Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of Individual Viral Gene Segments from Influenza A/H5N8 Virus on the Protective Efficacy of Inactivated Subtype-Specific Influenza Vaccine

Since its emergence in 2014, the highly pathogenic avian influenza H5N8 virus has continuously and rapidly spread worldwide in the poultry sector resulting in huge economic losses. A typical inactivated H5N8 vaccine is prepared using the six internal genes from A/PR8/1934 (H1N1) and the two major antigenic proteins (HA and NA) from the circulating H5N8 strain with the HA modified to a low pathogenic form (PR8HA/NA-H5N8). The contribution of the other internal proteins from H5N8, either individually or in combination, to the overall protective efficacy of PR8-based H5N8 vaccine has not been investigated. Using reverse genetics, a set of PR8-based vaccines expressing the individual proteins from an H5N8 strain were rescued and compared to the parent PR8 and low pathogenic H5N8 strains and the commonly used PR8HA/NA-H5N8. Except for the PR8-based vaccine strains expressing the HA of H5N8, none of the rescued combinations could efficiently elicit virus-neutralizing antibodies. Compared to PR8, the non-HA viral proteins provided some protection to infected chickens six days post infection. We assume that this late protection was related to cell-based immunity rather than antibody-mediated immunity. This may explain the slight advantage of using full low pathogenic H5N8 instead of PR8HA/NA-H5N8 to improve protection by both the innate and the humoral arms of the immune system.
Curcumin Alleviates LPS-Induced Oxidative Stress, Inflammation and Apoptosis in Bovine Mammary Epithelial Cells via the NFE2L2 Signaling Pathway

Lipopolysaccharide (LPS) is an endotoxin, which may cause immune response and inflammation of bovine mammary glands. Mastitis impairs animal health and results in economic loss. Curcumin (CUR) is a naturally occurring diketone compound, which has attracted widespread attention as a potential anti-inflammatory antioxidant. The purpose of this study is to investigate whether CUR can reduce the damage of bovine mammary epithelial cells (MAC-T) induced by LPS and its underlying molecular mechanism. The MAC-T cell line was treated with different concentrations of LPS and CUR for 24 h. The results showed that CUR rescued the decrease of MAC-T cell viability and cell damage induced by LPS. At the same time, 10 µM CUR and 100 µg/mL LPS were used to treat the cells in the follow-up study. The results showed CUR treatment reduced the accumulation of reactive oxygen species (ROS), the expression of inflammatory cytokines (tumor necrosis factor-a (TNF-α), interleukin-8 (IL-8), IL-6 and IL-1β) and the rate of apoptosis induced by LPS. These effects were associated with the activation of the nuclear factor E2-related factor 2 (NFE2L2)-antioxidant response element (ARE) pathway coupled with inactivation of the nuclear factor-κB (NF-κB) inflammatory and caspase/Bcl2 apoptotic pathways.
Neuronal Differentiation from Induced Pluripotent Stem Cell-Derived Neurospheres by the Application of Oxidized Alginate-Gelatin-Laminin Hydrogels

Biodegradable hydrogels that promote stem cell differentiation into neurons in three dimensions (3D) are highly desired in biomedical research to study drug neurotoxicity or to yield cell-containing biomaterials for neuronal tissue repair. Here, we demonstrate that oxidized alginate-gelatin-laminin (ADA-GEL-LAM) hydrogels facilitate neuronal differentiation and growth of embedded human induced pluripotent stem cell (hiPSC) derived neurospheres. ADA-GEL and ADA-GEL-LAM hydrogels exhibiting a stiffness close to ~5 kPa at initial cell culture conditions of 37 °C were prepared. Laminin supplemented ADA-GEL promoted an increase in neuronal differentiation in comparison to pristine ADA-GEL, with enhanced neuron migration from the neurospheres to the bulk 3D hydrogel matrix. The presence of laminin in ADA-GEL led to a more than two-fold increase in the number of neurospheres with migrated neurons. Our findings suggest that laminin addition to oxidized alginate—gelatin hydrogel matrices plays a crucial role to tailor oxidized alginate-gelatin hydrogels suitable for 3D neuronal cell culture applications.
Evaluation of a Novel Plasmid for Simultaneous Gene Electrotransfer-Mediated Silencing of CD105 and CD146 in Combination with Irradiation

Targeting tumor vasculature through specific endothelial cell markers represents a promising approach for cancer treatment. Here our aim was to construct an antibiotic resistance gene-free plasmid encoding shRNAs to simultaneously target two endothelial cell markers, CD105 and CD146, and to test its functionality and therapeutic potential in vitro when delivered by gene electrotransfer (GET) and combined with irradiation (IR). Functionality of the plasmid was evaluated by determining the silencing of the targeted genes using qRT-PCR. Antiproliferative and antiangiogenic effects were determined by the cytotoxicity assay tube formation assay and wound healing assay in murine endothelial cells 2H-11. The functionality of the plasmid construct was also evaluated in malignant melanoma tumor cell line B16F10. Additionally, potential activation of immune response was measured by induction of DNA sensor STING and proinflammatory cytokines by qRT-PCR in endothelial cells 2H-11. We demonstrated that the plasmid construction was successful and can efficiently silence the expression of the two targeted genes. As a consequence of silencing, reduced migration rate and angiogenic potential was confirmed in 2H-11 endothelial cells. Furthermore, induction of DNA sensor STING and proinflammatory cytokines were determined, which could add to the therapeutic effectiveness when used in vivo. To conclude, we successfully constructed a novel plasmid DNA with two shRNAs, which holds a great promise for further in vivo testing.
Risk Assessment of Endometrial Hyperplasia or Endometrial Cancer with Simplified Ultrasound-Based Scoring Systems

Background: Abnormal uterine bleeding (AUB) represents a common diagnostic challenge, as it might be related to both benign and malignant conditions. Endometrial cancer may not be detected with blind uterine cavity sampling by dilatation and curettage or suction devices. Several scoring systems using different ultrasound image characteristics were recently proposed to estimate the risk of endometrial cancer (EC) in women with AUB. Aim: The aim of the present study was to externally validate the predictive value of the recently proposed scoring systems including the Risk of Endometrial Cancer scoring model (REC) for EC risk stratification. Material and methods: It was a retrospective cohort study of women with postmenopausal bleeding. From June 2012 to June 2020 we studied a group of 394 women who underwent standard transvaginal ultrasound examination followed by power Doppler intrauterine vascularity assessment. Selected ultrasound features of endometrial lesions were assessed in each patient. Results: The median age was 60.3 years (range ± 10.7). The median body mass index (BMI) was 30.4 (range ± 6.0). Histological examination revealed 158 cases of endometrial hyperplasia (EH) and 236 cases of EC. Of the studied ultrasound endometrial features, the highest areas under the curve (AUCs) were found for endometrial thickness (ET) (AUC = 0.76; 95% CI: 0.71–0.81) and for interrupted endomyometrial junction (AUC = 0.70, 95% CI: 0.65–0.75). Selected scoring systems presented moderate to good predictive performance in differentiating EC and EH. The highest AUC was found for REC model (AUC = 0.75, 95% CI: 0.70–0.79) and for the basic model that included ET, Doppler score and interrupted endometrial junction (AUC = 0.77, 95% CI: 0.73–0.82). REC model was more accurate than other scoring systems and selected single features for differentiating benign hyperplasia from EC at early stages, regardless of menopausal status. Conclusions: New scoring systems, including the REC model may be used in women with AUB for more efficient differentiation between benign and malignant conditions.
Multi-Mycotoxin Contamination of Maize Silages in Flanders, Belgium: Monitoring Mycotoxin Levels from Seed to Feed

Abstract Maize silage, which in Europe is the main feed for dairy cattle in winter, can be contaminated by mycotoxins. Mycotoxigenic Fusarium spp. originating from field infections may survive in badly sealed silages or re-infect at the cutting edge during feed-out. In this way, mycotoxins produced in the field may persist during the silage process. In addition, typical silage fungi such as Penicillium spp. and Aspergillus spp. survive in silage conditions and produce mycotoxins. In this research, 56 maize silages in Flanders were sampled over the course of three years (2016–2018). The concentration of 22 different mycotoxins was investigated using a multi-mycotoxin liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and the presence of DNA of three Fusarium spp. (F. graminearum, F. culmorum and F. verticillioides) was analyzed in a selection of these samples using quantitative polymerase chain reaction (qPCR). Every maize silage contained at least two different mycotoxins. Nivalenol (NIV) and deoxynivalenol (DON) were the most prevalent (both in 97.7% of maize silages), followed by ENN B (88.7%). Concentrations often exceeded the EU recommendations for DON and zearalenone (ZEN), especially in 2017 (21.3% and 27.7% of the maize silages, respectively). No correlations were found between fungal DNA and mycotoxin concentrations. Furthermore, by ensiling maize with a known mycotoxin load in a net bag, the mycotoxin contamination could be monitored from seed to feed. Analysis of these net bag samples revealed that the average concentration of all detected mycotoxins decreased after fermentation. We hypothesize that mycotoxins are eluted, degraded, or adsorbed during fermentation, but certain badly preserved silages are prone to additional mycotoxin production during the stable phase due to oxygen ingression, leading to extremely high toxin levels.
Dynamic FDG PET Imaging to Probe for Cardiac Metabolic Remodeling in Adults Born Premature

Individuals born very premature have an increased cardiometabolic and heart failure risk. While the structural differences of the preterm heart are now well-described, metabolic insights into the physiologic mechanisms underpinning this risk are needed. Here, we used dynamic fluorodeoxyglucose (FDG) positron emission tomography/magnetic resonance imaging (PET-MRI) in young adults born term and preterm during normoxic (N = 28 preterm; 18 term) and hypoxic exposure (12% O2; N = 26 preterm; 17 term) to measure the myocardial metabolic rate of glucose (MMRglc) in young adults born term (N = 18) and preterm (N = 32), hypothesizing that young adults born preterm would have higher rates of MMRglc under normoxic conditions and a reduced ability to augment glucose metabolism under hypoxic conditions. MMRglc was calculated from the myocardial and blood pool time-activity curves by fitting the measured activities to the 3-compartment model of FDG kinetics. MMRglc was similar at rest between term and preterm subjects, and decreased during hypoxia exposure in both groups (p = 0.02 for MMRglc hypoxia effect). There were no differences observed between groups in the metabolic response to hypoxia, either globally (serum glucose and lactate measures) or within the myocardium. Thus, we did not find evidence of altered myocardial metabolism in the otherwise healthy preterm-born adult. However, whether subtle changes in myocardial metabolism may preceed or predict heart failure in this population remains to be determined.
The Role of Myeloid-Derived Suppressor Cells (MDSCs) in the Development and/or Progression of Endometriosis-State of the Art

Endometriosis (EMS) is a common gynecological disease characterized by the presence of endometrial tissue outside the uterus. Approximately 10% of women around the world suffer from this disease. Recent studies suggest that endometriosis has potential to transform into endometriosis-associated ovarian cancer (EAOC). Endometriosis is connected with chronic inflammation and changes in the phenotype, activity, and function of immune cells. The underlying mechanisms include quantitative and functional disturbances of neutrophils, monocytes/macrophages (MO/MA), natural killer cells (NK), and T cells. A few reports have shown that immunosuppressive cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) may promote the progression of endometriosis. MDSCs are a heterogeneous population of immature myeloid cells (dendritic cells, granulocytes, and MO/MA precursors), which play an important role in the development of immunological diseases such as chronic inflammation and cancer. The presence of MDSCs in pathological conditions correlates with immunosuppression, angiogenesis, or release of growth factors and cytokines, which promote progression of these diseases. In this paper, we review the impact of MDSCs on different populations of immune cells, focusing on their immunosuppressive role in the immune system, which may be related with the pathogenesis and/or progression of endometriosis and its transformation into ovarian cancer.
Study on Characteristics of Particulate Matter Resuspension in School Classroom through Experiments Using a Simulation Chamber: Influence of Humidity

Resuspension of particulate matter (PM) in classrooms, which increases the risk of negative impact on student health from exposure to PM, is influenced by humidity level in the indoor environment. The goal of this study is to investigate the properties of PM resuspension in accordance with relative humidity through classroom test chamber experiments. In actual classrooms, it is challenging to control factors influencing resuspension. Therefore, the classroom chamber that reflects the environment of elementary school classroom (e.g., structure, floor material) is used in this study. The humidity of the classroom chamber is adjusted to 35%, 55%, 75%, and 85% by placing it inside a real-size environmental chamber, which allows artificial control of climatic conditions. At the respective humidity conditions, PM resuspension concentration and resuspension factor caused by occupant walking across the classroom chamber are analyzed. The results show that both of the resuspension concentration and resuspension factor reveal a linear negative correlation to humidity increase. Furthermore, coefficient of determination (R2) indicating goodness-of-fit of the linear regression model between the resuspension concentration and humidity is 0.88 for PM10 and 0.93 for PM2.5. It implies that accuracy of the regression model for estimating PM10 and PM2.5 resuspension concentrations is 88% and 93%, respectively.
The Current Challenges for Drug Discovery in CNS Remyelination

The myelin sheath wraps around axons, allowing saltatory currents to be transmitted along neurons. Several genetic, viral, or environmental factors can damage the central nervous system (CNS) myelin sheath during life. Unless the myelin sheath is repaired, these insults will lead to neurodegeneration. Remyelination occurs spontaneously upon myelin injury in healthy individuals but can fail in several demyelination pathologies or as a consequence of aging. Thus, pharmacological intervention that promotes CNS remyelination could have a major impact on patient’s lives by delaying or even preventing neurodegeneration. Drugs promoting CNS remyelination in animal models have been identified recently, mostly as a result of repurposing phenotypical screening campaigns that used novel oligodendrocyte cellular models. Although none of these have as yet arrived in the clinic, promising candidates are on the way. Many questions remain. Among the most relevant is the question if there is a time window when remyelination drugs should be administrated and why adult remyelination fails in many neurodegenerative pathologies. Moreover, a significant challenge in the field is how to reconstitute the oligodendrocyte/axon interaction environment representative of healthy as well as disease microenvironments in drug screening campaigns, so that drugs can be screened in the most appropriate disease-relevant conditions. Here we will provide an overview of how the field of in vitro models developed over recent years and recent biological findings about how oligodendrocytes mature after reactivation of their staminal niche. These data have posed novel questions and opened new views about how the adult brain is repaired after myelin injury and we will discuss how these new findings might change future drug screening campaigns for CNS regenerative drugs.
Longitudinal Study Depicting Differences in Complementary Feeding and Anthropometric Parameters in Late Preterm Infants up to 2 Years of Age

Ensuring the nutritional demands of preterm (PT) infants during complementary feeding could contribute significantly to the infants’ long-term health and development. However, the dietary guidelines for complementary feeding in PT are scarce. Thus, describing dietary intake and identifying nutritional targets for these infants could be of great interest. The aim of this study is to assess the food intake and anthropometric parameters in a Mediterranean infant cohort from 6 to 24 months and to identify nutritional targets especially focused on late preterm infants. This is a longitudinal prospective study analyzing information from administered questionnaires about general characteristics and food frequency consumption in 115 infants (20 PT (32 to 36 gestational weeks), 95 full-term (FT)) at 6, 12 and 24 months of age. Results show that the differences in the prevalence of underweight observed in PT infants vs. FT infants are maintained for up to 6 months of age but disappear at 12 and 24 months. The age of inclusion of new foods and the average intake of the main food groups was not different from that of FTs. Although protein intake at 6 months was directly correlated with weight gain and growth in FT, these associations were not observed in PT. At the nutritional level, the low intake of vitamin D in preterm infants is noteworthy. These findings may be useful when designing new intervention strategies for this population group.
Low-Cost Chlorophyll Fluorescence Imaging for Stress Detection

Plants naturally contain high levels of the stress-responsive fluorophore chlorophyll. Chlorophyll fluorescence imaging (CFI) is a powerful tool to measure photosynthetic efficiency in plants and provides the ability to detect damage from a range of biotic and abiotic stresses before visible symptoms occur. However, most CFI systems are complex, expensive systems that use pulse amplitude modulation (PAM) fluorometry. Here, we test a simple CFI system, that does not require PAM fluorometry, but instead simply images fluorescence emitted by plants. We used this technique to visualize stress induced by the photosystem II-inhibitory herbicide atrazine. After applying atrazine as a soil drench, CFI and color images were taken at 15-minute intervals, alongside measurements from a PAM fluorometer and a leaf reflectometer. Pixel intensity of the CFI images was negatively correlated with the quantum yield of photosystem II (ΦPSII) (p < 0.0001) and positively correlated with the measured reflectance in the spectral region of chlorophyll fluorescence emissions (p < 0.0001). A fluorescence-based stress index was developed using the reflectometer measurements based on wavelengths with the highest (741.2 nm) and lowest variability (548.9 nm) in response to atrazine damage. This index was correlated with ΦPSII (p < 0.0001). Low-cost CFI imaging can detect herbicide-induced stress (and likely other stressors) before there is visual damage.
Differences and Similarities in Predictors of Expressive Vocabulary Development between Children with Down Syndrome and Young Typically Developing Children

The purpose of this study was to examine potential differences in the predictors of expressive vocabulary development between children with Down syndrome and typically developing children to support preparation for intervention development. An age cohort of 43 children with Down syndrome and 57 typically developing children with similar nonverbal mental age levels were assessed at three time points. Linear mixed models were used to investigate the predictors of expressive vocabulary over time. Both groups achieved progress in expressive vocabulary. The typically developing children had steeper growth than the children with Down syndrome (1.38 SD vs. 0.8 SD, p < 0.001). In both groups, receptive vocabulary, auditory memory, and the home literacy environment were significant predictors of development. In the children with Down syndrome, the phonological awareness and oral motor skills were also significant. Group comparisons showed that receptive vocabulary, auditory memory and oral motor skills were stronger predictors in the children with Down syndrome than in the typically developing children. These results indicate that children with Down syndrome are more vulnerable when it comes to risk factors that are known to influence expressive vocabulary than typically developing children. Children with Down syndrome therefore require early broad-based expressive vocabulary interventions.
Varicella-Zoster Virus Infection of Neurons Derived from Neural Stem Cells

Varicella-Zoster virus (VZV) is a human herpesvirus that causes varicella (chickenpox) as a primary infection, and, following a variable period of ganglionic latency in neurons, it reactivates to cause herpes zoster (shingles). An analysis of VZV infection in cultures of neural cells, in particular when these have been obtained from induced pluripotent stem cells (iPSCs) or neural stem cells consisting of highly purified neuronal cultures, has revealed much data that may be of neurobiological significance. Early studies of VZV infection of mature cultured neural cells were mainly descriptive, but more recent studies in homogeneous neural stem cell cultures have used both neuronal cell markers and advanced molecular technology. Two general findings from such studies have been that (a) VZV infection of neurons is less severe, based on several criteria, than that observed in human fibroblasts, and (b) VZV infection of neurons does not lead to apoptosis in these cells in contrast to apoptosis observed in fibroblastic cells. Insights gained from such studies in human neural stem cells suggest that a less severe initial lytic infection in neurons, which are resistant to apoptosis, is likely to facilitate a pathological pathway to a latent state of the virus in human ganglia.