Miracle-dz/UniFAR-FTUs huggingface dataset:
A Retrospective Analysis of the Coagulation Dysfunction in COVID-19 Patients

To discuss the coagulation dysfunction in COVID-19 patients and to find new biomarkers to separate severe COVID-19 patients from mild ones. We use a retrospective analysis of 88 COVID-19 patients, and compare the coagulation function between severe and mild groups. We found the prothrombin time (PT), thrombin time (TT), D-dimer were significantly higher in the severe group (P < 0.05), and the highest area under the curve (AUC) is 0.91 for D-dimer, while the AUC of PT and TT were 0.80 and 0.61 respectively. We identified that D-dimer has a better value in predicting patients who are likely to develop into severe cases, with the sensitivity and specificity were 84.4% and 88.8%, respectively. D-dimer may be a good biomarker to separate the severe COVID-19 patients from the mild ones.
Gene Editing by Extracellular Vesicles

CRISPR/Cas technologies have advanced dramatically in recent years. Many different systems with new properties have been characterized and a plethora of hybrid CRISPR/Cas systems able to modify the epigenome, regulate transcription, and correct mutations in DNA and RNA have been devised. However, practical application of CRISPR/Cas systems is severely limited by the lack of effective delivery tools. In this review, recent advances in developing vehicles for the delivery of CRISPR/Cas in the form of ribonucleoprotein complexes are outlined. Most importantly, we emphasize the use of extracellular vesicles (EVs) for CRISPR/Cas delivery and describe their unique properties: biocompatibility, safety, capacity for rational design, and ability to cross biological barriers. Available molecular tools that enable loading of desired protein and/or RNA cargo into the vesicles in a controllable manner and shape the surface of EVs for targeted delivery into specific tissues (e.g., using targeting ligands, peptides, or nanobodies) are discussed. Opportunities for both endogenous (intracellular production of CRISPR/Cas) and exogenous (post-production) loading of EVs are presented.
Remdesivir targets a structurally analogous region of the Ebola virus and SARS-CoV-2 polymerases

Significance Remdesivir is a nucleotide analog prodrug that has been evaluated in humans against acute Ebola virus disease; it also recently received emergency use authorization for treating COVID-19. For antiviral product development, the Food and Drug Administration recommends the characterization of in vitro selected resistant viruses to define the specific antiviral mechanism of action. This study identified a single amino acid residue in the Ebola virus polymerase that conferred low-level resistance to remdesivir. The significance of our study lies not only in characterizing this particular mutation, but also in relating it to a resistance mutation observed in a similar structural motif of coronaviruses. Our findings thereby indicate a consistent mechanism of action by remdesivir across genetically divergent RNA viruses causing diseases of high consequence in humans. Remdesivir is a broad-spectrum antiviral nucleotide prodrug that has been clinically evaluated in Ebola virus patients and recently received emergency use authorization (EUA) for treatment of COVID-19. With approvals from the Federal Select Agent Program and the Centers for Disease Control and Prevention’s Institutional Biosecurity Board, we characterized the resistance profile of remdesivir by serially passaging Ebola virus under remdesivir selection; we generated lineages with low-level reduced susceptibility to remdesivir after 35 passages. We found that a single amino acid substitution, F548S, in the Ebola virus polymerase conferred low-level reduced susceptibility to remdesivir. The F548 residue is highly conserved in filoviruses but should be subject to specific surveillance among novel filoviruses, in newly emerging variants in ongoing outbreaks, and also in Ebola virus patients undergoing remdesivir therapy. Homology modeling suggests that the Ebola virus polymerase F548 residue lies in the F-motif of the polymerase active site, a region that was previously identified as susceptible to resistance mutations in coronaviruses. Our data suggest that molecular surveillance of this region of the polymerase in remdesivir-treated COVID-19 patients is also warranted.
Endothelium

The endothelium is the layer of cells lining the blood vessels in animals. It weighs more than one kilogram in adult humans [2], and it covers a surface area of 4000 to 7000 square meters. The endothelium is the cellular interface between the circulating blood and underlying tissue. As the medium between these two sets of tissues, endothelium is part of many normal and disease processes throughout the body. The endothelium responds to signals from its surrounding environment to help regulate functions like the resistance that blood vessels need to pump blood through the body (vasomotor tone), the policing of substances trying to enter or exit the blood vessel (blood vessel permeability), and the ability of blood to clot (hemostasis). In addition to diseases like atherosclerosis, endothelium has been indicated as a component in pathologies like cancer, asthma, diabetes, hepatitis, multiple sclerosis, and sepsis. The shape, size, and appearance of endothelial cells, called their phenotypes, vary depending upon which part of the body the cells are from, a property called phenotypic heterogeneity. The endothelium, its properties, and its responses to stimuli are governed largely by the local environment of the cells.
IMPACTS OF ZINC OXIDE NANO-PARTICLES SUPPLEMENTATION IN BROILER DIETS ON GROWTH PERFORMANCE, SOME CARCASS CHARACTERISTICS AND IMMUNE ORGANS

A study was designed to investigate the effect of different levels of dietary nano zinc oxide (NZnO) on growth performance, carcass traits, digestive tract measurements, immune response and economic efficiency of broiler chicks. A total number of 192 unsexed day-old "Cobb" broiler chicks were distributed in a completely randomized design of six treatments with four replicates (8 chicks each). The control (T1) contained 100 mg inorganic zinc oxide (IZnO)/kg of diet. Treatments two to six contained 100, 80, 60, 40 and 20 mg NZnO/kg of diet, respectively. No significant differences were observed between treatments on growth parameters except for feed conversion ratio (FCR) and performance index (PI). However, birds fed 40 mg NZnO (T5) consumed less feed and recorded the highest LBW, TBWG and the best CPC and CCR compared with the other treatments. The best FCR (P≤0.01), PI (P≤0.05), economic efficiency (EE) and the relative EE were obtained by T5. The highest (P≤0.05) breast and thigh (P≤0.01) and the lowest abdominal fat percentages were observed with birds fed the control and T6 (20 mg NZnO) compared to other treatments. Thymus percentage was reduced (P≤0.01) by T5 compared with control, T3 and T4 while the bursa percentage was increased by T4 and T5 compared with the other treatments. It could be concluded that NZnO at a level of 40 mg/kg of diet had no harmful effect on health status and could be used instead of the traditional zinc sources in broiler diets.
Sociosexuality and Sex With New Partners: Indirect Effects Via Drinking at Parties and Bars.

OBJECTIVE The desire for many novel, concurrent, uncommitted sex partners (i.e., unrestricted sociosexuality) may encourage individuals to seek out contexts that facilitate casual sex. We tested a model in which the effects of sociosexuality on sex with new partners were mediated via drinking in specific contexts. We hypothesized that drinking at parties and bars, which are known to facilitate casual sex (but not drinking at home), would contribute to sex with new (but not with previous) partners. METHOD Participants were 427 male freshmen from a large, public northeastern university. They completed a baseline survey in their first semester followed by 56 days of daily reports on drinking and sexual activity during their second semester. RESULTS As predicted, sociosexuality measured at baseline positively predicted occasions of sex with a new partner, but not sex with a previous partner. In support of the model, effects were partially mediated by frequency of drinking at parties and bars across the 56-day reporting period, but not by drinking at home. CONCLUSIONS Previous research has demonstrated associations among sociosexuality, drinking, and casual sex. Our study is unique in suggesting that drinking in specific contexts--that is, drinking at parties and bars, but not drinking at home--partially mediates the effects of sociosexuality on sex with new partners. This pathway suggests that men with a desire for many novel, concurrent, uncommitted sex partners seek out drinking contexts as a way of facilitating these encounters.
Preclinical Comparison of the Blood–brain barrier Permeability of Osimertinib with Other EGFR TKIs

Purpose: Osimertinib is a potent and selective EGFR tyrosine kinase inhibitor (EGFR-TKI) of both sensitizing and T790M resistance mutations. To treat metastatic brain disease, blood–brain barrier (BBB) permeability is considered desirable for increasing clinical efficacy. Experimental Design: We examined the level of brain penetration for 16 irreversible and reversible EGFR-TKIs using multiple in vitro and in vivo BBB preclinical models. Results: In vitro osimertinib was the weakest substrate for human BBB efflux transporters (efflux ratio 3.2). In vivo rat free brain to free plasma ratios (Kpuu) show osimertinib has the most BBB penetrance (0.21), compared with the other TKIs (Kpuu ≤ 0.12). PET imaging in Cynomolgus macaques demonstrated osimertinib was the only TKI among those tested to achieve significant brain penetrance (Cmax %ID 1.5, brain/blood Kp 2.6). Desorption electrospray ionization mass spectroscopy images of brains from mouse PC9 macrometastases models showed osimertinib readily distributes across both healthy brain and tumor tissue. Comparison of osimertinib with the poorly BBB penetrant afatinib in a mouse PC9 model of subclinical brain metastases showed only osimertinib has a significant effect on rate of brain tumor growth. Conclusions: These preclinical studies indicate that osimertinib can achieve significant exposure in the brain compared with the other EGFR-TKIs tested and supports the ongoing clinical evaluation of osimertinib for the treatment of EGFR-mutant brain metastasis. This work also demonstrates the link between low in vitro transporter efflux ratios and increased brain penetrance in vivo supporting the use of in vitro transporter assays as an early screen in drug discovery.
Safety, Tolerability, and Pharmacokinetics of Mevidalen (LY3154207), a Centrally Acting Dopamine D1 Receptor‐Positive Allosteric Modulator (D1PAM), in Healthy Subjects

Activation of the brain dopamine D1 receptor has attracted attention because of its promising role in neuropsychiatric diseases. Although efforts to develop D1 agonists have been challenging, a positive allosteric modulator (PAM), represents an attractive approach with potential better drug‐like properties. Phase 1 single‐ascending‐dose (SAD; NCT03616795) and multiple‐ascending‐dose (MAD; NCT02562768) studies with the D1PAM mevidalen (LY3154207) were conducted with healthy subjects. There were no treatment‐related serious adverse events (AEs) in these studies. In the SAD study, 25‐200 mg administered orally showed dose‐proportional pharmacokinetics (PK) and acute dose‐related increases in systolic blood pressure (SBP) and diastolic blood pressure DBP) and pulse rate at doses ≥ 75 mg. AE related to central activation were seen at doses ≥ 75 mg. At 25 and 75 mg, central penetration of mevidalen was confirmed by measurement of mevidalen in cerebrospinal fluid. In the MAD study, once‐daily doses of mevidalen at 15‐150 mg for 14 days showed dose‐proportional PK. Acute dose‐dependent increases in SBP, DBP, and PR were observed on initial administration, but with repeated dosing the effects diminished and returned toward baseline levels. Overall, these findings support further investigation of mevidalen as a potential treatment for a range of neuropsychiatric disorders.
Bio-acoustic signaling; exploring the potential of sound as a mediator of low-dose radiation and stress responses in the environment

Abstract Objectives This commentary reviews and evaluates the role of sound signals as part of the infosome of cells and organisms. Emission and receipt of sound has recently been identified as a potentially important universal signaling mechanism invoked when organisms are stressed. Recent evidence from plants, animals and microbes suggests that it could be a stimulus for specific or general molecular cellular stress responses in different contexts, and for triggering population level responses. This paper reviews the current status of the field with particular reference to the potential role of sound signaling as an immediate/early bystander effector (RIBE) during radiation-induced stress. Conclusions While the chemical effectors involved in intercellular and inter-organismal signaling have been the subject of intense study in the field of Chemical Ecology, less appears to be known about physical signals in general and sound signals in particular. From this review we conclude that these signals are ubiquitous in each kingdom and behave very like physical bystander signals leading to regulation of metabolic pathways and gene expression patterns involved in adaptation, synchronization of population responses, and repair or defence against damage. We propose the hypothesis that acoustic energy released on interaction of biota with electromagnetic radiation may represent a signal released by irradiated cells leading to, or complementing, or interacting with, other responses, such as endosome release, responsible for signal relay within the unirradiated individuals in the targeted population.
Differentiating maximal and submaximal voluntary strength measures for the purposes of medico-legal assessments and para sport classification: A systematic review

Abstract Measurement of maximum voluntary muscle contractions are effort-dependent – valid measurement requires maximal voluntary effort (MVE) from participants. Submaximal efforts (SMEs) yield invalid and potentially misleading results. This is particularly problematic in medico-legal and Para sport assessments where low strength scores may confer a personal advantage. Therefore, objective methods for accurately differentiating MVE and SME are required. This systematic review aimed to identify, appraise and synthesise evidence from scientific studies evaluating the validity of objective methods for differentiating MVE from SME during maximal voluntary contractions. Four electronic databases were searched for original research articles published in English and secondary references appraised for relevance yielding 25 studies for review. Methods were categorised based on eight distinct underlying theories. For isokinetic strength assessment, methods based on two theories – Strength-measure Ratios and Inter-Trial Strength Consistency – correctly classified 100% MVE and > 92% SME. Consequently, research evaluating the relative suitability of these methods for translation into practice is warranted. During isometric strength assessments, methods based on Deceptive Visual Feedback and Force-length properties warrant further investigation. Both methods yielded statistically significant differences between MVE and SME, with minimal overlap in values, but their sensitivity and specificity have not been evaluated.
Wolbachia-Mitochondrial DNA Associations in Transitional Populations of Rhagoletis cerasi

Simple Summary Wolbachia is an endosymbiotic bacterium that infects numerous insects and crustaceans. Its ability to alter the reproduction of hosts results in incompatibilities of differentially infected individuals. Therefore, Wolbachia has been applied to suppress agricultural and medical insect pests. The European cherry fruit fly, Rhagoletis cerasi, is mainly distributed throughout Europe and Western Asia, and is infected with at least five different Wolbachia strains. The strain wCer2 causes incompatibilities between infected males and uninfected females, making it a potential candidate to control R. cerasi. Thus, the prediction of its spread is of practical importance. Like mitochondria, Wolbachia is inherited from mother to offspring, causing associations between mitochondrial DNA and endosymbiont infection. Misassociations, however, can be the result of imperfect maternal transmission, the loss of Wolbachia, or its horizontal transmission from infected to uninfected individuals. These are important parameters influencing the spread of infection. Here, we studied Wolbachia-mitochondrial haplotype associations in R. cerasi in two transition zones in the Czech Republic and Hungary, where wCer2 is currently spreading. Our results suggest imperfect maternal transmission only in the early phases of wCer2 invasion and no evidence of horizontal transmission of wCer2 in R. cerasi. Abstract The endosymbiont Wolbachia can manipulate arthropod host reproduction by inducing cytoplasmic incompatibility (CI), which results in embryonic mortality when infected males mate with uninfected females. A CI-driven invasion of Wolbachia can result in a selective sweep of associated mitochondrial haplotype. The co-inheritance of Wolbachia and host mitochondrial DNA can therefore provide significant information on the dynamics of an ongoing Wolbachia invasion. Therefore, transition zones (i.e., regions where a Wolbachia strain is currently spreading from infected to uninfected populations) represent an ideal area to investigate the relationship between Wolbachia and host mitochondrial haplotype. Here, we studied Wolbachia-mitochondrial haplotype associations in the European cherry fruit fly, Rhagoletis cerasi, in two transition zones in the Czech Republic and Hungary, where the CI-inducing strain wCer2 is currently spreading. The wCer2-infection status of 881 individuals was compared with the two known R. cerasi mitochondrial haplotypes, HT1 and HT2. In accordance with previous studies, wCer2-uninfected individuals were associated with HT1, and wCer2-infected individuals were mainly associated with HT2. We found misassociations only within the transition zones, where HT2 flies were wCer2-uninfected, suggesting the occurrence of imperfect maternal transmission. We did not find any HT1 flies that were wCer2-infected, suggesting that Wolbachia was not acquired horizontally. Our study provides new insights into the dynamics of the early phase of a Wolbachia invasion.
Can Population Effects of Pesticides Be Predicted from Demographic Toxicological Studies

Demographic toxicological analysis was evaluated as a method to estimate the total effect (lethal and sublethal) of pesticides on populations. Using the neem insecticide, Margosan-O and the pea aphid, Acyrthosiphon pisum (Harris), as a model, we questioned the necessity of evaluating the response of different life stages to pesticides to estimate effects adequately at the population level, and whether pesticide persistence should be considered. Population growth of the pea aphid was followed after exposure of neonates in the 1st study and adults in the 2nd study on broad bean, Vicia fava F. , treated with Margosan-O. For all of the parameters measured, the population exposed from birth was affected more than the population exposed as adults. The intrinsic rate of increase (r m ) for the population exposed from birth became negative when aphids were exposed to Margosan-O at the equivalent of 60 mg/liter (ppm) azadirachtin. However, when adult aphids were exposed to Margosan-O-treated plants, r m was not reduced even at rates as high as 100 ppm of azadirachtin. Thus, estimates of a population effect (r m ) of Margosan-O on A. pisum cannot be made by evaluating only one life stage even with a life table approach. The use of demography to predict population level effects of pesticides would therefore be misleading if done in the traditional way by exposing individuals from birth only. Persistence of Margosan-O, measured as mortality half-life, was 5.8 d under the conditions of this study. The longer adult aphids survive exposure to Margosan-O and produce offspring, the less pesticide residue will be available to cause damage to these offspring. Adults exposed to sublethal concentrations of a pesticide may therefore act as a reservoir for their young. We argue that the actual effect of Margosan-O on a mixed age population of pea aphid cannot be determined with experiments that evaluate only 1 animal life stage. We suggest that a stage-structured approach that includes the effects of temperature and pesticide persistence would improve the demographic method of toxicological analysis.
The Assessment of Physical Fitness and Morphofunctional State of Female First-Year Students in Non-Linguistic Higher Education Institutions

The purpose of this research paper is to study physical fitness and functional state of female first-year students in Prydniprovska State Academy of Civil Engineering and Architecture. Materials and methods. The study involved 100 female first-year students of general group aged 17-18, all after medical examination and obtaining doctor’s approval: the age group was 18 years old (n = 100). To meet the goals set, the following research methods were used: theoretical analysis and generalization of data in specialized scientific and methodological literature, pedagogical testing, anthropometric research methods, functional methods of cardiorespiratory system investigation and methods of mathematical statistics for processing the results of the research. Results. the conducted study proved the hypothesis on the necessity to improve the system of physical education in technical higher educational institutions, which is connected with the low level of physical fitness among students. Conclusions. The study revealed the low level of physical fitness among the investigated students in terms of speed and strength endurance indicators (with 83%), explosive physical force of the lower limbs (with 82%) and strength endurance of the upper limbs (with 68%), as well as reduced functional characteristics: resistance to hypoxia (according to the results of the Shtange test with 46% and the Gench test with 49%), workability (with 71%) and efficiency of cardiovascular system (with 55%). Low physical fitness levels among the tested girls necessitate the additional introduction of more intensive training. The high variability of the physical fitness indicators among the students requires personalization of the training process, as well as the obligatory use of express testing methods for the physical state of each student during a workout.
Networks of directors on Russian boards: The hidden part of the corporate governance iceberg

In this paper we apply social network analysis to study the boards of directors of 107 large listed Russian firms between 2009 and 2014. Traditional corporate governance metrics, such as demographic characteristics, experience or multiple directorships, confirm a previously established positive trend towards greater independence and better qualification of the boards of Russian firms. We also find a decrease in the centrality of directors, which corroborates the diminishing concentration of power of some directors. The most connected firms have a specific profile since they are larger, have lower market valuations, and stronger ties with government (both due to higher proportions of government owned shares and a greater number of directors who are former politicians). Our findings also demonstrate that the boards of financialinstitutions are less connected, whereas political and independent directors are more centralized.