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Trumble, B. C.

Publications and source records attributed to Trumble, B. C..

9 recordsLinked to original sources

Evaluating performance bias in face-to-BMI vision transformer models across diverse human populations

Computer vision models that estimate body mass index (BMI) from facial features offer a non-invasive, low-cost alternative to physical measurement, with uses in telemedicine, emergency care where a scale or measuring tools arent available, automated self-monitoring, and large-scale epidemiological research. Most of these models, however, are trained on government records, social media images, and celebrity photographs, sources that introduce dataset biases and fail to represent the general public. This study tests how well a face-to-BMI machine learning model generalizes across populations, specifically how morphological diversity and population-specific training data affect cross-cultural accuracy. We trained and evaluated Vision Transformer (ViT-H/14) models on paired BMI measurements and facial photographs from four Indigenous populations: the Orang Asli of Malaysia, the Ju/hoansi of Southern Africa, the Sama residing in the Philippines, and the Tsimane of Bolivia. To evaluate how training data composition affects predictions, we compared four training strategies, from single-population models (focal models) to models trained on the full combined global dataset (global models). In-distribution training always produced the best performance. Models exposed to a target populations morphology, whether focal or global, consistently predicted BMI most accurately for that population. But when a target population differed from the training sample, adding more cross-cultural variation to training improved out-of-distribution predictions. Therefore, training on a populations own data works best when that data exists, and training on data spanning a wide range of human morphology is the strongest fallback when it doesnt. These findings suggest that while target population training data produces the most accurate results, training on datasets that capture global morphological variation substantially improves performance in unrepresented populations. Broader diversity in training data is essential for developing machine learning health tools that generalize reliably across human populations.

bioinformatics↗

Inflammaging mediates testosterone declines in men while maintaining high testosterone increases mortality risk

Later life is accompanied by testosterone declines alongside the development of chronic inflammation, termed inflammaging. A new theoretical model posits these processes are related through an energetic trade-off. As somatic damage accumulates, this should chronically activate the energetically costly inflammatory response. As an energy conserving response to promote cellular repair, testosterone production is expected to be suppressed. Consistent with this model, we find that markers of inflammaging, including IL-6 and GDF-15, mediate age-related testosterone declines in a large sample of male participants from the UK Biobank (n = 18,347, mean age 57 years, range 40-70). GDF-15, a marker of chronic inflammation and a key metabolic stress signaling protein, was the strongest predictor and mediator of testosterone declines. Further, individuals with high testosterone given their health and level of inflammation showed elevated mortality risk over follow up, consistent with a trade-off between maintenance and reproduction. Our results highlight the importance of considering energetic trade-offs to understand later life testosterone declines. They also highlight the importance of alleviating cellular damage that augments inflammaging and its down-stream hormonal effects. Finally, our study raises concern for exogenous testosterone therapies in the context of chronic inflammation, which could increase mortality risk. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=103 SRC="FIGDIR/small/730222v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@19b673eorg.highwire.dtl.DTLVardef@19734feorg.highwire.dtl.DTLVardef@18149dorg.highwire.dtl.DTLVardef@f162f4_HPS_FORMAT_FIGEXP M_FIG C_FIG

evolutionary biology↗

Divergent Biological Consequences of APOE Isoforms Across Industrialized and Non-Industrial Environments

The apolipoprotein {varepsilon}4 (APOE {varepsilon}4) isoform directly alters cholesterol and immune biology and is associated with an increased risk of neurodegenerative and cardiometabolic disease in industrialized settings; nevertheless, APOE {varepsilon}4--which is ancestral in humans--has persisted over evolutionary time. One potential explanation is that the costs and benefits of APOE {varepsilon}4 were significantly different in the environments in which humans evolved compared to those we experience today. In support, previous work has suggested that living in a high pathogen environment, engaging in high levels of physical activity, or eating a low fat diet can dampen the detrimental effects of APOE {varepsilon}4, and has revealed positive effects for fertility. However, direct tests of whether APOE isoforms are associated with different biological outcomes in non-industrial versus industrialized contexts are lacking. Working with the Turkana of Kenya and the Orang Asli of Peninsular Malaysia--two Indigenous groups in which individuals of shared ancestry span a continuum of subsistence, non-industrial to urban, industrialized lifestyles--we investigated how APOE genotypes impact cholesterol, immunological, and reproductive traits and tested for genotype x environment (GxE) interactions. First, we confirmed established genotype effects across lifestyles, showing that more APOE {varepsilon}4 alleles are associated with higher total cholesterol, higher LDL cholesterol, and lower HDL cholesterol. Second, we tested for lifestyle interactions, finding lifestyle-dependent effects of genotype on innate immune biomarkers in the Orang Asli but not Turkana. Finally, we show that more APOE {varepsilon}4 alleles are correlated with an extended reproductive lifespan, however this effect is relatively weak, is not consistent across populations, and does not correspond with a higher reproductive output. Together, our study provides evidence that industrialized environments can modify the biology of APOE {varepsilon}4; however, we find that APOE {varepsilon}4 is not universally beneficial in non-industrial contexts, highlighting the role of local environmental variation in determining its specific costs and benefits.

evolutionary biology↗

Maternal glucocorticoids and behavior shape offspring developmental trade-offs in wild baboons

Mammalian mothers provide behavioral and physiological signals that offspring use to calibrate development in relation to maternal resources and environmental cues. Infants respond selectively as they prioritize certain developmental systems over others, creating developmental tradeoffs between competing biological systems. Here, we investigate the influence of maternal capital ("investment capacity") on the growth and development of their infants in wild olive baboons (Papio anubis) from Laikipia, Kenya. We posit that maternal capital is influenced by a mothers own early life experiences (e.g., drought, maternal loss) and her current life experiences (e.g., dominance rank, food availability), and is signaled to offspring via maternal effort (i.e., nursing and carrying time) and glucocorticoids. We used behavioral data on 40 infants (43% female) in the first year of life to quantify maternal effort, infant play, and infant independence (i.e., frequency of infant departures from mother). We matched these behavioral data with maternal fecal glucocorticoid measures from lactating mothers, and infant growth measures assessed via photogrammetry. Signals of low maternal capital predicted lower rates of infant play, less behavioral independence, and slower growth. There was a negative relationship between the rate of social contact play and growth rate, indicating a developmental tradeoff. Males were more sensitive than females to some of the maternal signals measured in our study. These results add to a growing body of evidence demonstrating that maternal behavioral and physiological signals shape infant development.

animal behavior and cognition↗

Evidence for an energetic trade-off model linking inflammaging and immunosenescence in the US Health and Retirement Study and UK Biobank

Later life is characterized by the development of chronic inflammation, termed inflammaging, alongside changes in immune cell profiles, or immunosenescence. While these features contribute to health risk, they have also been interpreted as adaptive remodeling of the immune system in response to accumulating somatic damage. Here we consider a recently developed theoretical framework to understand these processes as interrelated: the Brain-Body Energy Conservation model of aging. This model views functional declines, such as immunosenescence, as part of an energy conserving response to the rising energy expenditure of inflammaging. This response promotes short term survival against somatic damage at the expense of future health risk. For example, naive T cells, which enhance defense against future infections, decline with age. We find evidence consistent with this model in the US Health and Retirement Study (HRS) and UK Biobank (UKB). TNFR1, a key marker of inflammaging, mediated 10% and 5% of the age-related declines in naive CD4T and CD8T cells respectively in the HRS (n = 8,261). Consistent with an impaired immune response to future infections, TNFR1 also mediated 16% of the age-related increased risk of hospitalization or death from COVID-19 in the UKB (n = 522 hospitalized or died, full sample n = 40,638). GDF15, which is produced in response to metabolic stress and has been found to induce immune tolerance in response to chronic inflammation, mediated 28% of the TNFR1-related COVID-19 health risk, as well as 38% of the age-related increased risk independent of TNFR1.

evolutionary biology↗

Prehistoric Global Migration of Vanishing Gut Microbes With Humans

The gut microbiome is crucial for health and greatly affected by lifestyle. Many microbes common in non-industrialized populations are disappearing or extinct in industrialized populations. Understanding which microbes have been long-term residents of the human gut, and may have co-evolved with humans, has implications for the importance of microbial biodiversity loss for health. However, the genetic complexities of microbial evolution and the plasticity of gut microbiome composition have made it challenging to define these long-term associations. Here, we performed deep metagenomic sequencing of the Tsimane horticulturalists of Bolivia and compared their gut microbiomes with the Hadza hunter-gatherers of Tanzania. These two populations, whose ancestors were separated for tens of thousands of years, share 1,231 microbial species, most of which are absent in industrialized populations. Population genetic analyses in 636 of these shared species revealed patterns of microbial divergence and gene flow consistent with prehistoric human co-migration, with estimated split times that approximately align with human migration out of Africa and into the Americas. Our findings indicate that a diverse gut microbiome co-migrated with humans around the globe, persisting over millennia. However, many of these species are now vanishing in industrialized populations, and the consequences for human health remain uncertain.

microbiology↗

Cost-effective solutions for high-throughput enzymatic DNA methylation sequencing

Characterizing DNA methylation patterns is important for addressing key questions in evolutionary biology, geroscience, and medical genomics. While costs are decreasing, whole-genome DNA methylation profiling remains prohibitively expensive for most population-scale studies, creating a need for cost-effective, reduced representation approaches (i.e., assays that rely on microarrays, enzyme digests, or sequence capture to target a subset of the genome). Most common whole genome and reduced representation techniques rely on bisulfite conversion, which can damage DNA resulting in DNA loss and sequencing biases. Enzymatic methyl sequencing (EM-seq) was recently proposed to overcome these issues, but thorough benchmarking of EM-seq combined with cost-effective, reduced representation strategies has not yet been performed. To do so, we optimized Targeted Methylation Sequencing protocol (TMS)--which profiles [~]4 million CpG sites--for miniaturization, flexibility, and multispecies use at a cost of [~]$80. First, we tested modifications to increase throughput and reduce cost, including increasing multiplexing, decreasing DNA input, and using enzymatic rather than mechanical fragmentation to prepare DNA. Second, we compared our optimized TMS protocol to commonly used techniques, specifically the Infinium MethylationEPIC BeadChip (n=55 paired samples) and whole genome bisulfite sequencing (n=6 paired samples). In both cases, we found strong agreement between technologies (R{superscript 2} = 0.97 and 0.99, respectively). Third, we tested the optimized TMS protocol in three non-human primate species (rhesus macaques, geladas, and capuchins). We captured a high percentage (mean=77.1%) of targeted CpG sites and produced methylation level estimates that agreed with those generated from reduced representation bisulfite sequencing (R{superscript 2} = 0.98). Finally, we applied our protocol to profile age-associated DNA methylation variation in two subsistence-level populations--the Tsimane of lowland Bolivia and the Orang Asli of Peninsular Malaysia--and found age-methylation patterns that were strikingly similar to those reported in high income cohorts, despite known differences in age-health relationships between lifestyle contexts. Altogether, our optimized TMS protocol will enable cost-effective, population-scale studies of genome-wide DNA methylation levels across human and non-human primate species.

genomics↗

Helminth infection is associated with dampened cytokine responses to viral and bacterial stimulations in Tsimane hunter-horticulturalists.

BackgroundSoil-transmitted helminth (STH) infections can catalyze immunological changes that affect the response to subsequent infections, particularly those that elicit strong inflammatory responses. As globalization heightens the risk that remote communities with high STH prevalence will encounter novel pathogens, understanding how STHs shape immune responses to these downstream infections becomes increasingly crucial. MethodologyWe worked with Tsimane forager-horticulturalists in the Bolivian Amazon, where STHs are prevalent. We tested whether STHs and eosinophil levels--most likely indicative of infection in this population--are associated with dampened immune responses to in vitro stimulation with H1N1 and lipopolysaccharide (LPS) antigens. Whole blood samples (n = 179) were treated with H1N1 vaccine and LPS and assayed for 13 cytokines (interferon gamma [INF-{gamma}], interleukin [IL]-1{beta}, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, Granulocyte-macrophage colony-stimulating factor [GM-CSF], and Tumor necrosis factor-alpha [TNF-]). We evaluated how STHs and eosinophil levels affected cytokine responses and T helper (Th) 1 and Th2-cytokine suite responses to stimulation. ResultsInfection with Ascaris lumbricoides was significantly (p [≤] 0.05) associated with lower response of some cytokines to H1N1 and LPS in women. Eosinophils were significantly negatively associated with some cytokine responses to H1N1 and LPS, with the strongest effects in women, and associated with a reduced Th1- and Th2-cytokine response to H1N1 and LPS in women and men. Conclusions and implicationsWe find that STHs were associated with dampened cytokine responses to certain viral and bacterial antigens, and suggest that this mitigation of host-induced damage may reduce the incidence of cytokine storms in populations with high STH prevalence.

immunology↗

Effects of early life adversity on maternal effort and glucocorticoids in wild olive baboons

Adverse experiences during early life exert important effects on development, health, reproduction, and social bonds, with consequences often persisting across generations. A mothers early life experiences can impact her offsprings development through a number of pathways, such as maternal care, physiological signaling through glucocorticoids, or even intergenerational effects like epigenetic inheritance. Early life adversity in female yellow baboons (Papio cynocephalus) predicts elevated glucocorticoids, reduced sociality, shortened lifespan, and higher offspring mortality. If baboon mothers with more early life adversity, experience poorer condition and struggle to provide for their offspring, this could contribute to the persisting transgenerational effects of adversity. Here, we examined the effects of mothers early life adversity on their maternal effort, physiology, and offspring survivability in a population of olive baboons, Papio anubis. Mothers who experienced more adversity in their own early development exerted greater maternal effort (i.e., spent more time nursing and carrying) and had higher glucocorticoid metabolites than mothers with less early life adversity. Offspring of mothers with more early life adversity had reduced survivability compared to offspring of mothers with less early life adversity. There was no evidence that high maternal social rank buffered against the effects of early life adversity. Our data suggest early life experiences can have lasting consequences on maternal effort and physiology, which may function as proximate mechanisms for intergenerational effects of maternal experience.

zoology↗