Miracle-dz/UniFAR-FTUs huggingface dataset:
Drug targets for corona virus: A systematic review

The 2019-novel coronavirus (nCoV) is a major source of disaster in the 21th century. However, the lack of specific drugs to prevent/treat an attack is a major need at this current point of time. In this regard, we conducted a systematic review to identify major druggable targets in coronavirus (CoV). We searched PubMed and RCSB database with keywords HCoV, NCoV, corona virus, SERS-CoV, MERS-CoV, 2019-nCoV, crystal structure, X-ray crystallography structure, NMR structure, target, and drug target till Feb 3, 2020. The search identified seven major targets (spike protein, envelop protein, membrane protein, protease, nucleocapsid protein, hemagglutinin esterase, and helicase) for which drug design can be considered. There are other 16 nonstructural proteins (NSPs), which can also be considered from the drug design perspective. The major structural proteins and NSPs may serve an important role from drug design perspectives. However, the occurrence of frequent recombination events is a major deterrent factor toward the development of CoV-specific vaccines/drugs.
Applicability of Tanaka–Johnston, Moyers, and Bernabé and Flores–Mir Mixed Dentition Analyses in School-going Children of Sri Ganganagar City, Rajasthan (India): A Cross-sectional Study

Background: The orthodontic diagnosis and treatment planning are the fundamental goals during the mixed dentition period. Numerous methods have been proposed till date such as Nance method, Moyer's method, Staley–Kerber and Tanaka–Johnston's method, and Bernabé and Flores–Mir method. Aim: The aim of the study is to determine the mesiodistal widths of the lower permanent canines and premolars from Tanaka–Johnston, Moyers, and Bernabé E and Flores–Mir C mixed dentition analysis and to determine the correlation coefficients and the new prediction equation for Sri Ganganagar population. Setting and Design: A total of 3572 children were clinically examined from the contemporary population of Sri Ganganagar city and Outpatient Department of Pediatric and Preventive Dentistry in Sri Ganganagar, Rajasthan. A total of 150 individuals were randomly selected for the study based on the inclusion and exclusion criteria and were designated as “study samples. Materials and Methods: A total of 150 children aged 11–16 years of Sri Ganganagar city were randomly selected. The mesiodistal width of permanent incisors, canines, premolars, and molars was measured with the help of digital vernier caliper with an accuracy of ±0.01 mm. The measurements of canines and premolars were summed up and compared with those derived from Tanaka and Johnston equations, Moyers probability tables, and Bernabé and Flores-Mir equations. Statistical Analysis: The data obtained were subjected to statistical analysis using IBM SPSS Statistics Windows version “20.0” using Student's t-test, Pearson correlation coefficient, and Kruskal–Wallis test. Results: All the three methods overestimated the actual sum of permanent canine and premolars in both the arches in our population. The correlation coefficients and the new regression equations were derived for both maxilla and mandible in males and females for Sri Ganganagar population. Conclusion: The predicted values obtained from all the three methods overestimated the actual values.
Body size, sampling completeness, and extinction risk in the marine fossil record

Abstract. Larger body size has long been assumed to correlate with greater risk of extinction, helping to shape body-size distributions across the tree of life, but a lack of comprehensive size data for fossil taxa has left this hypothesis untested for most higher taxa across the vast majority of evolutionary time. Here we assess the relationship between body size and extinction using a data set comprising the body sizes, stratigraphic ranges, and occurrence patterns of 9408 genera of fossil marine animals spanning eight Linnaean classes across the past 485 Myr. We find that preferential extinction of smaller-bodied genera within classes is substantially more common than expected due to chance and that there is little evidence for preferential extinction of larger-bodied genera. Using a capture–mark–recapture analysis, we find that this size bias of extinction persists even after accounting for a pervasive bias against the sampling of smaller-bodied genera within classes. The size bias in extinction also persists after including geographic range as an additional predictor of extinction, indicating that correlation between body size and geographic range does not provide a simple explanation for the association between size and extinction. Regardless of the underlying causes, the preferential extinction of smaller-bodied genera across many higher taxa and most of geologic time indicates that the selective loss of large-bodied animals is the exception, rather than the rule, in the evolution of marine animals.
Screening at the Dental Office: An Opportunity for Bridging the Gap in the Early Diagnosis of Hypertension and Diabetes in Ghana

Background: The prevalence of hypertension and diabetes is increasing in Ghana and sub-Saharan Africa. Screening is a useful tool in improving the early detection of both diseases to reduce the mortality and morbidity associated with the conditions. This study set out to determine the prevalence of patients with hypertension and hyperglycemia attending a dental clinic in Accra. Methods: A cross-sectional study, modeling a screening exercise, was conducted in a major dental clinic in Accra. Hypertension and diabetes were screened for with serial blood pressure checks at rest and random blood glucose measurements, respectively. Other variables were the pulse rate, the respiratory rate, and the background characteristics of respondents. Data were analyzed with Stata Version 14, and descriptive statistics were generated and reported. Results: There were a total of 175 participants in the study, comprising 76 males (43.4%) and 99 females (56.6%). This represented a male-to-female ratio of 0.8:1. The ages ranged from 18 to 86 years, with the median and mean ages of 40 years and 43.1 years (±16.9), respectively. This study found the prevalence of hypertension and hyperglycemia i the dental clinic to be 31.4% and 24.6%, respectively. Conclusion: The results of this study demonstrate the importance of the dental clinic in detecting both undiagnosed hypertension and diabetes, as well as those who have previously been diagnosed, but do not have their blood pressure and blood sugar under adequate control. With efficient referrals and follow-up systems in place at dental offices, they could be harnessed as a fertile place for hypertension and diabetes screening.
Exploring the ready knowledge of drug prescribing among junior doctors in Libya

Background: Essential drug knowledge is a ready knowledge of frequently prescribed drugs acquired by the clinician for the rational prescription. The present study was undertaken with the aims of assessing the knowledge of Libyan junior doctors about commonly prescribed drugs that necessary for rational prescribing and to determine the level of their ready knowledge. Methods: A questionnaire was distributed to 162 junior doctors employed at primary health centers in the city of Tripoli, Libya, and were requested to answer questions about rational prescribing of three commonly prescribed drugs (bisoprolol, pseudoephedrine, and co-amoxiclav). All items were categorized into six sets of core knowledge: drug class, indications, method of administration, contraindication, interaction, and adverse effects. The knowledge level to which junior doctors answer these statements was examined with a face-to-face assessment. Results: A number of 19 statements per drug were considered to be ready knowledge important for rational prescribing. Overall, knowledge about “drug class” (74.5%) and “Methods of administration (86.4%)” comprise most of the essential ready knowledge. Items concerning “interactions” (23.8%) and “contra-indication” (36.1%) were little acknowledged. Conclusion: Junior doctors' ready knowledge, in our population sample, seems to be insufficient to good prescribing. Our findings could be used in measuring the prescribing skills of future junior doctors in Libya.
Intratumor Heterogeneity in Early Lung Adenocarcinoma

Lung cancer is one of the deadliest diseases in the world and is the leading cause of cancer-related deaths. Among the histological types, adenocarcinoma is the most common, and it is characterized by a high degree of heterogeneity at many levels including clinical, behavioral, cellular and molecular. While most lung cancers are known for their aggressive behavior, up to 18.5% of lung cancers detected by CT screening are indolent and put patients at risk for overdiagnosis and overtreatment. The cellular and molecular underpinnings of tumor behavior remain largely unknown. In the recent years, the study of intratumor heterogeneity has become an attractive strategy to understand tumor progression. This review will summarize some of the current known determinants of lung adenocarcinoma behavior and discuss recent efforts to dissect its intratumor heterogeneity.
Genome-Wide DNA Methylation Enhances Stemness in the Mechanical Selection of Tumor-Repopulating Cells

Background DNA methylation plays essential roles in tumor occurrence and stemness maintenance. Tumor-repopulating cells (TRCs) are cancer stem cell (CSC)-like cells with highly tumorigenic and self-renewing abilities, which were selected from tumor cells in soft three-dimensional (3D) fibrin gels. Methods Here, we presented a genome-wide map of methylated cytosines for time-series samples in TRC selection, in a 3D culture using whole-genome bisulfite sequencing (WGBS). Results A comparative analysis revealed that the methylation degrees of many differentially methylated genes (DMGs) were increased by the mechanical environment and changed from 2D rigid to 3D soft. DMGs were significantly enriched in stemness-related terms. In 1-day, TRCs had the highest non-CG methylation rate indicating its strong stemness. We found that genes with continuously increasing or decreasing methylation like CREB5/ADAMTS6/LMX1A may also affect the TRC screening process. Furthermore, results showed that stage-specific/common CSCs markers were biased toward changing their methylation in non-CG (CHG and CHH, where H corresponds to A, T, or C) methylation and enriched in gene body region. Conclusions WGBS provides DNA methylome in TRC screening. It was confirmed that non-CG DNA methylation plays an important role in TRC selection, which indicates that it is more sensitive to mechanical microenvironments and affects TRCs by regulating the expression of stemness genes in tumor cells.
Hope and Creative Self-Efficacy as Sequential Mediators in the Relationship Between Family Socioeconomic Status and Creativity

The purpose of this study was to evaluate how socioeconomic status (SES) predicts individual creativity through the mediating roles of hope and creative self-efficacy (CSE). Participants were recruited from ten universities in Mainland China. Students’ SES, hope, CSE, and creativity were assessed via the socioeconomic status scale, the adult hope scale, the creative self-efficacy scale, and the Runco Ideational Behavior Scale. Correlational analyses indicate that SES, creative ideation, hope, and CSE were significantly and positively associated with each other. Path analyses revealed that hope and CSE played sequential mediating roles in the link between SES and creative ideation. These findings suggest that hope and CSE underlie the effect of SES on individuals’ creative ideation.
New fixed point results in bv(s)-metric spaces

Abstract Z. D. Mitrović and S. Radenović introduced in [The Banach and Reich contractions in bv(s)-metric spaces, J. Fixed Point Theory Appl. 19 (2017), 3087–3095] a new class of generalized metric spaces and proved some fixed point theorems in this framework. The purpose of this paper is to consider other kinds of contractive mappings in bv(s)-metric spaces, and show how the work in the new settings differs from the one in standard metric and b-metric spaces. Examples show the usefulness of the obtained results.
The Unresolved Pathophysiology of Lymphedema

Lymphedema is the clinical manifestation of impaired lymphatic transport. It remains an under-recognized and under-documented clinical condition that still lacks a cure. Despite the substantial advances in the understanding of lymphatic vessel biology and function in the past two decades, there are still unsolved questions regarding the pathophysiology of lymphedema, especially in humans. As a consequence of impaired lymphatic drainage, proteins and lipids accumulate in the interstitial space, causing the regional tissue to undergo extensive and progressive architectural changes, including adipose tissue deposition and fibrosis. These changes are also associated with inflammation. However, the temporal sequence of these events, the relationship between these events, and their interplay during the progression are not clearly understood. Here, we review our current knowledge on the pathophysiology of lymphedema derived from human and animal studies. We also discuss the possible cellular and molecular mechanisms involved in adipose tissue and collagen accumulation during lymphedema. We suggest that more studies should be dedicated to enhancing our understanding of the human pathophysiology of lymphedema to pave the way for new diagnostic and therapeutic avenues for this condition.
The impact of the truck loads on the braking efficiency assessment

Abstract The paper deals with possibilities of assessment of braking efficiency during evaluation of braking system at technical inspection of trucks in conditions of the Slovak Republic. The braking efficiency of the vehicle is evaluated by measuring the braking forces at the roller brake tester. The magnitude of these forces also depends on the loads of the measured vehicle. The paper analyses the results of the practical tests of the braking efficiency measurement of a truck of category N3 and of a vehicle combination consisting of vehicles of category N3 and O4. The analysed vehicle combination was gradually loaded in four different ways and a special situation was the measurement of the braking efficiency of the tractor itself. The instantaneous load on each axle was recorded with portable axle weights. The braking efficiency evaluation was carried out in accordance with the valid methodology, which allows the application of the direct evaluation method, the method of linear extrapolation, the method of the reference braking forces and the indicative evaluation. A vehicle with the same braking system may be assessed as roadworthy or not roadworthy. This is due to the application of different methods of evaluating the braking efficiency and different way of loads at the loading area.
Translating Wittgenstein: A semiotic translation of the Tractatus

Abstract In this article, I introduce a semiosic translation of Wittgenstein’s Tractatus Logico-Philosophicus. The theoretical framework is Semiosic Translation, a theory that combines Peirce’s interpretive semiotics and Wittgenstein’s notions of rule-following and complex-fact. I seek to show that this approach is particularly adroit at the task of making the sometimes cryptic philosophy of Ludwig Wittgenstein accessible to readers. To support this assertion, I compare and analyze several canonical translations of the Tractatus with possible semiosic translations. The results show that Wittgenstein’s work throughout its different phases displays a continuity that reaches a genuine abductive peak in the Philosophical Investigations. This abductive, usage-based turn is, nonetheless, announced in the Tractatus in terms of a quest for semiotic accuracy.
Cannabidiol (CBD) Inhibited Rhodamine-123 Efflux in Cultured Vascular Endothelial Cells and Astrocytes Under Hypoxic Conditions

Despite the constant development of new antiepileptic drugs (AEDs), more than 30% of patients develop refractory epilepsy (RE) characterized by a multidrug-resistant (MDR) phenotype. The “transporters hypothesis” indicates that the mechanism of this MDR phenotype is the overexpression of ABC transporters such as P-glycoprotein (P-gp) in the neurovascular unit cells, limiting access of the AEDs to the brain. Recent clinical trials and basic studies have shown encouraging results for the use of cannabinoids in RE, although its mechanisms of action are still not fully understood. Here, we have employed astrocytes and vascular endothelial cell cultures subjected to hypoxia, to test the effect of cannabidiol (CBD) on the P-gp-dependent Rhodamine-123 (Rho-123) efflux. Results show that during hypoxia, intracellular Rho-123 accumulation after CBD treatment is similar to that induced by the P-gp inhibitor Tariquidar (Tq). Noteworthy, this inhibition is like that registered in non-hypoxia conditions. Additionally, docking studies predicted that CBD could behave as a P-gp substrate by the interaction with several residues in the α-helix of the P-gp transmembrane domain. Overall, these findings suggest a direct effect of CBD on the Rho-123 P-gp-dependent efflux activity, which might explain why the CBD add-on treatment regimen in RE patients results in a significant reduction in seizure frequency.
An observational case-control study comparing the recovery profile in patients receiving additional dose of anticonvulsant vs. regular dose during supratentorial craniotomy

Background and Aims: Anticonvulsants are used routinely for seizure prophylaxis in patients with supratentorial tumour who present with/without seizures. Excessive use of prophylactic anticonvulsant may delay the recovery from anaesthesia. We have studied the recovery profiles of patients who received an additional dose of anticonvulsant in comparison with those who received only the regular dose. Methods: In this prospective observational study, patients were anaesthetised using standard anaesthesia protocol. An additional dose of anticonvulsant was administered in one group, while the other group received only the regular dose. Time taken for extubation, eye opening, obeying commands and orientation were compared between the two groups. Haemodynamics, depth of anaesthesia, the plasma anticonvulsant levels and the incidence of seizures were compared between the two groups. Results: A total of 36 patients were studied, of which 19 received regular dose and 17 received an additional dose. There was no significant difference in recovery time between the two groups. Subgroup analysis was performed for phenytoin and sodium valproate. There was a clinically significant delay in recovery in patients who received an additional phenytoin compared to those who received regular dose (time to obey commands >15 min and orientation time >1hour) but, it was not statistically significant. Administration of an additional dose of valproate did not prolong the recovery time. Conclusion: An additional dose of sodium valproate did not cause a delay in recovery both, clinically and statistically. However, the administration of an additional dose of phenytoin caused a clinically significant delay in recovery but was not statistically significant.
Organic Amendments Alleviate Salinity Effects on Soil Microorganisms and Mineralisation Processes in Aerobic and Anaerobic Paddy Rice Soils

Sea-water level rise leads to increased saltwater intrusion causing soil salinity on arable land with negative effects on soil microbial processes. Organic amendments are known to reduce the effects of salinity on soil microorganisms, therefore positively influencing microbial activity and nutrient cycling. However, the extent of this effect in paddy rice soils under aerobic compared to anaerobic conditions is unknown. Consequently, benefits of organic matter addition on carbon (C) and nitrogen (N) mineralisation under saline conditions were evaluated in a short-term laboratory incubation experiment. Two soils from Bangladesh were incubated with rice straw, manure or a manure-rice straw mixture at 50 and 100% water holding capacity (25°C, 27 days). In addition, NaCl was added to half of the samples, which resulted in a set of non-saline (ECe = 1.1–1.3 dS m−1) and saline (ECe = 24.0–32.4 dS m−1) soils. Soil respiration (CO2-release) was measured throughout the experiment. At the end of the experiment, dissolved organic C, inorganic N, microbial biomass as well as bacterial, archaeal, and fungal domains were determined. Overall, effects of substrate addition overruled effects caused by salinity and water content. Microbial activity and biomass in particular fungi increased most strongly after rice straw addition and resulted in N immobilisation independent of moisture level. Rice straw and manure alleviated the effects of salinity on microorganisms; these were therefore mainly detectable in the non-amended soils. The reason for this is likely a higher C availability for soil microorganisms after amendment of organic materials, which allows them to produce osmolytes, counteracting the osmotic effects of increased salinity. However, the microbial communities of the two soils under investigation showed different response patterns to salinity reflected by a substantially higher fungi-bacteria ratio in soil B prone to salinity at 50% WHC as compared to soil A. Likewise, the metabolic quotient was higher in soil B and not affected by any of the short term treatments, revealing a soil legacy. Our results highlight the importance of organic amendments, such as rice straw to paddy soils under saline conditions to reduce negative effects on soil microbial processes, allowing them to maintain their major functions.
Metabolic Engineering of Saccharomyces cerevisiae for Enhanced Dihydroartemisinic Acid Production

Direct bioproduction of DHAA (dihydroartemisinic acid) rather than AA (artemisinic acid), as suggested by previous work would decrease the cost of semi-biosynthesis artemisinin by eliminating the step of initial hydrogenation of AA. The major challenge in microbial production of DHAA is how to efficiently manipulate consecutive key enzymes ADH1 (artemisinic alcohol dehydrogenase), DBR2 [artemisinic aldehyde Δ11(13) reductase] and ALDH1 (aldehyde dehydrogenase) to redirect metabolic flux and elevate the ratio of DHAA to AA (artemisinic acid). Herein, DHAA biosynthesis was achieved in Saccharomyces cerevisiae by introducing a series of heterologous enzymes: ADS (amorpha-4,11-diene synthase), CYP71AV1 (amorphadiene oxidase), ADH1, DBR2 and ALDH1, obtaining initial DHAA/AA ratio at 2.53. The flux toward DHAA was enhanced by pairing fusion proteins DBR2-ADH1 and DBR2-ALDH1, leading to 1.75-fold increase in DHAA/AA ratio (to 6.97). Moreover, to promote the substrate preference of ALDH1 to dihydroartemisinic aldehyde (the intermediate for DHAA synthesis) over artemisinic aldehyde (the intermediate for AA synthesis), two rational engineering strategies, including downsizing the active pocket and enhancing the stability of enzyme/cofactor complex, were proposed to engineer ALDH1. It was found that the mutant H194R, which showed better stability of the enzyme/NAD+ complex, obtained the highest DHAA to AA ratio at 3.73 among all the mutations. Then the mutant H194R was incorporated into above rebuilt fusion proteins, resulting in the highest ratio of DHAA to AA (10.05). Subsequently, the highest DHAA reported titer of 1.70 g/L (DHAA/AA ratio of 9.84) was achieved through 5 L bioreactor fermentation. The study highlights the synergy of metabolic engineering and protein engineering in metabolic flux redirection to get the most efficient product to the chemical process, and simplified downstream conversion process.