Data assimilation refers to methods for updating the state vector (initial condition) of a complex spatiotemporal model (such as a numerical weather model) by combining new observations with one or ...more prior forecasts. We consider the potential feasibility of this approach for making short-term (60-day) forecasts of the growth and spread of a malignant brain cancer (glioblastoma multiforme) in individual patient cases, where the observations are synthetic magnetic resonance images of a hypothetical tumor.
We apply a modern state estimation algorithm (the Local Ensemble Transform Kalman Filter), previously developed for numerical weather prediction, to two different mathematical models of glioblastoma, taking into account likely errors in model parameters and measurement uncertainties in magnetic resonance imaging. The filter can accurately shadow the growth of a representative synthetic tumor for 360 days (six 60-day forecast/update cycles) in the presence of a moderate degree of systematic model error and measurement noise.
The mathematical methodology described here may prove useful for other modeling efforts in biology and oncology. An accurate forecast system for glioblastoma may prove useful in clinical settings for treatment planning and patient counseling.
This article was reviewed by Anthony Almudevar, Tomas Radivoyevitch, and Kristin Swanson (nominated by Georg Luebeck).
The core 1 β1-3-galactosyltransferase (T-synthase) transfers Gal from UDP-Gal to GalNAcα1-Ser/Thr (Tn antigen) to form the core 1 O-glycan Galβ1-3GalNAcα1-Ser/Thr (T antigen). The T antigen is a ...precursor for extended and branched O-glycans of largely unknown function. We found that wild-type mice expressed the NeuAcα2-3Galβ1-3GalNAcα1-Ser/Thr primarily in endothelial, hematopoietic, and epithelial cells during development. Gene-targeted mice lacking T-synthase instead expressed the nonsialylated Tn antigen in these cells and developed brain hemorrhage that was uniformly fatal by embryonic day 14. T-synthase-deficient brains formed a chaotic microvascular network with distorted capillary lumens and defective association of endothelial cells with pericytes and extracellular matrix. These data reveal an unexpected requirement for core 1-derived O-glycans during angiogenesis.
An increasing number of custodial grandparents are raising grandchildren, and intensive childcare is stressful with many negative personal, interpersonal, economic, and health implications. ...Grandparents' strengths, including resilience, positive caregiving appraisal, and social support should be considered in the face of parenting stress and adversity. Guided by the stress and resilience model, the current study investigated the associations of parenting stress and coping resources with life satisfaction and mental wellness among custodial grandparents (N = 76). Data were collected between December 2020 and April 2021, through collaborations with community-based agencies located in two metropolitan areas, which provide supportive services to custodial grandparents and their families. Findings showed that more parenting stress was associated with less life satisfaction and worse mental health, and that stress management boosted life satisfaction and mental wellness. Grandparents with more informal social support and social service utilization fared better than their counterparts with less social support and no experience of service use. The results of this study suggest that social work interventions should focus on improving stress management to cope with daily and caregiving stressors. Social workers can help with informal social support and formal social services utilization to address caregiving needs among custodial grandparents.
The Epigenomics database at the National Center for Biotechnology Information (NCBI) is a new resource that has been created to serve as a comprehensive public resource for whole-genome epigenetic ...data sets (www.ncbi.nlm.nih.gov/epigenomics). Epigenetics is the study of stable and heritable changes in gene expression that occur independently of the primary DNA sequence. Epigenetic mechanisms include post-translational modifications of histones, DNA methylation, chromatin conformation and non-coding RNAs. It has been observed that misregulation of epigenetic processes has been associated with human disease. We have constructed the new resource by selecting the subset of epigenetics-specific data from general-purpose archives, such as the Gene Expression Omnibus, and Sequence Read Archives, and then subjecting them to further review, annotation and reorganization. Raw data is processed and mapped to genomic coordinates to generate 'tracks' that are a visual representation of the data. These data tracks can be viewed using popular genome browsers or downloaded for local analysis. The Epigenomics resource also provides the user with a unique interface that allows for intuitive browsing and searching of data sets based on biological attributes. Currently, there are 69 studies, 337 samples and over 1100 data tracks from five well-studied species that are viewable and downloadable in Epigenomics.
Medication-assisted treatment (MAT) is a combination of behavioural therapy and medications to assist with recovery and has been administered to individuals with alcohol and opioid withdrawal ...symptoms. Military veterans seeking MAT could have barriers preventing them from receiving the care they desire. The present study sought to compare outcomes in individuals who received MAT or those who participated in self-help groups for opioid or alcohol use disorder. In addition, the present study sought to compare outcomes between veterans and non-military-connected individuals.
We used the 2015-2017 United States Treatment Episode Data Set Discharges data from the Substance Abuse and Mental Health Services Administration. The data set included 138 594 unique discharges. A multinomial logistic regression model was used to examine differences in substance use outcomes for veterans/non-veterans in MAT and a self-help group.
Fewer veterans (2.58%) than non-veterans (4.28%) reported usage of MAT. Fewer veterans (38.94%) than non-veterans (40.17%) reported signing up for a self-help group. Finally, those who participated in MAT
a self-help group had a better outcome (66.64%)-defined as no substance use at discharge-than those who only received MAT (43.02%) and those who did not participate in MAT or self-help groups (34.84%).
Recommendations for future research on MAT and implementation for the veteran population would benefit the literature base.
Eating disorders, such as anorexia nervosa and bulimia nervosa, are common and severe mental illnesses of unknown etiology. Recently, we identified a rare missense mutation in the transcription ...factor estrogen-related receptor alpha (ESRRA) that is associated with the development of eating disorders. However, little is known about ESRRA function in brain. Here, we report that Esrra is expressed in the mouse brain and demonstrate that Esrra levels are regulated by energy reserves. Esrra-null female mice display a reduced operant response to high fat diet, compulsivity/behavioral rigidity, and social deficits. Selective Esrra knockdown in the prefrontal and orbitofrontal cortices of adult female mice recapitulates reduced operant response and increased compulsivity, respectively. These results indicate that Esrra deficiency in the mouse brain impairs behavioral responses in multiple functional domains.
Circulating levels of the gut microbe-derived metabolite trimethylamine-N-oxide (TMAO) have recently been linked to cardiovascular disease (CVD) risk. Here, we performed transcriptional profiling in ...mouse models of altered reverse cholesterol transport (RCT) and serendipitously identified the TMAO-generating enzyme flavin monooxygenase 3 (FMO3) as a powerful modifier of cholesterol metabolism and RCT. Knockdown of FMO3 in cholesterol-fed mice alters biliary lipid secretion, blunts intestinal cholesterol absorption, and limits the production of hepatic oxysterols and cholesteryl esters. Furthermore, FMO3 knockdown stimulates basal and liver X receptor (LXR)-stimulated macrophage RCT, thereby improving cholesterol balance. Conversely, FMO3 knockdown exacerbates hepatic endoplasmic reticulum (ER) stress and inflammation in part by decreasing hepatic oxysterol levels and subsequent LXR activation. FMO3 is thus identified as a central integrator of hepatic cholesterol and triacylglycerol metabolism, inflammation, and ER stress. These studies suggest that the gut microbiota-driven TMA/FMO3/TMAO pathway is a key regulator of lipid metabolism and inflammation.
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•Unbiased transcriptional profiling links FMO3 to reverse cholesterol transport•FMO3 knockdown substantially impacts whole-body cholesterol balance•FMO3 is a negative regulator of nonbiliary reverse cholesterol transport•FMO3 knockdown results in diminished LXR activity, promoting hepatic inflammation
Reverse cholesterol transport (RCT) can be mediated by either the classic biliary route or the nonbiliary transintestinal cholesterol excretion (TICE) pathway. Warrier et al. now identify a gut microbial-driven pathway that balances the amount of cholesterol entering the biliary and nonbiliary pathways. Inhibition of the enzyme flavin monooxygenase 3 (FMO3) diverts cholesterol away from biliary excretion into the nonbiliary TICE pathway, reorganizing total body cholesterol balance.
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