Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of population genetic structure of hereditary transthyretin amyloidosis in Bulgaria

Abstract The hereditary transthyretin amyloidosis (ATTRv amyloidosis) is an autosomal dominant genetic disease characterized by amyloid formation in different tissues due to pathogenic variants in the TTR gene. Great heterogeneity in the penetrance and manifestation of ATTRv amyloidosis is observed. In Bulgaria, the most common TTR pathogenic variant is Glu89Gln. Other TTR pathogenic variants are also found – Val30Met, Ser77Phe, Gly47Glu and Ser52Pro. There is a proven founder effect for the Glu89Gln variant, thus the aim of the present study is to investigate the founder effect for the other TTR pathogenic variants in Bulgaria. Haplotype analysis was performed by using microsatellite markers close to the TTR gene. DNA samples from ATTRv amyloidosis patients and their healthy relatives were analyzed. Theoretical haplotype reconstruction was done with Arlequin v.3. 01 software. The age of the most recent common ancestor (hypothetical founder) for the studied variants was calculated with the DMLE 2.2 software. In addition, DBS screening among 100 Roma newborns was done for the Gly47Glu TTR variant via direct Sanger sequencing. The reconstructed haplotypes of the patients were compared to their healthy relatives and to a control group of 40 healthy individuals. The results showed a possible founder effect for each of the studied variants. The Val30Met haplotype was compared to published haplotype data for this variant and no similarity was found. The result from the DBS screening showed no pathogenic TTR variants in exon 2 of the gene, so we considered the presence of the Gly47Glu variant in our population a sporadic event. With this study, we succeeded to gain a more complete picture of the population genetics of ATTRv amyloidosis in Bulgaria and made another step towards a more detailed understanding of the disease epidemiology.
Preparation and Properties of Wet-Spun Microcomposite Filaments from Various CNFs and Alginate

We aimed to improve the mechanical properties of alginate fibers by reinforcing with various cellulose nanofibrils (CNFs). Pure cellulose nanofibril (PCNF), lignocellulose nanofibril (LCNF) obtained via deep eutectic solvent (DES) pretreatment, and TEMPO-oxidized lignocellulose nanofibril (TOLCNF) were employed. Sodium alginate (AL) was mixed with PCNF, LCNF, and TOLCNF with a CNF content of 5–30%. To fabricate microcomposite filaments, the suspensions were wet-spun in calcium chloride (CaCl2) solution through a microfluidic channel. Average diameters of the microcomposite filaments were in the range of 40.2–73.7 μm, which increased with increasing CNF content and spinning rate. The tensile strength and elastic modulus improved as the CNF content increased to 10%, but the addition of 30% CNF deteriorated the tensile properties. The tensile strength and elastic modulus were in the order of LCNF/AL > PCNF/AL > TOLCNF/AL > AL. An increase in the spinning rate improved the tensile properties.
Aerobic Exercise Induces Alternative Splicing of Neurexins in Frontal Cortex

Aerobic exercise (AE) is known to produce beneficial effects on brain health by improving plasticity, connectivity, and cognitive functions, but the underlying molecular mechanisms are still limited. Neurexins (Nrxns) are a family of presynaptic cell adhesion molecules that are important in synapsis formation and maturation. In vertebrates, three-neurexin genes (NRXN1, NRXN2, and NRXN3) have been identified, each encoding for α and β neurexins, from two independent promoters. Moreover, each Nrxns gene (1–3) has several alternative exons and produces many splice variants that bind to a large variety of postsynaptic ligands, playing a role in trans-synaptic specification, strength, and plasticity. In this study, we investigated the impact of a continuous progressive (CP) AE program on alternative splicing (AS) of Nrxns on two brain regions: frontal cortex (FC) and hippocampus. We showed that exercise promoted Nrxns1–3 AS at splice site 4 (SS4) both in α and β isoforms, inducing a switch from exon-excluded isoforms (SS4−) to exon-included isoforms (SS4+) in FC but not in hippocampus. Additionally, we showed that the same AE program enhanced the expression level of other genes correlated with synaptic function and plasticity only in FC. Altogether, our findings demonstrated the positive effect of CP AE on FC in inducing molecular changes underlying synaptic plasticity and suggested that FC is possibly a more sensitive structure than hippocampus to show molecular changes.
Clinical study evaluating the efficacy of ivermectin in COVID‐19 treatment: A randomized controlled study

Researchers around the world are working at record speed to find the best ways to treat and prevent coronavirus disease 2019 (COVID‐19). This study aimed to evaluate the efficacy of ivermectin for the treatment of hospitalized mild to moderate COVID‐19 infected patients. This was a randomized open‐label controlled study that included 164 patients with COVID‐19. Patients were randomized into two groups where Group 1 (Ivermectin group) included patients who received ivermectin 12 mg once daily for 3 days with standard care and Group 2 (control group) included patients who received standard protocol of treatment alone for 14 days. The main outcomes were mortality, the length of hospital stay, and the need for mechanical ventilation. All patients were followed up for 1 month. Overall, 82 individuals were randomized to receive ivermectin plus standard of care and 82 to receive standard of care alone. Patients in the ivermectin group had a shorter length of hospital stay (8.82 ± 4.94 days) than the control group (10.97 ± 5.28 days), but this was not statistically significant (p = 0.085). Three patients (3.7%) in each group required mechanical ventilation (p = 1.00). The death rate was three patients in the ivermectin group (3.7%) versus four patients (4.9%) in the control group without any significant difference between the two groups (p = 1.00). Although there was no statistically significant difference in any endpoints by ivermectin doses (12 mg/day for 3 days); there was an observed trend to reducing hospital stay in the ivermectin‐treated group.
Glycine Attenuates Citrobacter rodentium-Induced Colitis by Regulating ATF6-Mediated Endoplasmic Reticulum Stress in Mice.

SCOPE Inflammatory bowel disease (IBD) is an inflammatory gastrointestinal disorder in which endoplasmic reticulum (ER) stress and dysbiosis of the intestinal microbiota are implicated. Glycine supplementation has been reported to reduce inflammatory responses in experimental colitis. However, the underlying mechanisms responsible for the beneficial effects remain unclear. METHODS AND RESULTS Female C57BL/6 mice were orally administered with glycine (3.5 or 5.2 g/kg body weight) for 14 continuous days. On day 8 post-glycine supplementation, the mice were orally inoculated with 2 × 109 CFU Citrobacter rodentium (C. rodentium). The results showed that glycine alleviated C. rodentium-induced body weight loss, increased disease activity index and spleen weight, colon length shortening, and colonic hyperplasia. Glycine suppressed the activation and infiltration of inflammatory cells, and secretion of pro-inflammatory cytokines in the colon tissues. The apoptosis of colon epithelial cells was also abrogated by glycine, which was associated with the inactivation of activating transcription factor 6α (ATF6α)-C/EBP homologous protein (CHOP) signaling. In addition, glycine administration increased α diversity, restored β diversity, and abolished the reduction in Lactobacillus, Bifidobacterium, Alistipes, Turicibacter, and Alloprevotella in the colon. CONCLUSIONS Glycine supplementation is a nutritional strategy that may ameliorate C. rodentium-induced colitis by regulating ATF6α-CHOP-mediated ER stress and enhancing the abundance of Lactobacillus. This article is protected by copyright. All rights reserved.
Polycyclic Aromatic Hydrocarbon Levels in Wistar Rats Exposed to Ambient Air of Port Harcourt, Nigeria: An Indicator for Tissue Toxicity

This study investigated the PAH levels in Wistar rats exposed to ambient air of the Port Harcourt metropolis. Twenty Wistar rats imported from a nonpolluted city (Enugu) were exposed to both indoor and outdoor air. Following the IACUC regulation, baseline data were obtained from 4 randomly selected rats, while the remaining 16 rats (8 each for indoor and outdoor) were left till day 90. Blood samples were obtained by cardiac puncture, and the PAH levels were determined using Gas Chromatography Flame-Ionization Detector (GC-FID). GraphPad Prism (version 8.0.2) Sidak’s (for multiple data set) and unpaired t-tests (for two data sets) were used to evaluate the differences in group means. Seven of the PAHs found in indoor and outdoor rats were absent in baseline rats. The mean concentrations of PAH in indoor and outdoor animals were higher than those of baseline animals, except for Benzo(a)pyrene, which was found in baseline animals but absent in other animal groups. Additionally, Dibenz(a,h)anthracene, Indeno(1,2,3-c,d)pyrene, Pyrene, 2-methyl, and other carcinogenic PAHs were all significantly higher (p < 0.05) in outdoor groups. The vulnerable groups in Port Harcourt are at the greatest risk of such pollution. Therefore, urgent environmental and public health measures are necessary to mitigate the looming danger.
SCARE: A Novel Switching and Collision Avoidance pRocEss for Connected Vehicles Using Virtualization and Edge Computing Paradigm

In this paper, some collision avoidance systems based on MEC in a VANET environment are proposed and investigated. Micro services at edge are considered to support service continuity in vehicle communication and advertising. This considered system makes use of cloud and edge computing, allowing to switch communication from edge to cloud server and vice versa when possible, trying to guarantee the required constraints and balancing the communication among the servers. Simulation results were used to evaluate the performance of three considered mechanisms: the first one considering only edge with load balancing, the second one using edge/cloud switching and the third one using edge with load balancing and collision avoidance advertising.
Biochemical Modification of Titanium Oral Implants: Evidence from In Vivo Studies

The discovery of osseointegration of titanium implants revolutionized the dental prosthesis field. Traditionally, implants have a surface that is processed by additive or subtractive techniques, which have positive effects on the osseointegration process by altering the topography. In the last decade, innovative implant surfaces have been developed, on which biologically active molecules have been immobilized with the aim of increasing stimulation at the implant–biological tissue interface, thus favoring the quality of osseointegration. Among these molecules, some are normally present in the human body, and the techniques for the immobilization of these molecules on the implant surface have been called Biochemical Modification of Titanium Surfaces (BMTiS). Different techniques have been described in order to immobilize those biomolecules on titanium implant surfaces. The aim of the present paper is to present evidence, available from in vivo studies, about the effects of biochemical modification of titanium oral implants on osseointegration.
FEVER: The Flexed Elbow Valgus External Rotation View for MRI Evaluation of the Ulnar Collateral Ligament in Throwing Athletes-A Pilot Study in Major League Baseball Pitchers.

Background: Ulnar collateral ligament (UCL) injuries are common in throwing athletes due to repetitive extreme valgus stress during overhead throwing maneuvers. Conventional positioning for elbow MRI provides suboptimal rendering of the UCL. Objective: To perform a prospective pilot study assessing the impact of a flexed elbow valgus external rotation (FEVER) view on ulnotrochlear (UT) joint space measurement and reader evaluation of the UCL when incorporated into standard elbow MRI in throwing athletes. Methods: A total of 44 Major League Baseball pitchers underwent elbow MRI including standard sequences and a coronal fat-saturated proton density-weighted sequence in the FEVER view that uses specific positioning maneuvers and sandbags to immobilize the elbow in valgus stress and visualize the UCL parallel to its long axis. Patients recorded pain during FEVER view [0 (none) to 10 (maximal)]. Two radiologists independently evaluated standard and FEVER views to measure the UT joint space, assess confidence in UCL-related findings, and assess the UCL as normal or abnormal. Results: Pain during FEVER view was: 0 (n=29), 1-3 (n=11), 4-7 (n=4), 8-10 (n=0). Intrareader agreement for UT joint space measurement was higher for FEVER [intraclass correlation coefficient (ICC)=0.92] than standard (ICC=0.54) views. Averaged between readers, mean UT joint space increase on FEVER compared with standard view was 1.80 mm (95% CI: 1.58, 2.03). Confidence was higher for FEVER than standard view for reader 1 for assessment of the UCL as normal versus abnormal (mean increase in confidence of 0.41), intensity of abnormal signal (0.44), injury grade (0.98), and retraction (0.20), and for reader 2, assessment of the UCL as normal versus abnormal (0.50), location of abnormal signal (0.42); intensity of abnormal signal (0.47), injury grade (0.89), and retraction (0.50). Readers 1 and 2 classified 3 and 2 additional UCLs as abnormal on FEVER compared with standard view; neither reader classified any UCL as abnormal in standard view but normal in FEVER view. Conclusion: The increased joint space width confirms elbow valgus stress with FEVER view. Diagnostic confidence increased, and additional UCLs were identified as abnormal. Clinical Impact: The FEVER view may improve MRI evaluation of the UCL in throwing athletes.
Real world use of FLT3 inhibitors for treatment of FLT3+ acute myeloid leukemia (AML): A single center, propensity-score matched, retrospective cohort study

Background Patients diagnosed with acute myeloid leukemia with a FLT3 mutation (FLT3+ AML) have historically had poor outcomes. While the addition of the FLT3 inhibitors to induction therapy has been shown to improve survival outcomes in FLT3+ AML, interactions and overlapping toxicities between FLT3 inhibitors and standard of care medications used during induction therapy (e.g. azole antifungals, anthracyclines) and logistical barriers have complicated their use. To avoid these concerns, our institution has opted to defer initiation of midostaurin until after completion of induction therapy. However, to our knowledge no study confirming the effectiveness of this strategy for real world FLT3 inhibitor use has been published. Methods We performed a single center, propensity-score matched, retrospective cohort study characterizing efficacy and safety of our strategy for use of FLT3 inhibitors in the treatment of FLT3+ AML. The primary outcome was median event-free survival (EFS), while secondary endpoints included median overall survival (OS), overall response rate (ORR), 30-day mortality, duration of neutropenia, duration of thrombocytopenia, consolidation cycle delays, documented infections, and all-cause hospital readmission. Results A total of 83 FLT3+ AML patients treated with intensive induction therapy were included in the study, of whom 48 were propensity-score matched and analyzed. Baseline characteristics were similar between the patients who received a FLT3 inhibitor after induction therapy and the historical control arm. Median EFS was not significantly different but compared favorably between the FLT3 inhibitor cohort and historical controls (not reached vs 8 months, p = 0.343) with 18-month EFS of 54% and 43% for the two cohorts, respectively. Similarly, no significant differences were noted with regard to median OS (not reached vs 28.7 months, p = 0.752), ORR (79.2% vs 79.2%), or safety outcomes between groups. Conclusion Compared to historical controls, addition of a FLT3 inhibitor to intensive chemotherapy post-induction may improve EFS or OS in a real world patient cohort with longer follow-up and a larger sample size. The omission of midostaurin in induction allowed for the use of an azole antifungal and the intensification of anthracycline dose may have contributed to high remission rates in both groups.
The Impact of Refrigerated Storage on the Chemical, Physiochemical and Sensory Characteristics of Some Fruit ectars

800x600 This study aimed to evaluate the effect of refrigerated storage on fruit nectars prepared from: guava, mango and orange fruits. Physiochemical, chemical and sensory analysis was carried out for fresh and stored fruit nectars at 5C°. Guava nectar had the highest stability compared with orange and mango nectars, and also it had the highest value of 2.9 ± 0.04 % fiber, 0.38 ± 0.02 % fat and 199 ± 0.22 mg/100gm ascorbic acid. The mango nectar had the highest values of total soluble solids (28.2 brix). As for orange nectar, it had the highest value of protein (0.80 ± 0.1%) and it had been changed during storage period. The sensory evaluation showed acceptance of fresh and stored fruit nectars at the second and fourth day of storage except orange nectars, which was accepted just as fresh and at second day of storage, indicating that it was more determinable than the other two fruit nectars. Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:. 0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman","serif";}
Anti-Inflammatory Activity of AF-13, an Antioxidant Compound Isolated from the Polar Fraction of Allomyrina dichotoma Larva, in Palmitate-Induced INS-1 Cells

This study was conducted to evaluate the fractions isolated from Allomyrina dichotoma larva extract (ADLE) that exhibited anti-apoptotic and anti-inflammatory effects. A total of 13 fractions were eluted from ADLE by centrifugal chromatography (CPC), and the polar AF-13 fraction was selected, which exerted a relatively protective effect against fat-induced toxicity in INS-1 cells. AF-13 treatment of palmitate-treated INS-1 cells decreased the expression level of apoptosis-related proteins and DNA fragmentation. AF-13 also significantly inhibited the production of nitric oxide and reactive oxygen species and the triglyceride content induced by palmitate, and the effect was found to be similar to that with ADLE treatment. Palmitate upregulated the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) through the activation of NF-κB p65; however, this effect was significantly attenuated by AF-13 treatment. In conclusion, AF-13 is one of the major components of ADLE responsible for anti-apoptotic and anti-inflammatory activities.
Effect of Epinephrine Administered during Cardiopulmonary Resuscitation on Cerebral Oxygenation after Restoration of Spontaneous Circulation in a Swine Model with a Clinically Relevant Duration of Untreated Cardiac Arrest

Severe neurological impairment was more prevalent in cardiac arrest survivors who were administered epinephrine than in those administered placebo in a randomized clinical trial; short-term reduction of brain tissue O2 tension (PbtO2) after epinephrine administration in swine following a short duration of untreated cardiac arrest has also been reported. We investigated the effects of epinephrine administered during cardiopulmonary resuscitation (CPR) on cerebral oxygenation after restoration of spontaneous circulation (ROSC) in a swine model with a clinically relevant duration of untreated cardiac arrest. After 7 min of ventricular fibrillation, 24 pigs randomly received either epinephrine or saline placebo during CPR. Parietal cortex measurements during 60-min post-resuscitation period showed that the area under the curve (AUC) for PbtO2 was smaller in the epinephrine group than in the placebo group during the initial 10-min period and subsequent 50-min period (both p < 0.05). The AUC for number of perfused cerebral capillaries was smaller in the epinephrine group during the initial 10-min period (p = 0.005), but not during the subsequent 50-min period. In conclusion, epinephrine administered during CPR reduced PbtO2 for longer than 10 min following ROSC in a swine model with a clinically relevant duration of untreated cardiac arrest.
The Meiosis-Specific Crs1 Cyclin Is Required for Efficient S-Phase Progression and Stable Nuclear Architecture

Cyclins and CDKs (Cyclin Dependent Kinases) are key players in the biology of eukaryotic cells, representing hubs for the orchestration of physiological conditions with cell cycle progression. Furthermore, as in the case of meiosis, cyclins and CDKs have acquired novel functions unrelated to this primal role in driving the division cycle. Meiosis is a specialized developmental program that ensures proper propagation of the genetic information to the next generation by the production of gametes with accurate chromosome content, and meiosis-specific cyclins are widespread in evolution. We have explored the diversification of CDK functions studying the meiosis-specific Crs1 cyclin in fission yeast. In addition to the reported role in DSB (Double Strand Break) formation, this cyclin is required for meiotic S-phase progression, a canonical role, and to maintain the architecture of the meiotic chromosomes. Crs1 localizes at the SPB (Spindle Pole Body) and is required to stabilize the cluster of telomeres at this location (bouquet configuration), as well as for normal SPB motion. In addition, Crs1 exhibits CDK(Cdc2)-dependent kinase activity in a biphasic manner during meiosis, in contrast to a single wave of protein expression, suggesting a post-translational control of its activity. Thus, Crs1 displays multiple functions, acting both in cell cycle progression and in several key meiosis-specific events.
The structural properties of a ZnCl2-ethylene glycol binary system and the peculiarities at the eutectic composition.

ATR-FTIR spectroscopy was performed on a series of ZnCl2-ethylene glycol (EG) mixtures with a wide-range of compositions (1 : 1.5-1 : 14 in molar ratios), involving the stable ZnCl2-4EG deep-eutectic solvent (DES) composition, to explore the spectral variations, structural heterogeneity, and hydrogen bonding (H-bonding) properties. To enhance the resolution of the spectra, excess absorption and two-dimensional correlation spectroscopies were employed. In the initial IR spectra, a quasi-isosbestic point was identified, signaling that the major disturbance on EG microstructures by adding ZnCl2 is to form a distinct complex. Further analysis uncovered the main transformation process to be from the EG tetramer to the ZnCl2-4EG complex. It was also found that as the EG content increases, negative charge increasingly transfers to ZnCl2, resulting in the strengthening of the Zn ← O coordination bonds and the weakening and finally dissociation of Zn-Cl bonds. Regarding the ZnCl2-4EG DES, several incomparable specificities were observed. It was found that ZnCl2 destructed the H-bonding network of pure EG to the largest extent, resulting in the highest production of the dimer and trimer of EG. Moreover, in comparison with other compositions, the ZnCl2-4EG DES showed abrupt increases in the negative charge of the salt, the length of the Zn-Cl bond, and the strength of the Zn ← O coordination bond. All these imply the strongest intermolecular interactions and the highest solvation of ZnCl2 in EG at the eutectic composition compared to those of other mixtures, resulting in a super-stable liquid mixture. The work provides physical insights into the structural and interactive properties of deep-eutectic solvents.