Biology subjects

Santos, A.

Publications and source records attributed to Santos, A..

At least 55 records · Page 3Linked to original sources

bioRxiv2022

Multimodal spatiotemporal phenotyping of human organoid development

Organoids generated from human pluripotent stem cells (PSCs) provide experimental systems to study development and disease. However, we lack quantitative spatiotemporal descriptions of organoid development that incorporate measurements across different molecular modalities. Here we focus on the retina and use a single-cell multimodal approach to reconstruct human retinal organoid development. We establish an experimental and computational pipeline to generate multiplexed spatial protein maps over a retinal organoid time course and primary adult human retina, registering protein expression features at the population, cellular, and subcellular levels. We develop an analytical toolkit to segment nuclei, identify local and global tissue units, infer morphology trajectories, and analyze cell neighborhoods from multiplexed imaging data. We use this toolkit to visualize progenitor and neuron location, the spatial arrangements of extracellular and subcellular components, and global patterning in each organoid and primary tissue. In addition, we generate a single-cell transcriptome and chromatin accessibility time course dataset and infer a gene regulatory network underlying organoid development. We then integrate genomic data with spatially segmented nuclei into a multi-modal atlas enabling virtual exploration of retinal organoid development. We visualize molecular, cellular, and regulatory dynamics during organoid lamination, and identify regulons associated with neuronal differentiation and maintenance. We use the integrated atlas to explore retinal ganglion cell (RGC) spatial neighborhoods, highlighting pathways involved in RGC cell death. Finally, we show that mosaic CRISPR/Cas genetic perturbations in retinal organoids provide insight into cell fate regulation. Altogether, our work is a major advance toward a virtual human retinal organoid, and provides new directions for how to approach disorders of the visual system. More broadly, our approaches can be adapted to many organoid systems.

systems biology↗

bioRxiv2022

The Brazilian population of Fusarium oxysporum f. sp. cubense is not structured by VCG or by geographic origin

Fusarium wilt, caused by the soil-borne fungus Fusarium oxysporum f. sp. cubense (Foc), is considered one of the most destructive diseases of bananas. Paradoxically, knowledge of the genetics of the pathogen population in the Americas is very limited. In this study, a collection of 178 monosporic isolates from several banana producing regions, located in different climatic zones along a South to North transect in Brazil, was formed to assess the genetic structure of the population of Foc. The isolates underwent pathogenicity tests, PCR diagnosis for the detection of Tropical race 4 and screening to SIX homologs. The VCG of 119 isolates was determined by pairing against 17 testers. A group of 158 isolates was selected for microsatellite genotyping. There was moderate diversity of Foc in Brazil. Eight VCGs were identified: 0120, 0122, 0124, 0125, 0128, 01215, 01220, and 01222, of which 78% of isolates belong to a single VCG, while 22% of isolates belong to complexes of VCGs. The distribution of VCGs is uneven and independent of the banana genotype. VCGs were correlated with homologs of the SIX genes and varied according to geographic regions. Four SSR loci were polymorphic and on average 7.5 alleles were detected per locus. Thirty-five multilocus genotypes (MLGs) were identified. There was no association between VCG and MLGs and no genetic structure of the population of Foc in Brazil was detected.

microbiology↗

bioRxiv2022

Dynamic human liver proteome atlas reveals functional insights into disease pathways

Deeper understanding of liver pathophysiology would benefit from a comprehensive quantitative proteome resource at cell-type resolution to predict outcome and design therapy. Here, we quantify more than 150,000 sequence-unique peptides aggregated into 10,000 proteins across total liver, the major liver cell types, time-course of primary cell cultures and liver disease states. Bioinformatic analysis reveals that half of hepatocyte protein mass is comprised of enzymes and 23% of mitochondrial proteins, twice the proportion of other liver cell types. Using primary cell cultures, we capture dynamic proteome remodeling from tissue states to cell line states, providing useful information for biological or pharmaceutical research. Our extensive data serves as spectral library to characterize a human cohort of non-alcoholic steatohepatitis and cirrhosis. Dramatic proteome changes in liver tissue include signatures of stellate cell activation resembling liver cirrhosis and providing functional insights. We built a web-based dashboard application for the interactively exploration of our resource. HighlightsO_LICell-type resolved liver proteome with copy numbers for 10,500 proteins C_LIO_LITime-course of human liver primary cells uncovers functional proteome shifts C_LIO_LIA human cohort study reveals liver proteome changes in NASH and cirrhosis C_LIO_LIAn interactive web portal integrates the results for easy exploration C_LI

systems biology↗

bioRxiv2021

daf-16/FOXO blocks adult cell fate in Caenorhabditis elegans dauer larvae via lin-41/TRIM71

Many tissue-specific stem cells maintain the ability to produce multiple cell types during long periods of non-division, or quiescence. FOXO transcription factors promote quiescence and stem cell maintenance, but the mechanisms by which FOXO proteins promote multipotency during quiescence are still emerging. The single FOXO ortholog in C. elegans, daf-16, promotes entry into a quiescent and stress-resistant larval stage called dauer in response to adverse environmental cues. During dauer, stem and progenitor cells maintain or re-establish multipotency to allow normal development to resume after dauer. We find that during dauer, daf-16/FOXO prevents epidermal stem cells (seam cells) from prematurely adopting differentiated, adult characteristics. In particular, dauer larvae that lack daf-16 misexpress collagens that are normally adult-enriched. Using col-19p::gfp as an adult cell fate marker, we find that all major daf-16 isoforms contribute to opposing col-19p::gfp expression during dauer. By contrast, daf-16(0) larvae that undergo non-dauer development do not misexpress col-19p::gfp. Adult cell fate and the timing of col-19p::gfp expression are regulated by the heterochronic gene network, including lin-41 and lin-29. lin-41 encodes an RNA-binding protein orthologous to LIN41/TRIM71 in mammals, and lin-29 encodes a conserved zinc finger transcription factor. In non-dauer development lin-41 opposes adult cell fate by inhibiting the translation of lin-29, which directly activates col-19 transcription and promotes adult cell fate. We find that during dauer, lin-41 blocks col-19p::gfp expression, but surprisingly, lin-29 is not required in this context. Additionally, daf-16 promotes the expression of lin-41 in dauer larvae. The col-19p::gfp misexpression phenotype observed in dauer larvae with reduced daf-16 requires the downregulation of lin-41, but does not require lin-29. Taken together, this work demonstrates a novel role for daf-16/FOXO as a heterochronic gene that promotes expression of lin-41/TRIM71 to contribute to multipotent cell fate in a quiescent stem cell model.

genetics↗

bioRxiv2021

Age-dependent changes in protein incorporation into collagen-rich tissues of mice by in vivo pulsed SILAC labelling

Collagen-rich tissues have poor reparative capacity that is further impaired with age, predisposing to common age-related disorders such as osteoporosis and osteoarthritis. We used in vivo pulsed SILAC labelling to quantify new protein incorporation into cartilage, bone, skin and plasma of mice across the life course. We report highly dynamic matrisome turnover in bone and cartilage during skeletal maturation, which was markedly reduced after skeletal maturity. Comparing young adult with older adult mice, new protein incorporation was reduced in all tissues. STRING clustering revealed epigenetic modulation across all tissues, a decline in chondroprotective growth factors such as FGF2 and TGFb in cartilage, and clusters indicating mitochondrial dysregulation and reduced collagen synthesis in bone. Several of these pathways have been associated with age-related disease. Fewer changes were observed for skin and plasma. This methodology provides dynamic protein data at a tissue level, uncovering age-related molecular changes that may predispose to disease.

developmental biology↗

bioRxiv2020

A paired liver biopsy and plasma proteomics study reveals circulating biomarkers for alcohol-related liver disease

Existing tests for detecting liver fibrosis, inflammation and steatosis, three stages of liver disease that are still reversible are severely hampered by limited accuracy or invasive nature. Here, we present a paired liver-plasma proteomics approach to infer molecular pathophysiology and to identify biomarkers in a cross-sectional alcohol-related liver disease cohort of nearly 600 individuals. Metabolic functions were downregulated whereas fibrosis-associated signaling and novel immune responses were upregulated, but only half of tissue proteome changes were transmitted to the circulation. Machine learning models based on our biomarker panels outperformed existing tests, laying the foundation for a generic proteomic liver health assessment.

biochemistry↗

bioRxiv2020

New insights into the paradoxical distribution of IRC7 in Saccharomyces cerevisiae and its associated phenotypic and genomic landscapes

Biotic and abiotic factors of wine fermentations have led to the accumulation of numerous genomic hallmarks of domestication in Saccharomyces cerevisiae wine strains. Here we have studied the paradoxical distribution of a dominant allele of IRC7 in wine yeast strains. This gene encodes a cysteine-S-{beta}-lyase and presents two alleles: a wild full-length allele (IRC7F) and a mutated one (IRC7S), harboring a 38bp-deletion. Interestingly, IRC7S-coding for a less active enzyme-appears in the great majority of wine strains. Studying its global distribution among phylogenetic clades, we observed that IRC7S allele is dominant just in wine strains, having a moderate presence in other domesticated clades (Beer, Bread and Wine-PDM), but being completely absent in wild clades, appearing as a new hallmark of domestication. To explain this paradoxical distribution, we performed an IRC7-rooted phenotypic-wide survey, demonstrating that IRC7S-homozygous (HS) wine strains have both fitness (lower lag phases and higher growth rates) and competitive (killer toxin resistance, pseudohyphal growth) advantages. Hence, we performed a genome-wide survey across domesticated clades, finding a set of mutations that are conserved among wine strains and potentially associated to IRC7S allele, which can help to explain the outstanding phenotype of HS strains and their dominant distribution in wines. Originality-Significance StatementS. cerevisiae is one of the best studied microbes due to its industrial importance and its use as a eukaryotic model organism. S. cerevisiae is also an interesting model for studying the effects of domestication in yeast genomic, phenotype and ecology. The study of how wild S. cerevisiae strains evolved into a greatly adapted domesticated strains and changed its lifestyle drastically is still of great interest. In the case of wine populations, strains have accumulated numerous hallmarks of domestication in their genome, related with their great phenotypic adaptation to this environment. Here, we report a new hallmark of domestication in wine strains; the IRC7 deleted allele (IRC7S) and present the first insights about its unexpected global distribution among phylogenetic clades, understanding the genomic context and the phenotypic implications of this allele in wine strains.

microbiology↗

bioRxiv2020

Spatially and cell-type resolved quantitative proteomic atlas of healthy human skin

Human skin provides both physical integrity and immunological protection from the external environment using functionally distinct layers, cell types and extracellular matrix. Despite its central role in human health and disease, the constituent proteins of skin have not been systematically characterized. Here, we combined advanced tissue dissection methods, flow cytometry and state-of-the-art proteomics to describe a spatially-resolved quantitative proteomic atlas of human skin. We quantified 10,701 proteins as a function of their spatial location and cellular origin. The resulting protein atlas and our initial data analyses demonstrate the value of proteomics for understanding cell-type diversity within the skin. We describe the quantitative distribution of structural proteins, known and novel proteins specific to cellular subsets and those with specialized immunological functions such as cytokines and chemokines. We anticipate that this proteomic atlas of human skin will become an essential community resource for basic and translational research (www.skin.science).

cell biology↗

bioRxiv2020

Clinical Knowledge Graph Integrates Proteomics Data into Clinical Decision-Making

The promise of precision medicine is to deliver personalized treatment based on the unique physiology of each patient. This concept was fueled by the genomic revolution, but it is now evident that integrating other types of omics data, like proteomics, into the clinical decision-making process will be essential to accomplish precision medicine goals. However, quantity and diversity of biomedical data, and the spread of clinically relevant knowledge across myriad biomedical databases and publications makes this exceptionally difficult. To address this, we developed the Clinical Knowledge Graph (CKG), an open source platform currently comprised of more than 16 million nodes and 220 million relationships to represent relevant experimental data, public databases and the literature. The CKG also incorporates the latest statistical and machine learning algorithms, drastically accelerating analysis and interpretation of typical proteomics workflows. We use several biomarker studies to illustrate how the CKG may support, enrich and accelerate clinical decision-making. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/084897v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@433689org.highwire.dtl.DTLVardef@b18068org.highwire.dtl.DTLVardef@1656084org.highwire.dtl.DTLVardef@a38201_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2020

Dopaminergic Gene Dosage in Autism versus Developmental Delay: From Complex Networks to Machine Learning approaches

The neural basis of behavioural changes in Autism Spectrum Disorders (ASD) remains a controversial issue. One factor contributing to this challenge is the phenotypic heterogeneity observed in ASD, which suggests that several different system disruptions may contribute to diverse patterns of impairment between and within study samples. Here, we took a retrospective approach, using SFARI data to study ASD by focusing on participants with genetic imbalances targeting the dopaminergic system. Using complex network analysis, we investigated the relations between participants, Gene Ontology (GO) and gene dosage related to dopaminergic neurotransmission from a polygenic point of view. We converted network analysis into a machine learning binary classification problem to differentiate ASD diagnosed participants from DD (developmental delay) diagnosed participants. Using 1846 participants to train a Random Forest algorithm, our best classifier achieved on average a diagnosis predicting accuracy of 85.18% (sd 1.11%) on a test sample of 790 participants using gene dosage features. In addition, we observed that if the classifier uses GO features it was also able to infer a correct response based on the previous examples because it is tied to a set of biological process, molecular functions and cellular components relevant to the problem. This yields a less variable and more compact set of features when comparing with gene dosage classifiers. Other facets of knowledge-based systems approaches addressing ASD through network analysis and machine learning, providing an interesting avenue of research for the future, are presented through the study. Lay SummaryThere are important issues in the differential diagnosis of Autism Spectrum Disorders. Gene dosage effects may be important in this context. In this work, we studied genetic alterations related to dopamine processes that could impact brain development and function of 2636 participants. On average, from a genetic sample we were able to correctly separate autism from developmental delay with an accuracy of 85%.

genetics↗

bioRxiv2020

Characterization of the oral microbiome of medically controlled type-2 diabetes patients

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that is becoming a significant global health care problem. Several studies have shown that people with diabetes are more susceptible to oral problems, such as periodontitis and, although the causes are still inconclusive, the oral microbiota seems to be an important factor in this interaction. This study aimed to characterize the oral microbiome of a sample representing T2DM patients from Portugal and exploit potential associations between some microorganisms and variables like teeth brushing, smoking habits, and nutrient intake. By sequencing the hypervariable regions V3-V4 of the 16S rRNA gene in 50 individuals belonging to a group of diabetes patients and a control group, we found a total of 233 taxa, from which only 65% were shared between both groups. No differences were found in terms of alpha and beta diversity between groups or habits categories. Also, there were no significant differences in the oral microbiome profiles of control and diabetes patients. Only the class Synergistia and the genus TG5, which are related to periodontitis, were statistically more frequent in the control group. This finding can be justified by the fact that these diabetic patients usually have their oral health under close medical control than an average healthy person, which in this study was represented by the control group. IMPORTANCEDiabetes has become a significant global health care issue as its incidence continues to increase exponentially, with type 2 diabetes being responsible for more than 90% of these cases. Portugal is one of the countries with a higher prevalence of diabetes in Europe. It has been reported that diabetic people have an increased risk of developing several health problems such as oral infections mostly caused by opportunistic pathogens. Some studies have pointed out a relationship between diabetes and oral microbiome. Therefore, the characterization of the microbial ecosystem of the mouth in reference groups is crucial to provide information to tackle oral health pathogen-borne conditions. In this study, we provide the first characterization of the oral microbiome of type 2 diabetes mellitus patients from Portugal, and therefore, contributing new data and knowledge to elucidate the relationship between diabetes and the oral microbiome.

microbiology↗

bioRxiv2020

Detection of hypermucoviscous Klebsiella pneumoniae sequence type 86 capsular type K2 in South America as an unexpected cause of a fatal outbreak in captivity marmosets

After the sudden death of eleven captives marmosets in a rehabilitation center of wildlife in Sao Paulo, Brazil, histological and microbiological study was conducted. Liver, spleen, intestine, central nervous system, lung, thymus, stomach, testicle tissues were analyzed by light microscopy and microbial cultures were conducted. Environmental cultures were also performed. Prophylactic antimicrobial therapy, restricted access to marmosets cages with dedicated staff, and additional sanitization of animals fruits were implemented. Histological findings were compatible with hyperacute septicemia, and microbiological cultures and molecular tests identified the etiologic agent as hypermucoviscous sequence type 86 capsular type K2 K. pneumoniae for the first time in South America. Implementation of prompt containment measures led to successful control of this outbreak. Detection of a hypervirulent and zoonotic pathogen, such as hypermucoviscous K. pneumoniae ST86 K2, in an unexpected and human interface reservoir underscores its potential threat in public health settings.

microbiology↗

bioRxiv2020

Proteomics dissection of cardiac protein profiles of humans and model organisms

The study of human cardiac pathologies often relies on research conducted in model organisms to gain molecular insight into disease and to develop novel treatment strategies; however, translating findings from model organisms back to human can present a significant challenge, in part due to a lack of knowledge about the differences across species in cardiac protein abundances and their interactions. Here we set out to bridge this knowledge gap by presenting a global analysis of cardiac protein expression profiles in humans and commonly used model organisms. Using quantitative mass spectrometry-based proteomics, we measured the abundance of ~7,000 proteins in samples from the separate chambers of human, pig, horse, rat, mouse and zebrafish hearts. This knowledgebase of cardiac protein signatures is accessible through an online database at: atlas.cardiacproteomics.com. Quantitative comparison of the protein profiles support the pig as model organism of choice for arrhythmogenic right ventricular cardiomyopathy whereas comparison of profiles from the two-chambered zebrafish heart suggests a better resemblance to the right side of mammalian hearts. This proteomics resource facilitates translational prospect of cardiac studies from model organisms to humans by enabling direct comparison of disease-linked protein networks across species.

systems biology↗

bioRxiv2019

Rainfall and other meteorological factors as drivers of urban transmission of leptospirosis

BackgroundLeptospirosis is an important public health problem affecting vulnerable urban slum populations in developing country settings. However, the complex interaction of meteorological factors driving the temporal trends of leptospirosis remain incompletely understood.\n\nMethods and findingsFrom 1996 to 2010, we investigated the association between the weekly incidence of leptospirosis and climatic variables in the city of Salvador, Brazil by using a dynamic generalized linear model that accounted for time lags, overall trend and seasonal variation. Our model showed an increase of leptospirosis cases associated with rainfall, lower temperature and higher humidity. There was a lag of one-to-two weeks between weekly values for significant meteorological variables and leptospirosis incidence. Independent of the season, a weekly cumulative rainfall of 20 mm increased the risk of the leptospirosis by 10% compared to a week without rain. Finally, over the 14 year study period the incidence of leptospirosis decreased significantly by four fold (12.8 versus 3.6 per 100,000 people), independently of variations in climate.\n\nConclusionsStrategies to control leptospirosis should focus on avoiding contact with contaminated sources of Leptospira as well as on increasing awareness in the population and health professionals within the short time window after both low-level and extreme rainfall events. Increased leptospirosis incidence was restricted to one-to-two weeks after those events suggesting that infectious Leptospira survival may be limited to short time intervals.\n\nAuthor SummaryTo determine the role of meteorological variables, seasonal variation and temporal trends in the incidence of leptospirosis, we investigated the time series of leptospirosis incidence amongst residents of Salvador, Brazil, from 1996 to 2010. Exploratory and confirmatory statistical methods detected associations between meteorological factors and disease incidence. Results showed the importance of extreme meteorological conditions, particularly rainfall, as short-term predictors of leptospirosis incidence. In addition, we found a long-term decreasing trend of in disease incidence over the observation period.

epidemiology↗

bioRxiv2019

Method to generate growth and degrowth models obtained from combinations of existing models applied to agrarian sciences

Mathematical models that describe gas production are widely used to estimate the rumen degradation digestibility and kinetics. The present study presents a method to generate models by combining existing models and to propose the von Bertalanffy-Gompertz two-compartment model based on this method. The proposed model was compared with the logistic two-compartment one to indicate which best describes the kinetic curve of gas production through the semi-automated in vitro technique from different pinto peanut cultivars. The data came from an experiment grown and harvested at the Far South Animal Sciences station (Essul) in Itabela, BA, Brazil and gas production was read at 2, 4, 6, 8, 10, 12, 14, 17, 20, 24, 28, 32, 48, 72, and 96 h after the start of the in vitro fermentation process. The parameters were estimated by the least squares method using the iterative Gauss-Newton process in the software R version 3.4.1. The best model to describe gas accumulation was based on the adjusted coefficient of determination, residual mean squares, mean absolute deviation, Akaike information criterion, and Bayesian information criterion. The von Bertalanffy-Gompertz two-compartment model had the best fit to describe the cumulative gas production over time according to the methodology and conditions of the present study.

developmental biology↗

bioRxiv2019

Anthropogenic Soils Promote Biodiversity in Amazonian Rainforests

Amazonian Dark Earths (ADEs) are fertile anthropic soils found throughout Amazonia, resulting from long-term occupation by pre-Columbian societies. Although the chemistry of these soils is well known, their biodiversity, particularly soil invertebrate communities have been neglected. To address this, we characterised soil macroinvertebrate communities and their activities in ADEs, comparing them with adjacent reference soils under forests and agriculture, at nine archaeological sites. We found 667 morphospecies and a tenacious pre-Columbian biodiversity footprint, with 40% of species found exclusively in ADEs. Soil biological activity was higher in ADEs than in adjacent soils, and associated with higher biomass and richness of organisms known to engineer the ecosystem. We show that these habitats have unique species pools, but that contemporary land-use causes nutrient loss and threatens their diversity. Both past and present human activities alter biodiversity and its distribution in Amazonia, and further efforts are needed to recognize and preserve these ADEs and their biodiversity.

zoology↗

bioRxiv2018

Integrative analysis of transcriptomic and clinical data uncovers the tumor suppressive activity of MITF in prostate cancer.

The dysregulation of gene expression is an enabling hallmark of cancer. Computational analysis of transcriptomics data from human cancer specimens, complemented with exhaustive clinical annotation, provides an opportunity to identify core regulators of the tumorigenic process. Here we exploit well-annotated clinical datasets of prostate cancer for the discovery of transcriptional regulators relevant to prostate cancer. Following this rationale, we identify Microphthalmia-associated transcription factor (MITF) as a prostate tumor suppressor among a subset of transcription factors. Importantly, we further interrogate transcriptomics and clinical data to refine MITF perturbation-based empirical assays and unveil Crystallin Alpha B (CRYAB) as an unprecedented direct target of the transcription factor that is, at least in part, responsible for its tumor suppressive activity in prostate cancer. This evidence was supported by the enhanced prognostic potential of a signature based on the concomitant alteration of MITF and CRYAB in prostate cancer patients. In sum, our study provides proof-of-concept evidence of the potential of the bioinformatics screen of publicly available cancer patient databases as discovery platforms, and demonstrates that the MITF-CRYAB axis controls prostate cancer biology.

cancer biology↗

bioRxiv2018

The association between 25(OH)D levels, frailty status and adiposity indices in older adults

BackgroundVitamin D deficiency is common in older adults and has been linked with frailty and obesity, but it remains to be studied whether frail obese older adults are at higher risk of vitamin D deficiency. Therefore, the aim of this study is to explore the association between frailty, adiposity indices and serum 25(OH)D concentrations.\n\nMethods1447 individuals with 65 years or older, participating in a cross-sectional study (Nutrition UP 65). Frailty, according to Fried et al., body mass index (BMI), waist circumference (WC), body roundness index (BRI) and body shape index (ABSI) were evaluated. A stepwise multinomial logistic regression was carried out to quantify the association between 25(OH)D quartiles and independent variables.\n\nResultsMedian 25(OH)D levels were lower in individuals presenting both frailty and obesity (p<0.001). In the multivariate analysis, pre-frailty (OR 2.65; 95% CI 1.63-4.32) and frailty (OR 3.76; 95% CI 2.08-6.81) were associated with increased odds of lower 25(OH)D serum levels (first quartile). Regarding adiposity indices, obesity (OR 1.75; 95% CI 1.07-2.87) and the highest categories of WC (OR 3.46; 95% CI 1.95-6.15), BRI (OR 4.35; 95% CI 2.60-7.29) and ABSI (OR 3.17 95% CI 1.86-5.38) were directly associated with lower 25(OH)D serum levels (first quartile).\n\nConclusionsA positive association between frailty or obesity and lower levels of vitamin D was found. Moreover, besides BMI and WC, other indicators of body adiposity, such as BRI and ABSI, were associated with lower 25(OH)D serum concentrations.

epidemiology↗