Miracle-dz/UniFAR-FTUs huggingface dataset:
RNA dependent RNA polymerase (RdRp) as a drug target for SARS-CoV2

Abstract RNA-dependent RNA polymerase (RdRp), also called nsp12, is considered a promising but challenging drug target for inhibiting replication and hence, the growth of various RNA-viruses. In this report, a computational study is performed to offer insights on the binding of Remdesivir and Galidesivir with SARS-CoV2 RdRp with natural substrate, ATP, as the control. It was observed that Remdesivir and Galidesivir exhibited similar binding energies for their best docked poses, −6.6 kcal/mole and −6.2 kcal/mole, respectively. ATP also displayed comparative and strong binding free energy of −6.3 kcal/mole in the catalytic site of RdRp. However, their binding locations within the active site are distinct. Further, the interaction of catalytic site residues (Asp760, Asp761, and Asp618) with Remdesivir and Galidesivir is comprehensively examined. Conformational changes of RdRp and bound molecules are demonstrated using 100 ns explicit solvent simulation of the protein-ligand complex. Simulation suggests that Galidesivir binds at the non-catalytic location and its binding strength is relatively weaker than ATP and Remdesivir. Remdesivir also binds at the catalytic site and showed high potency to inhibit the function of RdRp. Binding of co-factor units nsp7 and nsp8 with RdRp (nsp12) complexed with Remdesivir and Galidesivir was also examined. MMPBSA binding energy for all three complexes has been computed across the 100 ns simulation trajectory. Overall, this study suggests, Remdesivir has anti-RdRp activity via binding at a catalytic site. In contrast, Galidesivir may not have direct anti-RdRp activity but it can induce a conformational change in the RNA polymerase. Graphical Abstract Communicated by Ramaswamy H. Sarma
Cortisol-Producing Adrenal Adenomas With Intense Activity on 68Ga-Pentixafor PET/CT.

ABSTRACT CXC chemokine receptor type 4 as a G-protein-coupled receptor has been confirmed to be highly expressed in functional adrenocortical adenomas. 68Ga-pentixafor, a CXC chemokine receptor type 4-specific ligand, has been reported as a promising tracer to evaluate functional nature of adrenal adenomas. We report intense 68Ga-pentixafor activity of cortisol-producing adrenal adenomas in 2 patients with adrenocorticotropic hormone-independent Cushing syndrome.
Bioinformatics analysis to determine the prognostic value and prospective pathway signaling of miR-126 in non-small cell lung cancer

Background MicroRNAs (miRNAs) have been demonstrated to play crucial roles in the initiation and development of non-small cell lung cancer (NSCLC). However, further investigation of the specific role of miR-126 in NSCLC is still required. Methods An analysis of miR-126 expression in NSCLC was carried out using the Gene Expression Omnibus (GEO) database, and a literature review was also performed. The differentially expressed genes (DEGs) in three mRNA datasets, GSE18842, GSE19804, and GSE101929, from GEO were identified. Following the prediction of hsa-miR-126-5p target genes by TargetScan, the overlap of miR-126 target genes with DEGs in NSCLC was examined. After that, Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed. Finally, an analysis to identify the impact of hub genes on the prognosis of NSCLC was carried out on the basis of a protein-protein interaction (PPI) network constructed using STRING and Cytoscape. Results The data in the literature review revealed a trend that miR126 was downregulated in NSCLC. The number of both NSCLC-related and miR-126-related DEGs was 187. Dozens of DEGs were significantly enriched in biological regulation, cell membrane binding, and signal receptor binding. In the PPI network analysis, 3 of 10 identified hub genes, namely NCAPG, MELK, and KIAA0101, were obviously related to poor prognosis in NSCLC; the survival rate was low among patients with high expression levels of these genes. Furthermore, through network analysis, TPX2, HMMR, and ANLN were identified as recessive miR-126-related genes that may be involved in NSCLC. Conclusions MiR-126 plays an essential role in the biological processes of NSCLC through binding to target genes and influences the prognosis of patients with the disease.
EECP improves markers of functional capacity regardless of underlying ranolazine therapy.

OBJECTIVE Enhanced external counterpulsation (EECP) and ranolazine are approved treatments for patients with chronic stable angina by the United States Food and Drug Administration (FDA). Whether EECP offers clinical benefits regardless of underlying ranolazine therapy needs further investigation. METHODS This was a retrospective evaluation of patients referred to a specialized EECP center. Patients having data on 6-Minute Walk Distance (6MWD) or Duke Activity Status Index (DASI) were categorized into two groups (EECP with ranolazine or EECP only). The primary endpoints were change in 6MWD and DASI before and after a full course of EECP within each of the two groups. Inter-group differences were also assessed. The Wilcoxon test was utilized to compare the change from baseline within each group and the Mann-Whitney U test to compare difference between groups. RESULTS A total of 2836 patient records (age 66.9 ± 10 years) were identified (1193 in EECP and ranolazine group and 1643 in EECP only group). EECP added to baseline ranolazine resulted in a statistically significant improvement in 6MWD and DASI (+126 feet (IQR: 230 feet), and +13.35 (IQR: 17.11), respectively, P<0.001 for both). Similarly, the EECP only group showed a statistically significant improvement in 6MWD and DASI (+140 feet (IQR: 225 feet) and +13.49 (IQR: 18.02), respectively, P<0.001 for both). There was no statistically significant difference between the two groups when comparing the change from baseline in 6MWD and DASI score (P=0.256 and P=0.056 respectively). CONCLUSION EECP improves markers of functional capacity regardless of baseline ranolazine therapy. EECP's unique safety profile advocates for its early consideration in the treatment algorithm.
Theory of environmental sex determination: Trending populations in stressful environments

Species that have sex determined by environmental conditions during development (i.e., environmental sex determination [ESD]) are especially vulnerable to environmental change, including altered stress levels, habitat loss, and species translocations. These factors can produce multigenerational trends in population size and eco‐evolutionary dynamics not captured by existing theory based on lifetime reproductive success (R0). Here, we extend ESD theory to use per capita growth rate r as a more appropriate measure of evolutionary success (fitness), and we demonstrate the importance of this change when males and females can differ in maturation times and when maturation times vary with local conditions (plasticity). In these cases, we show that primary and secondary sex ratios may be strongly biased; that optimal maturation times, when locally plastic, depend on the balance between mortality and growth effects; and that plasticity of maturation times can ameliorate fitness costs of increasing environmental stress.
Ultrasound assessed peri-renal fat: an index of sub-clinical atherosclerosis.

OBJECTIVE Overweight/obesity has predicted cardiovascular disease (CVD) risk for long with its standard measure of body mass index (BMI), which later was found to mis-classify risk oftentimes. This is because it does not differentiate between fat and whole body mass. The finding that fat especially visceral fat was more culpable shifted attention to ectopic fat as a more precise measure of CVD risk. Peri-renal fat (PRF) is one such ectopic foci, which is hardly used despite the relative ease of assessment. We assessed PRF to correlate it with carotid intima media thickness (CIMT) to see if there was any significance in order to obviate need for heavy equipment in CVD risk assessment. METHODS This is secondary analysis of data generated in the course of studying sub-clinical atherosclerosis in apparently normal individuals. Subjects underwent routine anthropometry to determine BMI. They then underwent abdominal ultrasound studies wherein PRF was measured as the size of the echogenic strip between the posterior part of the liver and the right kidney. The CIMT was measured using the same equipment but a different transducer, as the distance between the intima and medial layers of the right common carotid artery 1 cm proximal to the carotid bulb. RESULTS The 221 subjects (82 M, 139 F) had mean ages of 37.01±10.97 and 36.86±11.62 years respectively. PRF correlated significantly with CIMT, age and all anthropometric measures. A PRF level of 0.26 cm turned out to be a significant value that determined presence of sub-clinical atherosclerosis deriving from the receiver operating characteristic curve analysis. CONCLUSION PRF has shown to be correlated significantly with indices that predict atherosclerosis. Being an ectopic fat focus, its local and systemic effects on the kidney increase systemic vascular resistance and CVD. Since it can easily be measured on abdominal ultrasound, a test readily available and requiring lower level skills it should be used to advantage. Levels above 0.26 cm should prompt initiation of curative or preventive action to control CVD in the population.
Systematic review of guidelines to identify recommendations for upper limb robotic rehabilitation after stroke.

INTRODUCTION Upper limb motor impairment is one of the most frequent stroke consequences. Robot therapy may represent a valid option for upper limb stroke rehabilitation, but there are still gaps between research evidences and their use in clinical practice. The aim of this study was to determine the quality, scope, and consistency of guidelines clinical practice recommendations for upper limb robotic rehabilitation in stroke populations. EVIDENCE ACQUISITION We searched for guideline recommendations on stroke published between January 1st, 2010 and January 1st, 2020. Only the most recent guidelines for writing group were selected. Electronic databases (n=4), guideline repertories and professional rehabilitation networks (n=12) were searched. We systematically reviewed and assessed guidelines containing recommendation statements about upper limb robotic rehabilitation for adults with stroke. PROSPERO registration number: CRD42020173386. EVIDENCE SYNTHESIS Four independent reviewers used the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, and textual syntheses were used to appraise and compare recommendations. From 1324 papers screened, eight eligible guidelines were identified from six different regions/countries. Half of the included guidelines focused on stroke management, the other half on stroke rehabilitation. Rehabilitation assisted by robotic devices is generally recommended to improve upper limb motor function and strength. The exact characteristics of patients who could benefit from this treatment as well as the correct timing to use it are not known. CONCLUSIONS This systematic review has identified many opportunities to modernize and otherwise improve stroke patients' upper limb robotic therapy. Rehabilitation assisted by robot or electromechanical devices for stroke needs to be improved in clinical practice guidelines in particular in terms of applicability.
A review of biochar as a low-cost adsorbent for aqueous heavy metal removal

ABSTRACT As a low-cost adsorbent, biochar can be used as a low-cost adsorbent for wastewater treatment, particularly with respect to treating heavy metals in wastewater. A number of studies have demonstrated effective removal of heavy metals from aqueous solutions by biochar and, in some cases, proven the superiority of biochars to activated carbons. Among several factors affecting the sorption ability of biochars, feedstock materials play a significant role. This review incorporates existing literature to understand the overall sorption behavior of heavy metals on biochar adsorbents. Depending on the biochar type, heavy metal can be removed by different mechanisms such as complexation, physical sorption, precipitation and electrostatic interactions. Mathematical sorption models can be used to understand the efficiency of biochar at removing heavy metals, and promote the application of biochar technology in water treatment.
The Kinetic Theory of a Special Type of Rigid Molecule

1. The present paper is an exercise in the classical kinetic theory, with no admixture of quantum theory, or of the modern theory of atomic structure. The researches of Chapman and Enskog suggest an attempt to see how far exact methods can be used when the molecule has rotational as well as translational energy. It is now well established that if λ is the thermal conductivity, μ the viscosity, and cv the specific heat at constant volume of a monatomic gas, λ/μ cv is nearly equal to 2·5. No exhaustive theory is yet in sight for polyatomic gases, but the views of Eucken are of great interest, and his formula λ/μ cv = ¼ (9γ - 5) agrees with many experiments. The present paper discusses the effect of energy of rotation on viscosity and thermal conductivity in a special case, and may help to elucidate certain points, notwithstanding the crudeness of the adopted model. The need of a molecular model which shall lend itself to calculation has often been felt. In his first paper on the kinetic theory, Maxwell considered the collision of perfectly elastic bodies of any form, and enunciated the theorem about energy of rotation which was afterwards included in the general doctrine of equipartition in the steady state. Of recent years more attention has been paid to slight departures from the steady state, with a view to obtaining a rigorous theory of thermal conductivity, diffusion, and viscosity. Jeans considered the perfectly elastic collisions of smooth spheres whose centres of mass and figure are different. Approximations were made by neglecting powers of r /σ higher than the second, where r is the eccentricity and σ the diameter of the molecule, so that we have rather an unfortunate limiting case in which energy of rotation only adjusts itself infinitely slowly in comparison with that of translation; while the free path phenomena were not treated in detail. It appeared to the writer that there would be less trouble with the molecular model suggested by Bryan. Imagine two spheres to collide and grip each other, so as to bring the points of contact to relative rest. A small elastic deformation is produced, which we suppose to be released immediately afterwards, the force during release being equal to that at the corresponding stage of compression. Thus the relative velocity of the points of contact is reversed by collision.
Carbon‐supported perovskite oxides as oxygen reduction reaction catalyst in single chambered microbial fuel cells

BACKGROUND: Pt-free cathodic catalyst is needed for microbial fuel cells (MFCs). Perovskite-type oxide could be a substitute for Pt because it has been proved to be a highly active and low-cost oxygen reduction catalyst in chemical fuel cells. RESULTS: A nano-sized La0.4Ca0. 6Co0.9Fe0. 1O3 perovskite-type oxide on a carbon support (LCCF/C) was prepared and tested for its performance and stability (15 cycles) in MFCs. An exchange current density of 7.030 × 10−5 (A cm−2) was obtained with fresh LCCF/C cathode and is increased to 7.438 × 10−5 (A cm−2) after 15 cycles operating in MFCs. A power density of 405 mW m−2 was achieved with the LCCF/C cathode at the 2nd cycle which was between those of Pt/C (560 mW m−2) and C (339 mW m−2) cathodes. At the end of the 15th cycle, the lowest decay (due to biofouling) rate on the open circuit voltage (2%) and the maximum power density (15%) were observed with LCCF/C cathode compared with those of Pt/C (4%, 17%) and C (22%, 69%) cathodes, respectively. CONCLUSIONS: This study demonstrated that perovskite-type oxide on carbon support catalysts could be a potential substitute for Pt for cathodic oxygen reduction reaction (ORR) in air-cathode MFCs. © 2012 Society of Chemical Industry
Therapy-related acute myeloid leukemia and its prevention.

BACKGROUND Secondary tumors, including therapy-related acute myeloid leukemia (t-AML), represent one of the most undesirable side effects of chemotherapy, which arise several years after primary cancer treatment. This review aims to analyze the current data on molecular pathogenesis of t-AML revealing potential criteria for predicting predisposition to the disease. Another objective is to analyze the information on promising approaches for t-AML prevention. METHODS We analyzed studies regarding t-AML and possible approaches for cancer prevention of drug-induced tumors. Publications in the databases, such as SciVerse Scopus (948), PubMed (1837) and Web of Science (935) were used. Among 92 the most important publications cited in the review, 79 were published during the last decade. RESULTS The review provides the information concerning t-AML pathogenesis, molecular markers of primary cancer patients with high risk of t-AML. The role of the bone marrow niche in clonal hematopoiesis and t-AML pathogenesis is discussed. Current approaches for t-AML prevention both at the stage of therapy and at the latent period are described. Inhibition effects of polyphenols on cell proliferation and on the appearance of hemopoetic clones of indeterminate potential are proposed for t-AML prevention. CONCLUSION The problem of the t-AML, a cancer induced by genotoxic chemotherapeutic drugs, is considered from the point of view of the fundamental mechanisms of chemical carcinogenesis, highlighting initiation and promotion stages. It enables to reveal the possible markers for the group of patients with high risk for t-AML and to demonstrate perspectives for the use of plant polyphenols for t-AML prevention.
Routine aspiration thrombectomy is associated with increased stroke rates during primary percutaneous coronary intervention for myocardial infarction.

BACKGROUND Recent studies have suggested that the routine use of aspiration thrombectomy catheters during primary percutaneous coronary intervention (PCI) do not result in improved mortality and may be associated with an increased stroke rate. This study sought to investigate this hypothesis. METHODS This was an observational study analysing data from a prospective database of 6366 patients undergoing primary PCI between August 2003 and May 2015 at a UK cardiac centre. Patients' details were collected from the hospital electronic database. Primary outcome was thirty-day stroke rates. RESULTS 3989 (62.7%) patients underwent PCI alone and 2,377 (37.3%) patients underwent PCI with adjuctive thrombus aspiration. PCI alone group had an older demographic (63 (± 14) years vs 60.7 (± 14)), a lower proportion of male participants 75% vs 79% (P=0.001) and cardiovascular risk factors such as hypertension 22.4% vs 25.3% (P=0.007), hypercholesterolemia 18.5% vs 22.6% (P<0.0001) and a history of smoking 33.5% vs 44.3% (P<0.0001). Thrombus aspiration was associated with a higher 30-day stroke rate [16 (0.7%) vs 11 (0.3%) (HR 2.51; 95% CI 1.03-6.08, P 0.03). Multivariate analysis suggested that this increased risk of stroke was maintained following adjustment for confounders (HR: 1.86; 95% CI 1.02-4.38). There was 379 deaths of which 114 (4.8%) were in the thrombus aspiration cohort vs 265 (6.6%) in PCI only cohort over the follow-up period (60 months). This resulted in a significantly lower rate of all-cause-mortality HR 0.70 (95% CI 0.52-0.94; P 0.02). There was no statistically significant difference in observed myocardial infarction rates HR 0.76 (95% CI 0.47-1.23; P 0.27) and the rates of unscheduled revascularisations HR 0.70 (95% CI 0.43-1.13; P 0.14) between the two groups. CONCLUSIONS Our data series of STEMI patients, suggest that routine thrombus aspiration during primary PCI is associated with a significantly higher stroke, rate however, thrombus aspiration reduced mortality rate. This is consistent with current guidelines which don't recommend the routine use of thrombus aspiration for primary PCI. A possible mortality reduction in patients with high thrombus grades was seen which may warrant further study.
Development and Validation of a Risk Prediction Model for Atherosclerotic Cardiovascular Disease in Japanese Adults: The Hisayama Study

Aim: To develop and validate a new risk prediction model for predicting the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) in Japanese adults. Methods: A total of 2,454 participants aged 40–84 years without a history of cardiovascular disease (CVD) were prospectively followed up for 24 years. An incident ASCVD event was defined as the first occurrence of coronary heart disease or atherothrombotic brain infarction. A Cox proportional hazards regression model was used to construct the prediction model. In addition, a simplified scoring system was translated from the developed prediction model. The model performance was evaluated using Harrell’s C statistics, a calibration plot with the Greenwood-Nam-D’Agostino test, and a bootstrap validation procedure. Results: During a median of a 24-year follow-up, 270 participants experienced the first ASCVD event. The predictors of the ASCVD events in the multivariable Cox model included age, sex, systolic blood pressure, diabetes, serum high-density lipoprotein cholesterol, serum low-density lipoprotein cholesterol, proteinuria, smoking habits, and regular exercise. The developed models exhibited good discrimination with negligible evidence of overfitting (Harrell’s C statistics: 0.786 for the multivariable model and 0.789 for the simplified score) and good calibrations (the Greenwood-Nam-D’Agostino test: P =0.29 for the multivariable model, 0.52 for the simplified score). Conclusion: We constructed a risk prediction model for the development of ASCVD in Japanese adults. This prediction model exhibits great potential as a tool for predicting the risk of ASCVD in clinical practice by enabling the identification of specific risk factors for ASCVD in individual patients.
Comparative study of collagen distribution in the dermis of the embryonic carapace of soft‐ and hard‐shelled cryptodiran turtles

Turtles are characterized by their typical carapace, which is primarily composed of corneous beta proteins in the horny part and collagen in the dermal part. The formation of the extracellular matrix in the dermis of the carapace in a hard‐shelled and a soft‐shelled turtle has been compared. The study examines carapace development, with an emphasis on collagen accumulation, in the soft‐shelled turtle Pelodiscus sinensis and hard‐shelled turtle Trachemys scripta elegans, using comparative morphological and embryological analyses. The histological results showed that collagen deposition in the turtle carapace increased as the embryos developed. However, significant differences were observed between the two turtle species at the developmental stages examined. The microstructure of the dermis of the carapace of P. sinensis showed light and dark banding of collagen bundles, with a higher overall collagen content, whereas the carapacial matrix of T. scripta was characterized by loosely packed and thinner collagenous fiber bundles with a lower percentage of type I collagen. Overall, the formation and distribution of collagen fibrils at specific developmental stages are different between the soft‐and hard‐shelled turtles. These results indicate that the pliable epidermis of the soft‐shelled turtle is supported by a strong dermis that is regularly distributed with collagen and that it allows improved maneuvering, whereas a strong but inflexible epidermis as observed in case of hard‐shelled turtles limits movement.