An outbreak of coronavirus disease 2019 (COVID‐19) occurred in Wuhan and it has rapidly spread to almost all parts of the world. For coronaviruses, RNA‐dependent RNA polymerase (RdRp) is an important ...protease that catalyzes the replication of RNA from RNA template and is an attractive therapeutic target. In this study, we screened these chemical structures from traditional Chinese medicinal compounds proven to show antiviral activity in severe acute respiratory syndrome coronavirus (SARS‐CoV) and the similar chemical structures through a molecular docking study to target RdRp of SARS‐CoV‐2, SARS‐CoV, and Middle East respiratory syndrome coronavirus (MERS‐CoV). We found that theaflavin has a lower idock score in the catalytic pocket of RdRp in SARS‐CoV‐2 (−9.11 kcal/mol), SARS‐CoV (−8.03 kcal/mol), and MERS‐CoV (−8.26 kcal/mol) from idock. To confirm the result, we discovered that theaflavin has lower binding energy of −8.8 kcal/mol when it docks in the catalytic pocket of SARS‐CoV‐2 RdRp by using the Blind Docking server. Regarding contact modes, hydrophobic interactions contribute significantly in binding and additional hydrogen bonds were found between theaflavin and RdRp. Moreover, one π‐cation interaction was formed between theaflavin and Arg553 from the Blind Docking server. Our results suggest that theaflavin could be a potential SARS‐CoV‐2 RdRp inhibitor for further study.
Highlights
Theaflavin has a lower idock score in the catalytic pocket of RdRp in SARS‐CoV‐2, SARS‐CoV and MERS‐CoV from idock.
Theaflavin has a lowest binding energy when it docks in the catalytic pocket of SARS‐CoV‐2 RdRp.
Theaflavin could be potential SARS‐CoV‐2 RdRp inhibitor.
Earthquake shaking of a liquid‐filled advanced reactor induces fluid‐structure interaction (FSI) between the reactor vessel (tank), its internal components, and the contained liquid. Seismic design, ...qualification, and risk assessment of such reactors must consider fluid‐structure responses, their geometries and support conditions, and three‐directional seismic inputs, all of which require numerical simulations. Numerical models used for analysis of safety‐related nuclear equipment must be verified and validated. This paper verifies numerical models of submerged components using analytical solutions. Seismic FSI analysis of the numerical models is performed using the Arbitrary Lagrangian‐Eulerian (ALE) and Incompressible Computational Fluid Dynamics (ICFD) solvers in LS‐DYNA. Prior analytical solutions are reworked in this paper, and calculation errors are identified and corrected. The solutions address frequencies of two concentric cylindrical pipes filled with liquid: the inner pipe is a submerged component, and the outer pipe contains the liquid. A unitless frequency coefficient is defined and presented for pipes of different materials, filled with different liquids, and with a range of dimensions for application to advanced reactors. The numerical models are verified here by comparing the lateral frequencies of submerged components with those calculated using the corrected analytical solutions. Recommendations for verification of numerical models of internal components in advanced reactors for seismic FSI analysis are provided. Although the unitless frequency coefficients and verification procedures are developed for application to advanced nuclear reactors, they are broadly applicable to FSI analysis of submerged components in liquid‐filled vessels such as storage tanks, boilers, and steam generators.
Seismic design and qualification of advanced reactors will rely heavily on the use of verified and validated numerical models capable of capturing the interaction of the vessel, its contained fluid, ...and the internal equipment: fluid‐structure interaction (FSI) analysis. Analytical solutions can be used for preliminary sizing and design of such vessels but their application is limited to simple geometries and boundary conditions, and small amplitude, translational (and rotational) inputs. To validate numerical models for seismic FSI analysis in finite element codes, a comprehensive set of experiments was performed on a liquid‐filled cylindrical vessel, using a 6 degree‐of‐freedom earthquake simulator. Results in terms of sloshing frequency, damping ratio in sloshing modes, and hydrodynamic responses (wave height, hydrodynamic pressure, base shear, and base moment) for multidirectional earthquake simulator inputs are reported and compared with analytical solutions for liquid‐filled vessels. The impact of seismic (base) isolation on hydrodynamic responses was studied using earthquake simulator inputs generated using a virtual isolation system. Data from the experiments are used to validate a numerical model of the fluid‐filled vessel using the Arbitrary Lagrangian Eulerian (ALE) solver in the commercial finite element program LS‐DYNA. Validation studies are presented for multidirectional seismic inputs, including rocking motions. Lagrangian modeling approaches using an elastic material formulation for the fluid are also investigated and their limitations and possible applications are identified. The results are broadly applicable to the seismic response of base supported, liquid‐filled vessels.
To evaluate the performance of machine learning (ML) algorithms and to compare them with logistic regression for the prediction of risk of cardiovascular diseases (CVDs), chronic kidney disease ...(CKD), diabetes (DM), and hypertension (HTN) and in a prospective cohort study using simple clinical predictors.
We conducted analyses in a population-based cohort study in Asian adults (n = 6,762). Five different ML models were considered—single-hidden-layer neural network, support vector machine, random forest, gradient boosting machine, and k-nearest neighbor—and were compared with standard logistic regression.
The incidences at 6 years of CVD, CKD, DM, and HTN cases were 4.0%, 7.0%, 9.2%, and 34.6%, respectively. Logistic regression reached the highest area under the receiver operating characteristic curve for CKD (0.905 0.88, 0.93) and DM (0.768 0.73, 0.81) predictions. For CVD and HTN, the best models were neural network (0.753 0.70, 0.81) and support vector machine (0.780 0.747, 0.812), respectively. However, the differences with logistic regression were small (less than 1%) and nonsignificant. Logistic regression, gradient boosting machine, and neural network were systematically ranked among the best models.
Logistic regression yields as good performance as ML models to predict the risk of major chronic diseases with low incidence and simple clinical predictors.
•Low-dimensional settings include low number of events and predictors.•In such settings, logistic regression yields as good performance as ML models.•ML techniques may not be warranted in such cases.
Spinal sarcopenia is a complex and multifactorial disorder associated with a loss of strength, increased frailty, and increased risks of fractures and falls. In addition, spinal sarcopenia has been ...associated with lumbar spine disorders and osteoporosis, which renders making decisions on treatment modalities difficult. Patients with spinal sarcopenia typically exhibit lower cumulative survival, a higher risk of in-hospital complications, prolonged hospital stays, higher postoperative costs, and higher rates of blood transfusion after thoracolumbar spine surgery. Several studies have focused on the relationships between spinal sarcopenia, appendicular muscle mass, and bone-related problems-such as osteoporotic fractures and low bone mineral density-and malnutrition and vitamin D deficiency. Although several techniques are available for measuring sarcopenia, each of them has its advantages and shortcomings. For treating spinal sarcopenia, nutrition, physical therapy, and medication have been proven to be effective; regenerative therapeutic options seem to be promising owing to their repair and regeneration potential. Therefore, in this narrative review, we summarize the characteristics, detection methodologies, and treatment options for spinal sarcopenia, as well as its role in spinal disorders.
To investigate the risk of poor prognosis regarding schizophrenic disorders, psychotic disorders, suicide, self-inflicted injury, and mortality after adult violence from 2000 to 2015 in Taiwan.
This ...study used data from National Health Insurance Research Database (NHIRD) on outpatient, emergency, and inpatient visits for two million people enrolled in the National Health Insurance (NHI) from 2000 to 2015. The case study defined ICD-9 diagnosis code N code 995.8 (abused adult) or E code E960-E969 (homicide and intentional injury of another). It analyzed first-time violence in adults aged 18-64 years (study group). 1:4 ratio was matched with injury and non-violent patients (control group). The paired variables were sex, age (± 1 year), pre-exposure to the Charlson comorbidity index, and year of medical treatment. Statistical analysis was conducted using SAS 9.4 and Cox regression for data analysis.
In total, 8,726 individuals experienced violence (case group) while34,904 did not experienced violence (control group) over 15 years. The prevalence of poor prognosis among victims of violence was 25.4/10
, 31.3/10
, 10.5/10,
and 104.6/10
for schizophrenic disorders, psychotic disorders, suicide or self-inflicted injury and mortality, respectively. Among adults, the risks of suicide or self-inflicted injury, schizophrenic disorders, psychotic disorders, and mortality after exposure to violence (average 9 years) were 6.87-, 5.63-, 4.10-, and 2.50-times (p < 0.01), respectively, compared with those without violence. Among males, the risks were 5.66-, 3.85-, 3.59- and 2.51-times higher, respectively, than those without violence (p < 0.01), and they were 21.93-, 5.57-, 4.60- and 2.46-times higher than those without violence (p < 0.01) among females.
The risk of poor prognosis regarding schizophrenic disorders, psychotic disorders, suicide, or self-inflicted injury and mortality after adult violence was higher than in those who have not experienced a violent injury. Adults at the highest risk for violent suicide or self-inflicted injuries due to exposure to violent injuries -males were at risk for schizophrenia and females were at risk for suicide or self-inflicted injuries. Therefore, it is necessary for social workers and medical personnel to pay attention to the psychological status of victims of violence.
Accumulating evidence indicates that circular RNAs (circRNAs) are abundant in the human transcriptome. However, their involvement in biological processes, including pluripotency, remains mostly ...undescribed. We identified a subset of circRNAs that are enriched in undifferentiated human embryonic stem cells (hESCs) and demonstrated that two, circBIRC6 and circCORO1C, are functionally associated with the pluripotent state. Mechanistically, we found that circBIRC6 is enriched in the AGO2 complex and directly interacts with microRNAs, miR-34a, and miR-145, which are known to modulate target genes that maintain pluripotency. Correspondingly, circBIRC6 attenuates the downregulation of these target genes and suppresses hESC differentiation. We further identified hESC-enriched splicing factors (SFs) and demonstrated that circBIRC6 biogenesis in hESCs is promoted by the SF ESRP1, whose expression is controlled by the core pluripotency-associated factors, OCT4 and NANOG. Collectively, our data suggest that circRNA serves as a microRNA "sponge" to regulate the molecular circuitry, which modulates human pluripotency and differentiation.
Earthquake shaking more intense than that used to size the horizontal clearance between a base‐isolated building and near‐rigid perimeter moat wall will result in hard impact, producing ...high‐frequency, high‐amplitude acceleration response in the structure and supported equipment. This paper provides a design solution for the damaging effects of hard impact by installing a compliant engineered element in the load path between the base‐isolated building and the moat wall, resulting in soft impact and a much smaller acceleration response. The engineered element assumed herein is a commercial‐off‐the‐shelf marine fender with mechanical properties determined by physical testing. The attachment of a flexible engineered element, with well‐defined stiffness and damping, to a near‐rigid moat wall, simplifies the numerical modeling of the building‐moat wall system and eliminates the need to bound the lateral stiffness of the wall for impact calculations. The simple model of the engineered element can be implemented in commercial finite element codes. Theory is developed for two‐sided impact of a single‐degree‐of‐freedom oscillator. Analytical solutions are derived for the shifted first‐mode frequency of the impacted oscillator and for its free‐vibration response. The shifted first‐mode frequency is a function of the composite lateral stiffness of the isolator‐engineered element assembly and its earthquake‐induced displacement. Local peaks in the spectral response of the impacted oscillator form at odd integer multiples of the shifted first‐mode frequency. The analytical solutions can be used to verify, in part, the numerical model used for impact analysis.
Summary Background Numerous population-based studies of age-related macular degeneration have been reported around the world, with the results of some studies suggesting racial or ethnic differences ...in disease prevalence. Integrating these resources to provide summarised data to establish worldwide prevalence and to project the number of people with age-related macular degeneration from 2020 to 2040 would be a useful guide for global strategies. Methods We did a systematic literature review to identify all population-based studies of age-related macular degeneration published before May, 2013. Only studies using retinal photographs and standardised grading classifications (the Wisconsin age-related maculopathy grading system, the international classification for age-related macular degeneration, or the Rotterdam staging system) were included. Hierarchical Bayesian approaches were used to estimate the pooled prevalence, the 95% credible intervals (CrI), and to examine the difference in prevalence by ethnicity (European, African, Hispanic, Asian) and region (Africa, Asia, Europe, Latin America and the Caribbean, North America, and Oceania). UN World Population Prospects were used to project the number of people affected in 2014 and 2040. Bayes factor was calculated as a measure of statistical evidence, with a score above three indicating substantial evidence. Findings Analysis of 129 664 individuals (aged 30–97 years), with 12 727 cases from 39 studies, showed the pooled prevalence (mapped to an age range of 45–85 years) of early, late, and any age-related macular degeneration to be 8·01% (95% CrI 3·98–15·49), 0·37% (0·18–0·77), and 8·69% (4·26–17·40), respectively. We found a higher prevalence of early and any age-related macular degeneration in Europeans than in Asians (early: 11·2% vs 6·8%, Bayes factor 3·9; any: 12·3% vs 7·4%, Bayes factor 4·3), and early, late, and any age-related macular degeneration to be more prevalent in Europeans than in Africans (early: 11·2% vs 7·1%, Bayes factor 12·2; late: 0·5% vs 0·3%, 3·7; any: 12·3% vs 7·5%, 31·3). There was no difference in prevalence between Asians and Africans (all Bayes factors <1). Europeans had a higher prevalence of geographic atrophy subtype (1·11%, 95% CrI 0·53–2·08) than Africans (0·14%, 0·04–0·45), Asians (0·21%, 0·04–0·87), and Hispanics (0·16%, 0·05–0·46). Between geographical regions, cases of early and any age-related macular degeneration were less prevalent in Asia than in Europe and North America (early: 6·3% vs 14.3% and 12·8% Bayes factor 2·3 and 7·6; any: 6·9% vs 18·3% and 14·3% 3·0 and 3·8). No significant gender effect was noted in prevalence (Bayes factor <1·0). The projected number of people with age-related macular degeneration in 2020 is 196 million (95% CrI 140–261), increasing to 288 million in 2040 (205–399). Interpretation These estimates indicate the substantial global burden of age-related macular degeneration. Summarised data provide information for understanding the effect of the condition and provide data towards designing eye-care strategies and health services around the world. Funding National Medical Research Council, Singapore.
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