Miracle-dz/UniFAR-FTUs huggingface dataset:
Antibacterial Activity of Non-Cytotoxic, Amino Acid-Modified Polycationic Dendrimers against Pseudomonas aeruginosa and Other Non-Fermenting Gram-Negative Bacteria

Due to the rapid increase of antimicrobial resistance with ensuring therapeutic failures, the purpose of this study was to identify novel synthetic molecules as alternatives to conventional available, but presently ineffective antibiotics. Variously structured cationic dendrimers previously reported have provided promising outcomes. However, the problem of their cytotoxicity towards eukaryotic cells has not been completely overcome. We have now investigated the antibacterial activities of three not cytotoxic cationic dendrimers (G5Ds: G5H, G5K, and G5HK) against several multidrug-resistant (MDR) clinical strains. All G5Ds displayed remarkable activity against MDR non-fermenting Gram-negative species such as P. aeruginosa, S. maltophilia, and A. baumannii (MICs = 0.5–33.2 µM). In particular, very low MIC values (0.5–2.1 µM) were observed for G5K, which proved to be more active than the potent colistin (2.1 versus 3.19 µM) against P. aeruginosa. Concerning its mechanism of action, in time-killing and turbidimetric studies, G5K displayed a rapid non-lytic bactericidal activity. Considering the absence of cytotoxicity of these new compounds and their potency, comparable or even higher than that provided by the dendrimers previously reported, G5Ds may be proposed as promising novel antibacterial agents capable of overcoming the alarming resistance rates of several nosocomial non-fermenting Gram-negative pathogens.
Characterization of the Role of SPL9 in Drought Stress Tolerance in Medicago sativa

Extreme environmental conditions, such as drought, are expected to increase in frequency and severity due to climate change, leading to substantial deficiencies in crop yield and quality. Medicago sativa (alfalfa) is an important crop that is relied upon as a staple source of forage in ruminant feed. Despite its economic importance, alfalfa production is constrained by abiotic stress, including drought. In this report, we investigate the role of Squamosa Promoter Binding Protein-Like 9 (SPL9), a target of miR156, in drought tolerance. Transgenic alfalfa plants with RNAi-silenced MsSPL9 (SPL9-RNAi) were compared to wild-type (WT) alfalfa for phenotypic changes and drought tolerance indicators. In SPL9-RNAi plants, both stem thickness and plant height were reduced in two- and six-month-old alfalfa, respectively; however, yield was unaffected. SPL9-RNAi plants showed less leaf senescence and had augmented relative water content under drought conditions, indicating that SPL9-RNAi plants had greater drought tolerance potential than WT plants. Interestingly, SPL9-RNAi plants accumulated more stress-alleviating anthocyanin compared to WT under both drought and well-watered control conditions, suggesting that MsSPL9 may contribute to drought tolerance in alfalfa, at least in part, by regulating anthocyanin biosynthesis. The results suggest that targeting MsSPL9 is a suitable means for improving alfalfa resilience towards drought conditions.
Biotransformation of Flaxseed Oil Cake into Bioactive Camembert-Analogue Using Lactic Acid Bacteria, Penicillium camemberti and Geotrichum candidum

This study aimed at investigating the antioxidant activity, oxidative stability, physicochemical and microbial changes of innovative vegan Camembert-analogue based on flaxseed oil cake (FOC) which was produced using lactic acid bacteria (LAB), mold Penicillium camemberti (PC) and yeast Geotrichum candidum (GC). Two variants were prepared, namely with LAB + PC and LAB + PC + GC. After fermentation for 24 h at room temperature, the samples were stored for 14 days at 12 °C and maturated for 14 days at 6 °C. Changes in microbial population, polyphenolics, flavonoids, radical scavenging capacity were evaluated. Additionally, textural changes, pH, acidity, levels of proteins, free amino acids, reducing sugars, oil content and its oxidative stability were determined. Results showed that LAB as well as fungi were capable of growing well in the FOC without any supplementation and the products were characterized by a high antioxidant potential (high polyphenolics and flavonoids contents as well as 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), superoxide (O2−) and hydroxyl (·OH) radicals scavenging activity). This study has demonstrated that bioactivity as well as the physicochemical properties depend on the starter culture used. Due to functional and biochemical characteristics conferred to the obtained Camembert-analogues, the use of P. camemberti and G. candidum showed a potential for industrial application. There is a potential for these products to be used where non-dairy alternatives are desired.
Evaluation of post-flexible cystoscopy urinary tract infection rates.

PURPOSE The risk of urinary tract infection (UTI) development after flexible cystoscopy (FC) is not well described. It remains difficult to assess the role of pre-FC antimicrobial prophylaxis to reduce UTI risk. METHODS In fall 2017, the urology service at the Providence Veterans Affairs Medical Center implemented routine oral antimicrobial prophylaxis in its outpatient FC clinic. Outpatients were randomly selected for a retrospective chart review to compare patients who received pre-FC antimicrobials (cefuroxime 500 mg tablet or sulfamethoxazole/trimethoprim [800 mg/160 mg] tablet) and those who underwent FC prior to fall 2017 and did not receive prophylaxis. The primary outcome was presence of symptomatic UTI within 30 days post FC. Secondary outcomes included symptomatic UTI that met colony-forming unit (CFU)/mL guideline requirements, and UTI treatment received. Potential risk factors for UTI were also assessed. RESULTS A total of 296 patients were included in the final analysis: 139 who did not receive and 157 who received a prophylactic antimicrobial before FC. Rates of symptomatic UTI, symptomatic UTI meeting CFU/mL guideline requirements, and postprocedure treatment for UTI were similar with and without antimicrobial prophylaxis (2.5% vs 2.2% [P > 0.99], 1.9% vs 1.4% [P > 0.99], and 2.5% vs 4.3% [P = 0.53], respectively). The mean number of days from FC to the start of UTI treatment was 7.9 (range, 1-18 days). Age over 65 years was the only risk factor present in all patients with a post-FC UTI, irrespective of antimicrobial prophylaxis. CONCLUSION The rate of post-FC symptomatic UTI was lower than rates previously described in the literature. The role of antimicrobial prophylaxis prior to FC warrants further exploration.
Improved High-Yield PMMA/Graphene Pressure Sensor and Sealed Gas Effect Analysis

Graphene with atomic thickness possesses excellent mechanical and electrical properties, which hold great potential for high performance pressure sensing. The exposed electron of graphene is always cross-sensitive to any pollution absorbed or desorbed on the surface, from which the long-term stability of the graphene pressure sensor suffers a lot. This is one of the main obstacles towards graphene commercial applications. In this paper, we utilized polymethylmethacrylate (PMMA)/graphene heterostructure to isolate graphene from the ambient environment and enhance its strength simultaneously. PMMA/graphene pressure sensors, with the finite-depth cavities and the through-hole cavities separately, were made for comparative study. The through-hole device obtained a comparable sensitivity per unit area to the state of the art of the bare graphene pressure sensor, since there were no leaking cracks or defects. Both the sensitivity and stability of the through-hole sensor are better than those of the sensor with 285-nm-deep cavities, which is due to the sealed gas effect in the pressure cavity. A modified piezoresistive model was derived by considering the pressure change of the sealed gas in the pressure cavity. The calculated result of the new model is consistent with the experimental results. Our findings point out a promising route for performance optimization of graphene pressure sensors.
Antioxidant, Antibacterial Activities and Mineral Content of Buffalo Yoghurt Fortified with Fenugreek and Moringa oleifera Seed Flours

Recently, there is an increasing demand for functional yoghurts by consumer, especially those produced through the incorporation of food of plant origin or its bioactive components. The current research was devoted to formulating functional buffalo yoghurt through the addition of 0.1 and 0.2% of fenugreek (Trigonella foenum-graecum) seed flour (F1 and F2) and Moringa oleifera seed flour (M1 and M2). The effects of fortification were evaluated on physicochemical, total phenolic content (TPC), antioxidant activity (AOA), the viability of yoghurt starter, and sensory acceptability of yoghurts during cold storage. Moringa oleifera seed flour had higher contents of TPC (140.12 mg GAE/g) and AOA (31.30%) as compared to fenugreek seed flour (47.4 mg GAE/g and 19.1%, respectively). Values of TPC and AOA significantly increased in fortified yoghurts, and M2 treatment had the highest values of TPC (31.61, 27.29, and 25.69 mg GAE/g) and AOA (89.32, 83.5, and 80.35%) at 1, 7, and 14 days of storage, respectively. M2 showed significantly higher antibacterial activity against E. coli, S. aureus, L. monocytogenes, and Salmonella spp. and the zones of inhibition were 12.65, 13.14, 17.23 and 14.49 mm, respectively. On the other hand, control yoghurt showed the lowest antibacterial activity and the zones of inhibition were (4.12, 5.21, 8.55, and 8.39 mm against E. coli, S. aureus, L. monocytogenes, and Salmonella spp., respectively). Incorporation of 0.1% and 0.2% of moringa seed flour (M1 and M2) led to a higher content of Ca, P, K, and Fe and lower content of Mg and Zn as compared to F1 and F2, respectively. Thus, it could be concluded that fenugreek and Moringa oleifera seed flour can be exploited in the preparation of functional novel yoghurt.
Effect of FHA and Prn on Bordetella pertussis colonization of mice is dependent on vaccine type and anatomical site

Bordetella pertussis vaccine escape mutants that lack expression of the pertussis antigen pertactin (Prn) have emerged in vaccinated populations in the last 10–20 years. Additionally, clinical isolates lacking another acellular pertussis (aP) vaccine component, filamentous hemagglutinin (FHA), have been found sporadically. Here, we show that both whole-cell pertussis (wP) and aP vaccines induced protection in the lungs of mice, but that the wP vaccine was more effective in nasal clearance. Importantly, bacterial populations isolated from the lungs shifted to an FHA-negative phenotype due to frameshift mutations in the fhaB gene. Loss of FHA expression was strongly selected for in Prn-deficient strains in the lungs following aP but not wP vaccination. The combined loss of Prn and FHA led to complete abrogation of bacterial surface binding by aP-induced serum antibodies. This study demonstrates vaccine- and anatomical site-dependent adaptation of B. pertussis and has major implications for the design of improved pertussis vaccines.
Optimal Antithrombotic Treatment of Patients with Atrial Fibrillation Early after an Acute Coronary Syndrome—Triple Therapy, Dual Antithrombotic Therapy with an Anticoagulant… Or, Rather, Temporary Dual Antiplatelet Therapy?

The combination of atrial fibrillation (AF) and acute coronary syndrome (ACS) is a complex situation in which a three-dimensional risk—cardioembolic, coronary, and hemorrhagic—has to be carefully managed. Triple antithrombotic therapy (TAT) is burdened with a high risk of serious bleeding, while dual antithrombotic therapy with an anticoagulant (DAT) likely provides only suboptimal coronary protection early after stent implantation. Moreover, TAT precludes the advantages provided by the use of the latest and more potent P2Y12 inhibitors in ACS patients. Here, we aimed to simulate and compare the expected coronary, cardioembolic, and hemorrhagic outcomes offered by DAT, TAT, or modern dual antiplatelet therapy (DAPT) with aspirin plus one of the latest P2Y12 inhibitors in AF patients early after an ACS. The comparison of numbers needed to treat to prevent major adverse events with the various antithrombotic regimens suggests that AF–ACS patients at high ischemic and hemorrhagic risk and at moderately low embolic risk (CHA2DS2VASc score 2–4) might safely withhold anticoagulation after revascularization for one month taking advantage of a modern DAPT, with a favorable risk-to-benefit ratio. In conclusion, this strategy, not sufficiently addressed in recent European and North American guidelines or consensus documents, adds to the spectrum of treatment options in these difficult patients; it might be the best choice in a substantial number of patients; and should be prospectively tested in a randomized controlled trial.
Genetic and Phenotypic Characterization of a Rabies Virus Strain Isolated from a Dog in Tokyo, Japan in the 1940s

The rabies virus strain Komatsugawa (Koma), which was isolated from a dog in Tokyo in the 1940s before eradication of rabies in Japan in 1957, is known as the only existent Japanese field strain (street strain). Although this strain potentially provides a useful model to study rabies pathogenesis, little is known about its genetic and phenotypic properties. Notably, this strain underwent serial passages in rodents after isolation, indicating the possibility that it may have lost biological characteristics as a street strain. In this study, to evaluate the utility of the Koma strain for studying rabies pathogenesis, we examined the genetic properties and in vitro and in vivo phenotypes. Genome-wide genetic analyses showed that, consistent with previous findings from partial sequence analyses, the Koma strain is closely related to a Russian street strain within the Arctic-related phylogenetic clade. Phenotypic examinations in vitro revealed that the Koma strain and the representative street strains are less neurotropic than the laboratory strains. Examination by using a mouse model demonstrated that the Koma strain and the street strains are more neuroinvasive than the laboratory strains. These findings indicate that the Koma strain retains phenotypes similar to those of street strains, and is therefore useful for studying rabies pathogenesis.
Comparative Nanofabrication of PLGA-Chitosan-PEG Systems Employing Microfluidics and Emulsification Solvent Evaporation Techniques

Poor circulation stability and inadequate cell membrane penetration are significant impediments in the implementation of nanocarriers as delivery systems for therapeutic agents with low bioavailability. This research discusses the fabrication of a biocompatible poly(lactide-co-glycolide) (PLGA) based nanocarrier with cationic and hydrophilic surface properties provided by natural polymer chitosan and coating polymer polyethylene glycol (PEG) for the entrapment of the hydrophobic drug disulfiram. The traditional emulsification solvent evaporation method was compared to a microfluidics-based method of fabrication, with the optimisation of the parameters for each method, and the PEGylation densities on the experimental nanoparticle formulations were varied. The size and surface properties of the intermediates and products were characterised and compared by dynamic light scattering, scanning electron microscopy and X-ray diffraction, while the thermal properties were investigated using thermogravimetric analysis and differential scanning calorimetry. Results showed optimal particle properties with an intermediate PEG density and a positive surface charge for greater biocompatibility, with nanoparticle surface characteristics shielding physical interaction of the entrapped drug with the exterior. The formulations prepared using the microfluidic method displayed superior surface charge, entrapment and drug release properties. The final system shows potential as a component of a biocompatible nanocarrier for poorly soluble drugs.
Viscoelastic Behavior of Glass-Fiber-Reinforced Silicone Composites Exposed to Cyclic Loading

The aim of this work was to analyze the influence of fibers on the mechanical behavior of fiber-reinforced elastomers under cyclic loading. Thus, the focus was on the characterization of structure–property interactions, in particular the dynamic mechanical and viscoelastic behavior. Endless twill-woven glass fibers were chosen as the reinforcement, along with silicone as the matrix material. For the characterization of the flexible composites, a novel testing device was developed. Apart from the conventional dynamic mechanical analysis, in which the effect of the fiber orientation was also considered, modified step cycle tests were conducted under tensile loading. The material viscoelastic behavior was studied, evaluating both the stress relaxation response and the capability of the material to dissipate energy under straining. The effects of the displacement rate of the strain level, the amplitude of the strain applied in the loading–unloading step cycle test, and the number of the applied cycles were evaluated. The results revealed that an optimized fiber orientation leads to 30-fold enhanced stiffness, along with 10 times higher bearable stress. The findings demonstrated that tailored reinforced elastomers with endless fibers have a strong influence on the mechanical performance, affecting the structural properties significantly.
Application of Artificial Neural Networks for Accurate Determination of the Complex Permittivity of Biological Tissue

Medical devices making use of radio frequency (RF) and microwave (MW) fields have been studied as alternatives to existing diagnostic and therapeutic modalities since they offer several advantages. However, the lack of accurate knowledge of the complex permittivity of different biological tissues continues to hinder progress in of these technologies. The most convenient and popular measurement method used to determine the complex permittivity of biological tissues is the open-ended coaxial line, in combination with a vector network analyser (VNA) to measure the reflection coefficient (S11) which is then converted to the corresponding tissue permittivity using either full-wave analysis or through the use of equivalent circuit models. This paper proposes an innovative method of using artificial neural networks (ANN) to convert measured S11 to tissue permittivity, circumventing the requirement of extending the VNA measurement plane to the coaxial line open end. The conventional three-step calibration technique used with coaxial open-ended probes lacks repeatability, unless applied with extreme care by experienced persons, and is not adaptable to alternative sensor antenna configurations necessitated by many potential diagnostic and monitoring applications. The method being proposed does not require calibration at the tip of the probe, thus simplifying the measurement procedure while allowing arbitrary sensor design, and was experimentally validated using S11 measurements and the corresponding complex permittivity of 60 standard liquid and 42 porcine tissue samples. Following ANN training, validation and testing, we obtained a prediction accuracy of 5% for the complex permittivity.
Highlights on Genomics Applications for Lysosomal Storage Diseases

Lysosomal storage diseases (LSDs) are a heterogeneous group of rare multisystem genetic disorders occurring mostly in infancy and childhood, characterized by a gradual accumulation of non-degraded substrates inside the lysosome. Although the cellular pathogenesis of LSDs is complex and still not fully understood, the approval of disease-specific therapies and the rapid emergence of novel diagnostic methods led to the implementation of extensive national newborn screening (NBS) programs in several countries. In the near future, this will help the development of standardized workflows aimed to more timely diagnose these conditions. Hereby, we report an overview of LSD diagnostic process and treatment strategies, provide an update on the worldwide NBS programs, and discuss the opportunities and challenges arising from genomics applications in screening, diagnosis, and research.
Suicidal Presentations to Emergency Departments in a Large Australian Public Health Service over 10 Years

This paper presents trends and characteristics for 32,094 suicidal presentations to two Emergency Departments (EDs) in a large health service in Australia across a 10-year period (2009–2018). Prevalence of annual suicidal presentations and for selected groups of consumers (by sex, age groups, and ethnicity) was determined from a machine learning diagnostic algorithm developed for this purpose and a Bayesian estimation approach. A linear increase in the number of suicidal presentations over 10 years was observed, which was 2.8-times higher than the increase noted in all ED presentations and 6.1-times higher than the increase in the population size. Females had higher presentation rates than males, particularly among younger age groups. The highest rates of presentations were by persons aged 15–24. Overseas-born persons had around half the rates of suicidal presentations than Australian-born persons, and Indigenous persons had 2.9-times higher rates than non-Indigenous persons. Of all presenters, 70.6% presented once, but 5.7% had five or more presentations. Seasonal distribution of presentations showed a peak at the end of spring and a decline in winter months. These findings can inform the allocation of health resources and guide the development of suicide prevention strategies for people presenting to hospitals in suicidal crisis.
Pattern of Recurrence and Patient Survival after Perioperative Chemotherapy with 5-FU, Leucovorin, Oxaliplatin and Docetaxel (FLOT) for Locally Advanced Esophagogastric Adenocarcinoma in Patients Treated Outside Clinical Trials

Background: The 5-FU, Leucovorin, Oxaliplatin and Docetaxel (FLOT) protocol provides superior oncologic results compared to other perioperative chemotherapeutic protocols for the treatment of non-metastatic esophagogastric cancer (EGAC). Survival and the pattern of recurrence of EGAC after FLOT and curative tumor resection are analyzed in a collective of patients treated outside clinical trials. Methods: Two-hundred-seventy-seven patients with EGAC (cT3-4 and/or cN+) were treated with perioperative FLOT-chemotherapy plus curative surgery between 2009 and 2018. Data were analyzed retrospectively from a prospective database. Results: Two-hundred-twenty-eight patients were included in the analysis. Postoperative in-hospital mortality was 2%. The median survival was 61–months, and median recurrence-free survival was 42 months. Multivariate analysis identified postoperative nodal status and T-stage as independent predictors of improved overall and recurrence-free survival. Administration of adjuvant chemotherapy failed to be significant for overall survival but was an independent predictor of recurrence-free survival. Recurrence occurred after a median of 9 months (range 1–46 months). Eighty-nine percent of recurrence occurred during the first 24 months. The rate of local recurrence was low. After surgery for gastric cancer, the major recurrence site was peritoneal carcinomatosis (56%), while esophageal cancer recurred mostly as metastasis to distant organs (78%). The specific site of recurrence had no impact on overall survival time. Conclusion: Real-life application of FLOT shows oncologic results comparable to clinical trials. Recurrence after FLOT and surgery for EGAC occurs predominantly early within the first two years after surgery and in the form of distant organ metastasis for esophageal tumors or peritoneal carcinomatosis for gastric tumors.