Miracle-dz/UniFAR-FTUs huggingface dataset:
Phosphoproteomics to Characterize Host Response During H3N2 Canine Influenza Virus Infection of Dog Lung

Avian-origin H3N2 canine influenza viruses (CIVs) cause severe contagious respiratory disease in dogs, and quickly adapt to new environments. To further understand the mechanism of virus infection and host-virus interactions, we characterized the complete phosphoproteome of dogs infected with H3N2 CIV. Nine-week-old Beagle dogs were inoculated intranasally with 106 EID50 of A/canine/Guangdong/04/2014 (H3N2) virus. Lung sections were harvested at 5 days post-inoculation (dpi) and processed for global and quantitative analysis of differentially expressed phosphoproteins. A total of 1,235 differentially expressed phosphorylated proteins were identified in the dog lung after H3N2 CIV infection, and 3,016 modification sites were identified among all differentially expressed proteins. We then performed an enrichment analysis of functional annotations using Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) database analyses to predict the functions of the identified differential phosphoproteins. Our data indicate that H3N2 CIV infection causes dramatic changes in the host protein phosphorylation of dog lungs. To our knowledge, this is the first study to assess the effect of H3N2 CIV infection on the phosphoproteome of beagles. These data provide novel insights into H3N2-CIV-triggered regulatory phosphorylation circuits and signaling networks and may improve our understanding of the mechanisms underlying CIV pathogenesis in dogs.
B Cell Subsets as Severity-Associated Signatures in COVID-19 Patients

Background SARS-CoV-2 infection represents a global health problem that has affected millions of people. The fine host immune response and its association with the disease course have not yet been fully elucidated. Consequently, we analyze circulating B cell subsets and their possible relationship with COVID-19 features and severity. Methods Using a multiparametric flow cytometric approach, we determined B cell subsets frequencies from 52 COVID-19 patients, grouped them by hierarchical cluster analysis, and correlated their values with clinical data. Results The frequency of CD19+ B cells is increased in severe COVID-19 compared to mild cases. Specific subset frequencies such as transitional B cell subsets increase in mild/moderate cases but decrease with the severity of the disease. Memory B compartment decreased in severe and critical cases, and antibody-secreting cells are increased according to the severity of the disease. Other non-typical subsets such as double-negative B cells also showed significant changes according to disease severity. Globally, these differences allow us to identify severity-associated patient clusters with specific altered subsets. Finally, respiratory parameters, biomarkers of inflammation, and clinical scores exhibited correlations with some of these subpopulations. Conclusions The severity of COVID-19 is accompanied by changes in the B cell subpopulations, either immature or terminally differentiated. Furthermore, the existing relationship of B cell subset frequencies with clinical and laboratory parameters suggest that these lymphocytes could serve as potential biomarkers and even active participants in the adaptive antiviral response mounted against SARS-CoV-2.
Climate as an Evolutionary Driver of Nest Morphology in Birds: A Review

Avian nests are critical for successful reproduction in birds. Nest microclimate can affect egg development, chick growth and fledgling success, suggesting that nest building behavior should be under strong selective pressure to nesting conditions. Given that the internal microclimate of the nest is critical for avian fitness, it is expected that nest morphology is shaped by the local environment. Here we review the relationship between nest morphology and climate across species’ distributions. We collate growing evidence that supports a link between environmental conditions and particular nest traits, within species and across species. We discuss the degree to which phenotypic plasticity in nesting behavior can contribute to observed variation in nest traits, the role of phylogenetic history in determining nest morphology, and which nest traits are likely to be influenced by climatic conditions. Finally, we identify gaps in our understanding of the evolution of nest morphology and suggest topics for future research. Overall, we argue that, and nests are part of the extended phenotype of a bird, they play a crucial role in their reproductive success, and may be an important factor in determining which species will be able to persist in the face of ongoing climate change.
Anti-quorum Sensing and Protective Efficacies of Naringin Against Aeromonas hydrophila Infection in Danio rerio

It is now well known that the quorum sensing (QS) mechanism coordinates the production of several virulence factors and biofilm formation in most pathogenic microorganisms. Aeromonas hydrophila is a prime pathogen responsible for frequent outbreaks in aquaculture settings. Recent studies have also continuously reported that A. hydrophila regulates virulence factor production and biofilm formation through the QS system. In addition to the presence of antibiotic resistance genes, biofilm-mediated antibiotic resistance increases the severity of A. hydrophila infections. To control the bacterial pathogenesis and subsequent infections, targeting the QS mechanism has become one of the best alternative methods. Though very few compounds were identified as QS inhibitors against A. hydrophila, to date, the screening and identification of new and effective natural QS inhibitors is a dire necessity to control the infectious A. hydrophila. The present study endorses naringin (NA) as an anti-QS and anti-infective agent against A. hydrophila. Initially, the NA showed a concentration-dependent biofilm reduction against A. hydrophila. Furthermore, the results of microscopic analyses and quantitative virulence assays displayed the promise of NA as a potential anti-QS agent. Subsequently, the downregulation of ahh1, aerA, lip and ahyB validate the interference of NA in virulence gene expression. Furthermore, the in vivo assays were carried out in zebrafish model system to evaluate the anti-infective potential of NA. The outcome of the immersion challenge assay showed that the recovery rate of the zebrafish has substantially increased upon treatment with NA. Furthermore, the quantification of the bacterial load upon NA treatment showed a decreased level of bacterial counts in zebrafish when compared to the untreated control. Moreover, the NA treatment averts the pathogen-induced histoarchitecture damages in vital organs of zebrafish, compared to their respective controls. The current study has thus analyzed the anti-QS and anti-infective capabilities of NA and could be employed to formulate effective treatment measures against A. hydrophila infections.
Severe Potential Drug-Drug Interactions and the Increased Length of Stay of Children in Intensive Care Unit

Children are exposed to drug-drug interactions (DDI) risks due to their organism’s complexity and the need for several medicines prescriptions in pediatric intensive care units (PICU). This study aimed to assess the prevalence of potential DDIs in a Brazilian PICU. We carried out a cross-sectional study at a pediatric teaching hospital from Rio de Janeiro (Brazil) over one year. Potential DDIs (pDDIs) between prescribed medicines for hospitalized children in PICU (n = 143) were analyzed according to severity using Micromedex®. Sex, age group, number of drugs prescribed, vasoactive amines use (a proxy of clinical complexity), and the PICU length of stay were summarized using descriptive statistics. Association between the PICU length stay, and variables sex, age, clinical condition complexity, number of drugs prescribed, and severity of pDDI were examined by univariate and multiple linear regression. Seventy percent of patients aged three days to 14 years old were exposed at least one potential DDIs during PICU stay. Two hundred eighty-four different types of pDDIs were identified, occurring 1,123 times. Nervous system drugs were implicated in 55% of the interactions, and fentanyl (10%) was most involving in pDDIs. Most pDDIs were classified as higher severity (56.2%), with reasonable documentation (64.6%) and unspecified onset time (63.8%). Worse clinical condition, ten or more drugs prescribed, and most severe pDDIs were associated with a longer PICU length of stay. Multiple linear regression analysis showed an increase of 9.83 days (95% confidence interval: 3.61–16.05; p = 0.002) in the PICU length of stay in children with major or contraindicated pDDIs. The results of this research may support the monitoring and prevention of pDDIs related to adverse events in children in intensive care and the design and conduction of new studies.
Prefrontal Cortex and Amygdala Subregion Morphology Are Associated With Obesity and Dietary Self-control in Children and Adolescents

A prefrontal control system that is less mature than the limbic reward system in adolescence is thought to impede self-regulatory abilities, which could contribute to poor dietary choices and obesity. We, therefore, aimed to examine whether structural morphology of the prefrontal cortex (PFC; involved in cognitive control) and the amygdala (a key brain region for reward-related processing) are associated with dietary decisions and obesity in children and adolescents. Seventy-one individuals between the ages of 8–22 years (17.35 ± 4.76 years, 51% female, 56% were overweight or obese) participated in this study; each participant completed a computer-based food choice task and a T1- and T2-weighted structural brain scans. Two indices of obesity were assessed, including age- and sex-specific body mass index (BMIz) and waist-to-height ratio (WHtR). The behavioral task included rating 60 food stimuli for tastiness, healthiness, and liking. Based on each participant’s self-ratings, 100 binary food choices were then made utilizing a computer mouse. Dietary “self-control” was calculated as the proportion of trials where the individual chose the healthier food item (vs. the tastier food item) over the total number of trials. Cortical thickness and amygdala subnuclei volumes were quantified using FreeSurfer 6.0 and CIT168 atlas, respectively. We found that WHtR was negatively associated with the thickness of bilateral superior frontal, left superior temporal, right insula, and right inferior temporal regions (p < 0.05, corrected for multiple comparisons). We also found WHtR to be positively associated with the volume of the central nucleus (CEN) region of the amygdala (p = 0.006), after adjusting for the hemisphere, age, sex, and intracranial volumes. A similar data pattern was observed when BMIz was used. Moreover, we found that across all participants, thinner right superior frontal cortex and larger left CEN volumes predicted lower dietary self-control. These results suggest that differential development of the PFC and amygdala relate to obesity and dietary self-control. Further longitudinal studies are merited to determine causal relationships among altered PFC to amygdala neural circuitry, dietary self-control, and obesity.
Determining the Different Mechanisms Used by Pseudomonas Species to Cope With Minimal Inhibitory Concentrations of Zinc via Comparative Transcriptomic Analyses

Pseudomonas is one of the most diverse bacterial genera identified in the environment. Genome sequence analysis has indicated that this genus can be clustered into three lineages and ten groups. Each group can adopt different mechanisms to thrive under zinc-depleted or high-zinc conditions, two environments that are frequently encountered during their environmental propagation. The response of three prominent Pseudomonas strains (Pseudomonas aeruginosa PAO1, Pseudomonas putida KT2440, and Pseudomonas fluorescens ATCC 13525T) to minimal inhibitory concentrations of zinc were compared using RNA-seq and ultra-performance liquid chromatography–tandem mass spectrometry analysis. Results demonstrated that the three strains shared only minimal similarity at the transcriptional level. Only four genes responsible for zinc efflux were commonly upregulated. P. aeruginosa PAO1 specifically downregulated the operons involved in siderophore synthesis and the genes that encode ribosomal protein, while upregulated the genes associated with antibiotic efflux and cell envelope biosynthesis. The membrane transporters in P. putida KT2440 were globally downregulated, indicating changes in cell permeability. Compared with P. aeruginosa PAO1 and P. putida KT2440, the most remarkable transcriptional variation in P. fluorescens ATCC 13525T is the significant downregulation of the type VI secretion system. Metabolite quantitative analysis showed that low concentrations of the metabolites involved in central carbon metabolism and amino acid synthesis were detected in the three strains. In summary, the cellular responses of the three strains under high-zinc condition is quite divergent. Although similar metal efflux systems were upregulated, the three strains employed different pathways to reduce zinc intrusion. In addition, zinc treatment can increase the difficulties of scavenging P. aeruginosa from its colonization area, and reduce the competitiveness of P. fluorescens in microbiota.
Pre-Exposure to Defibrotide Prevents Endothelial Cell Activation by Lipopolysaccharide: An Ingenuity Pathway Analysis

Defibrotide (DFB) effects on different endothelial cell pathways have been investigated focusing on a limited number of genes or molecules. This study explored the modulation of the gene expression profile of steady-state or lipopolysaccharide (LPS)-activated endothelial cells, following the DFB exposure. Starting from differentially regulated gene expression datasets, we utilized the Ingenuity Pathway Analysis (IPA) to infer novel information about the activity of this drug. We found that effects elicited by LPS deeply differ depending on cells were exposed to DFB and LPS at the same time, or if the DFB priming occurs before the LPS exposure. Only in the second case, we observed a significant down-regulation of various pathways activated by LPS. In IPA, the pathways most affected by DFB were leukocyte migration and activation, vasculogenesis, and inflammatory response. Furthermore, the activity of DFB seemed to be associated with the modulation of six key genes, including matrix-metalloproteinases 2 and 9, thrombin receptor, sphingosine-kinase1, alpha subunit of collagen XVIII, and endothelial-protein C receptor. Overall, our findings support a role for DFB in a wide range of diseases associated with an exaggerated inflammatory response of endothelial cells.
Surface Functionalization of Three Dimensional-Printed Polycaprolactone-Bioactive Glass Scaffolds by Grafting GelMA Under UV Irradiation

In this study, bioactive glass nanoparticles (BGNPs) with an average diameter of less than 10 nm were synthesized using a sol-gel method and then characterized by transmission electron microscopy (TEM), differential scanning calorimetric (DSC), Fourier transforms infrared spectroscopy (FTIR), and x-ray spectroscopy (XRD). Afterward, three dimensional (3D)-printed polycaprolactone (PCL) scaffolds along with fused deposition modeling (FDM) were incorporated with BGNPs, and the surface of the composite constructs was then functionalized by coating with the gelatin methacryloyl (GelMA) under UV irradiation. Field emission scanning electron microscopy micrographs demonstrated the interconnected porous microstructure with an average pore diameter of 260 µm and homogeneous distribution of BGNPs. Therefore, no noticeable shrinkage was observed in 3D-printed scaffolds compared with the computer-designed file. Besides, the surface was uniformly covered by GelMA, and no effect of surface modification was observed on the microstructure while surface roughness increased. The addition of the BGNPs the to PCL scaffolds showed a slight change in pore size and porosity; however, it increased surface roughness. According to mechanical analysis, the compression strength of the scaffolds was increased by the BGNPs addition and surface modification. Also, a reduction was observed in the absorption capacity and biodegradation of scaffolds in phosphate-buffered saline media after the incorporation of BGNPs, while the presence of the GelMA layer increased the swelling potential and stability of the composite matrixes. Moreover, the capability of inducing bio-mineralization of hydroxyapatite-like layers, as a function of BGNPs content, was proven by FE-SEM micrographs, EDX spectra, and x-ray diffraction spectra (XRD) after soaking the obtained samples in concentrated simulated body fluid. A higher potential of the modified constructs to interact with the aqueous media led to better precipitation of minerals. According to in-vitro assays, the modified scaffolds can provide a suitable surface for the attachment and spreading of the bone marrow mesenchymal stem cells (BMSCs). Furthermore, the number of the proliferated cells confirms the biocompatibility of the scaffolds, especially after a modification process. Cell differentiation was verified by alkaline phosphatase activity as well as the expression of osteogenic genes such as osteocalcin and osteopontin. Accordingly, the scaffolds showed an initial potential for reconstruction of the injured bone.
Pedestrians’ Understanding of a Fully Autonomous Vehicle’s Intent to Stop: A Learning Effect Over Time

This study explored pedestrians’ understanding of Fully Autonomous Vehicles (FAVs) intention to stop and what influences pedestrians’ decision to cross the road over time, i.e., learnability. Twenty participants saw fixed simulated urban road crossing scenes with a single FAV on the road as if they were pedestrians intending to cross. Scenes differed from one another in the FAV’s, distance from the crossing place, its physical size, and external Human-Machine Interfaces (e-HMI) message by background color (red/green), message type (status/advice), and presentation modality (text/symbol). Eye-tracking data and decision measurements were collected. Results revealed that pedestrians tend to look at the e-HMI before making their decision. However, they did not necessarily decide according to the e-HMIs’ color or message type. Moreover, when they complied with the e-HMI proposition, they tended to hesitate before making the decision. Overall, a learning effect over time was observed in all conditions regardless of e- HMI features and crossing context. Findings suggest that pedestrians’ decision making depends on a combination of the e-HMI implementation and the car distance. Moreover, since the learning curve exists in all conditions and has the same proportion, it is critical to design an interaction that would encourage higher probability of compatible decisions from the first phase. However, to extend all these findings, it is necessary to further examine dynamic situations.
Single-Shot Lightweight Model For The Detection of Lesions And The Prediction of COVID-19 From Chest CT Scans

We introduce a lightweight model based on Mask R-CNN with ResNet18 and ResNet34 backbone models that segments lesions and predicts COVID-19 from chest CT scans in a single shot. The model requires a small dataset to train: 650 images for the segmentation branch and 3000 for the classification branch, and it is evaluated on 21292 images to achieve a 42.45% average precision (main MS COCO criterion) on the segmentation test split (100 images), 93.00% COVID-19 sensitivity and F1-score of 96.76% on the classification test split (21192 images) across 3 classes: COVID-19, Common Pneumonia and Control/Negative. The full source code, models and pretrained weights are available on https://github.com/AlexTS1980/COVID-Single-Shot-Model.
An Integrative Computational Approach Based on Expression Similarity Signatures to Identify Protein–Protein Interaction Networks in Female-Specific Cancers

Breast, ovarian, and endometrial cancers have a major impact on mortality in women. These tumors share hormone-dependent mechanisms involved in female-specific cancers which support tumor growth in a different manner. Integrated computational approaches may allow us to better detect genomic similarities between these different female-specific cancers, helping us to deliver more sophisticated diagnosis and precise treatments. Recently, several initiatives of The Cancer Genome Atlas (TCGA) have encouraged integrated analyses of multiple cancers rather than individual tumors. These studies revealed common genetic alterations (driver genes) even in clinically distinct entities such as breast, ovarian, and endometrial cancers. In this study, we aimed to identify expression similarity signatures by extracting common genes among TCGA breast (BRCA), ovarian (OV), and uterine corpus endometrial carcinoma (UCEC) cohorts and infer co-regulatory protein–protein interaction networks that might have a relationship with the estrogen signaling pathway. Thus, we carried out an unsupervised principal component analysis (PCA)-based computational approach, using RNA sequencing data of 2,015 female cancer and 148 normal samples, in order to simultaneously capture the data heterogeneity of intertumors. Firstly, we identified tumor-associated genes from gene expression profiles. Secondly, we investigated the signaling pathways and co-regulatory protein–protein interaction networks underlying these three cancers by leveraging the Ingenuity Pathway Analysis software. In detail, we discovered 1,643 expression similarity signatures (638 downregulated and 1,005 upregulated genes, with respect to normal phenotype), denoted as tumor-associated genes. Through functional genomic analyses, we assessed that these genes were involved in the regulation of cell-cycle-dependent mechanisms, including metaphase kinetochore formation and estrogen-dependent S-phase entry. Furthermore, we generated putative co-regulatory protein–protein interaction networks, based on upstream regulators such as the ERBB2/HER2 gene. Moreover, we provided an ad-hoc bioinformatics workflow with a manageable list of intertumor expression similarity signatures for the three female-specific cancers. The expression similarity signatures identified in this study might uncover potential estrogen-dependent molecular mechanisms promoting carcinogenesis.