Miracle-dz/UniFAR-FTUs huggingface dataset:
Repurposing Cardiac Glycosides: Drugs for Heart Failure Surmounting Viruses

Drug repositioning is a successful approach in medicinal research. It significantly simplifies the long-term process of clinical drug evaluation, since the drug being tested has already been approved for another condition. One example of drug repositioning involves cardiac glycosides (CGs), which have, for a long time, been used in heart medicine. Moreover, it has been known for decades that CGs also have great potential in cancer treatment and, thus, many clinical trials now evaluate their anticancer potential. Interestingly, heart failure and cancer are not the only conditions for which CGs could be effectively used. In recent years, the antiviral potential of CGs has been extensively studied, and with the ongoing SARS-CoV-2 pandemic, this interest in CGs has increased even more. Therefore, here, we present CGs as potent and promising antiviral compounds, which can interfere with almost any steps of the viral life cycle, except for the viral attachment to a host cell. In this review article, we summarize the reported data on this hot topic and discuss the mechanisms of antiviral action of CGs, with reference to the particular viral life cycle phase they interfere with.
Exploring the Isomeric Precursors of Olive Oil Major Secoiridoids: An Insight into Olive Leaves and Drupes by Liquid-Chromatography and Fourier-Transform Tandem Mass Spectrometry

Secoiridoids play a key role in determining health benefits related to a regular consumption of extra-virgin olive oil (EVOO), in which they are generated from precursors of the same class naturally occurring in drupes and leaves of the olive (Olea europaea L.) plant. Here, reversed-phase liquid chromatography coupled to electrospray ionization and Fourier-transform single/tandem mass spectrometry (RPLC-ESI-FTMS and MS/MS) was employed for a structural elucidation of those precursors. The presence of three isoforms in both matrices was assessed for oleuropein ([M-H]− ion with m/z 539.1770) and was emphasized, for the first time, also for ligstroside (m/z 523.1821) and for the demethylated counterparts of the two compounds (m/z 525.1614 and 509.1665, respectively). However, only the prevailing isoform included an exocyclic double bond between carbon atoms C8 and C9, typical of oleuropein and ligstroside; the remaining, less abundant, isoforms included a C=C bond between C8 and C10. The same structural difference was also observed between secoiridoids named elenolic acid glucoside and secoxyloganin (m/z 403.1246). This study strengthens the hypothesis that secoiridoids including a C8=C10 bond, recently recognized as relevant species in EVOO extracts, arise mainly from specific enzymatic/chemical transformations occurring on major oleuropein/ligstroside-like precursors during EVOO production, rather than from precursors having that structural feature.
Membrane Interactions of Latarcins: Antimicrobial Peptides from Spider Venom

A group of seven peptides from spider venom with diverse sequences constitute the latarcin family. They have been described as membrane-active antibiotics, but their lipid interactions have not yet been addressed. Using circular dichroism and solid-state 15N-NMR, we systematically characterized and compared the conformation and helix alignment of all seven peptides in their membrane-bound state. These structural results could be correlated with activity assays (antimicrobial, hemolysis, fluorescence vesicle leakage). Functional synergy was not observed amongst any of the latarcins. In the presence of lipids, all peptides fold into amphiphilic α-helices as expected, the helices being either surface-bound or tilted in the bilayer. The most tilted peptide, Ltc2a, possesses a novel kind of amphiphilic profile with a coiled-coil-like hydrophobic strip and is the most aggressive of all. It indiscriminately permeabilizes natural membranes (antimicrobial, hemolysis) as well as artificial lipid bilayers through the segregation of anionic lipids and possibly enhanced motional averaging. Ltc1, Ltc3a, Ltc4a, and Ltc5a are efficient and selective in killing bacteria but without causing significant bilayer disturbance. They act rather slowly or may even translocate towards intracellular targets, suggesting more subtle lipid interactions. Ltc6a and Ltc7, finally, do not show much antimicrobial action but can nonetheless perturb model bilayers.
Fibroblast Growth Factor 21 as a Potential Biomarker for Improved Locomotion and Olfaction Detection Ability after Weight Reduction in Obese Mice

Obesity is one of the most challenging diseases of the 21st century and is accompanied by behavioural disorders. Exercise, dietary adjustments, or time-restricted feeding are the only successful long-term treatments to date. Fibroblast growth factor 21 (FGF21) plays a key role in dietary regulation, but FGF21 resistance is prevalent in obesity. The aim of this study was to investigate in obese mice whether weight reduction leads to improved behaviour and whether these behavioural changes are associated with decreased plasma FGF21 levels. After establishing a model for diet-induced obesity, mice were subjected to three different interventions for weight reduction, namely dietary change, treadmill exercise, or time-restricted feeding. In this study, we demonstrated that only the combination of dietary change and treadmill exercise affected all parameters leading to a reduction in weight, fat, and FGF21, as well as less anxious behaviour, higher overall activity, and improved olfactory detection abilities. To investigate the interrelationship between FGF21 and behavioural parameters, feature selection algorithms were applied designating FGF21 and body weight as one of five highly weighted features. In conclusion, we concluded from the complementary methods that FGF21 can be considered as a potential biomarker for improved behaviour in obese mice after weight reduction.
Tumor Necrosis Factor-Alpha Exacerbates Viral Entry in SARS-CoV2-Infected iPSC-Derived Cardiomyocytes

The coronavirus disease 2019 (COVID-19) pandemic with high infectivity and mortality has caused severe social and economic impacts worldwide. Growing reports of COVID-19 patients with multi-organ damage indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) may also disturb the cardiovascular system. Herein, we used human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) as the in vitro platform to examine the consequence of SARS-CoV2 infection on iCMs. Differentiated iCMs expressed the primary SARS-CoV2 receptor angiotensin-converting enzyme-II (ACE2) and the transmembrane protease serine type 2 (TMPRSS2) receptor suggesting the susceptibility of iCMs to SARS-CoV2. Following the infection of iCMs with SARS-CoV2, the viral nucleocapsid (N) protein was detected in the host cells, demonstrating the successful infection. Bioinformatics analysis revealed that the SARS-CoV2 infection upregulates several inflammation-related genes, including the proinflammatory cytokine tumor necrosis factor-α (TNF-α). The pretreatment of iCMs with TNF-α for 24 h, significantly increased the expression of ACE2 and TMPRSS2, SASR-CoV2 entry receptors. The TNF-α pretreatment enhanced the entry of GFP-expressing SARS-CoV2 pseudovirus into iCMs, and the neutralization of TNF-α ameliorated the TNF-α-enhanced viral entry. Collectively, SARS-CoV2 elevated TNF-α expression, which in turn enhanced the SARS-CoV2 viral entry. Our findings suggest that, TNF-α may participate in the cytokine storm and aggravate the myocardial damage in COVID-19 patients.
Deep Learning-Based Prediction of Paresthesia after Third Molar Extraction: A Preliminary Study

The purpose of this study was to determine whether convolutional neural networks (CNNs) can predict paresthesia of the inferior alveolar nerve using panoramic radiographic images before extraction of the mandibular third molar. The dataset consisted of a total of 300 preoperative panoramic radiographic images of patients who had planned mandibular third molar extraction. A total of 100 images taken of patients who had paresthesia after tooth extraction were classified as Group 1, and 200 images taken of patients without paresthesia were classified as Group 2. The dataset was randomly divided into a training and validation set (n = 150 [50%]), and a test set (n = 150 [50%]). CNNs of SSD300 and ResNet-18 were used for deep learning. The average accuracy, sensitivity, specificity, and area under the curve were 0.827, 0.84, 0.82, and 0.917, respectively. This study revealed that CNNs can assist in the prediction of paresthesia of the inferior alveolar nerve after third molar extraction using panoramic radiographic images.
Electrochemical Noise Measurement to Assess Corrosion of Steel Reinforcement in Concrete

The electrochemical noise method (ENM) has previously been employed to monitor the corrosion of steel reinforcement in concrete. The development of solid-state Ag/AgCl-based probes and dedicated monitoring technology (ProCoMeter) now offers a wider range of ENM configurations. The present study involves the laboratory investigation of three mortar samples containing steel bars and varying additions of chloride, with a view to future field application. ENM could be used to provide corrosion information on reinforcement without the need to provide direct electrical connections to the steel and without the risk or inducing or increasing corrosion. In addition to half-cell potentials, measurements were made using ENM in three different probe configurations over a total test period of 90 days. The samples were then broken open and the bars extracted and cleaned. A comparison was then made between the calculated metal thickness loss obtained from the Rn values and the actual metal thickness loss. The results showed that each configuration was able to order the results in the expected manner, with the simple single substrate (SSS) arrangement providing the best correlation with direct measurements. The study is ongoing with the intention of measurements being obtained in situ on existing reinforced concrete structures.
Association between Self-Reported Pain, Cognition, and Neuropathology in Older Adults Admitted to an Outpatient Memory Clinic—A Cross-Sectional Study

Cognitive impairment has been linked to reduced self-reporting of pain. However, it is unclear whether the various cognitive functions are similarly and/or independently associated with such pain report measures. In the present study, we explored how executive functioning (EF), memory, and global cognition relate to self-reported pain and investigated whether underlying neuropathology partially accounts for these results. We used Lasso categorical regression to analyze data from 179 individuals visiting a memory clinic. The data included the self-reported pain occurrence, intensity, severity and frequency, clinical diagnoses, neuropsychological scores, white matter hyperintensities, medial temporal lobe atrophy, depressive symptoms, and demographics. Our results showed that worse memory and EF performance predicted a lower pain occurrence. In those individuals who did report pain, worse memory predicted lower pain intensity, severity, and frequency levels, but for EF reversed effects were found, with worse EF predicting higher pain scores. These relationships were only partially explained by reductions in white matter and medial temporal lobe integrity. Similar effects were found for depressive symptoms. Our findings highlight the distinct associations of EF and memory with self-reported pain. A similar pattern of relationships found for both self-reported pain and depressive symptoms may reflect shared latent affective components.
Intention to Purchase Milk Packaged in Biodegradable Packaging: Evidence from Italian Consumers

The dairy industry generates large volumes of liquid waste that can be used to produce biopolymers, potentially employable for the creation of milk biodegradable bottles. In that regard, this paper aims to explore the consumers’ intention to purchase sustainable packages, as well as to assess the willingness to pay for it considering renewable packages made using organic waste feedstocks from the dairy industry (e.g., whey) and plant-based material (e.g., corn, sugarcane, etc.). To reach the stated objectives, we collected individual-level information (e.g., age, gender, education, income) from a convenient sample of 260 Italian consumers and a modified version of the Theory of Planned Behavior estimated using a structural equation model. Findings show that attitudes and perceived behavioral control are the most important drivers of the consumers’ intention to purchase sustainable packages. Finally, statistics show that respondents slightly prefer to purchase products packaged using plant-based biodegradable material, as well as most of the respondents show a low willingness to pay for milk offered in biodegradable packaging, regardless of the raw material used. Then, policymakers and companies should invest in educational/informational campaigns pointing out the beneficial effects on the environment from the purchase of foods in sustainable packaging. This may potentially increase the consumers’ intention to purchase, as well as their willingness to pay for plant-based and dairy whey-based packages by increasing the sustainability of the dairy supply chain.
Risk of Developing Epilepsy after Autoimmune Encephalitis

Background: Acute symptomatic seizures (ASS) are a common manifestation of autoimmune encephalitis (AE), but the risk of developing epilepsy as a sequela of AE remains unknown, and factors predisposing the development of epilepsy have not been fully identified. Objective: To assess the risk of developing epilepsy in AE and study related risk factors. Materials and methods: This was a retrospective single centre study including patients diagnosed with AE according to criteria described by Graus et al., with a minimum follow-up of 12 months after AE resolution. The sample was divided according to whether patients developed epilepsy or not. Results: A total of 19 patients were included; 3 (15.8%) had AE with intracellular antibodies, 9 (47.4%) with extracellular antibodies, and 7 (36.8%) were seronegative. During follow-up, 3 patients (15.8%) died, 4 (21.1%) presented relapses of AE, and 11 (57.89%) developed epilepsy. There was a significant association between the development of epilepsy and the presence of hippocampal atrophy in control brain magnetic resonance imaging (MRI) (p = 0.037), interictal epileptiform discharges (IED) on control electroencephalogram (EEG) (p = 0.045), and immunotherapy delay (p = 0.016). Conclusions: Hippocampal atrophy in neuroimaging, IED on EEG during follow-up, and immunotherapy delay could be predictors of the development of epilepsy in patients with AE.
Synthesis and Application of Silica-Coated Quantum Dots in Biomedicine

Quantum dots (QDs) are semiconductor nanoparticles with outstanding optoelectronic properties. More specifically, QDs are highly bright and exhibit wide absorption spectra, narrow light bands, and excellent photovoltaic stability, which make them useful in bioscience and medicine, particularly for sensing, optical imaging, cell separation, and diagnosis. In general, QDs are stabilized using a hydrophobic ligand during synthesis, and thus their hydrophobic surfaces must undergo hydrophilic modification if the QDs are to be used in bioapplications. Silica-coating is one of the most effective methods for overcoming the disadvantages of QDs, owing to silica’s physicochemical stability, nontoxicity, and excellent bioavailability. This review highlights recent progress in the design, preparation, and application of silica-coated QDs and presents an overview of the major challenges and prospects of their application.
Fundamental Movement Skills and Physical Activity of 3–4-Year-Old Children within Early Childhood Centers in New Zealand

We sought to describe and explore relationships between fundamental movement skills (FMS) and level of physical activity (PA; light-, medium-, vigorous, and kCal/hour) in preschool children, aged 3–4-years-old, across four early childhood education (ECE) settings. Children’s FMS were assessed using the Test for Gross Motor Development-2 (TGMD-2; n = 81) and PA via accelerometers (S = 53). Eighty-four children participated, with 50 in both assessments. The TGMD-2 showed as the children got older, their locomotor skills (p < 0.001, r = 0.512) and object control motor skills (p < 0.001, r = 0.383) improved. Accelerometry showed children were primarily inactive at ECE (78.3% of the time). There were significant correlations between kCal/hour and light (p < 0.001, r = −0.688), moderate (p < 0.001, r = 0.599) and vigorous (p < 0.001, rs = 0.707) activity, and between gross motor quotient and locomotor (p < 0.001, r = 0.798) and object control (p < 0.001, r = 0.367) skills. No correlation was observed between gross motor quotient and kCal/hour. To conclude, children in this cohort were primarily inactive during ECE center hours. Moreover, gross motor quotient was significantly correlated to locomotor and object control skills.
Directed Evolution Methods for Enzyme Engineering

Enzymes underpin the processes required for most biotransformations. However, natural enzymes are often not optimal for biotechnological uses and must be engineered for improved activity, specificity and stability. A rich and growing variety of wet-lab methods have been developed by researchers over decades to accomplish this goal. In this review such methods and their specific attributes are examined.
Detection of Circulating Serum Protein Biomarkers of Non-Muscle Invasive Bladder Cancer after Protein Corona-Silver Nanoparticles Analysis by SWATH-MS

Because cystoscopy is expensive and invasive, a new method of detecting non-invasive muscular bladder cancer (NMIBC) is needed. This study aims to identify potential serum protein markers for NMIBC to improve diagnosis and to find treatment approaches that avoid disease progression to a life-threatening phenotype (muscle-invasive bladder cancer, MIBC). Here, silver nanoparticles (AgNPs, 9.73 ± 1.70 nm) as a scavenging device together with sequential window acquisition of all theoretical mass spectra (SWATH-MS) were used to quantitatively analyze the blood serum protein alterations in two NMIBC subtypes, T1 and Ta, and they were compared to normal samples (HC). NMIBC’s analysis of serum samples identified three major groups of proteins, the relative content of which is different from the HC content: proteins implicated in the complement and coagulation cascade pathways and apolipoproteins. In conclusion, many biomarker proteins were identified that merit further examination to validate their useful significance and utility within the clinical management of NMIBC patients.
Microbiome Analysis of Carious Lesions in Pre-School Children with Early Childhood Caries and Congenital Heart Disease

Oral bacteria have been associated with several systemic diseases. Moreover, the abundance of bacteria associated with caries has been found to be higher in patients with congenital heart disease (CHD) than in healthy control groups (HCGs). Therefore, this study aimed to evaluate the dental microbiota in children with CHD compared to a HCG. The aim was to describe and compare the carious microbiome regarding the composition, diversity, and taxonomic patterns in these two groups. Twenty children with CHD and a HCG aged between two and six years participated. All of them were affected by early childhood caries. Microbiome profiling indicated that Fusobacterium, Prevotella, Capnocytophaga, and Oribacterium were more abundant in the CHD group, whereas Lactobacillus and Rothia were predominant in the HCG. Furthermore, microbiome analysis revealed three distinct clusters for the CHD and HCG samples. In the first cluster, we found mainly the genera Lactobacillus and Coriobacteriaceae. The second cluster showed a higher relative abundance of the genus Actinomyces and a more diverse composition consisting of more genera with a smaller relative lot. The third cluster was characterized by two genera, Streptococcus and Veillonella. These data can help us to understand the oral microbial community structures involved in caries and endodontic infections of pre-school children in relation to the general health of these high-risk patients.
Overview of Beneficial Effects of (Poly)phenol Metabolites in the Context of Neurodegenerative Diseases on Model Organisms

The rise of neurodegenerative diseases in an aging population is an increasing problem of health, social and economic consequences. Epidemiological and intervention studies have demonstrated that diets rich in (poly)phenols can have potent health benefits on cognitive decline and neurodegenerative diseases. Meanwhile, the role of gut microbiota is ever more evident in modulating the catabolism of (poly)phenols to dozens of low molecular weight (poly)phenol metabolites that have been identified in plasma and urine. These metabolites can reach circulation in higher concentrations than parent (poly)phenols and persist for longer periods of time. However, studies addressing their potential brain effects are still lacking. In this review, we will discuss different model organisms that have been used to study how low molecular weight (poly)phenol metabolites affect neuronal related mechanisms gathering critical insight on their potential to tackle the major hallmarks of neurodegeneration.
First Characterisation of the Phoma Species Complex on Maize Leaves in Central Europe

In the last decade, the cultivated area of maize has increased in Central Europe due to its high yield potential and diverse uses for feed and bio-energy. This has led to more intense maize cultivation, with narrowed crop rotations resulting in the increase in maize leaf diseases. During 2012 and 2013, an inventory of maize leaf spot diseases was carried out in various regions in Central Europe. In addition to the major leaf pathogens, isolates of Phoma-like species were obtained from oval to elliptical spots on leaves or found in lesions produced by other leaf pathogens. A total of 16 representative Phoma-like strains were characterised for their pathogenicity on maize leaves, for their morphological characteristics and with a phylogenetic analysis based on multilocus sequence analysis using part of the actin (ACT), calmodulin (CAL), β-tubulin (TUB), internal transcribed spacer (ITS) region of ribosomal DNA and large subunit ribosomal RNA (LSU) genes. The strains were grouped into four clades, and morphological studies supported this classification for most of them. Strains were compared with six reference Phoma-like species strains from the Westerndijk Fungal Biodiversity Institute collection reported to colonise maize. The pathogenic group of strains from our collection (after completion of Koch’s postulates) did not cluster with any of these species, indicating a different and novel Phoma-like species infecting maize leaves. To our knowledge, this is the first study dissecting the Phoma species complex on maize leaves in Central Europe.