Miracle-dz/UniFAR-FTUs huggingface dataset:
Treating arterial hypertension: from guidelines to physiology and back again – the issue of increased sympathetic drive

In the era of evidence-based medicine, the current European Society of Cardiology (ESC) guidelines for the management of arterial hypertension rely on results from randomized clinical trials. The 2018 version aims to simplify the management of hypertensive patients and generally recommends the combined use of a renin-angiotensin-aldosterone system inhibitor and a calcium channel blocker or a thiazide-like diuretic as first-line therapy. Drugs targeting the increased sympathetic drive are only recommended if the combination of all three drug classes fail to provide adequate control of blood pressure values. Although beta-blockers are still prescribed in hypertensive patients who have coronary artery disease and/or heart failure, alpha-blockers are seldom used. However, the sympathetic drive is an important link in the pathophysiology of arterial hypertension, raising the question whether some patients may obtain additional benefit from sympathetic inhibition.
Plan of Work – MSc thesis Role of CFTR in cell migration and epithelial wound repair

Background: Cystic Fibrosis (CF), the most common genetic disease among Caucasians, CF is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene encoding a Cl/HCO3 channel expressed at the apical membrane of epithelial cells. CF affects mostly the lungs and is characterized by mucus stasis, poor mucociliary clearance (MCC), recurrent bacterial infections and chronic inflammation in the airways that promote progressive lung destruction, and eventually lung failure. Upon injury (by pollutants, pathogens, etc), a healthy lung is able to rapidly regenerate and restore epithelial integrity in order to maintain epithelial integrity for an effective lung function. However, in patients with CF these wound healing mechanisms are impaired [1-3]. Several studies have shown that wound healing (a combination of both migration and proliferation) and cell differentiation are both altered in CF [3,4]. Moreover, it was shown that CFTR itself, which is defective in CF, plays a role in airway epithelial repair and vice versa, i.e., its traffic is regulated by epithelial differentiation [4]. However, the mechanistic relationship between CFTR and epithelial wound healing /differentiation has not been established. We have previously characterized the wound healing process in CF and our data indicate that it is mainly migration which is affected in CF. Cells migrating into the wound gap require lamellipodia protrusion at the cell front and the force that directs the plasma membrane is provided by actin polymerization at the leading edge [5,6]. Moreover, our data suggest that it is the efficiency of lamellipodia protrusion (determined by the extent of cytosolic actin assembly [5,6]) that is defective in CF (Pankonien, Amaral, unpublished data). It is known that CFTR is indirectly anchored to actin and this interaction may be needed for actin rearrangements at the plasma membrane [7]. It is also known that the formation of lamellipodia is controlled by Rac (a member of the Rho small GTPases [8]) and that manipulation of Rac1 signalling affects CFTR traffic [7]. Objective: To characterize how CFTR affects the wound healing in human bronchial epithelial (HBE) cells expressing either normal (wt-) CFTR or F508del-CFTR, namely to further explore the relationship between CFTR and lamellipodia protrusion. Methodology: The current MSc project will explore the role of CFTR in epithelial wound repair and comprise the following specific tasks:
Reproductive Performance of Koekoek Chickens at Different Levels of Feed Restrictions

The objective of the present study was to determine the impact of the feeding levels on the reproductive characteristics of Koekoek chickens. A total of 270 Koekoek chickens were randomly assigned to 4 feeding level treatments in a completely randomized design. The four feeding level treatments were fully fed during the rearing and laying phase (AA), fully fed during the rearing phase and restricted feeding during the laying phase (AR), restricted feeding during the rearing phase and fully fed during the laying phase (RA), and restricted both during the rearing and laying phase (RR). The General Linear Model procedure (SPSS software, version 17) was used to analyze the data set. The pubic bone measurements were 23.6, 25.1, 16.1, and 15.1 mm for chickens that received AA, AR, RA, and RR treatments, respectively, at 18 weeks of age. At 32 weeks of age, chickens given AA and RA treatments had wider pubic bones than chickens given AR and RR treatments. Combined ova and oviduct weights were higher in the fully fed chickens at 18 weeks of age. Koekoek chickens in AA treatment had the highest average egg production. Chickens given AR treatment had lower average egg weights than those given AA, AR, and RR treatments. Chickens treated with AA and AR reached puberty earlier than those that were treated with the RA and RR treatments. The eggs produced by chickens given RR treatment had a higher average hatching percentage. The lowest percentage of hatches was observed in chickens that were fed ad libitum during the rearing phase. In conclusion, the feed restriction only during the rearing phase improved the reproduction performance of Koekoek chickens.
ASSESSMENT OF DEFICIT VOLUMES UNDER CLIMATE CHANGE AND POSSIBLE ADAPTATION BY TECHNICAL MEASURES IN THE CZECH REPUBLIC

Climate change scenarios for the Czech Republic indicate the increase in frequency and volume of the deficit discharges (defined as the volume under given threshold). The Czech water management legislation considers a number of protected areas potentially suitable for construction of reservoirs for flood protection and/or improving the water balance in the drought periods. In present study we use hydrological modelling to quantify the volume of the deficit discharges as projected by an ensemble of transient regional climate model (RCM) simulations. Derived deficits are subsequently compared to the potential volume of the considered reservoirs. It is concluded that for many RCM simulations the deficits are significantly larger than the available volume of water in the reservoirs, therefore different adaptation measures should be considered also. The uncertainty is, however, large.
Effects of ozone exposure on the oxidative capacity for drug biotransformation in Wistar rats

The aim of the present study was to determine if ozone (O3) exposure modifies the oxidative capacity of cytochrome P450 (CYP450) using pharmacokinetic analysis of metronidazole. A total of 84 male Wistar rats were placed in two groups. Group I was subdivided into two subgroups of 30 and 12 rats. The metronidazole pharmacokinetic study was performed on the group of 30 rats, which was in turn divided into two subgroups of 15 rats each, one exposed to 0.15 ppm O3, the other not exposed (control group). The group of 12 rats was subdivided into two subgroups of 6 rats each; one was exposed to O3 (0.15 ppm), the other was not exposed (control). Liver microsomes were obtained from these two subgroups for immunodetection of CYP450 families. The same procedure was applied to group II, except for an O3 concentration of 0.45 ppm. Plasma metronidazole was determined by high performance liquid chromatography. The maximum plasma concentration (Cpmax), area under the curve (AUCo → ∞), volume of distribution (Vd), and clearance (CL) showed a significant increase in the group exposed to 0.15 ppm O3 compared to the group exposed to 0.45 ppm. Further, data were significantly increased compared to control. The elimination half-life time (t1/2el) in the 0.15 ppm O3 group was similar to the 0.45 ppm rats, however, these values were significantly decreased compared controls. No statistically significant differences were found among rats in the electrophoretic band pattern for any of the CYP450 families evaluated, 1A, 3A, 2B and 2E. The expression of these subfamilies in hepatic and renal tissue is in agreement with other reports.
Single EMG Sensor-Driven Robotic Glove Control for Reliable Augmentation of Power Grasping

The practical operation of wearable robots requires intuitive, compact, yet reliable control interfaces. However, current myoelectric interfaces based on surface electromyography (EMG) often fail to achieve these requirements by demanding multiple sensors and exhibiting unreliable performance under limb posture changes. In this study, we show that a myoelectric interface on the musculotendinous junctions (MTJs) of the flexor digitorum superficialis (FDS) enables reliable control of a robotic glove with a single EMG sensor by identifying power grasp intentions. We found that the myoelectric signals from the MTJs of the FDS show significantly increased amplitudes exclusively when a power grasp is performed, regardless of the arm posture. We systematically verified that, in identifying power grasp intentions, the proposed single-sensor myoelectric interface even outperforms a five-sensor myoelectric interface around the proximal forearm. By exploiting the unique biological feature of the MTJs, we devised two myoelectric control methods for a robotic glove—Dual-threshold control and Morse-code control—and further showed their performances in practical operations. Dual-threshold control enables direct co-operation between the user and the robotic glove, and Morse-code control provides various command options for the user.
Validation of Comparative Model of the Teacher Education Systems

The present study aimed to validate the comparative model of teacher education systems. For this quantitative study, correlation method and path analysis test were used in line with research purposes. The statistical population was faculty members of Farhangian University, Iran. The cluster sampling method was used to determine the sample size, and 250 faculty members from all over the country were selected as the study sample. A researcher made questionnaire including 50 items designed based on the components of the comparative model of the teacher education system was used to collect the data. Moreover, the exploratory factor analysis test was used to investigate the reliability of the instrument, employing the Principal Components Analysis (PC). The results showed that 7 factors had been identified according to the eigenvalues. The results of the explained variance showed that these 7 factors predicted a total of 70% of the structural changes. Then, in order to test the theoretical model, the proposed conceptual model analyzed by path analysis, employing the maximum probability method. After testing the model with fit indices, it was shown that the tested model enjoyed a good fit with the conceptual model and the collected data. In the end, suggestions were made, including that researchers and those involved in teacher education systems all over the world can use this model as a conceptual framework in their comparative approach in order to benefit from successful methods of teacher education.
A Comparison of the Apical Extrusion of Debris during the Preparation of Root Canal with Medin, RaCe, and ProTaper Rotary Systems

Statement of the Problem: The extrusion of intracanal debris is one of the challenging problems related to almost all root canal preparation systems, which may cause flare-ups and impairment in the healing process. Purpose: This study was conducted to evaluate the amount of apically-extruded debris during root canal preparation using Medin (MEDIN Co., Czech Republic) rotary system compared with two common rotary systems, including ProTaper (Dentsply Maillefer., Switzerland) and RaCe (FKG Dentaire, Switzerland). Materials and Method: In this in vitro study, Sixty mandibular premolars with single canal were randomly assigned to three groups (n=20). The root canals were prepared with Medin, ProTaper, and RaCe rotary instruments based on their manufacturers’ instructions. The debris were collected into pre-weighted Eppendorf tubes. The weight of the extruded debris was calculated by subtracting the pretreatment weight of the vials. Data were analyzed using the Kruskal-Wallis test at a 5% significance level. Results: Medin instrument caused significantly less debris extrusion in comparison with ProTaper and RaCe (p< 0.05). The differences between the ProTaper and RaCe rotary systems were not statistically significant (p= 0.752). Conclusion: Within the limitations of this in vitro study, Medin rotary system produced less apical extrusion than ProTaper and RaCe.
Enisamium Reduces Influenza Virus Shedding and Improves Patient Recovery by Inhibiting Viral RNA Polymerase Activity

Infections with respiratory viruses constitute a huge burden on our health and economy. Antivirals against some respiratory viruses are available, but further options are urgently needed. Enisamium iodide (laboratory code FAV00A, trade name Amizon) is an antiviral marketed in countries of the Commonwealth of Independent States for the treatment of viral respiratory infections, but its clinical efficacy and mode of action are not well understood. ABSTRACT Infections with respiratory viruses constitute a huge burden on our health and economy. Antivirals against some respiratory viruses are available, but further options are urgently needed. Enisamium iodide (laboratory code FAV00A, trade name Amizon) is an antiviral, marketed in countries of the Commonwealth of Independent States for the treatment of viral respiratory infections, but its clinical efficacy and mode of action are not well understood. In this study, we investigated the efficacy of enisamium in patients aged between 18 and 60 years with confirmed influenza virus and other viral respiratory infections. Enisamium treatment resulted in reduced influenza virus shedding (at day 3, 71.2% in the enisamium group tested negative versus 25.0% in placebo group [P < 0.0001]), faster patient recovery (at day 14, 93.9% in the enisamium group had recovered versus 32.5% in placebo group [P < 0.0001]), and reduced disease symptoms (from 9.6 ± 0.7 to 4.6 ± 0.9 score points in enisamium group versus 9.7 ± 1.1 to 5.6 ± 1.1 score points in placebo group [P < 0.0001]) compared to those in the placebo group. Using mass spectrometry, and cell-based and cell-free viral RNA synthesis assays, we identified a hydroxylated metabolite of enisamium, VR17-04. VR17-04 is capable of inhibiting influenza virus RNA synthesis and is present in plasma of patients treated with enisamium. VR17-04 inhibits the activity of the influenza virus RNA polymerase more potently than its parent compound. Overall, these results suggest that enisamium is metabolized in humans to an inhibitor of the influenza virus RNA polymerase that reduces viral shedding and improves patient recovery in influenza patients. (This study has been registered at ClinicalTrials.gov under identifier NCT04682444.)
The analytic configuration interaction gradient method: The calculation of one electron properties

The implementation of the analytical energy gradient method for the calculation of first order one electron properties using closed shell configuration interaction wave functions of the single reference plus single and double substitutions (CI‐SD) type is discussed. The method used is based on the Z vector formalism of Handy and Schaefer which is readily extended to allow a full orbital optimization to be carried out for a given CI‐SD wave function. The results of comparative test calculations are reported for the HF, H2O, CO, HCN, and O3 molecules, for which the dipole and quadrupole moments and the electric field gradients at the nuclei have been calculated by both the expectation value and the energy derivative formalisms using several standard basis sets. The effects of orbital optimization on the above properties at the equilibrium geometries as well as at a range of distorted geometries for HF, are also discussed. It is found that agreement between the different formalisms is best when the reference.
A Stark Spectroscopic Study of N(3)-Methyl, N(10)-Isobutyl-7,8-Dimethylisoalloxazine in Nonpolar Low-Temperature Glasses: Experiment and Comparison with Calculations

Flavins have unique electronic properties that have led to their utilization in biological redox chemistry. Despite this there is relatively little experimental information about such basic electronic properties as dipole moments and polarizabilities for these molecules. We have explored the electronic structure of the ground and first two excited electronic states of an oxidized flavin in nonpolar organic glasses using Stark spectroscopy. The dipole moment change for the S0 → S1 transition is about 3 times smaller than the dipole moment change for the S0 → S2 transition. Dipole moment directions for these excited states have been calculated using the experimental results along with predictions from calculations. The experimental results are consistent with computational predictions of intramolecular charge transfer for the S0 → S2 transition. In addition, we have verified that there is a large change in polarizability for the S2 state vs the S0 and S1 states. Both excited-state polarizability changes sho.
Syringa oblata Lindl var. alba as a source of oleuropein and related compounds

The leaf methanol extract of Syringa oblata Lindl var. alba was investigated as a source of oleuropein and related compounds. The extract had a high total phenol content and a radical scavenging activity similar to that of the respective extract from Olea europaea leaves. HPLC-DAD characterisation of the two most abundant phenolic compounds in the extract of S. oblata indicated that both had UV spectra matching that of oleuropein. The presence of oleuropein was verified by using LC-MS. Identification of the second compound was only feasible after isolation (preparative HPLC) and spectroscopic characterisation [LC-MS, 1H NMR and homonuclear two-dimensional correlated spectroscopy (COSY)]. The compound identified was the known bioactive syringopicroside. On the basis of MS data other peaks were assigned to oleuropein aglycone, verbascoside, ligstroside and syringopicroside derivatives, as well as to a luteolin rutinoside. The findings are promising for the potential exploitation of S. oblata leaf extract as a source for oleuropein and other bioactive ingredients. Copyright © 2006 Society of Chemical Industry
Independent and Synergistic Effects of Knocking out Two ABC Transporter Genes on Resistance to Bacillus thuringiensis Toxins Cry1Ac and Cry1Fa in Diamondback Moth

Insecticidal proteins from Bacillus thuringiensis (Bt) are used widely in sprays and transgenic crops to control insect pests. However, evolution of resistance by pests can reduce the efficacy of Bt toxins. Here we analyzed resistance to Bt toxins Cry1Ac and Cry1Fa in the diamondback moth (Plutella xylostella), one of the world’s most destructive pests of vegetable crops. We used CRISPR/Cas9 gene editing to create strains with knockouts of the ATP-binding cassette (ABC) transporter genes PxABCC2, PxABCC3, or both. Bioassay results show that knocking out either gene alone caused at most 2.9-fold resistance but knocking out both caused >10,320-fold resistance to Cry1Ac and 380-fold resistance to Cry1Fa. Cry1Ac resistance in the double knockout strain was recessive and genetically linked with the PxABCC2/PxABCC3 loci. The results provide insight into the mechanism of cross-resistance to Cry1Fa in diamondback moth. They also confirm previous work with this pest showing that mutations disrupting both genes cause higher resistance to Cry1Ac than mutations affecting either PxABCC2 or PxABCC3 alone. Together with previous work, the results here highlight the value of using single and multiple gene knockouts to better understand the independent and synergistic effects of putative Bt toxin receptors on resistance to Bt toxins.
TIME Is a Great Healer—Targeting Myeloid Cells in the Tumor Immune Microenvironment to Improve Triple-Negative Breast Cancer Outcomes

The word myeloid is derived from the Greek word muelós which means “marrow”. Therefore, myeloid cells are described as cells that arise in the bone marrow. They can be distinguished from lymphoid cells based on their different differentiation trajectories—Lymphoid cells (B and T cells) are usually born in the bone marrow, but they need to migrate to lymphoid organs to mature and differentiate usually in response to antigens produced due to infections and diseases like cancer. On the other hand, myeloid cells do not follow this differentiation trajectory. They arise from the bone marrow, and do not need an encounter with antigens to gain their functionality. Thus, while lymphoid cells are a part of the adaptive immune system, myeloid cells are a part of the innate immune system. Hematopoiesis gives rise to two progenitor cells—the common myeloid progenitor (CMP) and the common lymphoid progenitor (CLP). The CMP can give rise to megakaryocytes, erythrocytes, mast cells and myeloblasts. Myeloblasts in turn lead to the formation of basophils, neutrophils, eosinophils and monocytes that can further differentiate into macrophages. This review will focus on macrophages as well as the phenotypes they acquire with the tumor immune microenvironment (TIME) in triple-negative breast cancer (TNBC). It will address how cancer cells in the tumor microenvironment (TME) recruit macrophages and may switch to recruiting neutrophils upon depletion of these tumor-associated macrophages (TAMs). Finally, it will also shed light on past and current treatment options that specifically target these cells and how those affect patient outcomes in TNBC.
Carbapenem-Resistant Pseudomonas aeruginosa Strains-Distribution of the Essential Enzymatic Virulence Factors Genes

Pseudomonas aeruginosa is one of the most commonly isolated bacteria from clinical specimens, with increasing isolation frequency in nosocomial infections. Herein, we investigated whether antimicrobial-resistant P. aeruginosa strains, e.g., metallo-beta-lactamase (MBL)-producing isolates, may possess a reduced number of virulence genes, resulting from appropriate genome management to adapt to a changing hospital environment. Hospital conditions, such as selective pressure, may lead to the replacement of virulence genes by antimicrobial resistance genes that are crucial to survive under current conditions. The study aimed to compare, using PCR, the frequency of the chosen enzymatic virulence factor genes (alkaline protease-aprA, elastase B-lasB, neuraminidases-nan1 and nan2, and both variants of phospholipase C-plcH and plcN) to MBL distribution among 107 non-duplicated carbapenem-resistant P. aeruginosa isolates. The gene encoding alkaline protease was noted with the highest frequency (100%), while the neuraminidase-1 gene was observed in 37.4% of the examined strains. The difference in lasB and nan1 prevalence amongst the MBL-positive and MBL-negative strains, was statistically significant. Although P. aeruginosa virulence is generally more likely determined by the complex regulation of the virulence gene expression, herein, we found differences in the prevalence of various virulence genes in MBL-producers.