Miracle-dz/UniFAR-FTUs huggingface dataset:
HPLC Fingerprints for the Characterization of Walnuts and the Detection of Fraudulent Incidents

A high-pressure liquid chromatographic method coupled to diode array detector (HPLC-DAD) was developed for the determination of phenolic compounds that could be used as markers in authentication studies of walnuts belonging to the Chandler variety, originating from Bulgaria, Greece, and France. An ultrasound-assisted extraction (UAE) protocol applied in the extraction of phenolic compounds was optimized. The method was validated and the relative standard deviations (RSD%) of the within-day, and between-day assays was lower than 6.3 and 11.1, respectively, showing adequate precision, and good accuracy ranging from 86.4 (sinapic acid) to 98.4% (caffeic acid) for within-day assay, and from 90.1 (gallocatechin gallate) to 100.6% (gallic acid) for between-day assay. Eighteen phenolic compounds were determined belonging to the classes of phenolic acids and flavonoids. The quantification results were further processed with chemometrics, and a robust partial least square–discriminant analysis (PLS-DA) model was developed for the classification of the samples according to their geographical origin, proposing markers that could be used for the control of walnuts authenticity and the detection of fraudulent incidents.
Role of Antifungal Combinations in Difficult to Treat Candida Infections

Candida infections are varied and, depending on the immune status of the patient, a life-threatening form may develop. C. albicans is the most prevalent species isolated, however, a significant shift towards other Candida species has been noted. Monotherapy is frequently indicated, but the patient’s evolution is not always favorable. Drug combinations are a suitable option in specific situations. The aim of this review is to address this problem and to discuss the role of drug combinations in difficult to treat Candida infections. A search for eligible studies in PubMed and Google Scholar databases was performed. An analysis of the data was carried out to define in which cases a combination therapy is the most appropriate. Combination therapy may be used for refractory candidiasis, endocarditis, meningitis, eye infections and osteomyelitis, among others. The role of the drug combination would be to increase efficacy, reduce toxicity and improve the prognosis of the patient in infections that are difficult to treat. More clinical studies and reporting of cases in which drug combinations are used are needed in order to have more data that support the use of this therapeutic strategy.
Clinical Implications of Amyloid-Beta Accumulation in Occipital Lobes in Alzheimer’s Continuum

A substantial amount of amyloid-beta (Aβ) accumulates in the occipital cortices; however, it draws less attention. We investigated the clinical implications of Aβ accumulation in the occipital lobes in the Alzheimer’s disease (AD) continuum. [18F]-Florbetaben amyloid PET scans were performed in a total of 121 AD or amnestic mild cognitive impairment (aMCI) patients. Of the 121 patients, 74 Aβ positive patients were divided into occipital Aβ positive (OCC+) and occipital Aβ negative (OCC−) groups based on Aβ accumulation in the bilateral occipital lobes. The OCC+ group (41/74, 55.4%) was younger and had a younger age at onset than the OCC− group. The OCC+ group also had an increased standard uptake value ratio in the occipital lobes and greater cortical thinning in relevant areas. The OCC+ group had a higher global deterioration scale, lower performance for the copy, immediate recall, delayed recall, and recognition in Rey–Osterrieth Complex Figure tests than the OCC- group, although both groups had similar disease durations. AD or aMCI patients in the OCC+ group exhibited features noted in early onset AD with relevant neuropsychological and image findings. Occipital Aβ positivity in amyloid PET scans need to be considered as an underestimated marker of early onset AD continuum.
Developments in Synthesis and Potential Electronic and Magnetic Applications of Pristine and Doped Graphynes

Doping and its consequences on the electronic features, optoelectronic features, and magnetism of graphynes (GYs) are reviewed in this work. First, synthetic strategies that consider numerous chemically and dimensionally different structures are discussed. Simultaneous or subsequent doping with heteroatoms, controlling dimensions, applying strain, and applying external electric fields can serve as effective ways to modulate the band structure of these new sp2/sp allotropes of carbon. The fundamental band gap is crucially dependent on morphology, with low dimensional GYs displaying a broader band gap than their bulk counterparts. Accurately chosen precursors and synthesis conditions ensure complete control of the morphological, electronic, and physicochemical properties of resulting GY sheets as well as the distribution of dopants deposited on GY surfaces. The uniform and quantitative inclusion of non-metallic (B, Cl, N, O, or P) and metallic (Fe, Co, or Ni) elements into graphyne derivatives were theoretically and experimentally studied, which improved their electronic and magnetic properties as row systems or in heterojunction. The effect of heteroatoms associated with metallic impurities on the magnetic properties of GYs was investigated. Finally, the flexibility of doped GYs’ electronic and magnetic features recommends them for new electronic and optoelectronic applications.
Assessment of Dispersion and Bubble Entropy Measures for Enhancing Preterm Birth Prediction Based on Electrohysterographic Signals

One of the remaining challenges for the scientific-technical community is predicting preterm births, for which electrohysterography (EHG) has emerged as a highly sensitive prediction technique. Sample and fuzzy entropy have been used to characterize EHG signals, although they require optimizing many internal parameters. Both bubble entropy, which only requires one internal parameter, and dispersion entropy, which can detect any changes in frequency and amplitude, have been proposed to characterize biomedical signals. In this work, we attempted to determine the clinical value of these entropy measures for predicting preterm birth by analyzing their discriminatory capacity as an individual feature and their complementarity to other EHG characteristics by developing six prediction models using obstetrical data, linear and non-linear EHG features, and linear discriminant analysis using a genetic algorithm to select the features. Both dispersion and bubble entropy better discriminated between the preterm and term groups than sample, spectral, and fuzzy entropy. Entropy metrics provided complementary information to linear features, and indeed, the improvement in model performance by including other non-linear features was negligible. The best model performance obtained an F1-score of 90.1 ± 2% for testing the dataset. This model can easily be adapted to real-time applications, thereby contributing to the transferability of the EHG technique to clinical practice.
Exploring the Role of L10 Loop in New Delhi Metallo-β-lactamase (NDM-1): Kinetic and Dynamic Studies

Four NDM-1 mutants (L218T, L221T, L269H and L221T/Y229W) were generated in order to investigate the role of leucines positioned in L10 loop. A detailed kinetic analysis stated that these amino acid substitutions modified the hydrolytic profile of NDM-1 against some β-lactams. Significant reduction of kcat values of L218T and L221T for carbapenems, cefazolin, cefoxitin and cefepime was observed. The stability of the NDM-1 and its mutants was explored by thermofluor assay in real-time PCR. The determination of TmB and TmD demonstrated that NDM-1 and L218T were the most stable enzymes. Molecular dynamic studies were performed to justify the differences observed in the kinetic behavior of the mutants. In particular, L218T fluctuated more than NDM-1 in L10, whereas L221T would seem to cause a drift between residues 75 and 125. L221T/Y229W double mutant exhibited a decrease in the flexibility with respect to L221T, explaining enzyme activity improvement towards some β-lactams. Distances between Zn1-Zn2 and Zn1-OH- or Zn2-OH- remained unaffected in all systems analysed. Significant changes were found between Zn1/Zn2 and first sphere coordination residues.
Comprehensive Comparison of the Effect of Inotropes on Cardiorenal Syndrome in Patients with Advanced Heart Failure: A Network Meta-Analysis of Randomized Controlled Trials

Prevention of cardiorenal syndrome through treatment with inotropic agents remains challenging. This network meta-analysis evaluated the safety and renoprotective effects of inotropes on patients with advanced heart failure (HF) using a frequentist random-effects model. A systematic database search was performed until 31 January 2021, and a total of 37 trials were included. Inconsistency, publication bias, and subgroup analyses were conducted. The levosimendan group exhibited significantly decreased mortality compared with the control (odds ratio (OR): 0.62; 95% confidence interval (CI): 0.46–0.84), milrinone (OR: 0.50; 95% CI: 0.30–0.84), and dobutamine (OR: 0.75; 95% CI: 0.57–0.97) groups. In terms of renal protection, levosimendan (standardized mean difference (SMD): 1.67; 95% CI: 1.17–2.18) and dobutamine (SMD: 1.49; 95% CI: 0.87–2.12) more favorably improved the glomerular filtration rate (GFR) than the control treatment did, but they did not significantly reduce the incidence of acute kidney injury. Furthermore, levosimendan had the highest P-score, indicating that it most effectively reduced mortality and improved renal function (e.g., GFR and serum creatinine level), even in patients with renal insufficiency. In conclusion, levosimendan is a safe alternative for protecting renal function on cardiorenal syndrome in patients with advanced HF.
The pH-Dependent Controlled Release of Encapsulated Vitamin B1 from Liposomal Nanocarrier

In this work, we firstly presented a simple encapsulation method to prepare thiamine hydrochloride (vitamin B1)-loaded asolectin-based liposomes with average hydrodynamic diameter of ca. 225 and 245 nm under physiological and acidic conditions, respectively. In addition to the optimization of the sonication and magnetic stirring times used for size regulation, the effect of the concentrations of both asolectin carrier and initial vitamin B1 on the entrapment efficiency (EE %) was also investigated. Thermoanalytical measurements clearly demonstrated that after the successful encapsulation, only weak interactions were discovered between the carriers and the drug molecules. Moreover, the dissolution profiles under physiological (pH = 7.40) and gastric conditions (pH = 1.50) were also registered and the release profiles of our liposomal B1 system were compared with the dissolution profile of the pure drug solution and a manufactured tablet containing thiamin hydrochloride as active ingredient. The release curves were evaluated by nonlinear fitting of six different kinetic models. The best goodness of fit, where the correlation coefficients in the case of all three systems were larger than 0.98, was reached by application of the well-known second-order kinetic model. Based on the evaluation, it was estimated that our liposomal nanocarrier system shows 4.5-fold and 1.5-fold larger drug retention compared to the unpackaged vitamin B1 under physiological conditions and in artificial gastric juice, respectively.
Nitrogen Balance after the Administration of a Prolonged-Release Protein Substitute for Phenylketonuria as a Single Dose in Healthy Volunteers

Nitrogen balance is the difference between nitrogen excreted as urea and nitrogen ingested, mainly in proteins. Increased circulating concentrations of amino acids (AA) in the bloodstream are usually associated with proportional increases in the production and excretion of urea. Previously, we reported results from a randomized, controlled, single-dose, crossover trial in healthy adult volunteers (n = 30) (Trial Registration: ISRCTN11016729), in which a Test product (prolonged-release AA mixture formulated with Physiomimic Technology™ (PT™)) significantly slowed down the release and reduced the peak plasma concentrations of essential AAs compared with a free AA mixture (Reference product) while maintaining essential AA bioavailability. Here, we report an assessment of the nitrogen balance from the same study. The amount of nitrogen contained in plasma AAs, levels of blood urea nitrogen (BUN) (p < 0.0001) and changes in BUN (p < 0.0001) were smaller after the Test product compared with the Reference product. These findings suggest that the production of urea in proportion to systemic AA availability was significantly smaller after the administration of the Test product compared with the Reference product and that the test product conferred the increased utilization of AAs for protein synthesis and reduced their oxidation and conversion to urea. In the clinical setting, it is possible that the effects of PT™ observed on the disposition of free AAs in this study may translate to health benefits in terms of physiological body composition and growth if used for the treatment of subjects with phenylketonuria (PKU). Further investigation in patients with PKU is warranted.
Oxidative Quality of Acid Oils and Fatty Acid Distillates Used in Animal Feeding

Simple Summary Feed producers and farmers seek alternative and economical fat ingredients to supply animals with energy and beneficial components, such as natural antioxidants. Some byproducts from the edible oil refining industry, such as acid oils (AO) and fatty acid distillates (FAD), fulfil these requirements, but differences in the animal performance have been reported as their main drawback, which might be due to their high variable composition, including their oxidation status. Therefore, the valorization of these byproducts as feed ingredients requires ensuring standardized products with adequate quality in terms of oxidation parameters. In this study, 92 AO and FAD were characterized, finding a huge variability in their oxidation status and stability. They all showed low primary oxidation values (peroxide values). The content of secondary oxidation compounds was higher in FAD (which are released from physical refining processes) than in AO (which originate from chemical refining), while polymeric compounds were higher in the latter. The fatty acid and tocol compositions that were related with the botanical origin influenced their oxidative stability. Thus, in the quality control of these products, apart from the compositional parameters, it is recommended to include the evaluation of the oxidation status, both by primary and secondary oxidation parameters. Abstract Acid oils (AO) and fatty acid distillates (FAD) are byproducts from chemical and physical refining of edible oils and fats, respectively. Their high energy value makes their upcycling interesting as alternatives to conventional fats in animal feeding. The objective of this study is to characterize their oxidative quality and to provide recommendations about their evaluation for animal feeding purposes. The oxidation status (peroxide value (PV), p-Anisidine value (p-AnV), % polymeric compounds (POL)), the oxidative stability (induction time by the Rancimat at 120 °C (IT)), the fatty acid composition (FA), and tocopherol and tocotrienol content of 92 AO and FAD samples from the Spanish market were analyzed. Both AO and FAD showed low PV (0.8 and 1 meq O2/kg); however, p-AnV was higher in FAD (36.4 vs. 16.4 in AO) and POL was higher in AO (2.5% vs. not detected in FAD) as a consequence of the type of refining process. The botanical origin of AO and FAD influenced FA and tocol composition, and they influenced IT. A high variability was observed for most analyzed parameters, reinforcing the need for standardizing AO and FAD to obtain reliable feed ingredients and to include primary and secondary oxidative parameters within their quality control.
Association of Primary Hypertension and Risk of Cerebrovascular Diseases with Overweight and Physical Activity in Korean Women: A Longitudinal Study

Cerebrovascular diseases include stroke, intracranial stenosis, aneurysms, and vascular malformations; primary hypertension is typically associated with cerebrovascular disease. The incidence of these diseases is higher in men than in women, and low physical activity and obesity are known to increase the risk of cerebrovascular disease. This study aimed to longitudinally analyze the adjusted relative risk (ARR) of primary hypertension and cerebrovascular diseases, in relation to body mass index (BMI) and physical activity (PA), in Korean women. The study retrieved the data of 1,464,377 adult Korean women (aged 50–79 years), who participated in the national health screening program from 2002 to 2003. The participants had no history of primary hypertension or cerebrovascular diseases, and were followed up by the International Statistical Classification of Diseases and Related Health Problems (ICD) until 2013. The participants were divided into the following groups: normal weight (18.5–24.9), overweight (25.0–29.9), and obese (≥30.0) kg/m2, based on the World Health Organization (WHO) classification. The frequency of PA (days) was determined using a physical activity questionnaire, and defined as low (0–2), medium (3–4), and high (5–7) days. The RR was calculated using Cox regression. Three models were created based on the adjusted variables. The ARR for hypertension was 0.933 (95% CI; 0.920–0.955, p < 0.001) in obese patients with medium PA. Primary hypertension was lower (ARR: 0.943; 95% CI; 0.928–0.961, p < 0.001) in overweight participants with medium PA, than in those with low PA. The incidence of cerebrovascular disease was lower in overweight individuals with medium PA (ARR: 0.945, 95% CI; 0.925–0.976, p < 0.001), than in those with low PA. The risk of cerebrovascular disease was reduced in normal-weight participants with medium PA (ARR: 0.889; 95% CI: 0.854–0.919; p < 0.001), than in those with high PA (ARR 0.913; 95% CI; 0.889–0.953, p < 0.001). In the obese group, there was no significant difference in the risk of cerebrovascular disease, based on the frequency of PA. In conclusion, the relative risk of primary hypertension in women was lower with moderate activity than with low activity, in the normal-weight and overweight groups. The relative risk of cerebrovascular disease was lower in the participants with moderate and high activity than in those with low activity, even at normal weight. In obese individuals, moderate and high activity reduced cerebrovascular disease compared to low activity. Therefore, regardless of obesity, PA may contribute to the prevention of primary hypertension and cerebrovascular disease in adult women.
Experimental and Numerical Study of Shear Interface Response of Hybrid Thin CFRP–Concrete Slabs

Hybrid slabs made of carbon-fiber-reinforced polymer (CFRP) and concrete provide a solution that takes advantage of the strength properties of both materials. The performance of the system strongly depends on the CFRP–concrete interaction. This study investigates the shear behavior in the interface of the two materials. Eight full-scale experiments were carried out to characterize the interface shear response of these hybrid elements using different connection solutions. An untreated surface is compared to a surface with aggregates, with a novel system comprising a flexible, straight glass fiber mesh and an inclined glass fiber mesh. The experimental results show that the fabric connection improves the friction between materials and is responsible for the pseudo-plastic performance of the specimens. The inclined mesh produces a more uniform tightening effect compared to the straight mesh. In simulations via the finite element method, we used an adjusted frictional model to reproduce the experiments.
Antistress Action of Melanocortin Derivatives Associated with Correction of Gene Expression Patterns in the Hippocampus of Male Rats Following Acute Stress

Natural melanocortins (MCs) have been used in the successful development of drugs with neuroprotective properties. Here, we studied the behavioral effects and molecular genetic mechanisms of two synthetic MC derivatives-ACTH(4–7)PGP (Semax) and ACTH(6–9)PGP under normal and acute restraint stress (ARS) conditions. Administration of Semax or ACTH(6–9)PGP (100 μg/kg) to rats 30 min before ARS attenuated ARS-induced behavioral alterations. Using high-throughput RNA sequencing (RNA-Seq), we identified 1359 differentially expressed genes (DEGs) in the hippocampus of vehicle-treated rats subjected to ARS, using a cutoff of >1.5 fold change and adjusted p-value (Padj) < 0.05, in samples collected 4.5 h after the ARS. Semax administration produced > 1500 DEGs, whereas ACTH(6–9)PGP administration led to <400 DEGs at 4.5 h after ARS. Nevertheless, ~250 overlapping DEGs were identified, and expression of these DEGs was changed unidirectionally by both peptides under ARS conditions. Modulation of the expression of genes associated with biogenesis, translation of RNA, DNA replication, and immune and nervous system function was produced by both peptides. Furthermore, both peptides upregulated the expression levels of many genes that displayed decreased expression after ARS, and vice versa, the MC peptides downregulated the expression levels of genes that were upregulated by ARS. Consequently, the antistress action of MC peptides may be associated with a correction of gene expression patterns that are disrupted during ARS.
A Small Virus to Deliver Small Antibodies: New Targeted Therapies Based on AAV Delivery of Nanobodies

Nanobodies are camelid-derived single-domain antibodies that present some advantages versus conventional antibodies, such as a smaller size, and higher tissue penetrability, stability, and hydrophilicity. Although nanobodies can be delivered as proteins, in vivo expression from adeno-associated viral (AAV) vectors represents an attractive strategy. This is due to the fact that AAV vectors, that can provide long-term expression of recombinant genes, have shown an excellent safety profile, and can accommodate genes for one or several nanobodies. In fact, several studies showed that AAV vectors can provide sustained nanobody expression both locally or systemically in preclinical models of human diseases. Some of the pathologies addressed with this technology include cancer, neurological, cardiovascular, infectious, and genetic diseases. Depending on the indication, AAV-delivered nanobodies can be expressed extracellularly or inside cells. Intracellular nanobodies or “intrabodies” carry out their function by interacting with cell proteins involved in disease and have also been designed to help elucidate cellular mechanisms by interfering with normal cell processes. Finally, nanobodies can also be used to retarget AAV vectors, when tethered to viral capsid proteins. This review covers applications in which AAV vectors have been used to deliver nanobodies, with a focus on their therapeutic use.