Since the 2019 novel coronavirus disease (COVID-19) outbreak in 2019 and the pandemic continues for more than one year, a vast amount of drug research has been conducted and few of them got FDA ...approval. Our objective is to prioritize repurposable drugs using a pipeline that systematically integrates the interaction between COVID-19 and drugs, deep graph neural networks, and in vitro/population-based validations. We first collected all available drugs (n = 3635) related to COVID-19 patient treatment through CTDbase. We built a COVID-19 knowledge graph based on the interactions among virus baits, host genes, pathways, drugs, and phenotypes. A deep graph neural network approach was used to derive the candidate drug's representation based on the biological interactions. We prioritized the candidate drugs using clinical trial history, and then validated them with their genetic profiles, in vitro experimental efficacy, and population-based treatment effect. We highlight the top 22 drugs including Azithromycin, Atorvastatin, Aspirin, Acetaminophen, and Albuterol. We further pinpointed drug combinations that may synergistically target COVID-19. In summary, we demonstrated that the integration of extensive interactions, deep neural networks, and multiple evidence can facilitate the rapid identification of candidate drugs for COVID-19 treatment.
•We synthesized high-quality single crystals of bridgmanite up to 300 μm in size.•Bridgmanite crystals contain less than 50 ppm wt. H2O at the uppermost lower mantle.•The majority of the top of a ...pyrolitic lower mantle is nearly dry.
Water solubility in the dominant lower-mantle bridgmanite phase remains controversial. Discrepancies between previous results highlight the importance of the growth high-quality single crystals of bridgmanite under high-pressure and high-temperature conditions corresponding to the top of the lower mantle. Here we synthesized high-quality single crystals of aluminous bridgmanite up to 300 μm in size that were saturated with hydrous melt at 24–26 GPa and 1700–1900 K using both stoichiometric and MgO-rich non-stoichiometric hydrous starting materials in a multi-anvil press. Fourier-transform infrared spectroscopy measurements on clear and pure spots of the single-crystal bridgmanites did not detect any pronounced OH-stretching bands, which were prominent in some earlier studies. The present results support that the lower-mantle dominated bridgmanite is nearly dry, at least at the top of the lower mantle, and that Al3+ and Fe3+ cannot enhance water incorporation into the crystal structure even in the presence of oxygen vacancies. Large partition coefficients of water between transition-zone minerals and dry lower-mantle dominated bridgmanite further support dehydration melting at the top of the lower mantle. We suggest that the majority of the top of a pyrolitic lower mantle is nearly dry based on the dry principal minerals and stability of hydrous phases in this region.
Agglomeration of CoB catalysts is a severe problem in hydrogen generation from NaBH4 hydrolysis. Herein, highly dispersed carbon nanofiber immobilized CoB catalysts (CoB/CN) were synthesized by a ...combined prereduction and carbonization method, which is used in hydrogen generation from NaBH4 hydrolysis. Morphological evolution of carbon nanofibers, phase structure and elemental distribution of CoB/CN catalysts are explored by X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). Compared to Co/carbon nanofiber catalysts (Co/CN) without prereduction, CoB/CN catalysts can afford higher CoB dispersity and specific surface area because the migration rate of cobalt species during carbonization is effectively retarded by prereduction. Hence the agglomeration of magnetic CoB nanoparticles can be effectively inhibited. The hydrogen generation experiment shows that CoB/CN catalysts process higher catalytic activity and lower activation energy than Co/CN.
•Carbon nanofiber immobilized CoB catalysts were prepared.•Agglomeration of magnetic CoB nanoparticles was inhibited.•CoB/CN catalysts exhibit a high surface area of about 292 m2 g−1.•The deep oxidation of CoB in carbon nanofibers can be retarded.•CoB/CN catalysts exhibit excellent catalytic activity.
Bronchoalveolar lavage (BAL) galactomannan (GM) assay has been used for diagnosing invasive aspergillosis (IA). We aimed to derive a definitive estimate of the overall accuracy of BAL-GM for ...diagnosing IA.
We undertook a systematic review of thirty diagnostic studies that evaluated the BAL-GM assay for diagnosing IA. PubMed and CBM (China Biological Medicine Database) databases were searched for relevant studies published in all languages up until Feb 2012. The pooled diagnostic odds ratio (DOR) and summary receiver operating characteristic (SROC) were constructed for each cutoff value. Additionally, pooled sensitivity (SEN), specificity (SPE), and positive and negative likelihood ratios (PLR and NLR, respectively) were calculated for summarizing overall test performance. Thirty studies were included in this meta-analysis. The summary estimates of pooled DOR, SEN, SPE, PLR, and NLR of the BAL-GM assay (cutoff value 0.5) for proven or probable IA were 52.7 (95% confidence interval (CI) 31.8-87.3), 0.87 (95% CI 0.79-0.92), 0.89 (95% CI 0.85-0.92), 8.0 (95% CI 5.7-11.1) and 0.15 (95% CI 0.10-0.23) respectively. The SROC was 0.94 (95% CI 0.92-0.96). Compared with cutoff value of 0.5, it has higher DOR, SPE and PLR, and similar SEN and NLR with cutoff value of 1.0, which indicated the optimal cutoff value might be 1.0. Compared with BAL-GM, serum GM has a lower SEN and higher SPE, while PCR displays a lower SEN and a similar SPE.
With the optimal cutoff value of 1.0, the BAL-GM assay has higher SEN compared to PCR and serum GM test. It is a useful adjunct in the diagnosis of proven and probable IA.
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Exploring the transition-metal-based bifunctional electrocatalysts with high performance for efficient water-splitting and urea electrolysis is significant but challenging. This work ...presents the in situ preparation of holey NiFe-LDH nanosheets on Ni foam (H-NiFe-LDH/NF) via a one-step hydrothermal method in the presence of PEO-PPO-PEO as the soft template. The holey NiFe-LDH nanosheets provide a high electrochemical surface area, more edge catalytic sites, and abundant oxygen vacancies. Consequently, H-NiFe-LDH/NF exhibits excellent catalytic activity to oxygen evolution, urea oxidation, and hydrogen evolution reactions (OER, UOR, and HER) with good stability in alkaline electrolytes. This electrode requires an overpotential of 261 mV for the OER, a potential of 1.480 V for the UOR to achieve a current density of 100 mA cm−2 in alkaline solutions. By employing the self-supported electrode as both the anode and cathode, this electrolysis cell (H-NiFe-LDH/NF||H-NiFe-LDH/NF) gains current densities of 10 and 100 mA cm−2 at low cell voltages of 1.575 and 1.933 V in the 1.0 M KOH solution. After adding 0.33 M urea, the voltages to deliver 10 and 100 mA cm−2 respectively decrease to 1.418 and 1.691 V. The H-NiFe-LDH/NF electrode also shows excellent stability for water-splitting and urea electrolysis. This work not only contributes to developing a low-cost, high-efficiency, bifunctional electrocatalyst but also provides a practically feasible approach for urea-rich wastewater electrolysis.
The ability to use word category information (WCI) for syntactic structure building has been hypothesized to be the essence of human language faculty. The neural substrate of the ability of using the ...WCI for the complex syntactic hierarchical structure processing, however, is yet unknown. Therefore, we directly conducted an fMRI experiment by using a pseudo‐Chinese artificial language with syntactic structures containing a center‐embedded relative clause. Thirty non‐Chinese native (Korean) speakers were randomly divided into two groups: one acquired WCI and WCI‐based syntactic rules (the WCI group) before the scanning session, and the other did not (the non‐WCI group). Both groups were required to judge the grammaticality of the testing sentences, with critical long‐distance dependencies between two elements (the main verb and the relativizer). Behaviorally, the WCI group's accuracy was significantly higher and its reaction time was shorter. The scanning results showed that the left superior temporal gyrus (STG) and Broca's area were more strongly activated for the WCI group, and the dynamic causal modeling analyses revealed a distinct effective connectivity pattern for this group. Therefore, the present research, for the first time, reveals that the activation of and the functional connectivity between Broca's area and the left STG play a critical role in the ability of the rule‐based use of the WCI which is crucial for complex hierarchical structure building, and might be substantially corresponding to the “labeling competence” within the linguistic framework.
To improve the reliability and safety of myoelectric prosthetic control, many researchers tend to use multi-modal signals. The combination of electromyography (EMG) and forcemyography (FMG) has been ...proved to be a practical choice. However, an integrative and compact design of this hybrid sensor is lacking. This paper presents a novel modular EMG-FMG sensor; the sensing module has a novel design that consists of floating electrodes, which act as the sensing probe of both the EMG and FMG. This design improves the integration of the sensor. The whole system contains one data acquisition unit and eight identical sensor modules. Experiments were conducted to evaluate the performance of the sensor system. The results show that the EMG and FMG signals have good consistency under standard conditions; the FMG signal shows a better and more robust performance than the EMG. The average accuracy is 99.07% while using both the EMG and FMG signals for recognition of six hand gestures under standard conditions. Even with two layers of gauze isolated between the sensor and the skin, the average accuracy reaches 90.9% while using only the EMG signal; if we use both the EMG and FMG signals for classification, the average accuracy is 99.42%.
Animals may consider both biotic and abiotic factors in foraging site choice. Among the biotic factors, food availability and predation risk are two widely reported important factors in determining ...foraging site fidelity. Their earlier investments, such as those retreat‐building species' efforts in retreats construction, however, have been largely ignored. The orb‐web spider Cyclosa monticola constructs a long column of masquerading detritus decoration in its web for predator avoidance purpose. This detritus decoration also functions as a retreat. However, the role of the detritus decoration for its foraging site fidelity is unknown. By manipulating three factors, presence of detritus decoration, prey availability and predation risk to the spider webs in the field, we show that the self‐constructed detritus decoration is as important as prey availability and predation risk in mediating foraging site fidelity. In addition, the web area also has a significant impact to the foraging site fidelity of the spider, those with larger webs were more likely to leave after being manipulated. However, other factors such as spider body size, decoration length and rain all have no significant impact. Our study may strengthen the current understanding of the movement and foraging of animals, especially those building retreats.
Increasing evidence suggests that inflammation plays an essential role in cancer development and progression. The inflammation marker neutrophil-lymphocyte ratio (NLR) is correlated with prognosis ...across a wide variety of tumor types, but its prognostic value in prostate cancer (PCa) remains controversial. In the present meta-analysis, the prognostic value of NLR in PCa patients is investigated.
We performed a meta-analysis to determine the predictive value of NLR for overall survival (OS), recurrence-free survival (RFS), and clinical features in patients with PCa. We systematically searched PubMed, ISI Web of Science, and Embase for relevant studies published up to October 2015.
A total of 9418 patients from 18 studies were included in the meta-analysis. Elevated pretreatment NLR predicted poor OS (HR 1.628, 95% CI 1.410-1.879) and RFS (HR 1.357, 95% CI 1.126-1.636) in all patients with PCa. However, NLR was insignificantly associated with OS in the subgroup of patients with localized PCa (HR 1.439, 95% CI 0.753-2.75). Increased NLR was also significantly correlated with lymph node involvement (OR 1.616, 95% CI 1.167-2.239) but not with pathological stage (OR 0.827, 95% CI 0.637-1.074) or Gleason score (OR 0.761, 95% CI 0.555-1.044).
The present meta-analysis indicated that NLR could predict the prognosis for patients with locally advanced or castration-resistant PCa. Patients with higher NLR are more likely to have poorer prognosis than those with lower NLR.
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