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At least 199 records · Page 11
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium

Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18–72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18–73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.55 years (95% CI: 2.91, 4.19; I 2 = 57.53%) compared to controls, after adjusting for age, sex and site (Cohen’s d = 0.48). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Association of post-COVID phenotypic manifestations with new-onset psychiatric disease

Acute COVID-19 infection can be followed by diverse clinical manifestations referred to as Post Acute Sequelae of SARS-CoV2 Infection (PASC). Studies have shown an increased risk of being diagnosed with new-onset psychiatric disease following a diagnosis of acute COVID-19. However, it was unclear whether non-psychiatric PASC-associated manifestations (PASC-AMs) are associated with an increased risk of new-onset psychiatric disease following COVID-19. A retrospective electronic health record (EHR) cohort study of 2,391,006 individuals with acute COVID-19 was performed to evaluate whether non-psychiatric PASC-AMs are associated with new-onset psychiatric disease. Data were obtained from the National COVID Cohort Collaborative (N3C), which has EHR data from 76 clinical organizations. EHR codes were mapped to 151 non-psychiatric PASC-AMs recorded 28–120 days following SARS-CoV-2 diagnosis and before diagnosis of new-onset psychiatric disease. Association of newly diagnosed psychiatric disease with age, sex, race, pre-existing comorbidities, and PASC-AMs in seven categories was assessed by logistic regression. There were significant associations between a diagnosis of any psychiatric disease and five categories of PASC-AMs with odds ratios highest for neurological, cardiovascular, and constitutional PASC-AMs with odds ratios of 1.31, 1.29, and 1.23 respectively. Secondary analysis revealed that the proportions of 50 individual clinical features significantly differed between patients diagnosed with different psychiatric diseases. Our study provides evidence for association between non-psychiatric PASC-AMs and the incidence of newly diagnosed psychiatric disease. Significant associations were found for features related to multiple organ systems. This information could prove useful in understanding risk stratification for new-onset psychiatric disease following COVID-19. Prospective studies are needed to corroborate these findings.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Multidrug-resistant Shigella flexneri outbreak affecting humans and non-human primates in New Mexico, USA

Shigellosis is a gastrointestinal infection caused by species of Shigella . A large outbreak of Shigella flexneri serotype 2a occurred in Albuquerque, New Mexico between May 2021 and November 2023 that involved humans and non-human primates (NHP) from a local zoo. We analyzed the genomes of 202 New Mexican isolates as well as 15 closely related isolates from other states, and four from NHP. The outbreak was initially detected within men who have sex with men but then predominantly affected people experiencing homelessness. Nearly 70% of cases were hospitalized and there was one human death. The outbreak extended into Albuquerque’s BioPark Zoo, causing high morbidity and six deaths in NHPs. All isolates were multidrug-resistant, including towards fluoroquinolones, a first line treatment option which led to treatment failures in human and NHP populations. We show the circulation of the same S. flexneri strain in humans and NHPs, causing fatalities in both populations. This study demonstrates the threat of antimicrobial resistant organisms to vulnerable human and NHP populations and emphasizes the value of genomic surveillance within a One Health framework.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

The impact of bilateral injuries on the pathophysiology and functional outcomes of volumetric muscle loss

Volumetric muscle loss (VML)—defined as the irrecoverable loss of skeletal muscle tissue with associated persistent functional deficits—is among the most common and highly debilitating combat-related extremity injuries. This is particularly true in cases of severe polytrauma wherein multiple extremities may be involved as a result of high energy wounding mechanisms. As such, significant investment and effort has been made toward developing a clinically viable intervention capable of restoring the form and function of the affected musculature. While these investigations conducted to date have varied with respect to the species, breed, and sex of the chosen pre-clinical in-vivo model system, the majority of these studies have been performed in unilateral injury models, an aspect which may not fully exemplify the clinical representation of the multiply injured patient. Furthermore, while various components of the basal pathophysiology of VML (e.g., fibrosis and inflammation) have been investigated, relatively little effort has focused on how the pathophysiology and efficacy of pro-regenerative technologies is altered when there are multiple VML injuries. Thus, the purpose of this study was two-fold: (1) to investigate if/how the pathophysiology of unilateral VML injuries differs from bilateral VML injuries and (2) to interrogate the effect of bilateral VML injuries on the efficacy of a well-characterized regenerative therapy, minced muscle autograft (MMG). In contrast to our hypothesis, we show that bilateral VML injuries exhibit a similar systemic inflammatory response and improved muscle functional recovery, compared to unilateral injured animals. Furthermore, MMG treatment was found to only be effective at promoting an increase in functional outcomes in unilateral VML injuries. The findings presented herein add to the growing knowledge base of the pathophysiology of VML, and, importantly, reiterate the importance of comprehensively characterizing preclinical models which are utilized for early-stage screening of putative therapies as they can directly influence the translational research pipeline.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Temporal dynamics of the multi-omic response to endurance exercise training

Regular exercise promotes whole-body health and prevents disease, but the underlying molecular mechanisms are incompletely understood. Here, the Molecular Transducers of Physical Activity Consortium profiled the temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome and immunome in whole blood, plasma and 18 solid tissues in male and female Rattus norvegicus over eight weeks of endurance exercise training. The resulting data compendium encompasses 9,466 assays across 19 tissues, 25 molecular platforms and 4 training time points. Thousands of shared and tissue-specific molecular alterations were identified, with sex differences found in multiple tissues. Temporal multi-omic and multi-tissue analyses revealed expansive biological insights into the adaptive responses to endurance training, including widespread regulation of immune, metabolic, stress response and mitochondrial pathways. Many changes were relevant to human health, including non-alcoholic fatty liver disease, inflammatory bowel disease, cardiovascular health and tissue injury and recovery. The data and analyses presented in this study will serve as valuable resources for understanding and exploring the multi-tissue molecular effects of endurance training and are provided in a public repository (https://motrpac-data.org/).

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Genome-scale metabolic reconstruction of 7,302 human microorganisms for personalized medicine

The human microbiome influences the efficacy and safety of a wide variety of commonly prescribed drugs. Designing precision medicine approaches that incorporate microbial metabolism would require strain- and molecule-resolved, scalable computational modeling. Here, we extend our previous resource of genome-scale metabolic reconstructions of human gut microorganisms with a greatly expanded version. AGORA2 (assembly of gut organisms through reconstruction and analysis, version 2) accounts for 7,302 strains, includes strain-resolved drug degradation and biotransformation capabilities for 98 drugs, and was extensively curated based on comparative genomics and literature searches. The microbial reconstructions performed very well against three independently assembled experimental datasets with an accuracy of 0.72 to 0.84, surpassing other reconstruction resources and predicted known microbial drug transformations with an accuracy of 0.81. We demonstrate that AGORA2 enables personalized, strain-resolved modeling by predicting the drug conversion potential of the gut microbiomes from 616 patients with colorectal cancer and controls, which greatly varied between individuals and correlated with age, sex, body mass index and disease stages. AGORA2 serves as a knowledge base for the human microbiome and paves the way to personalized, predictive analysis of host–microbiome metabolic interactions.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Heterogeneous estimations of non-pharmaceutical mitigation behavior during the COVID-19 pandemic

The COVID-19 pandemic highlighted the importance of human behavior in mitigating the spread of disease. Nonetheless, human behavior is often overlooked in models of disease spread, particularly by underutilizing real-world data. We address this by estimating probabilities that individuals engage in behaviors that influence SARS-CoV-2 transmission risk during the COVID-19 pandemic, between September 2020 and June 2022. These behaviors include wearing a mask, using public transportation, spending time with others, avoiding contact with others, and going to work. Our estimates account for the age and sex of individuals and are generated for every county in the United States. We utilized multiple open-source datasets and United States Census data to produce these estimates. Multiple datasets were used for validation, showing our estimates demonstrated comparable accuracy and robustness. Our estimates aid in understanding human behavior dynamics during the COVID-19 pandemic and could be used to inform monthly or longer-term behavior in simulations of COVID-19. Moreover, the methods presented can be applied to other behaviors and features for future simulations of infectious disease.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2020

Quantile-specific heritability of sibling leptin concentrations and its implications for gene-environment interactions

“Quantile-dependent expressivity” occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g., leptin) is high or low relative to its distribution. Leptin concentrations are strongly related to adiposity, whose heritability is quantile dependent. Whether inheritance of leptin concentrations is quantile dependent, and whether this explains the greater heritability in women than men in accordance with their greater adiposity, and explains other gene-environment interactions, remains to be determined. Therefore, leptin and leptin receptor concentrations from 3068 siblings in 1133 sibships from the Framingham Heart Study Third Generation Cohort were analyzed. Free leptin index (FLI) was calculated as the ratio of leptin to soluble leptin receptor concentrations. Full-sib (β FS ) regression slopes were robustly estimated by quantile regression with nonparametric significance assigned from 1000 bootstrap samples. The analyses showed β FS increased significantly with increasing percentiles of the offspring’s age- and sex-adjusted leptin distribution (P linear = 0.0001), which was accelerated at the higher concentrations (P quadratic = 0.0003). β FS at the 90th percentile (0.418 ± 0.066) was 4.7-fold greater than at the 10th percentile (0.089 ± 0.032, P difference = 3.6 × 10 –6 ). Consistent with quantile-dependent expressivity, the β FS was greater in female sibs, which was attributable to their higher leptin concentrations. Reported gene-environment interactions involving adiposity and LEP , LEPR , MnSOD , PPARγ , PPARγ2 , and IRS-1 polymorphisms were consistent with quantile-dependent expressivity of leptin concentrations. β FS for leptin receptor concentrations and free leptin index also increased significantly with increasing percentiles of their distributions (P linear = 0.04 and P linear = 8.5 × 10 –6 , respectively). In conclusion, inherited genetic and shared environmental effects on leptin concentrations were quantile dependent, which likely explains male–female differences in heritability and some gene-environment interactions.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Behavioral state resource selection in invasive wild pigs in the Southeastern United States

Elucidating correlations between wild pig ( Sus scrofa ) behavior and landscape attributes can aid in the advancement of management strategies for controlling populations. Using GPS data from 49 wild pigs in the southeastern U.S., we used hidden Markov models to define movement path characteristics and assign behaviors (e.g., resting, foraging, travelling). We then explored the connection between these behaviors and resource selection for both sexes between two distinct seasons based on forage availability (i.e., low forage, high forage). Females demonstrated a crepuscular activity pattern in the high-forage season and a variable pattern in the low-forage season, while males exhibited nocturnal activity patterns across both seasons. Wild pigs selected for bottomland hardwoods and dense canopy cover in all behavioral states in both seasons. Males selected for diversity in vegetation types while foraging in the low-forage season compared to the high-forage season and demonstrated an increased use of linear anthropogenic features across seasons while traveling. Wild pigs can establish populations and home ranges in an array of landscapes, but our results demonstrate male and female pigs exhibit clear differences in movement behavior and there are key resources associated with common behaviors that can be targeted to improve the efficiency of management programs.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2022

Effects of vessel traffic and ocean noise on gray whale stress hormones

Human use of marinescapes is rapidly increasing, especially in populated nearshore regions where recreational vessel traffic can be dense. Marine animals can have a physiological response to such elevated human activity that can impact individual health and population dynamics. To understand the physiological impacts of vessel traffic on baleen whales, we investigated the adrenal stress response of gray whales (Eschrichtius robustus) to variable vessel traffic levels through an assessment of fecal glucocorticoid metabolite (fGC) concentrations. This analysis was conducted at the individual level, at multiple temporal scales (1–7 days), and accounted for factors that may confound fGC: sex, age, nutritional status, and reproductive state. Data were collected in Oregon, USA, from June to October of 2016–2018. Results indicate significant correlations between fGC, month, and vessel counts from the day prior to fecal sample collection. Furthermore, we show a significant positive correlation between vessel traffic and underwater ambient noise levels, which indicates that noise produced by vessel traffic may be a causal factor for the increased fGC. This study increases knowledge of gray whale physiological response to vessel traffic and may inform management decisions regarding regulations of vessel traffic activities and thresholds near critical whale habitats.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

DNA metabarcoding reveals consumption of diverse community of amphibians by invasive wild pigs (Sus scrofa) in the southeastern United States

Abstract Invasive wild pigs ( Sus scrofa ) are one of the most widespread, destructive vertebrate species globally. Their success can largely be attributed to their generalist diets, which are dominated by plant material but also include diverse animal taxa. Wild pigs are demonstrated nest predators of ground-nesting birds and reptiles, and likely pose a threat to amphibians given their extensive overlap in wetland use. DNA metabarcoding of fecal samples from 222 adult wild pigs culled monthly from 2017 to 2018 revealed a diverse diet dominated by plant material, with 166 plant genera from 56 families and 18 vertebrate species identified. Diet composition varied seasonally with availability for plants and was consistent between sexes. Amphibians were the most frequent vertebrate group consumed and represented the majority of vertebrate species detected, suggesting amphibians are potentially vulnerable to predation by wild pigs in our study region. Mammal, reptile, and bird species were also detected in pig diets, but infrequently. Our results highlight the need for research on the impacts of wild pigs on amphibians to better inform management and conservation of imperiled species.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

High dimensional predictions of suicide risk in 4.2 million US Veterans using ensemble transfer learning

We present an ensemble transfer learning method to predict suicide from Veterans Affairs (VA) electronic medical records (EMR). A diverse set of base models was trained to predict a binary outcome constructed from reported suicide, suicide attempt, and overdose diagnoses with varying choices of study design and prediction methodology. Each model used twenty cross-sectional and 190 longitudinal variables observed in eight time intervals covering 7.5 years prior to the time of prediction. Ensembles of seven base models were created and fine-tuned with ten variables expected to change with study design and outcome definition in order to predict suicide and combined outcome in a prospective cohort. The ensemble models achieved c-statistics of 0.73 on 2-year suicide risk and 0.83 on the combined outcome when predicting on a prospective cohort of ~4.2 M veterans. The ensembles rely on nonlinear base models trained using a matched retrospective nested case-control (Rcc) study cohort and show good calibration across a diversity of subgroups, including risk strata, age, sex, race, and level of healthcare utilization. In addition, a linear Rcc base model provided a rich set of biological predictors, including indicators of suicide, substance use disorder, mental health diagnoses and treatments, hypoxia and vascular damage, and demographics. Similar content being viewed by others

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

An integrated host-microbiome response to atrazine exposure mediates toxicity in Drosophila

Abstract The gut microbiome produces vitamins, nutrients, and neurotransmitters, and helps to modulate the host immune system—and also plays a major role in the metabolism of many exogenous compounds, including drugs and chemical toxicants. However, the extent to which specific microbial species or communities modulate hazard upon exposure to chemicals remains largely opaque. Focusing on the effects of collateral dietary exposure to the widely used herbicide atrazine, we applied integrated omics and phenotypic screening to assess the role of the gut microbiome in modulating host resilience in Drosophila melanogaster . Transcriptional and metabolic responses to these compounds are sex-specific and depend strongly on the presence of the commensal microbiome. Sequencing the genomes of all abundant microbes in the fly gut revealed an enzymatic pathway responsible for atrazine detoxification unique to Acetobacter tropicalis . We find that Acetobacter tropicalis alone, in gnotobiotic animals, is sufficient to rescue increased atrazine toxicity to wild-type, conventionally reared levels. This work points toward the derivation of biotic strategies to improve host resilience to environmental chemical exposures, and illustrates the power of integrative omics to identify pathways responsible for adverse health outcomes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

A clearer picture of who lives in the world’s cities

A new city-level dataset examines how urban population structures have changed worldwide between 2000 and 2020. Here, the work reveals divergent age distributions, sex ratios and migration patterns across more than 10,000 cities, and it provides evidence for locally tailored urban planning.

Zimmer, Andrew [Oak Ridge National Laboratory (ORN↗
DOE OSTI2023

Prevalence of Self-Reported Bothersome Tinnitus in U.S. Army Soldiers From January 1, 2015, Through September 30, 2019

Purpose: Tinnitus is a symptom of auditory dysfunction or injury and can be a precursor to permanent hearing loss. Tinnitus can interfere with communication, sleep, concentration, and mood; when this occurs, it is referred to as bothersome tinnitus. Annual hearing surveillance in the U.S. Army includes screening for bothersome tinnitus. Estimating the prevalence of self-reported bothersome tinnitus can facilitate prioritization of prevention and education efforts. The objective of this study was to examine Army hearing conservation data to estimate the prevalence of self-reported bothersome tinnitus as a function of age, hearing, sex, service component, and pay grade. Method: The study employed a cross-sectional, retrospective design. Records from 1,485,059 U.S. Army Soldiers retrieved from the Defense Occupational and Environmental Health Readiness System–Hearing Conservation were analyzed. Descriptive statistics and multinomial logistic regression analysis were used to estimate the prevalence of bothersome tinnitus and its associations with Soldiers' demographic characteristics. Results: The estimated prevalence of self-reported bothersome tinnitus was 17.1% between January 1, 2015, and September 30, 2019; 13.6% of the Soldiers reported “bothered a little” and 3.5% reported “bothered a lot.” Proportionally, the prevalence of self-reported bothersome tinnitus was higher for males, older Soldiers, and Reserve Component Soldiers. For every 1-year increase in age, the odds of self-reporting “bothered a little” tinnitus relative to “bothered not at all tinnitus” would be expected to increase by 2.2% (2.1%, 2.3%), and the odds of self-reporting “bothered a lot” tinnitus relative to “bothered not at all” tinnitus would be expected to increase by 3.6% (3.5%, 3.7%). Conclusions: The self-reported prevalence of bothersome tinnitus in the U.S. Army (17.1%) is substantially higher than that of the general population, where prevalence of bothersome tinnitus is estimated at 6.6%. Examination of bothersome tinnitus among Soldiers is an important step toward optimizing prevention, education, and intervention efforts.

Audiology & Speech-Language Pathology↗
DOE OSTI2020

A population of free-living highland wild dogs in Indonesian Papua

A 10-day rapid assessment has confirmed a small population of indigenous wild-living dogs in the highlands of Papua Province, Indonesia. The goal of the assessment was to observe, census, assess health and reproductive status, and collect biological samples or other data for this understudied canid. Trail cameras and DNA hair traps were deployed and baited with scent attractants, and game calls were used to elicit vocal responses or lure the dogs within observation range. Adults and pups of both sexes as well as a den were documented in 149 photographs. DNA testing of scat samples confirmed a canid origin with a close relationship to other oceanic canids including NGSD (New Guinea Singing Dog) and dingoes.

Zoology↗
DOE OSTI2020

Relationship of estrogen synthesis capacity in the brain with obesity and self-control in men and women

Significance Obesity is a major public health problem in a growing proportion of children and adults in the developed world. Estrogen influences body weight and behavioral responses to appetitive stimuli. Estrogen biosynthesis is catalyzed by the enzyme aromatase in all organs measured, including the brain. Using the aromatase radiotracer [ 11 C]vorozole, we measured aromatase availability in the amygdala in healthy-weight to obese adults. Obesity was associated with lower aromatase availability and less constraint independent of sex and age. Variability in brain estrogen synthesis may contribute to obesity by directly regulating feeding and broadly by affecting self-control. These findings suggest that brain aromatase imaging offers a method for characterizing the role of brain estrogen in obesity and other impairments in self-regulation.

Biegon, Anat↗
DOE OSTI2023

Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Left–right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case–control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case–control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case–control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case–control status. Subtle case–control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.

60 APPLIED LIFE SCIENCES↗