Miracle-dz/UniFAR-FTUs huggingface dataset:
Antibiotics Prescription by Spanish General Practitioners in Primary Dental Care

The aim of this study was to analyze the antibiotics prescription habits, both prophylactically and therapeutically, of Spanish general dental practitioners in the management of endodontic infections in primary care. Two hundred Spanish general dental practitioners were asked to respond to a survey on indications for antibiotics prescription in the treatment of endodontic infections, being 190 general dentists (95%) included in the study. Data were analyzed using descriptive statistics and the chi-square test. The average duration of antibiotics therapy was 6.5 ± 1.0 days. In patients without medical allergies, most of them (97%) selected amoxicillin as the antibiotic of the first choice, alone (51.1%) or associated with clavulanic acid (45.8%); in patients with penicillin allergies, the drug of choice was clindamycin 300 mg (70%). For cases of symptomatic irreversible pulpitis, 44% of the respondents prescribed antibiotics, in the scenario of prophylactic antibiotic prescription, up to 27% of the general dentists prescribe according to non-current guidelines (1 g 1 h before or 1 g 1 h before and 1 g 1 h after) in non-indicated cases (16% in patients taking oral bisphosphonates). It is necessary to improve the antibiotic prescription habits of Spanish general dentists in endodontics.
Determinants for α4β2 vs. α3β4 Subtype Selectivity of Pyrrolidine-Based nAChRs Ligands: A Computational Perspective with Focus on Recent cryo-EM Receptor Structures

The selectivity of α4β2 nAChR agonists over the α3β4 nicotinic receptor subtype, predominant in ganglia, primarily conditions their therapeutic range and it is still a complex and challenging issue for medicinal chemists and pharmacologists. Here, we investigate the determinants for such subtype selectivity in a series of more than forty α4β2 ligands we have previously reported, docking them into the structures of the two human subtypes, recently determined by cryo-electron microscopy. They are all pyrrolidine based analogues of the well-known α4β2 agonist N-methylprolinol pyridyl ether A-84543 and differ in the flexibility and pattern substitution of their aromatic portion. Indeed, the direct or water mediated interaction with hydrophilic residues of the relatively narrower β2 minus side through the elements decorating the aromatic ring and the stabilization of the latter by facing to the not conserved β2-Phe119 result as key distinctive features for the α4β2 affinity. Consistently, these compounds show, despite the structural similarity, very different α4β2 vs. α3β4 selectivities, from modest to very high, which relate to rigidity/extensibility degree of the portion containing the aromatic ring and to substitutions at the latter. Furthermore, the structural rationalization of the rat vs. human differences of α4β2 vs. α3β4 selectivity ratios is here proposed.
Nanocellulose Production Using Ionic Liquids with Enzymatic Pretreatment

Nanocellulose has gained increasing attention during the past decade, which is related to its unique properties and wide application. In this paper, nanocellulose samples were produced via hydrolysis with ionic liquids (1-ethyl-3-methylimidazole acetate (EmimOAc) and 1-allyl-3-methylimidazolium chloride (AmimCl)) from microcrystalline celluloses (Avicel and Whatman) subjected to enzymatic pretreatment. The obtained material was characterized using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), dynamic light scattering (DLS), scanning electron microscopy (SEM), and thermogravimetric analysis (TG). The results showed that the nanocellulose had a regular and spherical structure with diameters of 30–40 nm and exhibited lower crystallinity and thermal stability than the material obtained after hydrolysis with Trichoderma reesei enzymes. However, the enzyme-pretreated Avicel had a particle size of about 200 nm and a cellulose II structure. A two-step process involving enzyme pretreatment and hydrolysis with ionic liquids resulted in the production of nanocellulose. Moreover, the particle size of nanocellulose and its structure depend on the ionic liquid used.
Forecasting Air Temperature on Edge Devices with Embedded AI †

With the advent of the Smart Agriculture, the joint utilization of Internet of Things (IoT) and Machine Learning (ML) holds the promise to significantly improve agricultural production and sustainability. In this paper, the design of a Neural Network (NN)-based prediction model of a greenhouse’s internal air temperature, to be deployed and run on an edge device with constrained capabilities, is investigated. The model relies on a time series-oriented approach, taking as input variables the past and present values of the air temperature to forecast the future ones. In detail, we evaluate three different NN architecture types—namely, Long Short-Term Memory (LSTM) networks, Recurrent NNs (RNNs) and Artificial NNs (ANNs)—with various values of the sliding window associated with input data. Experimental results show that the three best-performing models have a Root Mean Squared Error (RMSE) value in the range 0.289÷0.402 ∘C, a Mean Absolute Percentage Error (MAPE) in the range of 0.87÷1.04%, and a coefficient of determination (R2) not smaller than 0.997. The overall best performing model, based on an ANN, has a good prediction performance together with low computational and architectural complexities (evaluated on the basis of the NetScore metric), making its deployment on an edge device feasible.
Bispecific T Cell Engagers for the Treatment of Multiple Myeloma: Achievements and Challenges

Simple Summary Here we list the benefits and disadvantages of using bispecific T cell engagers (BTCEs) for the treatment of multiple myeloma (MM). We summarize the mechanism of action; the various targets used for BTCE therapy for MM such as BCMA, CD38, FcRH5, CD19, and CD138; and novel strategies used to circumvent the limitations of BTCE therapy. Abstract MM is the second most common hematological malignancy and represents approximately 20% of deaths from hematopoietic cancers. The advent of novel agents has changed the therapeutic landscape of MM treatment; however, MM remains incurable. T cell-based immunotherapy such as BTCEs is a promising modality for the treatment of MM. This review article discusses the advancements and future directions of BTCE treatments for MM.
Chemical Diversity and Biological Activity of Secondary Metabolites from Soft Coral Genus Sinularia since 2013

Sinularia is one of the conspicuous soft coral species widely distributed in the world’s oceans at a depth of about 12 m. Secondary metabolites from the genus Sinularia show great chemical diversity. More than 700 secondary metabolites have been reported to date, including terpenoids, norterpenoids, steroids/steroidal glycosides, and other types. They showed a broad range of potent biological activities. There were detailed reviews on the terpenoids from Sinularia in 2013, and now, it still plays a vital role in the innovation of lead compounds for drug development. The structures, names, and pharmacological activities of compounds isolated from the genus Sinularia from 2013 to March 2021 are summarized in this review.
Chemical defense in developmental stages and adult of the sea star Echinaster (Othilia) brasiliensis

To date, evidence regarding the performance of secondary metabolites from larval stages of sea stars as an anti-predation defense relates only to a few species/specimens from a few geographic ranges. Unfortunately, this hinders a comprehensive global understanding of this inter-specific predator-prey interaction. Here, we present laboratory experimental evidence of chemical defense action in the early developmental stages and adults of the sea star Echinaster (Othilia) brasiliensis from Brazil against sympatric and allopatric invertebrate consumers. Blastulae, early and late brachiolarias of E. (O.) brasiliensis were not consumed by the sympatric and allopatric crabs Mithraculus forceps. Blastulae were also avoided by the sympatric and allopatric individuals of the anemone Anemonia sargassensis, but not the larval stages. Extracts from embryos (blastula) and brachiolarias of E. (O.) brasiliensis from one sampled population (João Fernandes beach) significantly inhibited the consumption by sympatric M. forceps, but not by allopatric crabs and A. sargassensi anemone. In this same site, extracts from adults E. (O.) brasiliensis significantly inhibited the consumption by sympatric and allopatric specimens of the crab in a range of concentrations. Whereas equivalent extract concentrations of E. (O.) brasiliensis from other population (Itaipu beach)inhibited the predation by allopatric M. forceps, while sympatric individuals of this crab avoided the only the higher level tested. Then, early stages and adult specimens of E. (O.) brasiliensis can be chemically defended against consumers, but this action is quite variable, depending on the type (anemone or crab) and the origin of the consumer (sympatric or allopatric).
Applying Pulsed Electric Fields to Whole Carrots Enhances the Bioaccessibility of Carotenoid and Phenolic Compounds in Derived Products

We propose the application of pulsed electric fields (PEF) to carrots to obtain derived products with increased phenolic and carotenoid bioaccessibility. For this purpose, juices, purees, and oil-added purees were obtained from whole PEF-treated carrots (five pulses of 3.5 kV cm−1; 0.61 kJ kg−1). In order to obtain shelf-stable products, the effect of a thermal treatment (70 °C for 10 min) was also studied. Carrot juices exhibited the highest carotenoid (43.4 mg/100 g fresh weight) and phenolic (322 mg kg−1 dry weight) contents. However, caffeic and coumaric acid derivatives were highly sensitive to PEF. The phenolic bioaccessibility reached 100% in purees obtained from the PEF-treated carrots, whereas the further thermally treated oil-added purees exhibited the greatest carotenoid bioaccessibility (7.8%). The increase in carotenoid bioaccessibility could be related to their better release and solubilization into micelles. The results suggest that food matrix aspects apart from particle size (e.g., pectin characteristics) are involved in phenolic bioaccessibility.
Shelf Life of Fresh Sliced Sea Bream Pack in PET Nanocomposite Trays

Spoilage of fish due to microbiological activity is one of the biggest problems found by producers to take fresh fish products to customers. It is necessary packaging improvements to be able to increase fish shelf life and, thus, be able to travel further and to keep product freshness longer at customer’s houses. In the present work, a new material is developed for fish packaging in modified atmosphere (MAP). This material is poly(ethylene terephathalate) (PET) extruded with a polyamide (PA) nanocomposite containing nanosepiolite. Here, it is shown the production procedure from laboratory to industrial scale. Permeability to oxygen and impact mechanical properties results are shown for different samples, both at laboratory and industrial processes. At the end, a material composition is chosen to produce the finale tray which will contain the sliced sea bream. Microbiological analysis is done over the packed fish, resulting is a lower microbiological count compared to a PET control sample. This means that shelf life of pack sea bream could increase from 2–4 to 7–9 days, which is very important for both producers and customers. On the other hand, trays obtained comply with European regulations in food contact materials (FCM) and, overall, they are suitable for food packaging materials.
Altered Expression of ESR1, ESR2, PELP1 and c-SRC Genes Is Associated with Ovarian Cancer Manifestation

Ovarian cancer remains the leading cause of death due to gynecologic malignancy. Estrogen-related pathways genes, such as estrogen receptors (ESR1 and ESR2) and their coregulators, proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), and proto-oncogene tyrosine-protein kinase c-Src (SRC) are involved in ovarian cancer induction and development, still they require in-depth study. In our study, tissue samples were obtained from 52 females of Caucasian descent (control group without cancerous evidence (n = 27), including noncancerous benign changes (n = 15), and the ovarian carcinoma (n = 25)). Using quantitative analyses, we investigated ESRs, PELP1, and SRC mRNA expression association with ovarian tumorigenesis. Proteins’ presence and their location were determined by Western blot and immunohistochemistry. Results showed that PELP1 and SRC expression levels were found to differ in tissues of different sample types. The expression patterns were complex and differed in the case of ovarian cancer patients compared to controls. The most robust protein immunoreactivity was observed for PELP1 and the weakest for ESR1. The expression patterns of analyzed genes represent a potentially interesting target in ovarian cancer biology, especially PELP1. This study suggests that specific estrogen-mediated functions in the ovary and ovary-derived cancer might result from different local interactions of estrogen with their receptors and coregulators.
Molecular and Functional Evolution of the Spermatophyte Sesquiterpene Synthases

Sesquiterpenes are important defense and signal molecules for plants to adapt to the environment, cope with stress, and communicate with the outside world, and their evolutionary history is closely related to physiological functions. In this study, the information of plant sesquiterpene synthases (STSs) with identified functions were collected and sorted to form a dataset containing about 500 members. The phylogeny of spermatophyte functional STSs was constructed based on the structural comparative analysis to reveal the sequence–structure–function relationships. We propose the evolutionary history of plant sesquiterpene skeletons, from chain structure to small rings, followed by large rings for the first time and put forward a more detailed function-driven hypothesis. Then, the evolutionary origins and history of spermatophyte STSs are also discussed. In addition, three newly identified STSs CaSTS2, CaSTS3, and CaSTS4 were analyzed in this functional evolutionary system, and their germacrene D products were consistent with the functional prediction. This demonstrates an application of the structure-based phylogeny in predicting STS function. This work will help us to understand evolutionary patterns and dynamics of plant sesquiterpenes and STSs and screen or design STSs with specific product profiles as functional elements for synthetic biology application.
Mycotoxins Affecting Animals, Foods, Humans, and Plants: Types, Occurrence, Toxicities, Action Mechanisms, Prevention, and Detoxification Strategies—A Revisit

Mycotoxins are produced by fungi and are known to be toxic to humans and animals. Common mycotoxins include aflatoxins, ochratoxins, zearalenone, patulin, sterigmatocystin, citrinin, ergot alkaloids, deoxynivalenol, fumonisins, trichothecenes, Alternaria toxins, tremorgenic mycotoxins, fusarins, 3-nitropropionic acid, cyclochlorotine, sporidesmin, etc. These mycotoxins can pose several health risks to both animals and humans, including death. As several mycotoxins simultaneously occur in nature, especially in foods and feeds, the detoxification and/or total removal of mycotoxins remains challenging. Moreover, given that the volume of scientific literature regarding mycotoxins is steadily on the rise, there is need for continuous synthesis of the body of knowledge. To supplement existing information, knowledge of mycotoxins affecting animals, foods, humans, and plants, with more focus on types, toxicity, and prevention measures, including strategies employed in detoxification and removal, were revisited in this work. Our synthesis revealed that mycotoxin decontamination, control, and detoxification strategies cut across pre-and post-harvest preventive measures. In particular, pre-harvest measures can include good agricultural practices, fertilization/irrigation, crop rotation, using resistant varieties of crops, avoiding insect damage, early harvesting, maintaining adequate humidity, and removing debris from the preceding harvests. On the other hand, post-harvest measures can include processing, chemical, biological, and physical measures. Additionally, chemical-based methods and other emerging strategies for mycotoxin detoxification can involve the usage of chitosan, ozone, nanoparticles, and plant extracts.
Fabrication of Capsaicin Loaded Nanocrystals: Physical Characterizations and In Vivo Evaluation

Nano-crystallization is a new emerging strategy to promote the saturation solubility, dissolution rate and subsequent bioavailability of Biopharmaceutical Class II drugs. Capsaicin belongs to BCS class-II drugs having low water solubility and dissolution rate. Nano-crystals (NC) of pure Capsaicin was developed and optimized in order to increase its water solubility, dissolution and further to promote its adhesiveness to skin epidermis layer. NC formulations were subjected to stability studies, droplet size, surface charge, poly-dispensability index, drug content, entrapment efficiency, thermal analysis, surface morphology, crystalline studies, solubility profile, in vitro release and ex vivo permeation studies. In vivo anti-inflammatory assay (Carrageenan-induced paw edema) was performed in Sprague Dawley rats. Nanocrystals loaded with capsaicin showed particle size 120 ± 3.0 nm with surface charge of −20.7 ± 3.5 and PDI was 0.48 ± 1.5. Drug content and entrapment efficiency of T3 was 85% and 90 ± 1.9% respectively. Thermal studies predicted that melting peak of capsaicin was present in the formulation suggested that there was no interaction between active moieties and excipients in NC formulation. Surface morphology confirmed the presence of Nano-size crystals having rough crystalline surface. XRD proved that the capsaicin NC are successfully developed by using high speed homogenization. The solubility of capsaicin was found to be 12.0 ± 0.013 μg/mL in water. In vitro study revealed that 89.94 ± 1.9% of drug was released within 24 h. Similarly, drug permeation was 68.32 ± 1.83%, drug retained in skin was 16.13 ± 1.11% while drug retained on skin was 9.12 ± 0.14% after 12 h. The nanocrystals showed higher anti-inflammatory activity as compared to marketed product (Dicloran®). The study concluded that improvement in dissolution rate of capsaicin may potentially provide the opportunities in the development of a much cost-effective dosage forms that will produce improved pharmacological effects, but at low dose as compared to the already available products.
Phospholipase A2 Drives Tumorigenesis and Cancer Aggressiveness through Its Interaction with Annexin A1

Phospholipids are suggested to drive tumorigenesis through their essential role in inflammation. Phospholipase A2 (PLA2) is a phospholipid metabolizing enzyme that releases free fatty acids, mostly arachidonic acid, and lysophospholipids, which contribute to the development of the tumor microenvironment (TME), promoting immune evasion, angiogenesis, tumor growth, and invasiveness. The mechanisms mediated by PLA2 are not fully understood, especially because an important inhibitory molecule, Annexin A1, is present in the TME but does not exert its action. Here, we will discuss how Annexin A1 in cancer does not inhibit PLA2 leading to both pro-inflammatory and pro-tumoral signaling pathways. Moreover, Annexin A1 promotes the release of cancer-derived exosomes, which also lead to the enrichment of PLA2 and COX-1 and COX-2 enzymes, contributing to TME formation. In this review, we aim to describe the role of PLA2 in the establishment of TME, focusing on cancer-derived exosomes, and modulatory activities of Annexin A1. Unraveling how these proteins interact in the cancer context can reveal new strategies for the treatment of different tumors. We will also describe the possible strategies to inhibit PLA2 and the approaches that could be used in order to resume the anti-PLA2 function of Annexin A1.
Coenzyme Q10 and Cardiovascular Diseases

Coenzyme Q10 (CoQ10), which plays a key role in the electron transport chain by providing an adequate, efficient supply of energy, has another relevant function as an antioxidant, acting in mitochondria, other cell compartments, and plasma lipoproteins. CoQ10 deficiency is present in chronic and age-related diseases. In particular, in cardiovascular diseases (CVDs), there is a reduced bioavailability of CoQ10 since statins, one of the most common lipid-lowering drugs, inhibit the common pathway shared by CoQ10 endogenous biosynthesis and cholesterol biosynthesis. Different clinical trials have analyzed the effect of CoQ10 supplementation as a treatment to ameliorate these deficiencies in the context of CVDs. In this review, we focus on recent advances in CoQ10 supplementation and the clinical implications in the reduction of cardiovascular risk factors (such as lipid and lipoprotein levels, blood pressure, or endothelial function) as well as in a therapeutic approach for the reduction of the clinical complications of CVD.
β-Thujaplicin Enhances TRAIL-Induced Apoptosis via the Dual Effects of XIAP Inhibition and Degradation in NCI-H460 Human Lung Cancer Cells

Abstract Background: β-thujaplicin, a natural tropolone derivative, has anticancer effects on various cancer cells via apoptosis. However, the apoptosis regulatory proteins involved in this process have yet to be revealed. Methods: Trypan blue staining, a WST-8 assay, and a caspase-3/7 activity assay were used to investigate whether β-thujaplicin sensitizes cancer cells to TNF-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. Additionally, western blotting was performed to clarify the effects of β-thujaplicin on X-linked inhibitor of apoptosis protein (XIAP) in NCI-H460 cells and a fluorescence polarization binding assay was used to evaluate the binding-inhibitory activity of β-thujaplicin against XIAP-BIR3. Results: β- and γ-thujaplicins decreased the viability of NCI-H460 cells in a dose-dependent manner; they also sensitized the cells to TRAIL-induced cell growth inhibition and apoptosis. β-thujaplicin significantly potentiated the apoptosis induction effect of TRAIL on NCI-H460 cells, which was accompanied by enhanced caspase-3/7 activity. Interestingly, β-thujaplicin treatment in NCI-H460 cells decreased XIAP levels. Furthermore, β-thujaplicin was able to bind XIAP-BIR3 at the Smac binding site. Conclusions: These findings indicate that β-thujaplicin could enhance TRAIL-induced apoptosis in NCI-H460 cells via XIAP inhibition and degradation. Thus, the tropolone scaffold may be useful for designing novel nonpeptidic small-molecule inhibitors of XIAP and developing new types of anticancer drugs.