Miracle-dz/UniFAR-FTUs huggingface dataset:
Elevated Epidermal Growth Factor (EGF) as Candidate Biomarker of Mood Disorders—Longitudinal Study in Adolescent and Young Adult Patients

Bipolar disorder (BD) is a chronic mental disorder that affects more than 1% of the population worldwide. Over 65% of patients experience early onset of the disease. Most cases of juvenile bipolar disorder begin with a depressed mood episode, and up to 50% of youth initially diagnosed with major depression go onto developing a BD. Our study aimed to find biomarkers of diagnosis conversion in young patients with mood disorders. We performed a two-year follow-up study on 79 adolescent patients diagnosed with MDD or BD, with a detailed clinical assessment at five visits. We monitored diagnosis change from MDD to BD. The control group consisted of 31 healthy youths. According to the neurodevelopmental and neuroimmunological hypotheses of mood disorders, we analyzed serum levels of brain-derived neurotrophic factor (BDNF), proBDNF, epidermal growth factor (EGF), migration inhibitory factor (MIF), stem cell factor (SCF), and correlations with clinical factors. We detected a significant disease-dependent increase in EGF level in MDD and BP patients at baseline exacerbation of depressive or hypomanic/manic episodes as well as in euthymic state compared to healthy controls. No potential biological predictors of disease conversion were found. Replication studies on a larger cohort of patients are needed.
PD-L1 Expression Is Significantly Associated with Tumor Mutation Burden and Microsatellite Instability Score

Simple Summary Biomarkers for predicting the response to immune checkpoint blockade (ICB) includes programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC), microsatellite instability (MSI), and tumor mutation burden (TMB). This study investigated the relationship of these biomarkers using comprehensive cancer panel assay (CCPA) with >500 genes in 588 advanced cancer patients. The work demonstrates that PD-L1 expression is significantly associated with TMB and MSI score, according to primary tumor origin. Abstract Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC), microsatellite instability (MSI), and tumor mutation burden (TMB) have been proposed as a predictive biomarker to predict response to immune checkpoint blockade (ICB). We aimed to find the relationship of PD-L1 IHC to TMB and MSI using a comprehensive cancer panel assay (CCPA) with >500 genes in advanced cancer patients. CCPA results from 588 archived tissue samples were analyzed for TMB and MSI. In seven samples, whole exome sequencing confirmed TMB with Pearson’s correlation coefficient of 0.972 and all MSI-high cases were validated by pentaplex PCR. Association of TMB and MSI with their corresponding PD-L1 IHC was analyzed. The median TMB value of 588 cases was 8.25 mutations (mut)/Mb (range 0–426.8) with different distributions among the tumor types, with high proportions of high-TMB (>10mut/Mb) in tumors from melanoma, colorectal, gastric, and biliary tract. The TMB values significantly correlated with PD-L1 expression, and this correlation was prominent in gastric and biliary tract cancers. Moreover, the MSI score, the proportion of unstable MSI sites to total assessed MSI sites, showed a significant correlation with the TMB values and PD-L1 scores. This study demonstrates that PD-L1 expression is significantly associated with TMB and MSI score and this correlation depends on the location of the primary tumor.
Astaxanthin Mitigates Thiacloprid-Induced Liver Injury and Immunotoxicity in Male Rats

Thiacloprid (TCP) is a widely used neonicotinoid insecticide with a probable toxic hazard to animals and human beings. This hazard has intensified the demand for natural compounds to alleviate the expected toxic insults. This study aimed at determining whether astaxanthin (ASX) could mitigate the hepatotoxic effect of TCP and diminish its suppressive effect on immune responses in rats. Animals received TCP by gavage at 62.1 mg/kg (1/10th LD50) with or without ASX at 40 mg/kg for 60 days. Intoxicated rats showed modulation of serum transaminases and protein profiles. The hemagglutination antibody titer to sheep red blood cells (SRBC) and the number of plaque-forming cells in the spleen were reduced. The cell-mediated immunity and phagocytosis were suppressed, while serum interleukins IL-1β, IL-6, and IL-10 were elevated. Additionally, malondialdehyde, nitric oxide, and 8-hydroxy-2′-deoxyguanosine levels were increased in the liver, spleen, and thymus, with depletion of glutathione and suppression of superoxide dismutase and catalase activities. The expressions of inducible nitric oxide synthase and the high mobility group box protein 1 genes were upregulated with histomorphological alterations in the aforementioned organs. Cotreatment with ASX markedly ameliorated the toxic effects of TCP, and all markers showed a regression trend towards control values. Collectively, our data suggest that the protective effects of ASX on the liver and immune system of TCP-treated animals depend upon improving the antioxidant status and relieving the inflammatory response, and thus it may be used as a promising therapeutic agent to provide superior hepato- and immunoprotection.
A Mobile App for Measuring Real Time Fatigue in Patients with Multiple Sclerosis: Introducing the Fimo Health App

Although fatigue is one of the most disabling symptoms of MS, its pathogenesis is not well understood yet. This study aims to introduce a new holistic approach to measure fatigue and its influencing factors via a mobile app. Fatigue is measured with different patient-reported outcome measures (Visual Analog Scale, Fatigue Severity Scale) and tests (Symbol Digit Modalities Test). The influencing vital and environmental factors are captured with a smartwatch and phone sensors. Patients can track these factors within the app. To individually counteract their fatigue, a fatigue course, based on the current treatment guidelines, was implemented. The course implies knowledge about fatigue and MS, exercises, energy-conservation management, and cognitive behavioral therapy. Based on the Transtheoretical Model of Behavior Change, the design of the Fimo health app follows the ten strategies of the process of change, which is a proven approach to designing health intervention programs. By monitoring fatigue and individual influencing factors, patients can better understand and manage their fatigue. They can share their data and insights about fatigue and its influencing factors with their doctors. Thus, they can receive individualized therapies and drug plans.
Isolation and Characterization of Endophyte Bacillus velezensis KOF112 from Grapevine Shoot Xylem as Biological Control Agent for Fungal Diseases

As the use of chemical fungicides has raised environmental concerns, biological control agents have attracted interest as an alternative to chemical fungicides for plant-disease control. In this study, we attempted to explore biological control agents for three fungal phytopathogens causing downy mildew, gray mold, and ripe rot in grapevines, which are derived from shoot xylem of grapevines. KOF112, which was isolated from the Japanese indigenous wine grape Vitis sp. cv. Koshu, inhibited mycelial growth of Botrytis cinerea, Colletotrichum gloeosporioides, and Phytophthora infestans. The KOF112-inhibited mycelial tips were swollen or ruptured, suggesting that KOF112 produces antifungal substances. Analysis of the 16S rDNA sequence revealed that KOF112 is a strain of Bacillus velezensis. Comparative genome analysis indicated significant differences in the synthesis of non-ribosomal synthesized antimicrobial peptides and polyketides between KOF112 and the antagonistic B. velezensis FZB42. KOF112 showed biocontrol activities against gray mold caused by B. cinerea, anthracnose by C. gloeosporioides, and downy mildew by Plasmopara viticola. In the KOF112–P. viticola interaction, KOF112 inhibited zoospore release from P. viticola zoosporangia but not zoospore germination. In addition, KOF112 drastically upregulated the expression of genes encoding class IV chitinase and β-1,3-glucanase in grape leaves, suggesting that KOF112 also works as a biotic elicitor in grapevine. Because it is considered that endophytic KOF112 can colonize well in and/or on grapevine, KOF112 may contribute to pest-management strategies in viticulture and potentially reduce the frequency of chemical fungicide application.
Comparing Pathological Risk Factors for Dementia between Cognitively Normal Japanese and Americans

The Alzheimer’s Disease Neuroimaging Initiative showed that Japanese had significantly lower brain Aβ burden than Americans among a cognitively normal population. This cross-sectional study aimed to compare vascular disease burden, Aβ burden, and neurodegeneration between cognitively normal elderly Japanese and Americans. Japanese and American participants were matched for age (±4-year-old), sex, and Apolipoprotein E (APOE) genotype. Brain vascular disease burden and brain Aβ burden were measured using white matter lesions (WMLs) and 11C-labeled Pittsburgh Compound B (PiB) retention, respectively. Neurodegeneration was measured using hippocampal volumes and cortical thickness. A total of 95 Japanese and 95 Americans were recruited (50.5% men, mean age = 82). Compared to Americans, Japanese participants had larger WMLs, and a similar global Aβ standardized uptake value ratio (SUVR), cortical thickness and hippocampal volumes. Japanese had significantly lower regional Aβ SUVR in the anterior ventral striatum, posterior cingulate cortex, and precuneus. Cognitively normal elderly Japanese and Americans had different profiles regarding vascular disease and Aβ burden. This suggests that multiple risk factors are likely to be involved in the development of dementia. Additionally, Japanese might have a lower risk of dementia due to lower Aβ burden than Americans. Longitudinal follow-up of these cohorts is warranted to ascertain the predictive accuracy of these findings.
Lipid-Based Drug Delivery Systems in Regenerative Medicine

The most important goal of regenerative medicine is to repair, restore, and regenerate tissues and organs that have been damaged as a result of an injury, congenital defect or disease, as well as reversing the aging process of the body by utilizing its natural healing potential. Regenerative medicine utilizes products of cell therapy, as well as biomedical or tissue engineering, and is a huge field for development. In regenerative medicine, stem cells and growth factor are mainly used; thus, innovative drug delivery technologies are being studied for improved delivery. Drug delivery systems offer the protection of therapeutic proteins and peptides against proteolytic degradation where controlled delivery is achievable. Similarly, the delivery systems in combination with stem cells offer improvement of cell survival, differentiation, and engraftment. The present review summarizes the significance of biomaterials in tissue engineering and the importance of colloidal drug delivery systems in providing cells with a local environment that enables them to proliferate and differentiate efficiently, resulting in successful tissue regeneration.
The PUB4 E3 Ubiquitin Ligase Is Responsible for the Variegated Phenotype Observed upon Alteration of Chloroplast Protein Homeostasis in Arabidopsis Cotyledons

During a plant’s life cycle, plastids undergo several modifications, from undifferentiated pro-plastids to either photosynthetically-active chloroplasts, ezioplasts, chromoplasts or storage organelles, such as amyloplasts, elaioplasts and proteinoplasts. Plastid proteome rearrangements and protein homeostasis, together with intracellular communication pathways, are key factors for correct plastid differentiation and functioning. When plastid development is affected, aberrant organelles are degraded and recycled in a process that involves plastid protein ubiquitination. In this study, we have analysed the Arabidopsis gun1-102 ftsh5-3 double mutant, lacking both the plastid-located protein GUN1 (Genomes Uncoupled 1), involved in plastid-to-nucleus communication, and the chloroplast-located FTSH5 (Filamentous temperature-sensitive H5), a metalloprotease with a role in photosystem repair and chloroplast biogenesis. gun1-102 ftsh5-3 seedlings show variegated cotyledons and true leaves that we attempted to suppress by introgressing second-site mutations in genes involved in: (i) plastid translation, (ii) plastid folding/import and (iii) cytosolic protein ubiquitination. Different phenotypic effects, ranging from seedling-lethality to partial or complete suppression of the variegated phenotype, were observed in the corresponding triple mutants. Our findings indicate that Plant U-Box 4 (PUB4) E3 ubiquitin ligase plays a major role in the target degradation of damaged chloroplasts and is the main contributor to the variegated phenotype observed in gun1-102 ftsh5-3 seedlings.
Influence of Geocomposite Properties on the Crack Propagation and Interlayer Bonding of Asphalt Pavements

The application of geocomposites as reinforcement in asphalt pavements is a promising solution for the maintenance/rehabilitation of existing pavements and for the construction of new pavements, whose effectiveness strongly depends on the physical and mechanical properties of the geocomposite. This study aims at assessing the influence of four different geocomposites, obtained by combining a reinforcing geosynthetic with a bituminous membrane, on the crack propagation and interlayer bonding of asphalt pavements. First, a laboratory investigation was carried out on double-layered asphalt specimens. The crack propagation resistance under static and dynamic loads was investigated through three-point bending tests (carried out on specimens with and without notch) and reflective cracking tests respectively, whereas the interlayer shear strength was evaluated through Leutner tests. Then, a trial section was constructed along an Italian motorway and a Falling Weight Deflectometer (FWD) testing campaign was carried out. The laboratory investigation highlighted that—as compared to the unreinforced system—the geocomposites increased the crack propagation energy in the layer above the reinforcement from five to ten times, indicating that they can significantly extend the service life of the pavement by delaying bottom-up and reflective cracking. However, they also worsened the interlayer bonding between the asphalt layers (de-bonding effect). The field investigation indicated that all geocomposites decreased the stiffness of the asphalt layers with respect to the unreinforced pavement as a consequence of the de-bonding effect, thus corroborating the laboratory results. Based on the results obtained, it is desirable that the geocomposite possess a high energy dissipation capability and an upper coating ensuring good adhesion between the asphalt layers. The monitoring of the existing trial section in the future will provide useful data on the long-term field performance of reinforced pavements subjected to actual motorway traffic.
Non-Viral Gene Delivery Systems for Treatment of Myocardial Infarction: Targeting Strategies and Cardiac Cell Modulation

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide. Conventional therapies involving surgery or pharmacological strategies have shown limited therapeutic effects due to a lack of cardiac tissue repair. Gene therapy has opened an avenue for the treatment of cardiac diseases through manipulating the underlying gene mechanics. Several gene therapies for cardiac diseases have been assessed in clinical trials, while the clinical translation greatly depends on the delivery technologies. Non-viral vectors are attracting much attention due to their safety and facile production compared to viral vectors. In this review, we discuss the recent progress of non-viral gene therapies for the treatment of cardiovascular diseases, with a particular focus on myocardial infarction (MI). Through a summary of delivery strategies with which to target cardiac tissue and different cardiac cells for MI treatment, this review aims to inspire new insights into the design/exploitation of non-viral delivery systems for gene cargos to promote cardiac repair/regeneration.
Whole-Genome Sequencing-Based Characterization of a Listeria monocytogenes Strain from an Aborted Water Buffalo in Southern Italy

Listeria monocytogenes is a Gram-positive pathogen causing life-threatening infections both in humans and animals. In livestock farms, it can persist for a long time and primarily causes uterine infections and encephalitis in farmed animals. Whole genome sequencing (WGS) is currently becoming the best method for molecular typing of this pathogen due to its high discriminatory power and efficiency of characterization. This study describes the WGS-based characterization of an L. monocytogenes strain from an aborted water buffalo fetus in southern Italy. The strain under study was classified as molecular serogroup IVb, phylogenetic lineage I, MLST sequence type 6, Clonal Complex 6, and cgMLST type CT3331, sublineage 6. Molecular analysis indicated the presence of 61 virulence genes and 4 antibiotic resistance genes. Phylogenetic analysis, including all the publicly available European L. monocytogenes serogroup IVb isolates, indicated that our strain clusterized with all the other CC6 strains and that different CCs were variably distributed within countries and isolation sources. This study contributes to the current understanding of the genetic diversity of L. monocytogenes from animal sources and highlights how the WGS strategy can provide insights into the pathogenic potential of this microorganism, acting as an important tool for epidemiological studies.
Fouling Release Coatings Based on Acrylate–MQ Silicone Copolymers Incorporated with Non-Reactive Phenylmethylsilicone Oil

Copolymers containing MQ silicone and acrylate were synthesized by controlling the additive amount of compositions. Subsequently, fouling release coatings based on the copolymer with the incorporation of non-reactive phenylmethylsilicone oil were prepared. The surface properties of the coating (CAMQ40) were consistent with that of the polydimethylsiloxane (PDMS) elastomer, which ensured good hydrophobicity. Moreover, the seawater volume swelling rate of all prepared coatings was less than 5%, especially for CAMQ40 with only 1.37%. Copolymers enhanced the mechanical properties of the coatings, while the enhancement was proportional to the molar content of structural units from acrylate in the copolymer. More importantly, the adhesion performance between the prepared coatings and substrates indicated that pull-off strength values were more than 1.6 MPa, meaning a high adhesion strength. The phenylmethylsilicone oil leaching observation determined that the oil leaching efficiency increased with the increase in the structural unit’s molar content from MQ silicone in the copolymer, which was mainly owing to the decrease in compatibility between oil and the cured coating, as well as the decrease in mechanical properties. High oil leaching efficiency could make up for the decrease in the biofouling removal rate due to the enhancement of the elastic modulus. For CAMQ40, it had an excellent antifouling performance at 30 days of exposure time with more than 92% of biofouling removal rate, which was confirmed by biofilm adhesion assay.
Sexual Exposure to HIV Infection during the COVID-19 Pandemic in Men Who Have Sex with Men (MSM): A Multicentric Study

The practice of sex with casual partners without the use of adequate prevention in the period of social distancing due to the COVID-19 pandemic among men who have sex with men (MSM) can expose them to the risk of infection by the HIV virus. To assess this, we conducted an online survey in April and May 2020 in the entire national territory of Brazil and Portugal. We used the snowball technique for sampling, associated with circulation in social networks, totaling 2934 participants. Bivariate and multivariate logistic regression was used to produce the adjusted Odds Ratio (aOR). Eight-hundred-and-forty-two (28.7%) MSM presented at-risk sexual exposure in this period. In general, the types of sexual practices that most increased the chances of sexual exposure were having multiple partners (aOR:14.045); having practiced chemsex (aOR:2.246) and group sex (aOR:2.431), as well as presenting a history of at-risk sexual exposure (aOR:5.136). When we consider each country separately, the chances are increased in Brazil since the probability of the outcome was increased in those who practiced group sex (aOR:5.928), had multiple partners (aOR:19.132), and reported a sexual history of at-risk exposure (aOR:8.861). Our findings indicate that practices that are classically associated with greater chances of engaging in risky sexual exposure to HIV infection were the factors that most increased the chances of acquiring the virus in the pandemic context.
Focusness Extraction from Images for Automatic Camera Control by Measuring Objectness

Current digital cameras have various automatic control systems. In automatic camera systems, extracting focusness from an image is a very important problem. Automatic extraction of the main subject makes taking photos very easy, even for an amateur photographer. Methods have been proposed to evaluate focusness by visual saliency, which assume that an area with high saliency also has high focusness. However, various differences exist between focusness and saliency. In this study, we compare the values between focusness and saliency maps. We evaluate the focusness of 80 images in an image evaluation experiment with 20 observers. Saliency maps are calculated using six conventional algorithms. We show that the individual variations of focusness are very few in images that include only one major object. Furthermore, we apply a GIST feature to the saliency method by using a center-surround histogram and extract focusness from images with high accuracy.
Computational Insights into the Interaction between Cytoadherence Receptor gC1qR and the DBLβ12 Domain of a Plasmodium falciparum PfEMP1 Ligand

Human receptor gC1qR is a 32 kD protein that mediates the cytoadherence of Plasmodium falciparum-infected erythrocytes (IEs) to human brain microvascular endothelial cells (HBMEC) and platelets. The cytoadherence of IEs to gC1qR has been associated with severe malaria symptoms. The cytoadherence to gC1qR is mediated by the Duffy binding-like β12 (DBLβ12) domain of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), PFD0020c. Here, we report the structural insights into the binding of the DBLβ12 domain of PfEMP1 with the human receptor gC1qR using computational methods. A molecular model of the DBLβ12 domain was generated and used for protein–protein docking with the host receptor gC1qR. The protein–protein docking revealed that the DBLβ12 asymmetrically interacts with two subunits of the gC1qR trimer at the solution face of gC1qR. A total of 21 amino acid residues of DBLβ12 interact with 26 amino acid residues in the gC1qR trimer through 99 nonbonding interactions and 4 hydrogen bonds. Comparative analysis of binding sites on the DBL domain fold for the two receptors gC1qR and ICAM1 showed that the two sites are distinct. This is the first study that provides structural insights into DBLβ12 binding with its receptor gC1qR and may help in designing novel antisevere malaria interventions.