Miracle-dz/UniFAR-FTUs huggingface dataset:
Developmental Exposure to Low Concentrations of Methylmercury Causes Increase in Anxiety-Related Behaviour and Locomotor Impairments in Zebrafish

Methylmercury (MeHg) is a ubiquitous pollutant shown to cause developmental neurotoxicity, even at low levels. However, there is still a large gap in our understanding of the mechanisms linking early-life exposure to life-long behavioural impairments. Our aim was to characterise the short- and long-term effects of developmental exposure to low doses of MeHg on anxiety-related behaviours in zebrafish, and to test the involvement of neurological pathways related to stress-response. Zebrafish embryos were exposed to sub-acute doses of MeHg (0, 5, 10, 15, 30 nM) throughout embryo-development, and tested for anxiety-related behaviours and locomotor activity at larval (light/dark locomotor activity) and adult (novel tank and tap assays) life-stages. Exposure to all doses of MeHg caused increased anxiety-related responses; heightened response to the transition from light to dark in larvae, and a stronger dive response in adults. In addition, impairment in locomotor activity was observed in the higher doses in both larvae and adults. Finally, the expressions of several neural stress-response genes from the HPI-axis and dopaminergic system were found to be disrupted in both life-stages. Our results provide important insights into dose-dependent differences in exposure outcomes, the development of delayed effects over the life-time of exposed individuals and the potential mechanisms underlying these effects.
Molecular Characterization and Defense Functions of the Nile Tilapia (Oreochromis niloticus) DnaJ B9b and DnaJ C3a Genes in Response to Pathogenic Bacteria under High-Temperature Stress Conditions

DnaJ proteins or heat shock protein 40s (HSP40s) form one of the largest heat shock protein families. In this study, 2 cDNAs encoding Nile tilapia (Oreochromis niloticus) DnaJ proteins (On-DnaJ B9b and On-DnaJ C3a) were successfully cloned and characterized. The structures and organizations of these two genes are first reported in the present study. On-DnaJ B9b is approximately 2.1 kb long and contains 2 exons and 1 intron, while On-DnaJ C3a is approximately 12 kb long and contains 12 exons and 11 introns. Under normal conditions, On-DnaJ B9b mRNA is highly expressed in gonad and trunk kidney tissues, while On-DnaJ C3a transcripts are abundantly expressed in gills, intestine, liver, and trunk kidney tissues. Following pathogenic infections, the expression of both genes is induced in the liver, spleen and head kidney tissues of Nile tilapia that were infected with two virulent pathogenic bacteria, Streptococcus agalactiae and Flavobacterium columnare. Silencing of these two genes was first carried out, and the results clearly indicated their crucial roles under both heat and bacterial stress conditions. The fundamental knowledge obtained from this study indicates the characteristic basic biofunctions of heat shock proteins in the regulation of intracellular proteins during infection, which involve preventing protein aggregation, promoting protein refolding, and activating unfolded protein degradation.
Work Task Association with Lead Urine and Blood Concentrations in Informal Electronic Waste Recyclers in Thailand and Chile

The informal recycling of electronic waste (“e-waste”) is a lucrative business for workers in low- and middle-income countries across the globe. Workers dismantle e-waste to recover valuable materials that can be sold for income. However, workers expose themselves and the surrounding environment to hazardous agents during the process, including toxic metals like lead (Pb). To assess which tools, tasks, and job characteristics result in higher concentrations of urine and blood lead levels among workers, ten random samples of 2 min video clips were analyzed per participant from video recordings of workers at e-waste recycling sites in Thailand and Chile to enumerate potential predictors of lead burden. Blood and urine samples were collected from participants to measure lead concentration. Boosted regression trees (BRTs) were run to determine the relative importance of video-derived work variables and demographics, and their relationship with the urine and blood concentrations. Of 45 variables considered, five job characteristics consisting of close-toed shoes (relative importance of 43.9%), the use of blunt striking instruments (14%), bending the back (5.7%), dismantling random parts (4.4%), and bending the neck (3.5%) were observed to be the most important predictors of urinary Pb levels. A further five job characteristics, including lifting objects <20 lbs. (6.2%), the use of screwdrivers (4.2%), the use of pliers/scissors (4.2%), repetitive arm motion (3.3%), and lifting objects >20 pounds (3.2%) were observed to be among the most important factors of blood Pb levels. Overall, our findings indicate ten job characteristics that may strongly influence Pb levels in e-waste recycling workers’ urine and blood.
An Adaptive Rank Aggregation-Based Ensemble Multi-Filter Feature Selection Method in Software Defect Prediction

Feature selection is known to be an applicable solution to address the problem of high dimensionality in software defect prediction (SDP). However, choosing an appropriate filter feature selection (FFS) method that will generate and guarantee optimal features in SDP is an open research issue, known as the filter rank selection problem. As a solution, the combination of multiple filter methods can alleviate the filter rank selection problem. In this study, a novel adaptive rank aggregation-based ensemble multi-filter feature selection (AREMFFS) method is proposed to resolve high dimensionality and filter rank selection problems in SDP. Specifically, the proposed AREMFFS method is based on assessing and combining the strengths of individual FFS methods by aggregating multiple rank lists in the generation and subsequent selection of top-ranked features to be used in the SDP process. The efficacy of the proposed AREMFFS method is evaluated with decision tree (DT) and naïve Bayes (NB) models on defect datasets from different repositories with diverse defect granularities. Findings from the experimental results indicated the superiority of AREMFFS over other baseline FFS methods that were evaluated, existing rank aggregation based multi-filter FS methods, and variants of AREMFFS as developed in this study. That is, the proposed AREMFFS method not only had a superior effect on prediction performances of SDP models but also outperformed baseline FS methods and existing rank aggregation based multi-filter FS methods. Therefore, this study recommends the combination of multiple FFS methods to utilize the strength of respective FFS methods and take advantage of filter–filter relationships in selecting optimal features for SDP processes.
10-Year Changes in Adiposity in Cameroon School-Age Children: Evidence for Increasing Central Adiposity and Higher Adiposity Levels in Tallest-for-Age Children

Objective To examine changes in measures of adiposity and determine the prevalence of excess adiposity in relation to height in school children between 2010 and 2020. Methods 5–12-year-old urban school-age children participated in two cross-sectional surveys in 2010 (n = 1274) and 2020 (n = 1550). Standard procedures were used for anthropometric measurements. Changes in BMI, waist circumference (WC), and waist-to-height ratio (WHtR) and the corresponding proportions of children with excess adiposity were analyzed and adjusted for design variables (class and school type) and age. Children were classified according to quartiles of height z-score and prevalence of excess adiposity estimated across each quartile. Results There was a 2.4% and 3.3% increase in adjusted mean BMI and WC, respectively, between 2010 and 2020. The prevalence of central overweight/obesity (WC) and WHtR ≥ 0.5 increased by 7.3% (X2 = 27.151, p < 0.001) and 5.3% (X2 = 26.117, p < 0.001), respectively, between the two surveys except BMI overweight/obesity. The odds of excess adiposity significantly increased in 2020 for central overweight/obesity (WC) (OR 2.8, 95% CI 2.0–3.6) and WHtR ≥ 0.5 (OR 1.8, 95% CI 1.3–2.4) and not for BMI overweight/obesity (OR 1.3, 95% CI 0.8–1.7). The prevalence of BMI overweight/obesity significantly increased from 33% in 2010 to 51.5% in 2020 in the fourth quartile of height z-score (X2 = 19.198, p < 0.001). Similarly, the prevalence of central overweight/obesity (WC) significantly increased from 23.5% in 2010 to 42.4% in 2020 in the fourth quartile of height z-score (X2 = 18.733, p < 0.001). Conclusion Central overweight/obesity has increased more than BMI overweight/obesity over the last decade. Children with a higher height-for-age tend to accumulate more adiposity. Objective monitoring of adiposity levels and height of children is needed in future to identify groups for targeted intervention and prevention of chronic diseases.
Serum miR-373-3p and miR-194-5p Are Associated with Early Tumor Progression during FOLFIRINOX Treatment in Pancreatic Cancer Patients: A Prospective Multicenter Study

In this study, we explored the predictive value of serum microRNA (miRNA) expression for early tumor progression during FOLFIRINOX chemotherapy and its association with overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). A total of 132 PDAC patients of all disease stages were included in this study, of whom 25% showed progressive disease during FOLFIRINOX according to the RECIST criteria. MiRNA expression was analyzed in serum collected before the start and after one cycle of chemotherapy. In the discovery cohort (n = 12), a 352-miRNA RT-qPCR panel was used. In the validation cohorts (total n = 120), miRNA expression was detected using individual RT-qPCR miRNA primers. Before the start of FOLFIRINOX, serum miR-373-3p expression was higher in patients with progressive disease compared to patients with disease control after FOLFIRINOX (Log2 fold difference (FD) 0.88, p = 0.006). MiR-194-5p expression after one cycle of FOLFIRINOX was lower in patients with progressive disease (Log2 FD −0.29, p = 0.044). Both miRNAs were predictors of early tumor progression in a multivariable model including disease stage and baseline CA19-9 level (miR-373-3p odds ratio (OR) 3.99, 95% CI 1.10–14.49; miR-194-5p OR 0.91, 95% CI 0.83–0.99). MiR-373-3p and miR-194-5p did not show an association with OS after adjustment for disease stage, baseline CA19-9, and chemotherapy response. In conclusion, high serum miR-373-3p before the start and low serum miR-194-5p after one cycle are associated with early tumor progression during FOLFIRINOX.
Moroccan Strawberry Tree (Arbutus unedo L.) Fruits: Nutritional Value and Mineral Composition

The strawberry tree (Arbutus unedo L.), grown throughout the Mediterranean, produces edible fruit; as it is easily bruised, the sweet, reddish fruit is used mostly to prepare jams, marmalades and alcoholic beverages. As the genus is paraphyletic, phytochemical analysis can assist in defining the fruit composition with the species Arbutus unedo L. (A. unedo). Here we report on the carbohydrate, total sugar, protein, fat, fiber, ash, and mineral content of wild fruit, harvested from 45 specimens from five locations. The dominant nutrients were carbohydrates (78.2–84.8 g/100 g), total sugars (52.1–67.2 g/100 g) and dietary fiber (11.0–20.1 g/100 g). Other important nutrients supplied by A. unedo fruit include P, K, and Fe. The fruit was observed to contain health-promoting components providing 42 and 36%, of recommended daily allowance (RDA) for fiber and zinc, respectively, as well as iron and manganese, at levels exceeding minimum RDA. The free-sugar profile revealed high glucose followed by fructose content with minor amounts of sucrose (14, 11, and 6 g/100 g, respectively). Significant differences both between regions and within individuals were observed for several traits. The richness of fruit nutrients in A. unedo confers nutritional value and as such, a promising alternative fruit source.
Description of Joint Alterations Observed in a Family Carrying p.Asn453Ser COMP Variant: Clinical Phenotypes, In Silico Prediction of Functional Impact on COMP Protein and Stability, and Review of the Literature

The role of genetics in the development of osteoarthritis is well established but the molecular bases are not fully understood. Here, we describe a family carrying a germline mutation in COMP (Cartilage Oligomeric Matrix Protein) associated with three distinct phenotypes. The index case was enrolled for a familial form of idiopathic early-onset osteoarthritis. By screening potential causal genes for osteoarthritis, we identified a heterozygous missense mutation of COMP (c.1358C>T, p.Asn453Ser), absent from genome databases, located on a highly conserved residue and predicted to be deleterious. Molecular dynamics simulation suggests that the mutation destabilizes the overall COMP protein structure and consequently the calcium releases from neighboring calcium binding sites. This mutation was once reported in the literature as causal for severe multiple epiphyseal dysplasia (MED). However, no sign of dysplasia was present in the index case. The mutation was also identified in one of her brothers diagnosed with MED and secondary osteoarthritis, and in her sister affected by an atypical syndrome including peripheral inflammatory arthritis of unknown cause, without osteoarthritis nor dysplasia. This article suggests that this mutation of COMP is not only causal for idiopathic early-onset osteoarthritis or severe MED, but can also be associated to a broad phenotypic variability with always joint alterations.
Measurement Invariance of the Sexual Orientation Microaggression Inventory across LGB Males and Females in Taiwan: Bifactor Structure Fits the Best

The present study examined the factor structure and concurrent validity of the traditional Chinese version of the Sexual Orientation Microaggression Inventory (SOMI) among lesbian, gay, and bisexual (LGB) individuals in Taiwan. In total, 1000 self-identified LGB individuals completed the SOMI, HIV and Homosexuality Related Stigma Scale (HHRSS), and Acceptance and Action Questionnaire-II (AAQ). Different factor structures (including one-factor, four-factor, bifactor, and higher-order factor structures) were evaluated using confirmatory factor analysis. The bifactor structure significantly outperformed all others on the SOMI. The bifactor structure with one general factor and four trait factors was found to be measurement invariant across biological sex with satisfactory fit indices. The SOMI general factor was significantly associated with HHRSS-Homosexuality score and AAQ score. The findings indicate that the SOMI is a psychometrically sound instrument for Taiwan sexual minority groups. More specifically, SOMI can be used to accurately assess microaggression among LGB individuals. The measure on microaggression may also provide insights for healthcare providers about LGB individuals’ sexuality-related stigma. Moreover, healthcare providers and relevant stakeholders can use the SOMI to understand how LGB individuals perceive and feel microaggression.
COVID-19 Infection Alters the Microbiome: Elite Athletes and Sedentary Patients Have Similar Bacterial Flora

Regular exercise can upgrade the efficiency of the immune system and beneficially alter the composition of the gastro-intestinal microbiome. We tested the hypothesis that active athletes have a more diverse microbiome than sedentary subjects, which could provide better protection against COVID-19 during infection. Twenty active competing athletes (CA) (16 male and 4 females of the national first and second leagues), aged 24.15 ± 4.7 years, and 20 sedentary subjects (SED) (15 male and 5 females), aged 27.75 ± 7.5 years, who had been diagnosed as positive for COVID-19 by a PCR test, served as subjects for the study. Fecal samples collected five to eight days after diagnosis and three weeks after a negative COVID-19 PCR test were used for microbiome analysis. Except for two individuals, all subjects reported very mild and/or mild symptoms of COVID-19 and stayed at home under quarantine. Significant differences were not found in the bacterial flora of trained and untrained subjects. On the other hand, during COVID-19 infection, at the phylum level, the relative abundance of Bacteroidetes was elevated during COVID-19 compared to the level measured three weeks after a negative PCR test (p < 0.05) when all subjects were included in the statistical analysis. Since it is known that Bacteroidetes can suppress toll-like receptor 4 and ACE2-dependent signaling, thus enhancing resistance against pro-inflammatory cytokines, it is suggested that Bacteroidetes provide protection against severe COVID-19 infection. There is no difference in the microbiome bacterial flora of trained and untrained subjects during and after a mild level of COVID-19 infection.
Integrative Map of HIF1A Regulatory Elements and Variations

Hypoxia-inducible factor (HIF) family of transcription factors (HIF1A, EPAS1, and HIF3A) are regulators of the cellular response to hypoxia. They have been shown to be involved in development of various diseases such as cancer, diabetes, and erythrocytosis. A complete map of connections between HIF family of genes with various omics types has not yet been developed. The main aim of the present analysis was to construct the integrative map of genomic elements associated with HIF1A gene and prioritize potentially deleterious variants. Various genomic databases and bioinformatics tools were used, including Ensembl, MirTarBase, STRING, Cytoscape, MethPrimer, CADD, SIFT, and UALCAN. Integrative HIF1A gene map was visualized and includes transcriptional and post-transcriptional regulators, downstream targets, and genetic variants. One CpG island overlaps transcription start site of the HIF1A gene. Out of over 450 missense variants, four have predicted deleterious effect on protein function by at least five bioinformatics tools. Currently there are 85 miRNAs reported to target HIF1A. HIF1A downstream targets include protein-coding genes, long noncoding RNAs, and microRNAs (hypoxamiRs). The study presents the first integration of heterogeneous molecular interactions associated with HIF1A gene enabling a holistic view of the gene and lays the groundwork for supplementing the data in the future.
Lung Fibrosis Is Improved by Extracellular Vesicles from IFNγ-Primed Mesenchymal Stromal Cells in Murine Systemic Sclerosis

Background: Systemic sclerosis (SSc) is a severe autoimmune disease for which mesenchymal stromal cells (MSCs)-based therapy was reported to reduce SSc-related symptoms in pre-clinical studies. Recently, extracellular vesicles released by MSCs (MSC-EVs) were shown to mediate most of their therapeutic effect. Here, we aimed at improving their efficacy by increasing the MSC-EV dose or by IFNγ-priming of MSCs. Methods: small size (ssEVs) and large size EVs (lsEVs) were recovered from murine MSCs that were pre-activated using 1 or 20 ng/mL of IFNγ. In the HOCl-induced model of SSc, mice were treated with EVs at day 21 and sacrificed at day 42. Lung and skin samples were collected for histological and molecular analyses. Results: increasing the dose of MSC-EVs did not add benefit to the dose previously reported to be efficient in SSc. By contrast, IFNγ pre-activation improved MSC-EVs-based treatment, essentially in the lungs. Low doses of IFNγ decreased the expression of fibrotic markers, while high doses improved remodeling and anti-inflammatory markers. IFNγ pre-activation upregulated iNos, IL1ra and Il6 in MSCs and ssEVs and the PGE2 protein in lsEVs. Conclusion: IFNγ-pre-activation improved the therapeutic effect of MSC-EVs preferentially in the lungs of SSc mice by modulating anti-inflammatory and anti-fibrotic markers.
Imaging Modalities Employed in Diabetic Retinopathy Screening: A Review and Meta-Analysis

Introduction: Urbanization has caused dramatic changes in lifestyle, and these rapid transitions have led to an increased risk of noncommunicable diseases, such as type 2 diabetes. In terms of cost-effectiveness, screening for diabetic retinopathy is a critical aspect in diabetes management. The aim of this study was to review the imaging modalities employed for retinal examination in diabetic retinopathy screening. Methods: The PubMed and Web of Science databases were the main sources used to investigate the medical literature. An extensive search was performed to identify relevant articles concerning “imaging”, “diabetic retinopathy” and “screening” up to 1 June 2021. Imaging techniques were divided into the following: (i) mydriatic fundus photography, (ii) non-mydriatic fundus photography, (iii) smartphone-based imaging, and (iv) ultrawide-field imaging. A meta-analysis was performed to analyze the performance and technical failure rate of each method. Results: The technical failure rates for mydriatic and non-mydriatic digital fundus photography, smartphone-based and ultrawide-field imaging were 3.4% (95% CI: 2.3–4.6%), 12.1% (95% CI: 5.4–18.7%), 5.3% (95% CI: 1.5–9.0%) and 2.2% (95% CI: 0.3–4.0%), respectively. The rate was significantly different between all analyzed techniques (p < 0.001), and the overall failure rate was 6.6% (4.9–8.3%; I2 = 97.2%). The publication bias factor for smartphone-based imaging was significantly higher than for mydriatic digital fundus photography and non-mydriatic digital fundus photography (b = −8.61, b = −2.59 and b = −7.03, respectively; p < 0.001). Ultrawide-field imaging studies were excluded from the final sensitivity/specificity analysis, as the total number of patients included was too small. Conclusions: Regardless of the type of the device used, retinal photographs should be taken on eyes with dilated pupils, unless contraindicated, as this setting decreases the rate of ungradable images. Smartphone-based and ultrawide-field imaging may become potential alternative methods for optimized DR screening; however, there is not yet enough evidence for these techniques to displace mydriatic fundus photography.