV) 2B viroporin in an experimental, plasmid-based, virus-like particle (VLP) vaccine. Inclusion of the FMDV viroporin 2B into the human Adenovirus 5 vectored FMD vaccine enhanced transgene expression despite independent 2B expression negatively affecting cell viability. Evaluating both wildtype 2B and mutants with disrupted viroporin activity, we confirmed that viroporin activity is detrimental to overall transgene expression when expressed independently. However, the incorporation of 2B into an FMD molecular vaccine construct containing a wildtype FMDV 3C protease, a viral encoded protease responsible for processing structural proteins, resulted in enhancement of transgene expression, validating previous observations. This benefit to transgene expression was negated when using the FMDV 3CL127P mutant, which has reduced processing of host cellular proteins, a reversion resulting from 2B viroporin activity. Inclusion of 2B into VLP production constructs also adversely impacted antigen extraction, a possible side effect of 2B-dependent rearrangement of cellular membranes. These results demonstrate that inclusion of 2B enhanced transgene expression when a wildtype 3C protease is present but was detrimental to transgene expression with the 3CL127P mutant. This has implications for future molecular FMD vaccine constructs, which may utilize mutant FMDV 3C proteases.

2B↗
NASA NTRS1997

Identification of defective illegitimate recombinational repair of oxidatively-induced DNA double-strand breaks in ataxia-telangiectasia cells

Ataxia-telangiectasia (A-T) is an autosomal-recessive lethal human disease. Homozygotes suffer from a number of neurological disorders, as well as very high cancer incidence. Heterozygotes may also have a higher than normal risk of cancer, particularly for the breast. The gene responsible for the disease (ATM) has been cloned, but its role in mechanisms of the disease remain unknown. Cellular A-T phenotypes, such as radiosensitivity and genomic instability, suggest that a deficiency in the repair of DNA double-strand breaks (DSBs) may be the primary defect; however, overall levels of DSB rejoining appear normal. We used the shuttle vector, pZ189, containing an oxidatively-induced DSB, to compare the integrity of DSB rejoining in one normal and two A-T fibroblast cells lines. Mutation frequencies were two-fold higher in A-T cells, and the mutational spectrum was different. The majority of the mutations found in all three cell lines were deletions (44-63%). The DNA sequence analysis indicated that 17 of the 17 plasmids with deletion mutations in normal cells occurred between short direct-repeat sequences (removing one of the repeats plus the intervening sequences), implicating illegitimate recombination in DSB rejoining. The combined data from both A-T cell lines showed that 21 of 24 deletions did not involve direct-repeats sequences, implicating a defect in the illegitimate recombination pathway. These findings suggest that the A-T gene product may either directly participate in illegitimate recombination or modulate the pathway. Regardless, this defect is likely to be important to a mechanistic understanding of this lethal disease.

Non-NASA Center↗
NASA NTRS2010

Equivalent Dipole Vector Analysis for Detecting Pulmonary Hypertension

Various 12-lead ECG criteria have been established to detect right ventricular hypertrophy as a marker of pulmonary hypertension (PH). While some criteria offer good specificity they lack sensitivity because of a low prevalence of positive findings in the PH population. We hypothesized that three-dimensional equivalent dipole (ED) model could serve as a better detection tool of PH. We enrolled: 1) 17 patients (12 female, 5 male, mean age 57 years, range 19-79 years) with echocardiographically detected PH (systolic pulmonary arterial pressure greater than 35 mmHg) and no significant left ventricular disease; and 2) 19 healthy controls (7 female, 12 male, mean age 44, range 31-53 years) with no known heart disease. In each subject we recorded a 5-minute high-resolution 12-lead conventional ECG and constructed principal signals using singular value decomposition. Assuming a standard thorax dimension of an adult person with homogenous and isotropic distribution of thorax conductance, we determined moving equivalent dipoles (ED), characterized by the 3D location in the thorax, dipolar strength and the spatial orientation, in time intervals of 5 ms. We used the sum of all ED vectors in the second half of the QRS complex to derive the amplitude of the right-sided ED vector (RV), if the orientation of ED was to the right side of the thorax, and in the first half the QRS to derive the amplitude of the left-sided vector (LV), if the orientation was leftward. Finally, the parameter RV/LV ratio was determined over an average of 256 complexes. The groups differed in age and gender to some extent. There was a non-significant trend toward higher RV in patients with PH (438 units 284) than in controls (280 plus or minus 140) (p = 0.066) but the overlap was such that RV alone was not a good predictor of PH. On the other hand, the RV/LV ratio was a better predictor of PH, with 11/17 (64.7%) of PH patients but only in 1/19 (5.3%) control subjects having RV/LV ratio greater than or equal to 0.70 (p less than 0.001). The use of ED for evaluating PH shows good specificity at a reasonable sensitivity. The results are limited due to the small study groups and differences in age and gender, but further investigations are warranted, including of ED's diagnostic accuracy for PH versus that of other proposed ECG and VCG criteria.

Harlander, Matevz↗
NASA NTRS1995

Satellite cell proliferation in adult skeletal muscle

Novel methods of retroviral-mediated gene transfer for the in vivo corporation and stable expression of eukaryotic or prokaryotic foreign genes in tissues of living animals is described. More specifically, methods of incorporating foreign genes into mitotically active cells are disclosed. The constitutive and stable expression of E. coli .beta.-galactosidase gene under the promoter control of the Moloney murine leukemia virus long terminal repeat is employed as a particularly preferred embodiment, by way of example, establishes the model upon which the incorporation of a foreign gene into a mitotically-active living eukaryotic tissue is based. Use of the described methods in therapeutic treatments for genetic diseases, such as those muscular degenerative diseases, is also presented. In muscle tissue, the described processes result in genetically-altered satellite cells which proliferate daughter myoblasts which preferentially fuse to form a single undamaged muscle fiber replacing damaged muscle tissue in a treated animal. The retroviral vector, by way of example, includes a dystrophin gene construct for use in treating muscular dystrophy. The present invention also comprises an experimental model utilizable in the study of the physiological regulation of skeletal muscle gene expression in intact animals.

Booth, Frank W.↗
NASA NTRS2015

Municipality Level Simulations of Dengue Fever Incidence in Puerto Rico Using Ground Based and Remotely Sensed Climate Data

Dengue fever (DF) is caused by a virus transmitted between humans and Aedes genus mosquitoes through blood feeding. In recent decades incidence of the disease has drastically increased in the tropical Americas, culminating with the Pan American outbreak in 2010 which resulted in 1.7 million reported cases. In Puerto Rico dengue is endemic, however, there is significant inter‐annual, intraannual, and spatial variability in case loads. Variability in climate and the environment, herd immunity and virus genetics, and demographic characteristics may all contribute to differing patterns of transmission both spatially and temporally. Knowledge of climate influences on dengue incidence could facilitate development of early warning systems allowing public health workers to implement appropriate transmission intervention strategies. In this study, we simulate dengue incidence in several municipalities in Puerto Rico using population and meteorological data derived from ground based stations and remote sensing instruments. This data was used to drive a process based model of vector population development and virus transmission. Model parameter values for container composition, vector characteristics, and incubation period were chosen by employing a Monte Carlo approach. Multiple simulations were performed for each municipality and the results were compared with reported dengue cases. The best performing simulations were retained and their parameter values and meteorological input were compared between years and municipalities. Parameter values varied by municipality and year illustrating the complexity and sensitivity of the disease system. Local characteristics including the natural and built environment impact transmission dynamics and produce varying responses to meteorological conditions.

Remote Sensing↗
NASA NTRS1992

Effect of antiorthostatic BedRest (BR) on GastroIntestinal Motility (GIM) of normal subjects

The combined effects of postural changes, fluid shifts and diuresis associated with the absence of the gravity vector may decrease gastrointestinal motility (GIM) during space flight. GIM can be estimated from the mouth to cecum transit time (MCTT) of orally administered lactulose (LAC); this test is used to assess changes in GIM in normal subjects and in patients with GI pathology and related disease conditions. Since bedrest (BR) mimics some of the physiological changes that occur during space flight, the effect of ten days of BR on GIM was evaluated from the MCTT of LAC. Methods: Subjects were 12 nonsmoking males between the ages of 35 and 50. After an 8-10 hour fast, subjects ingested Cephulac (registered) (20 g solution) with a low-fiber breakfast on four different days (45, 30, 25, and 20) before BR and on three separate days (4, 7, and 10) during BR. Breath-H2 concentrations were measured before and at 10 minute intervals for 4 hours after breakfast using a Quintron breathalyzer and MCTT was determined from these data. Results: MCTT ranged between 10 and 122 minutes during ambulation and 80 to 120 minutes during BR with means of 79 minutes and 122 minutes respectively. Conclusion: Mean MCTT during BR was 54 percent longer than during ambulation, suggesting that absorption and availability of orally administered medications and nutrients may be delayed or impaired as a result of decreased GIM during bedrest.

Putcha, L.↗
NASA NTRS2004

NASA Classroom Bioreactor

Exploration of space provides a compelling need for cell-based research into the basic mechanisms that underlie the profound changes that occur in terrestrial life that is transitioned to low gravity environments. Toward that end, NASA developed a rotating bioreactor in which cells are cultured while continuously suspended in a cylinder in which the culture medium rotates with the cylinder. The randomization of the gravity vector accomplished by the continuous rotation, in a low shear environment, provides an analog of microgravity. Because cultures grown in bioreactors develop structures and functions that are much closer to those exhibited by native tissue than can be achieved with traditional culture methods, bioreactors have contributed substantially to advancing research in the fields of cancer, diabetes, infectious disease modeling for vaccine production, drug efficacy, and tissue engineering. NASA has developed a Classroom Bioreactor (CB) that is built from parts that are easily obtained and assembled, user-friendly and versatile. It can be easily used in simple school settings to examine the effect cultures of seeds or cells. An educational brief provides assembly instructions and lesson plans that describes activities in science, math and technology that explore free fall, microgravity, orbits, bioreactors, structure-function relationships and the scientific method.

Scully, Robert↗
DOE OSTI2025

ARCH: Large-scale knowledge graph via aggregated narrative codified health records analysis

Objective: Electronic health record (EHR) systems contain a wealth of clinical data stored as both codified data and free-text narrative notes (NLP). The complexity of EHR presents challenges in feature representation, information extraction, and uncertainty quantification. Here, to address these challenges, we proposed an efficient Aggregated naRrative Codified Health (ARCH) records analysis to generate a large-scale knowledge graph (KG) for a comprehensive set of EHR codified and narrative features. Methods: Using data from 12.5 million Veterans Affairs patients, ARCH first derives embedding vectors and generates similarities along with associated p-values to measure the strength of relatedness between clinical features with statistical certainty quantification. Next, ARCH performs a sparse embedding regression to remove indirect linkage between features to build a sparse KG. Finally, ARCH was validated on various clinical tasks, including detecting known relationships between entity pairs, predicting drug side effects, disease phenotyping, as well as sub-typing Alzheimer’s disease patients. Results: ARCH produces high-quality clinical embeddings and KG for over 60,000 codified and narrative EHR concepts. The KG and embeddings are visualized in the R-shiny powered web-API.3 ARCH achieved high accuracy in detecting EHR concept relationships, with AUCs of 0.926 (codified) and 0.861 (NLP) for similar EHR concepts, and 0.810 (codified) and 0.843 (NLP) for related pairs. It detected drug side effects with a 0.723 AUC, which improved to 0.826 after fine-tuning. Using both codified and NLP features, the detection power increased significantly. Compared to other methods, ARCH has superior accuracy and enhances weakly supervised phenotyping algorithms’ performance. Notably, it successfully categorized Alzheimer’s patients into two subgroups with varying mortality rates. Conclusion: The proposed ARCH algorithm generates large-scale high-quality semantic representations and knowledge graph for both codified and NLP EHR features, useful for a wide range of predictive modeling tasks.

Electronic health records↗