Miracle-dz/UniFAR-FTUs huggingface dataset:
Adapted Physical Activity to Ensure the Physical and Psychological Well-Being of COVID-19 Patients

The novel coronavirus disease 2019 (COVID-19) has been responsible for a global pandemic involving massive increases in the daily numbers of cases and deaths. Due to the emergency caused by the pandemic, huge efforts have been made to develop COVID-19 vaccines, the first of which were released in December 2020. Effective vaccines for COVID-19 are needed to protect the population, especially healthcare professionals and fragile individuals, such as older people or chronic-disease-affected patients. Physical exercise training generally has health benefits and assists in the prevention of several chronic diseases. Moreover, physical activity improves mental health by reducing anxiety, depression, and negative mood and improving self-esteem. Therefore, the present review aims to provide a detailed view of the literature, presenting updated evidence on the beneficial effects of adapted physical activity, based on personalized and tailor-made exercise, in preventing, treating, and counteracting the consequences of COVID-19.
Edible Microalgae and Their Bioactive Compounds in the Prevention and Treatment of Metabolic Alterations

Marine and freshwater algae and their products are in growing demand worldwide because of their nutritional and functional properties. Microalgae (unicellular algae) will constitute one of the major foods of the future for nutritional and environmental reasons. They are sources of high-quality protein and bioactive molecules with potential application in the modern epidemics of obesity and diabetes. They may also contribute decisively to sustainability through carbon dioxide fixation and minimization of agricultural land use. This paper reviews current knowledge of the effects of consuming edible microalgae on the metabolic alterations known as metabolic syndrome (MS). These microalgae include Chlorella, Spirulina (Arthrospira) and Tetraselmis as well as Isochrysis and Nannochloropsis as candidates for human consumption. Chlorella biomass has shown antioxidant, antidiabetic, immunomodulatory, antihypertensive, and antihyperlipidemic effects in humans and other mammals. The components of microalgae reviewed suggest that they may be effective against MS at two levels: in the early stages, to work against the development of insulin resistance (IR), and later, when pancreatic -cell function is already compromised. The active components at both stages are antioxidant scavengers and anti-inflammatory lipid mediators such as carotenoids and -3 PUFAs (eicosapentaenoic acid/docosahexaenoic acid; EPA/DHA), prebiotic polysaccharides, phenolics, antihypertensive peptides, several pigments such as phycobilins and phycocyanin, and some vitamins, such as folate. As a source of high-quality protein, including an array of bioactive molecules with potential activity against the modern epidemics of obesity and diabetes, microalgae are proposed as excellent foods for the future. Moreover, their incorporation into the human diet would decisively contribute to a more sustainable world because of their roles in carbon dioxide fixation and reducing the use of land for agricultural purposes.
Optimization theory explains nighttime stomatal responses.

Nocturnal transpiration is widely observed across species and biomes, and may significantly impact global water, carbon, and energy budgets. However, it remains elusive why plants lose water at night and how to model it at large scales. We hypothesized that plants optimize nighttime leaf diffusive conductance (gwn) to balance potential daytime photosynthetic benefits and nocturnal transpiration benefits. We quantified nighttime benefits from respiratory reductions because of evaporative leaf cooling. We described nighttime costs as lost of carbon gain during the day because of water use at night. We measured nighttime stomatal responses and tested our model with water birch (Betula occidentalis Hook.) saplings grown in a greenhouse. The gwn of water birch decreased with drier soil, higher atmospheric CO2, wetter air, lower leaf temperature, and lower leaf respiration rate. Our model predicted all these responses correctly, except for gwn response to air humidity. Our results also suggested that the slow decrease of gwn after sunset could be associated with decreasing leaf respiration. The optimality-based nocturnal transpiration model smoothly integrates with daytime stomatal optimization approaches, and thus has the potential to quantitatively predict nocturnal transpiration across space and time.
Interaction between Parkin and α-Synuclein in PARK2-Mediated Parkinson’s Disease

Parkin and α-synuclein are two key proteins involved in the pathophysiology of Parkinson’s disease (PD). Neurotoxic alterations of α-synuclein that lead to the formation of toxic oligomers and fibrils contribute to PD through synaptic dysfunction, mitochondrial impairment, defective endoplasmic reticulum and Golgi function, and nuclear dysfunction. In half of the cases, the recessively inherited early-onset PD is caused by loss of function mutations in the PARK2 gene that encodes the E3-ubiquitin ligase, parkin. Parkin is involved in the clearance of misfolded and aggregated proteins by the ubiquitin-proteasome system and regulates mitophagy and mitochondrial biogenesis. PARK2-related PD is generally thought not to be associated with Lewy body formation although it is a neuropathological hallmark of PD. In this review article, we provide an overview of post-mortem neuropathological examinations of PARK2 patients and present the current knowledge of a functional interaction between parkin and α-synuclein in the regulation of protein aggregates including Lewy bodies. Furthermore, we describe prevailing hypotheses about the formation of intracellular micro-aggregates (synuclein inclusions) that might be more likely than Lewy bodies to occur in PARK2-related PD. This information may inform future studies aiming to unveil primary signaling processes involved in PD and related neurodegenerative disorders.
Investigations on Olenite with Excess Boron fromthe Koralpe, Styria, Austria

Chemical analyses of tourmaline crystals from a small pegmatite body, nearby the Stoihtte, Koralpe (Styria, Austria), exhibit a pronounced excess in boron, expressed by the simpli¢ed formula (Na0.43 Ca0.24&0:33) (Al2.43Li0.33&0:28)Al6(BO3)3(B1.23 Si4.87 O18)(O0.64(OH)3.36). A substantial substitution of silicon by boron in the tetrahedral position is in agree- ment with an occupation re¢nement in single crystal X-ray work: the average (Si, B)-O bond length measures1.610—. This is the ¢rst example forasubstitutionofsiliconbyboroninanaturaltourmaline,thatcouldbe veri¢ed bycrystallographic methods.
A Review on Ionic Liquid Gas Separation Membranes

Ionic liquids have attracted the attention of the industry and research community as versatile solvents with unique properties, such as ionic conductivity, low volatility, high solubility of gases and vapors, thermal stability, and the possibility to combine anions and cations to yield an almost endless list of different structures. These features open perspectives for numerous applications, such as the reaction medium for chemical synthesis, electrolytes for batteries, solvent for gas sorption processes, and also membranes for gas separation. In the search for better-performing membrane materials and membranes for gas and vapor separation, ionic liquids have been investigated extensively in the last decade and a half. This review gives a complete overview of the main developments in the field of ionic liquid membranes since their first introduction. It covers all different materials, membrane types, their preparation, pure and mixed gas transport properties, and examples of potential gas separation applications. Special systems will also be discussed, including facilitated transport membranes and mixed matrix membranes. The main strengths and weaknesses of the different membrane types will be discussed, subdividing them into supported ionic liquid membranes (SILMs), poly(ionic liquids) or polymerized ionic liquids (PILs), polymer/ionic liquid blends (physically or chemically cross-linked ‘ion-gels’), and PIL/IL blends. Since membrane processes are advancing as an energy-efficient alternative to traditional separation processes, having shown promising results for complex new separation challenges like carbon capture as well, they may be the key to developing a more sustainable future society. In this light, this review presents the state-of-the-art of ionic liquid membranes, to analyze their potential in the gas separation processes of the future.
New Prenylated Indole Homodimeric and Pteridine Alkaloids from the Marine-Derived Fungus Aspergillus austroafricanus Y32-2

Chemical investigation of secondary metabolites from the marine-derived fungus Aspergillus austroafricanus Y32-2 resulted in the isolation of two new prenylated indole alkaloid homodimers, di-6-hydroxydeoxybrevianamide E (1) and dinotoamide J (2), one new pteridine alkaloid asperpteridinate A (3), with eleven known compounds (4–14). Their structures were elucidated by various spectroscopic methods including HRESIMS and NMR, while their absolute configurations were determined by ECD calculations. Each compound was evaluated for pro-angiogenic, anti-inflammatory effects in zebrafish models and cytotoxicity for HepG2 human liver carcinoma cells. As a result, compounds 2, 4, 5, 7, 10 exhibited pro-angiogenic activity in a PTK787-induced vascular injury zebrafish model in a dose-dependent manner, compounds 7, 8, 10, 11 displayed anti-inflammatory activity in a CuSO4-induced zebrafish inflammation model, and compound 6 showed significant cytotoxicity against HepG2 cells with an IC50 value of 30 µg/mL.
Targeting Innate Immunity in Cancer Therapy

The majority of current cancer immunotherapy strategies target and potentiate antitumor adaptive immune responses. Unfortunately, the efficacy of these treatments has been limited to a fraction of patients within a subset of tumor types, with an aggregate response rate of approximately 20% to date across all malignancies. The success of therapeutic inhibition of programmed death protein 1 (PD-1), protein death ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) with immune checkpoint inhibitors (ICI) has been limited to “hot” tumors characterized by preexisting T cell infiltration, whereas “cold” tumors, which lack T cell infiltration, have not achieved durable benefit. There are several mechanisms by which “cold” tumors fail to generate spontaneous immune infiltration, which converge upon the generation of an immunosuppressive tumor microenvironment (TME). The role of the innate immune system in tumor immunosurveillance and generation of antitumor immune responses has been long recognized. In recent years, novel strategies to target innate immunity in cancer therapy have emerged, including therapeutic stimulation of pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs); the DNA sensing cGAS/STING pathway; nucleotide-binding oligomerization domain-like receptors (NLRs), such as NLRP3; and the retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs). In addition, therapeutic modulation of key innate immune cell types, such as macrophages and natural killer cells, has been investigated. Herein, we review therapeutic approaches to activate innate immunity within the TME to enhance antitumor immune responses, with the goal of disease eradication in “cold” tumors. In addition, we discuss rational immune-oncology combination strategies that activate both innate and adaptive immunity, with the potential to enhance the efficacy of current immunotherapeutic approaches.
Voltammetric Behavior and Determination of Cinnarizine in Pharmaceutical Formulations and Serum

Abstract The electrochemical reduction of cinnarizine was investigated by cyclic and linear sweep adsorptive voltammetry at glassy carbon electrode in Britton-Robinson buffers over the pH range 2.5–11.5. For analytical purposes, a well-defined adsorption-controlled cathodic peak was obtained at pH 2.5. By cathodic adsorptive linear sweep voltammetry, a linear calibration plot was obtained in the range of 2.0 × 10−7 to 5.0 × 10−6 mol L−1 with detection limit of 9.0 × 10−9 mol L−1. The method was successfully applied to the determination of cinnarizine in commercial formulations with mean recovery and relative standard deviation of 100.24% and 1.46, respectively. The proposed method was also applied for drug determination in spiked serum samples by applying the standard addition method with a mean recovery of 97.80% and standard deviation of 3.06.
Modulatory Impact of Adipose-Derived Mesenchymal Stem Cells of Ankylosing Spondylitis Patients on T Helper Cell Differentiation

The domination of pro-inflammatory Th subsets (Th1, Th17) is characteristic of ankylosing spondylitis (AS). Mesenchymal stem cells (MSC) were reported to normalize Th imbalance, but whether MSCs from AS adipose tissue (AS/ASCs) possess such properties is unknown. We examined AS/ASCs’ impact on Th-cell differentiation, using healthy donors ASCs (HD/ASCs) as a control. The assessment of the expression of transcription factors defining Th1 (T-bet), Th2 (GATA3), Th17 (RORc), and Treg (FoxP3) subsets by quantitative RT-PCR, the concentrations of subset-specific cytokines by ELISA, and Treg (CD4+CD25highFoxP3+) formation by flow cytometry, were performed in the co-cultures of ASCs with activated CD4+ T cells or peripheral blood mononuclear cells (PBMCs). AS/ASCs and HD/ASCs exerted similar immunomodulatory effects. Acting directly on CD4+ T cells, ASCs decreased the T-bet/GATA3 and RORc/FoxP3 ratios, diminished Treg formation, but increase IFNγ and IL-17AF production, while ASCs co-cultured with PBMCs enhanced Treg generation and reduced IFNγ release. ASCs failed to up-regulate the anti-inflammatory IL-10 and TGFβ. AS/ASCs’ impact on allogeneic and autologous PBMCs was similar. In conclusion, to shift Th differentiation to a functional anti-inflammatory direction, ASCs require accessory cell support, whereas their direct effect may be pro-inflammatory. Because ASCs neither inhibit IL-17AF nor up-regulate anti-inflammatory cytokines, their usefulness for AS patients’ treatment remains uncertain.
Thresholds of Glycemia and the Outcomes of COVID-19 Complicated With Diabetes: A Retrospective Exploratory Study Using Continuous Glucose Monitoring

OBJECTIVE Although elevated glucose levels are reported to be associated with adverse outcomes of coronavirus disease 2019 (COVID-19), the optimal range of glucose in patients with COVID-19 and diabetes remains unknown. This study aimed to investigate the threshold of glycemia and its association with the outcomes of COVID-19. RESEARCH DESIGN AND METHODS Glucose levels were assessed through intermittently scanned continuous glucose monitoring in 35 patients for an average period of 10.2 days. The percentages of time above range (TAR), time below range (TBR), time in range (TIR), and coefficient of variation (CV) were calculated. Composite adverse outcomes were defined as either the need for admission to the intensive care unit, need for mechanical ventilation, or morbidity with critical illness. RESULTS TARs using thresholds from 160 to 200 mg/dL were significantly associated with composite adverse outcomes after adjustment of covariates. Both TBR (<70 mg/dL) and TIR (70–160 mg/dL), but not mean sensor glucose level, were significantly associated with composite adverse outcomes and prolonged hospitalization. The multivariate-adjusted odds ratios of the CV of sensor glucose across tertiles for composite adverse outcomes of COVID-19 were 1.00, 1.18, and 25.2, respectively. CONCLUSIONS Patients with diabetes and COVID-19 have an increased risk of adverse outcomes with glucose levels >160 mg/dL and <70 mg/dL and a high CV. Therapies that improve these metrics of glycemic control may result in better prognoses for these patients.
Imaging Viral Infection by Fluorescence Microscopy: Focus on HIV-1 Early Stage

During the last two decades, progresses in bioimaging and the development of various strategies to fluorescently label the viral components opened a wide range of possibilities to visualize the early phase of Human Immunodeficiency Virus 1 (HIV-1) life cycle directly in infected cells. After fusion of the viral envelope with the cell membrane, the viral core is released into the cytoplasm and the viral RNA (vRNA) is retro-transcribed into DNA by the reverse transcriptase. During this process, the RNA-based viral complex transforms into a pre-integration complex (PIC), composed of the viral genomic DNA (vDNA) coated with viral and host cellular proteins. The protective capsid shell disassembles during a process called uncoating. The viral genome is transported into the cell nucleus and integrates into the host cell chromatin. Unlike biochemical approaches that provide global data about the whole population of viral particles, imaging techniques enable following individual viruses on a single particle level. In this context, quantitative microscopy has brought original data shedding light on the dynamics of the viral entry into the host cell, the cytoplasmic transport, the nuclear import, and the selection of the integration site. In parallel, multi-color imaging studies have elucidated the mechanism of action of host cell factors implicated in HIV-1 viral cycle progression. In this review, we describe the labeling strategies used for HIV-1 fluorescence imaging and report on the main advancements that imaging studies have brought in the understanding of the infection mechanisms from the viral entry into the host cell until the provirus integration step.
Seasonal Changes of Nuclear DNA Fragmentation in Boar Spermatozoa in Spain

Simple Summary Artificial insemination is widely used in pig production and currently a boar performs several thousand matings per year. Traditionally sperm quality is focused on the number of spermatozoa, their motility and morphology. However, the quality of sperm DNA, which contains genetic information, is also related to fertility problems. The aim of this research was to study the effect of natural light hours and age of the boar on the status of the sperm DNA. After a powerful statistical analysis, it was found that the percentage of spermatozoa with fragmented DNA decreases within the observed age range as the boar gets older. On the other hand, the amount of spermatozoa with fragmented DNA was the lowest in autumn while it was the highest in summer. This study demonstrates the remaining seasonality of boars in Spain and highlights the importance of controlling the environmental conditions in the farms. Sperm DNA testing provides a basis for improving the selection of AI boars by excluding males with higher DNA fragmentation due to their very young reproductive age that may pose a potential subfertility. Abstract There are numerous cases when conventional spermiogram parameters are all within an acceptable range but boar subfertility persists. The total sperm nuclear DNA fragmentation index (tDFI) is a trait related to fertility and prolificacy problems that is not routinely evaluated in commercial AI boars. The aim of this research was to study the effect of the photoperiod, season and reproductive age of the boar on tDFI (measured by SCSA) of 1279 ejaculates from 372 different boars belonging to 6 different breeds located in 6 AI studs in Spain. tDFI data ranged from 0.018% to 20.1%. Although there was a significant single boar effect in the tDFI occurrence, a negative correlation between the tDFI and the age of the boar was found (p < 0.001). tDFI would decrease due to aging of the boar 0.66% each year old within the observed age range. After including age as a covariate in the ANCOVA, no differences were found in tDFI between photoperiods when the sperm collection date was evaluated. However, when the date of the production of semen in the testis was evaluated, the total percentage of spermatozoa with fragmented nuclear DNA was 1.46% higher in the increasing photoperiod in comparison to the decreasing photoperiod (p < 0.0001). On the other hand, for both dates, the lowest tDFI values corresponded to minimum day length for decreasing photoperiod phase (autumn), while the highest tDFI values were found in summer (maximum day length for decreasing photoperiod phase).
Epidermal T cell subsets—Effect of age and antigen exposure in humans and mice

Epidermal T cells play a central role in immune surveillance and in inflammatory skin diseases. Major differences in the epidermal T cell composition are found between adult humans and antigen‐inexperienced laboratory mice. Whether this is due to inborn species differences, to different environmental exposures, or a combination of the two is a matter of debate.
Inflammation and Apolipoproteins Are Potential Biomarkers for Stratification of Cutaneous Melanoma Patients for Immunotherapy and Targeted Therapy

This study identifies a potential biomarker panel that could improve the selection of therapy for cutaneous melanoma patients. Malignant cutaneous melanoma is one of the most common cancers in young adults. During the last decade, targeted and immunotherapies have significantly increased the overall survival of patients with malignant cutaneous melanoma. Nevertheless, disease progression is common, and a lack of predictive biomarkers of patient response to therapy hinders individualized treatment strategies. To address this issue, we performed a longitudinal study using an unbiased proteomics approach to identify and quantify proteins in plasma both before and during treatment from 109 patients treated with either targeted or immunotherapy. Linear modeling and machine learning approaches identified 43 potential prognostic and predictive biomarkers. A reverse correlation between apolipoproteins and proteins related to inflammation was observed. In the immunotherapy group, patients with low pretreatment expression of apolipoproteins and high expression of inflammation markers had shorter progression-free survival. Similarly, increased expression of LDHB during treatment elicited a significant impact on response to immunotherapy. Overall, we identified potential common and treatment-specific biomarkers in malignant cutaneous melanoma, paving the way for clinical use of these biomarkers following validation on a larger cohort. Significance: This study identifies a potential biomarker panel that could improve the selection of therapy for patients with cutaneous melanoma.
Improving Liver Graft Function Using CD47 Blockade in the Setting of Normothermic Machine Perfusion

Supplemental Digital Content is available in the text. Background. Toward the goal of using more livers for transplantation, transplant centers are looking to increase the use of organs from “marginal” donors. Livers from these donors, however, have been shown to be more susceptible to preservation and reperfusion injury. Methods. Using a porcine model of donation after circulatory death, we studied the use of antibody-mediated CD47 blockade to further improve liver graft function undergoing normothermic machine perfusion. Livers from 20 pigs (5 per group) were brought under either 30 or 60 min of warm ischemia time followed by the administration of CD47 monoclonal antibody (CD47mAb) treatment or immunoglobulin G control antibodies and 6 h of normothermic extracorporeal liver perfusion. Results. After 6 h of normothermic extracorporeal liver perfusion, CD47mAb-treated livers with 30 or 60 min warm ischemia time had significantly lower alanine transaminase levels and higher bile production compared with their respective control groups. Blockade of the CD47 signaling pathway resulted in significantly lower thrombospondin-1 protein levels, lower expression of caspase-3, and higher expression of phosphorylated extracellular signal-regulated kinase. Conclusions. These findings suggested that CD47mAb treatment decreases ischemia/reperfusion injury through CD47/thrombospondin-1 signaling downregulation and the presence of necrosis/apoptosis after reperfusion and could increase liver regeneration during normothermic perfusion of the liver.