Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacological Modulators of Autophagy as a Potential Strategy for the Treatment of COVID-19

The family of coronaviruses (CoVs) uses the autophagy machinery of host cells to promote their growth and replication; thus, this process stands out as a potential target to combat COVID-19. Considering the different roles of autophagy during viral infection, including SARS-CoV-2 infection, in this review, we discuss several clinically used drugs that have effects at different stages of autophagy. Among them, we mention (1) lysosomotropic agents, which can prevent CoVs infection by alkalinizing the acid pH in the endolysosomal system, such as chloroquine and hydroxychloroquine, azithromycin, artemisinins, two-pore channel modulators and imatinib; (2) protease inhibitors that can inhibit the proteolytic cleavage of the spike CoVs protein, which is necessary for viral entry into host cells, such as camostat mesylate, lopinavir, umifenovir and teicoplanin and (3) modulators of PI3K/AKT/mTOR signaling pathways, such as rapamycin, heparin, glucocorticoids, angiotensin-converting enzyme inhibitors (IECAs) and cannabidiol. Thus, this review aims to highlight and discuss autophagy-related drugs for COVID-19, from in vitro to in vivo studies. We identified specific compounds that may modulate autophagy and exhibit antiviral properties. We hope that research initiatives and efforts will identify novel or “off-label” drugs that can be used to effectively treat patients infected with SARS-CoV-2, reducing the risk of mortality.
Emergency Medical Services (EMS) Transportation of Trauma Patients by Geographic Locations and In-Hospital Outcomes: Experience from Qatar

Background: Prehospital care provided by emergency medical services (EMS) plays an important role in improving patient outcomes. Globally, prehospital care varies across countries and even within the same country by the geographic location and access to medical services. We aimed to explore the prehospital trauma care and in-hospital outcomes within the urban and rural areas in the state of Qatar. Methods: A retrospective analysis was conducted utilizing data from the Qatar National Trauma Registry for trauma patients who were transported by EMS to a level 1 trauma center between 2017 and 2018. Data were analyzed and compared between urban and rural areas and among the different municipalities in which the incidents occurred. Results: Across the study duration, 1761 patients were transported by EMS. Of that, 59% were transported from an urban area and 41% from rural areas. There were significant differences in the on-scene time and total prehospital time as a function of urban and rural areas and municipalities; however, the response time across the study groups was comparable. There were no significant differences in blood transfusion, intubation, hospital length of stay, and mortality. Conclusion: Within different areas in Qatar, the EMS response time and in-hospital outcomes were comparable. This indicates that the provision of prehospital care across the country is similar. The prehospital and acute in-hospital care are accessible for everyone in the country at no cost. Understanding the differences in EMS utilization and prehospital times contributes to the policy development in terms of equitable distribution of healthcare resources.
Gene Amplification-Associated Overexpression of the Selenoprotein tRNA Enzyme TRIT1 Confers Sensitivity to Arsenic Trioxide in Small-Cell Lung Cancer

Simple Summary Small-cell lung cancer accounts for approximately 13% of all new lung cancer diagnoses, but in contrast to non-small-cell lung cancer, the implementation of targeted treatments in small-cell lung cancer has been limited, with little improvement in the clinical outcome in the last several decades. Exploring new pathways for targeted therapy, we have observed that extra-copies of the tRNA modifier TRIT1, involved in the translation of selenoproteins, confers sensitivity to arsenic trioxide in small-cell lung cancer. This finding could open a new therapeutic niche for a tumor type with such a dismal clinical course. Abstract The alteration of RNA modification patterns is emerging as a common feature of human malignancies. If these changes affect key RNA molecules for mRNA translation, such as transfer RNA, they can have important consequences for cell transformation. TRIT1 is the enzyme responsible for the hypermodification of adenosine 37 in the anticodon region of human tRNAs containing serine and selenocysteine. Herein, we show that TRIT1 undergoes gene amplification-associated overexpression in cancer cell lines and primary samples of small-cell lung cancer. From growth and functional standpoints, the induced depletion of TRIT1 expression in amplified cells reduces their tumorigenic potential and downregulates the selenoprotein transcripts. We observed that TRIT1-amplified cells are sensitive to arsenic trioxide, a compound that regulates selenoproteins, whereas reduction of TRIT1 levels confers loss of sensitivity to the drug. Overall, our results indicate a role for TRIT1 as a small-cell lung cancer-relevant gene that, when undergoing gene amplification-associated activation, can be targeted with the differentiation agent arsenic trioxide.
Liquid Biopsy Targeting Monocarboxylate Transporter 1 on the Surface Membrane of Tumor-Derived Extracellular Vesicles from Synovial Sarcoma

Simple Summary Synovial sarcoma (SS) is associated with a high risk of recurrence and poor prognosis, and no biomarker useful in monitoring tumor burden exists. We identified monocarboxylate transporter 1 (MCT1) expressed in extracellular vesicles (EVs) derived from synovial sarcoma as a potential such marker. Circulating levels of MCT1+CD9+ EVs were significantly correlated with tumor volume in a SS mouse model. Serum levels of MCT1+CD9+ EVs reflected tumor burden and treatment response in SS patients. Patients with MCT1 expression on the plasma membrane have significantly worse overall survival than those with nuclear expression. Silencing of MCT1 reduced the malignant phenotype including cellular viability, migration, and invasion of SS cells. MCT1 may thus be a promising novel target for liquid biopsies and a novel therapeutic target. Abstract The lack of noninvasive biomarkers that can be used for tumor monitoring is a major problem for soft-tissue sarcomas. Here we describe a sensitive analytical technique for tumor monitoring by detecting circulating extracellular vesicles (EVs) of patients with synovial sarcoma (SS). The proteomic analysis of purified EVs from SYO-1, HS-SY-II, and YaFuSS identified 199 common proteins. DAVID GO analysis identified monocarboxylate transporter 1 (MCT1) as a surface marker of SS-derived EVs, which was also highly expressed in SS patient-derived EVs compared with healthy individuals. MCT1+CD9+ EVs were also detected from SS-bearing mice and their expression levels were significantly correlated with tumor volume (p = 0.003). Furthermore, serum levels of MCT1+CD9+ EVs reflected tumor burden in SS patients. Immunohistochemistry revealed that MCT1 was positive in 96.7% of SS specimens and its expression on the cytoplasm/plasma membrane was significantly associated with worse overall survival (p = 0.002). Silencing of MCT1 reduced the cellular viability, and migration and invasion capability of SS cells. This work describes a new liquid biopsy technique to sensitively monitor SS using circulating MCT1+CD9+ EVs and indicates the therapeutic potential of MCT1 in SS.
A Low-Sodium Diet Boosts Ang (1–7) Production and NO-cGMP Bioavailability to Reduce Edema and Enhance Survival in Experimental Heart Failure

Sodium restriction is often recommended in heart failure (HF) to block symptomatic edema, despite limited evidence for benefit. However, a low-sodium diet (LSD) activates the classical renin-angiotensin-aldosterone system (RAAS), which may adversely affect HF progression and mortality in patients with dilated cardiomyopathy (DCM). We performed a randomized, blinded pre-clinical trial to compare the effects of a normal (human-equivalent) sodium diet and a LSD on HF progression in a normotensive model of DCM in mice that has translational relevance to human HF. The LSD reduced HF progression by suppressing the development of pleural effusions (p < 0.01), blocking pathological increases in systemic extracellular water (p < 0.001) and prolonging median survival (15%, p < 0.01). The LSD activated the classical RAAS by increasing plasma renin activity, angiotensin II and aldosterone levels. However, the LSD also significantly up-elevated the counter-regulatory RAAS by boosting plasma angiotensin converting enzyme 2 (ACE2) and angiotensin (1–7) levels, promoting nitric oxide bioavailability and stimulating 3′-5′-cyclic guanosine monophosphate (cGMP) production. Plasma HF biomarkers associated with poor outcomes, such as B-type natriuretic peptide and neprilysin were decreased by a LSD. Cardiac systolic function, blood pressure and renal function were not affected. Although a LSD activates the classical RAAS system, we conclude that the LSD delayed HF progression and mortality in experimental DCM, in part through protective stimulation of the counter-regulatory RAAS to increase plasma ACE2 and angiotensin (1–7) levels, nitric oxide bioavailability and cGMP production.
Which Green Space Metric Best Predicts a Lowered Odds of Type 2 Diabetes?

The choice of a green space metric may affect what relationship is found with health outcomes. In this research, we investigated the relationship between percent green space area, a novel metric developed by us (based on the average contiguous green space area a spatial buffer has contact with), in three different types of buffers and type 2 diabetes (T2D). We obtained information about diagnosed T2D and relevant covariates at the individual level from the large and representative 45 and Up Study. Average contiguous green space and the percentage of green space within 500 m, 1 km, and 2 km of circular buffer, line-based road network (LBRN) buffers, and polygon-based road network (PBRN) buffers around participants’ residences were used as proxies for geographic access to green space. Generalized estimating equation regression models were used to determine associations between access to green space and T2D status of individuals. It was found that 30%–40% green space within 500 m LBRN or PBRN buffers, and 2 km PBRN buffers, but not within circular buffers, significantly reduced the risk of T2D. The novel average green space area metric did not appear to be particularly effective at measuring reductions in T2D. This study complements an existing research body on optimal buffers for green space measurement.
Native Structure-Based Peptides as Potential Protein–Protein Interaction Inhibitors of SARS-CoV-2 Spike Protein and Human ACE2 Receptor

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is a positive-strand RNA virus that causes severe respiratory syndrome in humans, which is now referred to as coronavirus disease 2019 (COVID-19). Since December 2019, the new pathogen has rapidly spread globally, with over 65 million cases reported to the beginning of December 2020, including over 1.5 million deaths. Unfortunately, currently, there is no specific and effective treatment for COVID-19. As SARS-CoV-2 relies on its spike proteins (S) to bind to a host cell-surface receptor angiotensin-converting enzyme-2(ACE2), and this interaction is proved to be responsible for entering a virus into host cells, it makes an ideal target for antiviral drug development. In this work, we design three very short peptides based on the ACE2 sequence/structure fragments, which may effectively bind to the receptor-binding domain (RBD) of S protein and may, in turn, disrupt the important virus-host protein–protein interactions, blocking early steps of SARS-CoV-2 infection. Two of our peptides bind to virus protein with affinity in nanomolar range, and as very short peptides have great potential for drug development.
β-Ionone: Its Occurrence and Biological Function and Metabolic Engineering

β-Ionone is a natural plant volatile compound, and it is the 9,10 and 9′,10′ cleavage product of β-carotene by the carotenoid cleavage dioxygenase. β-Ionone is widely distributed in flowers, fruits, and vegetables. β-Ionone and other apocarotenoids comprise flavors, aromas, pigments, growth regulators, and defense compounds; serve as ecological cues; have roles as insect attractants or repellants, and have antibacterial and fungicidal properties. In recent years, β-ionone has also received increased attention from the biomedical community for its potential as an anticancer treatment and for other human health benefits. However, β-ionone is typically produced at relatively low levels in plants. Thus, expressing plant biosynthetic pathway genes in microbial hosts and engineering the metabolic pathway/host to increase metabolite production is an appealing alternative. In the present review, we discuss β-ionone occurrence, the biological activities of β-ionone, emphasizing insect attractant/repellant activities, and the current strategies and achievements used to reconstruct enzyme pathways in microorganisms in an effort to to attain higher amounts of the desired β-ionone.
Adherence Is More Than Just Being Present: Example of a Lay-Led Home-Based Programme with Physical Exercise, Nutritional Improvement and Social Support, in Prefrail and Frail Community-Dwelling Older Adults

Background: Little is known about the implementation of lifestyle interventions in frail, community-dwelling people. This study highlights different domains of adherence to explain an effectively delivered home-based intervention. Methods: Eighty prefrail and frail persons (≥65 years) participated in a physical training, nutritional, and social support intervention over 24 weeks. A detailed log book was kept for comprehensive documentation in order to assess adherence and further organizational, exercise, and nutritional parameters. Results: Participants reached an adherence rate (performed home visits/number of planned visits) of 84.0/80.5% from week 1–12/13–24. Out of those, 59% carried out ≥75% of the offered visits. Older age was associated with a higher adherence rate. A mean of 1.5 (0.6) visits/week (2 were planned) were realized lasting for a mean of 1.5 (0.9) hours (154% of the planned duration). Per visit, 1.2 (0.6) circuits of strength training were performed (60.5% of the planned value) and 0.5 (0.3) nutritional interventions (47%). After twelve months, 4.2% still carried out the home visits regularly and 25.0% occasionally. Conclusion: Adherence is much more than “being there”. Adherence rate and category are limited parameters to describe the implementation of a complex lifestyle intervention, therefore a comprehensive documentation is needed.
Biohybrid Bovine Bone Matrix for Controlled Release of Mesenchymal Stem/Stromal Cell Lyosecretome: A Device for Bone Regeneration

SmartBone® (SB) is a biohybrid bone substitute advantageously proposed as a class III medical device for bone regeneration in reconstructive surgeries (oral, maxillofacial, orthopedic, and oncology). In the present study, a new strategy to improve SB osteoinductivity was developed. SB scaffolds were loaded with lyosecretome, a freeze-dried formulation of mesenchymal stem cell (MSC)-secretome, containing proteins and extracellular vesicles (EVs). Lyosecretome-loaded SB scaffolds (SBlyo) were prepared using an absorption method. A burst release of proteins and EVs (38% and 50% after 30 min, respectively) was observed, and then proteins were released more slowly with respect to EVs, most likely because they more strongly adsorbed onto the SB surface. In vitro tests were conducted using adipose tissue-derived stromal vascular fraction (SVF) plated on SB or SBlyo. After 14 days, significant cell proliferation improvement was observed on SBlyo with respect to SB, where cells filled the cavities between the native trabeculae. On SB, on the other hand, the process was still present, but tissue formation was less organized at 60 days. On both scaffolds, cells differentiated into osteoblasts and were able to mineralize after 60 days. Nonetheless, SBlyo showed a higher expression of osteoblast markers and a higher quantity of newly formed trabeculae than SB alone. The quantification analysis of the newly formed mineralized tissue and the immunohistochemical studies demonstrated that SBlyo induces bone formation more effectively. This osteoinductive effect is likely due to the osteogenic factors present in the lyosecretome, such as fibronectin, alpha-2-macroglobulin, apolipoprotein A, and TGF-β.
Load Resistance Optimization of a Magnetically Coupled Two-Degree-of-Freedom Bistable Energy Harvester Considering Third-Harmonic Distortion in Forced Oscillation

In this study, the external load resistance of a magnetically coupled two-degree-of-freedom bistable energy harvester (2-DOF MCBEH) was optimized to maximize the harvested power output, considering the third-harmonic distortion in forced response. First, the nonlinear dynamic analysis was performed to investigate the characteristics of the large-amplitude interwell motions of the 2-DOF MCBEH. From the analysis results, it was found that the third-harmonic distortion occurs in the interwell motion of the 2-DOF MCBEH system due to the nonlinear magnetic coupling between the beams. Thus, in this study, the third-harmonic distortion was considered in the optimization process of the external load resistance of the 2-DOF MCBEH, which is different from the process of conventional impedance matching techniques suitable for linear systems. The optimal load resistances were estimated for harmonic and swept-sine excitations by using the proposed method, and all the results of the power outputs were in excellent agreements with the numerically optimized results. Furthermore, the associated power outputs were compared with the power outputs obtained by using the conventional impedance matching technique. The results of the power outputs are discussed in terms of the improvement in energy harvesting performance.
In Vitro Efficacy of Bacterial Cellulose Dressings Chemisorbed with Antiseptics against Biofilm Formed by Pathogens Isolated from Chronic Wounds

Local administration of antiseptics is required to prevent and fight against biofilm-based infections of chronic wounds. One of the methods used for delivering antiseptics to infected wounds is the application of dressings chemisorbed with antimicrobials. Dressings made of bacterial cellulose (BC) display several features, making them suitable for such a purpose. This work aimed to compare the activity of commonly used antiseptic molecules: octenidine, polyhexanide, povidone-iodine, chlorhexidine, ethacridine lactate, and hypochlorous solutions and to evaluate their usefulness as active substances of BC dressings against 48 bacterial strains (8 species) and 6 yeast strains (1 species). A silver dressing was applied as a control material of proven antimicrobial activity. The methodology applied included the assessment of minimal inhibitory concentrations (MIC) and minimal biofilm eradication concentration (MBEC), the modified disc-diffusion method, and the modified antibiofilm dressing activity measurement (A.D.A.M.) method. While in 96-well plate-based methods (MIC and MBEC assessment), the highest antimicrobial activity was recorded for chlorhexidine, in the modified disc-diffusion method and in the modified A.D.A.M test, povidone-iodine performed the best. In an in vitro setting simulating chronic wound conditions, BC dressings chemisorbed with polyhexanide, octenidine, or povidone-iodine displayed a similar or even higher antibiofilm activity than the control dressing containing silver molecules. If translated into clinical conditions, the obtained results suggest high applicability of BC dressings chemisorbed with antiseptics to eradicate biofilm from chronic wounds.
Membrane Carriers and Transporters in Kidney Physiology and Disease

The growing information suggests that chronic kidney disease may affect expression and function of membrane carriers and transporters in the kidney. The dysfunction of carriers and transporters entails deficient elimination of uremic solutes as well as xenobiotics (drugs and toxins) with subsequent clinical consequences. The renal carriers and transporters are also targets of drugs used in clinical practice, and intentional drug–drug interactions in the kidney are produced to increase therapeutic efficacy. The understanding of membrane carriers and transporters function in chronic kidney disease is important not only to better characterize drug pharmacokinetics, drug actions in the kidney, or drug–drug interactions but also to define the organ pathophysiology.
Would Parents Get Their Children Vaccinated Against SARS-CoV-2? Rate and Predictors of Vaccine Hesitancy According to a Survey over 5000 Families from Bologna, Italy

In the near future, COVID-19 vaccine efficacy trials in larger cohorts may offer the possibility to implement child and adolescent vaccination. The opening of the vaccination for these strata may play a key role in order to limit virus circulation, infection spreading towards the most vulnerable subjects, and plan safe school reopening. Vaccine hesitancy (VH) could limit the ability to reach the coverage threshold required to ensure herd immunity. The aim of this study was to investigate the prevalence and determinants of VH among parents/guardians toward a potentially available COVID-19 vaccination for children and adolescents. An online survey was performed in parents/guardians of children aged <18 years old, living in Bologna. Overall, 5054 questionnaires were collected. A vast majority (60.4%) of the parents/guardians were inclined to vaccinate, while 29.6% were still considering the opportunity, and 9.9% were hesitant. Highest vaccine hesitancy rates were detected in female parents/guardians of children aged 6–10 years, ≤29 years old, with low educational level, relying on information found in the web/social media, and disliking mandatory vaccination policies. Although preliminary, these data could help in designing target strategies to implement adherence to a vaccination campaign, with special regard to web-based information.
Produção de Biodiesel Metílico de Soja com o Auxílio de um Coletor Solar Sustentável

A busca por fontes de energias alternativas tem aumentado substancialmente na ultima decada, devido a expectativa de diminuicao gradativa das reservas de petroleo e aumento da preocupacao com as questoes ambientais. O biodiesel vem se consolidando como potencial substituto para o diesel, porem, um dos gargalos da producao ainda e o custo operacional. Uma alternativa ao processo e utilizar coletores solares para realizar o aquecimento da reacao de transesterificacao. O presente trabalho propos a construcao de um prototipo de coletor solar constituido de materias potencialmente reciclaveis como garrafas PET e embalagens do tipo Tetra Pak. As garrafas PET foram recortadas na sua parte inferior para um encaixe futuro, tendo como funcao a protecao da parte absorvedora do painel do prototipo. As embalagens Tetra Pak foram pintadas de preto fosco em apenas um dos lados com intuito de absorver com maior eficiencia os raios solares. Apos a construcao do coletor, foram realizados testes de aquecimento, para verificar se o mesmo forneceria a temperatura minima desejada para haver a reacao de transesterificacao. O perfil de esteres presentes no biodiesel, bem como, o seu teor de ester foram avaliados por cromatografia gasosa e seu valor enquadrado na resolucao ANP N° 14 de 2012.