Drug repositioning, also known as drug repurposing, defines new indications for existing drugs and can be used as an alternative to drug development. In recent years, the accumulation of large ...volumes of information related to drugs and diseases has led to the development of various computational approaches for drug repositioning. Although herbal medicines have had a great impact on current drug discovery, there are still a large number of herbal compounds that have no definite indications.
In the present study, we constructed a computational model to predict the unknown pharmacological effects of herbal compounds using machine learning techniques. Based on the assumption that similar diseases can be treated with similar drugs, we used four categories of drug-drug similarity (e.g., chemical structure, side-effects, gene ontology, and targets) and three categories of disease-disease similarity (e.g., phenotypes, human phenotype ontology, and gene ontology). Then, associations between drug and disease were predicted using the employed similarity features. The prediction models were constructed using classification algorithms, including logistic regression, random forest and support vector machine algorithms. Upon cross-validation, the random forest approach showed the best performance (AUC = 0.948) and also performed well in an external validation assessment using an unseen independent dataset (AUC = 0.828). Finally, the constructed model was applied to predict potential indications for existing drugs and herbal compounds. As a result, new indications for 20 existing drugs and 31 herbal compounds were predicted and validated using clinical trial data.
The predicted results were validated manually confirming the performance and underlying mechanisms - for example, irinotecan as a treatment for neuroblastoma. From the prediction, herbal compounds were considered to be drug candidates for related diseases which is important to be further developed. The proposed prediction model can contribute to drug discovery by suggesting drug candidates from herbal compounds which have potentials but few were studied.
Electrochemical deposition of MnO2 onto carbon nanotube (CNT) yarn gives a high‐performance, flexible yarn supercapacitor. The hybrid yarn's blended structure, resulting from trapping of MnO2 in its ...internal pores, effectively enlarges electrochemical area and reduces charge diffusion length. Accordingly, the yarn supercapacitor exhibits high values of capacitance, energy density, and average power density. Applications in wearable electronics can be envisaged.
Pulse rate variability (PRV) analysis appears as the first alternative to heart rate variability analysis for wearable devices; however, there is a constraint on computational load and energy ...consumption for the limited system resources available to the devices. Considering that adjustment of the sampling frequency is one of the strategies for reducing computational load and power consumption, this study aimed to investigate the influence of sampling frequency (fs) on PRV analysis and to find the minimum sampling frequency while maintaining reliability. We generated 5000, 2500, 1000, 500, 250, 100, 50, 25, 20, 15, 10, 5 Hz down-sampled photoplethysmograms from 10 kHz-sampled PPGs and derived time- and frequency-domain variables of the PRV. These included AVNN, SDNN, SDSD, RMSSD, NN50, pNN50, total power, VLF, LF, HF, LF/HF, nLF and nHF for each down-sampled signal. Derived variables were compared with heart rate variability of the 10 kHz-sampled electrocardiograms, and then statistically investigated using one-way ANOVA test and Bland-Altman analysis. As a result, significant differences (P < 0.05) were found for SDNN, SDSD, RMSSD, NN50, pNN50, TP, HF, LF/HF, nLF and nHF, but not for AVNN, VLF and LF. Based on the post hoc tests, it was found that the NN50 and pNN50, SDSD and RMSSD, LF/HF and nHF, SDNN, TP and nLF analysis had significant differences at fs 20 Hz, fs 15 Hz, fs 10 Hz; fs = 5 Hz, respectively. In other words, a significant difference was not seen for any variable if the fs was greater than 25 Hz. Consequently, our pilot study suggests that analysis of variability in the time and frequency domain from pulse rate obtained through PPG may be potentially as reliable as that derived from the analysis of the electrocardiogram, provided that fs 25 Hz sampling frequency is used.
Sex is increasingly recognized as an important factor in the epidemiology and outcome of many diseases. This also appears to hold for coronavirus disease 2019 (COVID-19). Evidence from China and ...Europe has suggested that mortality from COVID-19 infection is higher in men than women, but evidence from US populations is lacking. Utilizing data from a large healthcare provider, we determined if males, as compared to females have a higher likelihood of SARS-CoV-2 susceptibility, and if among the hospitalized COVID-19 patients, male sex is independently associated with COVID-19 severity and poor in-hospital outcomes.
Using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines, we conducted a cross-sectional analysis of data from a COVID-19 Surveillance and Outcomes Registry (CURATOR). Data were extracted from Electronic Medical Records (EMR). A total of 96,473 individuals tested for SARS-CoV-2 RNA in nasopharyngeal swab specimens via Polymerized Chain Reaction (PCR) tests were included. For hospital-based analyses, all patients admitted during the same time-period were included. Of the 96,473 patients tested, 14,992 (15.6%) tested positive, of whom 4,785 (31.9%) were hospitalized and 452 (9.5%) died. Among all patients tested, men were significantly older. The overall SARS-CoV-2 positivity among all tested individuals was 15.5%, and was higher in males as compared to females 17.0% vs. 14.6% OR 1.20. This sex difference held after adjusting for age, race, ethnicity, marital status, insurance type, median income, BMI, smoking and 17 comorbidities included in Charlson Comorbidity Index (CCI) aOR 1.39. A higher proportion of males (vs. females) experienced pulmonary (ARDS, hypoxic respiratory failure) and extra-pulmonary (acute renal injury) complications during their hospital course. After adjustment, length of stay (LOS), need for mechanical ventilation, and in-hospital mortality were significantly higher in males as compared to females.
In this analysis of a large US cohort, males were more likely to test positive for COVID-19. In hospitalized patients, males were more likely to have complications, require ICU admission and mechanical ventilation, and had higher mortality than females, independent of age. Sex disparities in COVID-19 vulnerability are present, and emphasize the importance of examining sex-disaggregated data to improve our understanding of the biological processes involved to potentially tailor treatment and risk stratify patients.
Abstract
We present measurements of the weak gravitational lensing shear power spectrum based on
$450 \deg ^2$
of imaging data from the Kilo Degree Survey. We employ a quadratic estimator in two and ...three redshift bins and extract band powers of redshift autocorrelation and cross-correlation spectra in the multipole range 76 ≤ ℓ ≤ 1310. The cosmological interpretation of the measured shear power spectra is performed in a Bayesian framework assuming a ΛCDM model with spatially flat geometry, while accounting for small residual uncertainties in the shear calibration and redshift distributions as well as marginalizing over intrinsic alignments, baryon feedback and an excess-noise power model. Moreover, massive neutrinos are included in the modelling. The cosmological main result is expressed in terms of the parameter combination
$S_8 \equiv \sigma _8 \sqrt{\Omega _{\rm m}/0.3}$
yielding S
8 = 0.651 ± 0.058 (three z-bins), confirming the recently reported tension in this parameter with constraints from Planck at 3.2σ (three z-bins). We cross-check the results of the three z-bin analysis with the weaker constraints from the two z-bin analysis and find them to be consistent. The high-level data products of this analysis, such as the band power measurements, covariance matrices, redshift distributions and likelihood evaluation chains are available at http://kids.strw.leidenuniv.nl.
Foraging animals balance the need to seek food and energy against the accompanying dangers of injury and predation. To do so, they rely on learning systems encoding reward and danger. Whereas much is ...known about these separate learning systems, little is known about how they interact to shape and guide behavior. Here we show a key role for the rat paraventricular nucleus of the thalamus (PVT), a nucleus of the dorsal midline thalamus, in this interaction. First, we show behavioral competition between reward and danger: the opportunity to seek food reward negatively modulates expression of species-typical defensive behavior. Then, using a chemogenetic approach expressing the inhibitory hM4Di designer receptor exclusively activated by a designer drug in PVT neurons, we show that the PVT is central to this behavioral competition. Chemogenetic PVT silencing biases behavior toward either defense or reward depending on the experimental conditions, but does not consistently favor expression of one over the other. This bias could not be attributed to changes in fear memory retrieval, learned safety, or memory interference. Rather, our results demonstrate that the PVT is essential for balancing conflicting behavioral tendencies toward danger and reward, enabling adaptive responding under this basic selection pressure.
Among the most basic survival problems faced by animals is balancing the need to seek food and energy against the accompanying dangers of injury and predation. Although much is known about the brain mechanisms that underpin learning about reward and danger, little is known about how these interact to solve basic survival problems. Here we show competition between defensive (to avoid predatory detection) and approach (to obtain food) behavior. We show that the paraventricular thalamus, a nucleus of the dorsal midline thalamus, is integral to this behavioral competition. The paraventricular thalamus balances the competing behavioral demands of danger and reward, enabling adaptive responding under this selection pressure.
Video‐based flipped class instruction can strengthen the learning motivation of students. The effectiveness of flipped class instruction on teaching effectiveness and subject satisfaction has been ...evaluated previously. The present study aims to examine the impact of two aspects of subject reading motivation. A total of 100 secondary school students were recruited from 4 classes of 25 students (ie, video‐based flipped Mathematics class, traditional Mathematics class, video‐based flipped Liberal Studies (LS) class and traditional LS class) in two local secondary schools. The same teachers taught both the traditional and video‐based flipped classes in their subject. The students filled in questionnaires which measured: motivation for general reading; motivation for subject reading; academic subject satisfaction and perceived teaching effectiveness of the teachers. Analysis of covariance controlling for motivation for general reading revealed that students in the flipped classes reported significantly lower motivation for subject reading including reading curiosity, reading importance and reading compliance (t (1,98) = 10.52, p < 0.001; t (1,98) = 7.68, p < 0.001; t (1,98) = 20.39, p < 0.001, respectively). However, students in the flipped classes reported significantly higher satisfaction and teaching effectiveness than those in the traditional classes (t (1,98) = −15.61. p < 0.001; t (1,98) = −11.98, p <0.001, respectively). A partial correlation controlling for motivation for general reading indicated that motivation for subject reading was negatively associated with academic subject satisfaction and perceived teaching effectiveness of teachers (rs ranged from −0.51 to −0.62, p < 0.001). Video‐based flipped class instruction was not only related to increased academic subject satisfaction and teaching effectiveness but also associated with lower motivation for subject reading. These findings suggest that video‐based flipped class instruction had limited capability to strengthen the learning motivation of students.
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•Catalytic cracking of chlorinated heavy wax from pyrolysis of plastic wastes.•Fe loaded HY catalyst has a dual function of catalytic cracking and dechlorination.•Fe3/HY yielded a ...light liquid fraction of 66.9 wt.% with low Cl content <200 ppm.•Spent catalyst deposited coke and chlorine was restored by calcination in air.
Catalytic conversion of useless chlorinated heavy wax (chlorine, 0.14 wt%) obtained from pyrolysis of refuse plastic fuel was studied using iron oxide impregnated HY zeolite to produce a useful liquid product. It was found that the largest liquid fraction (gasoline and kerosene/ diesel, 66.9 wt.%) with very low chlorine content was achieved when using Fe3/HY among impregnated HY catalysts. This demonstrated that the Fe impregnated HY catalyst had a dual function of catalytic cracking of HY zeolite and dechlorination of iron oxide. Excessive impregnation of Fe, i.e., Fe20/HY, showed the least cracking activity of heavy wax owing to the catalyst having lowest total acid sites, but yielded liquid product with the lowest chlorine content (60 ppm) among the tested catalysts. The spent catalysts were deposited by a significant amount of soft coke and chlorine, and they were totally restored by thermal treatment in air (700 ℃).
This study aimed to identify clinical or microbiological factors affecting the clinical relevance of Corynebacterium striatum isolated from blood cultures. A total of 64 isolates from 51 patients ...identified as C. striatum by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequencing were assessed. More than two blood cultures were positive in 25 (48.1%) patients. Diabetes, solid tumor, and a history of previous exposure to antibiotics were more common in patients with multiple positive blood cultures. Charlson comorbidity scores were also higher, and more isolates were recovered after 48 hours of hospital stay in patients with multiple positive blood cultures. Strains recovered from patients with multiple positive blood cultures produced significantly more biofilm. Based on multilocus sequence typing (MLST), sequence type (ST) 20 (31.3%) was the most dominant, followed by ST2 (20.3%) and ST23 (10.9%). There was no relationship between the number of positive blood culture sets and sequence typing. In multivariate analyses, Carlson comorbidity score (odds ratio OR, 1.91; 95% confidence interval CI, 1.09-3.36; P = 0.03) and biofilm formation were associated with multiple positive blood cultures (OR, 17.43; 95% CI, 3.71-81.91; P = 0.03). This study provides evidence that the biofilm phenotype could contribute to determining the clinical significance of C. striatum in patients with severe underlying conditions. The predominance of certain STs suggests the relatedness of C. striatum infection and the nosocomial environment.
This study investigated attentional bias toward game-related cues in Internet gaming disorder (IGD) using electrophysiological markers of late positive potential (LPP) and identifying the sources of ...LPP. In addition, the association between LPP and decision-making ability was investigated. The IGD (n = 40) and healthy control (HC; n = 39) participants viewed a series of game-related and neutral pictures, while their event-related potentials (ERPs) were recorded. LPPs were calculated as the mean amplitudes between 400 and 700 ms at the centro-parietal (CP3, CP1, Cpz, CP2, and CP4) and parietal (P3, P1, Pz, P2, and P4) electrode sites. The source activations of LPP were estimated using standardized low-resolution brain electromagnetic tomography (sLORETA). In addition, decision-making ability was evaluated by the Cambridge Gambling Task. Higher LPP amplitudes were found for game-related cues in the IGD group than in the HC group. sLORETA showed that the IGD group was more active in the superior and middle temporal gyri, which are involved in social perception, than in the HC group, whereas it was less active in the frontal area. Individuals with IGD have deficits in decision-making ability. In addition, in the HC group, the lower the LPP when looking at the game-related stimuli, the better the quality of decision-making, but not in the IGD group. Enhanced LPP amplitudes are associated with emotional arousal to gaming cues and decision-making deficits in IGD. In addition, source activities suggest that patients with IGD perceive game-related cues as social stimuli. LPP can be used as a neurophysiological marker of IGD.
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