Miracle-dz/UniFAR-FTUs huggingface dataset:
Management of Dyspepsia and Gastroparesis in Patients with Diabetes. A Clinical Point of View in the Year 2021

Diabetes mellitus is a widespread disease, and represents an important public health burden worldwide. Together with cardiovascular, renal and neurological complications, many patients with diabetes present with gastrointestinal symptoms, which configure the so-called diabetic enteropathy. In this review, we will focus on upper gastrointestinal symptoms in patients with diabetes, with particular attention to dyspepsia and diabetic gastroparesis (DG). These two clinical entities share similar pathogenetic mechanisms, which include autonomic neuropathy, alterations in enteric nervous system and histological abnormalities, such as interstitial cells of Cajal depletion. Moreover, the differential diagnosis may be challenging because of overlapping clinical features. Delayed gastric emptying should be documented to differentiate between DG and dyspepsia and it can be assessed through radioactive or non-radioactive methods. The clinical management of dyspepsia includes a wide range of different approaches, above all Helicobacter pylori test and treat. As regards DG treatment, a central role is played by dietary modification and glucose control and the first-line pharmacological therapy is represented by the use of prokinetics. A minority of patients with DG refractory to medical treatment may require more invasive therapeutic approaches, including supplemental nutrition, gastric electric stimulation, pyloromyotomy and gastrectomy.
Relationships between the Content of Phenolic Compounds and the Antioxidant Activity of Polish Honey Varieties as a Tool for Botanical Discrimination

The study compared the content of eight phenolic acids and four flavonoids and the antioxidant activity of six Polish varietal honeys. An attempt was also made to determine the correlations between the antioxidant parameters of the honeys and their polyphenol profile using principal component analysis. Total phenolic content (TPC), total flavonoid content (TFC), antioxidant activity (ABTS) and reduction capacity (FRAP) were determined spectrophotometrically, and the phenolic compounds were determined using high-performance liquid chromatography (HPLC). The buckwheat honeys showed the strongest antioxidant activity, most likely because they had the highest concentrations of total phenols, total flavonoids, p-hydroxybenzoic acid, caffeic acid, p-coumaric acid, vanillic acid and chrysin. The principal component analysis (PCA) of the data showed significant relationships between the botanic origin of the honey, the total content of phenolic compounds and flavonoids and the antioxidant activity of the six Polish varietal honeys. The strongest, significant correlations were shown for parameters of antioxidant activity and TPC, TFC, p-hydroxybenzoic acid, caffeic acid and p-coumaric acid. Analysis of four principal components (explaining 86.9% of the total variance), as a classification tool, confirmed the distinctiveness of the Polish honeys in terms of their antioxidant activity and content of phenolic compounds.
MiR-10a in Pancreatic Juice as a Biomarker for Invasive Intraductal Papillary Mucinous Neoplasm by miRNA Sequencing

New biomarkers are needed to further stratify the risk of malignancy in intraductal papillary mucinous neoplasm (IPMN). Although microRNAs (miRNAs) are expected to be stable biomarkers, they can vary owing to a lack of definite internal controls. To identify universal biomarkers for invasive IPMN, we performed miRNA sequencing using tumor-normal paired samples. A total of 19 resected tissues and 13 pancreatic juice samples from 32 IPMN patients were analyzed for miRNA expression by next-generation sequencing with a two-step normalization of miRNA sequence data. The miRNAs involved in IPMN associated with invasive carcinoma were identified from this tissue analysis and further verified with the pancreatic juice samples. From the tumor-normal paired tissue analysis of the expression levels of 2792 miRNAs, 20 upregulated and 17 downregulated miRNAs were identified. In IPMN associated with invasive carcinoma (INV), miR-10a-5p and miR-221-3p were upregulated and miR-148a-3p was downregulated when compared with noninvasive IPMN. When these findings were further validated with pancreatic juice samples, miR-10a-5p was found to be elevated in INV (p = 0.002). Therefore, three differentially expressed miRNAs were identified in tissues with INV, and the expression of miR-10a-5p was also elevated in pancreatic juice samples with INV. MiR-10a-5p is a promising additional biomarker for invasive IPMN.
The Melting Point Alternation in α,ω-Alkanedicarboxylic Acids†

Single-crystal X-ray diffraction analyses of α,ω-alkanedicarboxylic acids (HOOC−(CH2)n-2−COOH, n = 2−10) have been carried out at 130 and 298 K. Dimorphism is prevalent in odd carbon members, and the crystal structures of α- and β-forms of C7-diacid have been determined. Diacids show an alternation in their melting points with members containing an even number of carbon atoms exhibiting systematically higher melting points compared to odd ones. On the contrary, the solid-state densities of odd members with Cn ≥ 5 are higher than those of even members. Closest packing is therefore not the reason for alternating melting points in diacids. Diacids with Cn ≥ 5 show distinct packing regularities within even series and also within α- and β-series of odd members. The gross structural features are similar in even and (both forms of) odd diacids: (a) carboxy groups form hydrogen bonded dimers at both ends of the molecules, leading to infinite chains, and (b) methylene chains stack into columns through hydrophobic.
Relationship between Sleep Duration Trajectories and Self-Rated Depressive Symptoms in South Koreans with Physical Disabilities

Physically disabled persons can have sleep problems, which affects their mental health more than those in non-disabled people. However, there are few studies on the relationship between sleep duration and mental health targeting physically disabled people in South Korea, and existing studies on the disabled have mostly used data collected from convenience rather than nationally representative samples, limiting the generalization of the results. This study used data from the second wave of the Panel Survey of Employment for the Disabled (PSED, 2016–2018, 1st–3rd year). Participants included 1851 physically disabled individuals. The Chi-square test and generalized estimating equation (GEE) were used and the Akaike information criterion (AIC) value and the AIC log Bayes factor approximation were used to select sleep trajectories. This is the first study to elucidate multiple sleep trajectories in physically disabled people in Korea, and the relationship between sleep duration trajectories and self-rated depressive symptoms. People with physical disabilities who sleep more than 9 h have the highest risk of depression and need more intensive management as a priority intervention.
Mammalian and Avian Host Cell Influenza A Restriction Factors

The threat of a new influenza pandemic is real. With past pandemics claiming millions of lives, finding new ways to combat this virus is essential. Host cells have developed a multi-modular system to detect incoming pathogens, a phenomenon called sensing. The signaling cascade triggered by sensing subsequently induces protection for themselves and their surrounding neighbors, termed interferon (IFN) response. This response induces the upregulation of hundreds of interferon-stimulated genes (ISGs), including antiviral effectors, establishing an antiviral state. As well as the antiviral proteins induced through the IFN system, cells also possess a so-called intrinsic immunity, constituted of antiviral proteins that are constitutively expressed, creating a first barrier preceding the induction of the interferon system. All these combined antiviral effectors inhibit the virus at various stages of the viral lifecycle, using a wide array of mechanisms. Here, we provide a review of mammalian and avian influenza A restriction factors, detailing their mechanism of action and in vivo relevance, when known. Understanding their mode of action might help pave the way for the development of new influenza treatments, which are absolutely required if we want to be prepared to face a new pandemic.
Antiproliferative Properties of Scandium Exopolysaccharide Complexes on Several Cancer Cell Lines

Antimetastatic properties on both murine and human osteosarcoma cell lines (POS-1 and KHOS) have been evidenced using exopolysaccharide (EPS) derivatives, produced by Alteromonas infernus bacterium. These derivatives had no significant effect on the cell cycle neither a pro-apoptotic effect on osteosarcoma cells. Based on this observation, these EPSs could be employed as new drug delivery systems for therapeutic uses. A theranostic approach, i.e., combination of a predictive biomarker with a therapeutic agent, has been developed notably by combining with true pair of theranostic radionuclides, such as scandium 47Sc/44Sc. However, it is crucial to ensure that, once complexation is done, the biological properties of the vector remain intact, allowing the molecular tropism of the ligand to recognize its molecular target. It is important to assess if the biological properties of EPS evidenced on osteosarcoma cell lines remain when scandium is complexed to the polymers and can be extended to other cancer cell types. Scandium-EPS complexes were thus tested in vitro on human cell lines: MNNG/HOS osteosarcoma, A375 melanoma, A549 lung adenocarcinoma, U251 glioma, MDA231 breast cancer, and Caco2 colon cancer cells. An xCELLigence Real Cell Time Analysis (RTCA) technology assay was used to monitor for 160 h, the proliferation kinetics of the different cell lines. The tested complexes exhibited an anti-proliferative effect, this effect was more effective compared to EPS alone. This increase of the antiproliferative properties was explained by a change in conformation of EPS complexes due to their polyelectrolyte nature that was induced by complexation. Alterations of both growth factor-receptor signaling, and transmembrane protein interactions could be the principal cause of the antiproliferative effect. These results are very promising and reveal that EPS can be coupled to scandium for improving its biological effects and also suggesting that no major structural modification occurs on the ligand.
Quantum Chemical Microsolvation by Automated Water Placement

We developed a quantitative approach to quantum chemical microsolvation. Key in our methodology is the automatic placement of individual solvent molecules based on the free energy solvation thermodynamics derived from molecular dynamics (MD) simulations and grid inhomogeneous solvation theory (GIST). This protocol enabled us to rigorously define the number, position, and orientation of individual solvent molecules and to determine their interaction with the solute based on physical quantities. The generated solute–solvent clusters served as an input for subsequent quantum chemical investigations. We showcased the applicability, scope, and limitations of this computational approach for a number of small molecules, including urea, 2-aminobenzothiazole, (+)-syn-benzotriborneol, benzoic acid, and helicene. Our results show excellent agreement with the available ab initio molecular dynamics data and experimental results.
Adherence to Food-Based Dietary Guidelines: A Systemic Review of High-Income and Low- and Middle-Income Countries

Research comparing the adherence to food-based dietary guidelines (FBDGs) across countries with different socio-economic status is lacking, which may be a concern for developing nutrition policies. The aim was to report on the adherence to FBDGs in high-income (HIC) and low-and-middle-income countries (LMIC). A systematic review with searches in six databases was performed up to June 2020. English language articles were included if they investigated a population of healthy children and adults (7–65 years), using an observational or experimental design evaluating adherence to national FBDGs. Findings indicate that almost 40% of populations in both HIC and LMIC do not adhere to their national FBDGs. Fruit and vegetables (FV) were most adhered to and the prevalence of adhering FV guidelines was between 7% to 67.3%. HIC have higher consumption of discretionary foods, while results were mixed for LMIC. Grains and dairy were consumed below recommendations in both HIC and LMIC. Consumption of animal proteins (>30%), particularly red meat, exceeded the recommendations. Individuals from HIC and LMIC may be falling short of at least one dietary recommendation from their country’s guidelines. Future health policies, behavioral-change strategies, and dietary guidelines may consider these results in their development.
Antitumoral Activity of the MEK Inhibitor Trametinib (TMT212) Alone and in Combination with the CDK4/6 Inhibitor Ribociclib (LEE011) in Neuroendocrine Tumor Cells In Vitro

Simple Summary Systemic treatment options for advanced neuroendocrine tumors have significantly been improved in the last decade. However efficacy of systemic therapy is limited by tumor resistance and therefore there is a need for further treatment options. Inhibition of the Ras-Raf-Mek-Erk signaling cascade might be a promising new treatment strategy in neuroendocrine neoplasms. In this study we investigated the effects of the MEK inhibitor trametinib, the ERK inhibitor SCH772984 and the CDK4/6 inhibitor ribociclib in human neuroendocrine tumor cell lines BON1, QGP1 and NCI-H727 in vitro. Trametinib alone and in synergism with ribociclib demonstrated antiproliferative effects. Combination therapy of MEK inhibitors and CDK4/6 inhibitors might be a potential strategy to overcome CDK4/6 inhibitor resistance in neuroendocrine tumors. Abstract Objectives: This study assessed the antitumoral activity of the MEK inhibitor trametinib (TMT212) and the ERK1/2 inhibitor SCH772984, alone and in combination with the CDK4/6 inhibitor ribociclib (LEE011) in human neuroendocrine tumor (NET) cell lines in vitro. Methods: Human NET cell lines BON1, QGP-1, and NCI-H727 were treated with trametinib or SCH772984, alone and in combination with ribociclib, to assess cell proliferation, cell cycle distribution, and protein signaling using cell proliferation, flow cytometry, and Western blot assays, respectively. Results: Trametinib and SCH772984, alone and in combination with ribociclib, significantly reduced NET cell viability and arrested NET cells at the G1 phase of the cell cycle in all three cell lines tested. In addition, trametinib also caused subG1 events and apoptotic PARP cleavage in QGP1 and NCI-H727 cells. A western blot analysis demonstrated the use of trametinib alone and trametinib in combination with ribociclib to decrease the expression of pERK, cMyc, Chk1, pChk2, pCDK1, CyclinD1, and c-myc in a time-dependent manner in NCI-H727 and QGP-1 cells. Conclusions: MEK and ERK inhibition causes antiproliferative effects in human NET cell lines in vitro. The combination of the MEK inhibitor trametinib (TMT212) with the CDK4/6 inhibitor ribociclib (LEE011) causes additive antiproliferative effects. Future preclinical and clinical studies of MEK inhibition in NETs should be performed.
The Impact of Fluid Loss and Carbohydrate Consumption during Exercise, on Young Cyclists’ Fatigue Perception in Relation to Training Load Level

High-level young athletes need to face a wide spectrum of stressors on their journey to élite categories. The aims of the present study are (i) to evaluate session rate of perceived exertion (sRPE) at different training impulse (TRIMP) categories and the correlations between these two variables and, (ii) evaluate the correlations between sRPE, fluid loss, and carbohydrate consumption during exercise. Data on Edward’s TRIMP, sRPE, body mass loss pre- and post- exercise (∆), and carbohydrate consumption (CHO/h) during exercise have been acquired from eight male junior cyclists during a competitive season. One-way ANOVA and correlation analysis with linear regression have been performed on acquired data. sRPE resulted in a significant difference in the three TRIMP categories (p < 0.001). sRPE resulted in being very largely positively associated with TRIMP values (p < 0.001; R = 0.71). ∆ as well as CHO/h was largely negatively related with sRPE in all TRIMP categories (p < 0.001). The results confirmed the role of fluid balance and carbohydrate consumption on the perception of fatigue and fatigue accumulation dynamics independently from the training load. Young athletes’ training load monitoring and nutritional-hydration support represent important aspects in athlete’s exercise-induced fatigue management.
Inhalationally Administered Semifluorinated Alkanes (SFAs) as Drug Carriers in an Experimental Model of Acute Respiratory Distress Syndrome

Aerosol therapy in patients suffering from acute respiratory distress syndrome (ARDS) has so far failed in improving patients’ outcomes. This might be because dependent lung areas cannot be reached by conventional aerosols. Due to their physicochemical properties, semifluorinated alkanes (SFAs) could address this problem. After induction of ARDS, 26 pigs were randomized into three groups: (1) control (Sham), (2) perfluorohexyloctane (F6H8), and (3) F6H8-ibuprofen. Using a nebulization catheter, (2) received 1 mL/kg F6H8 while (3) received 1 mL/kg F6H8 with 6 mg/mL ibuprofen. Ibuprofen plasma and lung tissue concentration, bronchoalveolar lavage (BAL) fluid concentration of TNF-α, IL-8, and IL-6, and lung mechanics were measured. The ibuprofen concentration was equally distributed to the dependent parts of the right lungs. Pharmacokinetic data demonstrated systemic absorption of ibuprofen proofing a transport across the alveolo-capillary membrane. A significantly lower TNF-α concentration was observed in (2) and (3) when compared to the control group (1). There were no significant differences in IL-8 and IL-6 concentrations and lung mechanics. F6H8 aerosol seemed to be a suitable carrier for pulmonary drug delivery to dependent ARDS lung regions without having negative effects on lung mechanics.
Influence of Welding Speed on Fracture Toughness of Friction Stir Welded AA2024-T351 Joints

In order to ensure a quality welded joint, and thus safe operation and high reliability of the welded part or structure achieved by friction stir welding, it is necessary to select the optimal welding parameters. The parameters of friction stir welding significantly affect the structure of the welded joint, and thus the mechanical properties of the welded joint. Investigation of the influence of friction stir welding parameters was performed on 6-mm thick plates of aluminum alloy AA2024 T351. The quality of the welded joint is predominantly influenced by the tool rotation speed n and the welding speed v. In this research, constant tool rotation speed was adopted n = 750 rpm, and the welding speed was varied (v = 73, 116 and 150 mm/min). By the visual method and radiographic examination, imperfections of the face and roots of the welded specimens were not found. This paper presents the performed experimental tests of the macro and microstructure of welded joints, followed by tests of micro hardness and fracture behavior of Friction Stir Welded AA2024-T351 joints. It can be concluded that the welding speed of v = 116 mm/min is favorable with regard to the fracture behavior of the analysed FSW-joint.
Selective Interaction of Sugarcane eIF4E with VPgs from Sugarcane Mosaic Pathogens

Eukaryotic translation initiation factor 4E (eIF4E) plays a key role in the infection of potyviruses in susceptible plants by interacting with viral genome-linked protein (VPg). Sugarcane (Saccharum spp.) production is threatened by mosaic disease caused by Sugarcane mosaic virus (SCMV), Sorghum mosaic virus (SrMV), and Sugarcane streak mosaic virus (SCSMV). In this study, two eIF4Es and their isoform eIF(iso)4E and 4E-binding protein coding genes were cloned from sugarcane cultivar ROC22 and designated SceIF4Ea, SceIF4Eb, SceIF(iso)4E, and ScnCBP, respectively. Real-time quantitative PCR analysis showed different expression profiles of these four genes upon SCMV challenge. A subcellular localization assay showed that SceIF4Ea, SceIF4Eb, SceIF(iso)4E, and ScnCBP were distributed in the nucleus and cytoplasm. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays showed that SceIF4Ea/b and SceIF(iso)4E were selectively employed by different sugarcane mosaic pathogens, i.e., SCMV-VPg interacted with SceIF4Ea/b and SceIF(iso)4E, SrMV-VPg interacted with both SceIF4Eb and SceIF(iso)4E, and SCSMV-VPg interacted only with SceIF(iso)4E. Intriguingly, the BiFC assays, but not the Y2H assays, showed that ScnCBP interacted with the VPgs of SCMV, SrMV, and SCSMV. Competitive interaction assays showed that SCMV-VPg, SrMV-VPg, and SCMV-VPg did not compete with each other to interact with SceIF(iso)4E, and SceIF(iso)4E competed with SceIF4Eb to interact with SrMV-VPg but not SCMV-VPg. This study sheds light on the molecular mechanism of sugarcane mosaic pathogen infection of sugarcane plants and benefits sugarcane breeding against the sugarcane mosaic disease.
A Metataxonomic Approach Reveals Diversified Bacterial Communities in Antarctic Sponges

Marine sponges commonly host a repertoire of bacterial-associated organisms, which significantly contribute to their health and survival by producing several anti-predatory molecules. Many of these compounds are produced by sponge-associated bacteria and represent an incredible source of novel bioactive metabolites with biotechnological relevance. Although most investigations are focused on tropical and temperate species, to date, few studies have described the composition of microbiota hosted by Antarctic sponges and the secondary metabolites that they produce. The investigation was conducted on four sponges collected from two different sites in the framework of the XXXIV Italian National Antarctic Research Program (PNRA) in November–December 2018. Collected species were characterized as Mycale (Oxymycale) acerata, Haliclona (Rhizoniera) dancoi, Hemigellius pilosus and Microxina sarai by morphological analysis of spicules and amplification of four molecular markers. Metataxonomic analysis of these four Antarctic sponges revealed a considerable abundance of Amplicon Sequence Variants (ASVs) belonging to the phyla Proteobacteria, Bacteroidetes, Actinobacteria and Verrucomicrobia. In particular, M. (Oxymycale) acerata, displayed several genera of great interest, such as Endozoicomonas, Rubritalea, Ulvibacter, Fulvivirga and Colwellia. On the other hand, the sponges H. pilosus and H. (Rhizoniera) dancoi hosted bacteria belonging to the genera Pseudhongella, Roseobacter and Bdellovibrio, whereas M. sarai was the sole species showing some strains affiliated to the genus Polaribacter. Considering that most of the bacteria identified in the present study are known to produce valuable secondary metabolites, the four Antarctic sponges could be proposed as potential tools for the discovery of novel pharmacologically active compounds.