Miracle-dz/UniFAR-FTUs huggingface dataset:
Nicotinic Receptors in Sleep-Related Hypermotor Epilepsy: Pathophysiology and Pharmacology

Sleep-related hypermotor epilepsy (SHE) is characterized by hyperkinetic focal seizures, mainly arising in the neocortex during non-rapid eye movements (NREM) sleep. The familial form is autosomal dominant SHE (ADSHE), which can be caused by mutations in genes encoding subunits of the neuronal nicotinic acetylcholine receptor (nAChR), Na+-gated K+ channels, as well as non-channel signaling proteins, such as components of the gap activity toward rags 1 (GATOR1) macromolecular complex. The causative genes may have different roles in developing and mature brains. Under this respect, nicotinic receptors are paradigmatic, as different pathophysiological roles are exerted by distinct nAChR subunits in adult and developing brains. The widest evidence concerns α4 and β2 subunits. These participate in heteromeric nAChRs that are major modulators of excitability in mature neocortical circuits as well as regulate postnatal synaptogenesis. However, growing evidence implicates mutant α2 subunits in ADSHE, which poses interpretive difficulties as very little is known about the function of α2-containing (α2*) nAChRs in the human brain. Planning rational therapy must consider that pharmacological treatment could have different effects on synaptic maturation and adult excitability. We discuss recent attempts towards precision medicine in the mature brain and possible approaches to target developmental stages. These issues have general relevance in epilepsy treatment, as the pathogenesis of genetic epilepsies is increasingly recognized to involve developmental alterations.
Traditional Chinese Medicine guidelines for coronavirus disease 2019.

OBJECTIVE To summarize the evidence from Traditional Chinese Medicine (TCM) practice in the treatment of coronavirus disease 2019 (COVID-19) and provide timely clinical practice guidance. METHODS The guidelines were developed in accordance with the World Health Organization rapid guideline process. The evidence on TCM for COVID-19 from published guidelines, direct and indirect published clinical evidence, first hand clinical data, and expert experience and consensus were collected. The grading of recommendations assessment, development and evaluation (GRADE) method was used to grade the evidence and make the recommendations. RESULTS Based on the available evidence, the guidelines recommended 17 Chinese medicines for COVID-19: 2 Chinese herbal granules, 7 Chinese patent medicines, and 8 Chinese herbal injections. CONCLUSION As the literature search was conducted on March, any subsequent versions of these guidelines require an up-to-date literature review. We hope that the evidence summary in these will be helpful in global efforts to address COVID-19.
Evolution of H9N2 avian influenza viruses in Iran, 2017-2019.

Since its first detection in 1998, avian influenza virus (AIV) subtype H9N2 has been enzootic in Iran. To better understand the evolutionary history of H9N2 viruses in Iran, we sequenced 15 currently circulating H9N2 viruses from domestic poultry during 2017-2019 and performed phylogenetic analysis of complete genome sequences. Phylogenetic analyses indicated that the Iranian H9N2 viruses formed multiple well-supported monophyletic groups within the G1-lineage of H9N2 virus. Our analysis of viral population dynamics revealed an increase in genetic diversity until 2007, corresponding to the multiple introductions and diversification of H9N2 viruses into multiple genetic groups (named Iran 1-4 subgroups), followed by a sudden decrease after 2008. Only the Iran 4 subgroup has survived, expanded, and currently circulates in Iran. The H9N2 viruses possessed many molecular markers associated with mammalian adaption in all gene segments, except neuraminidase gene. Considering the presence of mammalian host-specific markers, the public health threat of H9N2 viruses continues. Molecular analysis showed that Iranian H9N2 strains have continued to evolve and recent strains have multiple amino acid changes and addition of potential N-glycosylation on the antigenic sites of hemagglutinin. Continued antigenic and molecular surveillance of H9N2 viruses in poultry and mammals would be required to monitor further increments in viral evolution and their potential threat to public health.
The Intrinsic Cardiac Nervous System and Its Role in Cardiac Pacemaking and Conduction

The cardiac autonomic nervous system (CANS) plays a key role for the regulation of cardiac activity with its dysregulation being involved in various heart diseases, such as cardiac arrhythmias. The CANS comprises the extrinsic and intrinsic innervation of the heart. The intrinsic cardiac nervous system (ICNS) includes the network of the intracardiac ganglia and interconnecting neurons. The cardiac ganglia contribute to the tight modulation of cardiac electrophysiology, working as a local hub integrating the inputs of the extrinsic innervation and the ICNS. A better understanding of the role of the ICNS for the modulation of the cardiac conduction system will be crucial for targeted therapies of various arrhythmias. We describe the embryonic development, anatomy, and physiology of the ICNS. By correlating the topography of the intracardiac neurons with what is known regarding their biophysical and neurochemical properties, we outline their physiological role in the control of pacemaker activity of the sinoatrial and atrioventricular nodes. We conclude by highlighting cardiac disorders with a putative involvement of the ICNS and outline open questions that need to be addressed in order to better understand the physiology and pathophysiology of the ICNS.
Crystallization Process for Superionic Li7P3S11 Glass–Ceramic Electrolytes

The crystallization process of the 70Li 2 S · 30P 2 S 5 (mol%) glass was investigated to obtain a guideline for enhancing the crystallinity of Li 7 P 3 S 11 crystals in a glass-ceramic. Results show that the glass softened at around 240°C and that surface crystallization of the glass started at around 250°C. The heat-treatment conditions with a maximum nucleation rate for the glass were estimated using DSC measurements. The glass-ceramic prepared using two-step heat treatment of 210°C for 30 min (nucleation) and 280°C for 1 h (crystallization) exhibited high conductivity of 5.2 x 10 -3 S/cm at room temperature.
EEG-Based Emotion Classification Using Long Short-Term Memory Network with Attention Mechanism

Recently, studies that analyze emotions based on physiological signals, such as electroencephalogram (EEG), by applying a deep learning algorithm have been actively conducted. However, the study of sequence modeling considering the change of emotional signals over time has not been fully investigated. To consider long-term interaction of emotion, in this study, we propose a long short-term memory network to consider changes in emotion over time and apply an attention mechanism to assign weights to the emotional states appearing at specific moments based on the peak–end rule in psychology. We used 32-channel EEG data from the DEAP database. Two-level (low and high) and three-level (low, middle, and high) classification experiments were performed on the valence and arousal emotion models. The results show accuracies of 90.1% and 87.9% using the two-level classification for the valence and arousal models with four-fold cross validation, respectively. In the case of the three-level classification, these values were obtained as 83.5% and 82.6%, respectively. Additional experiments were conducted using a network combining a convolutional neural network (CNN) submodule with the proposed model. The obtained results showed accuracies of 90.1% and 88.3% in the case of the two-level classification and 86.9% and 84.1% in the case of the three-level classification for the valence and arousal models with four-fold cross validation, respectively. In 10-fold cross validation, there were 91.8% for valence and 91.6% for arousal accuracy, respectively.
The Possible Importance of Glutamine Supplementation to Mood and Cognition in Hypoxia from High Altitude

Hypoxia induced by low O2 pressure is responsible for several physiological and behavioral alterations. Changes in physiological systems are frequent, including inflammation and psychobiological declines such as mood and cognition worsening, resulting in increased reaction time, difficulty solving problems, reduced memory and concentration. The paper discusses the possible relationship between glutamine supplementation and worsening cognition mediated by inflammation induced by high altitude hypoxia. The paper is a narrative literature review conducted to verify the effects of glutamine supplementation on psychobiological aspects. We searched MEDLINE/PubMed and Web of Science databases and gray literature by Google Scholar for English articles. Mechanistic pathways mediated by glutamine suggest potential positive effects of its supplementation on mood and cognition, mainly its potential effect on inflammation. However, clinical studies are scarce, making any conclusions impossible. Although glutamine plays an important role and seems to mitigate inflammation, clinical studies should test this hypothesis, which will contribute to a better mood and cognition state for several people who suffer from problems mediated by hypoxia.
Is lorcaserin really associated with increased risk of cancer? A systematic review and meta‐analysis

The US Food and Drug Administration (FDA) reported in February 2020 an increased risk of cancer with lorcaserin in the follow‐up of the CAMELLIA‐TIMI 61 trial. This systematic review and meta‐analysis addresses whether lorcaserin is associated with higher incidence of cancer compared with other interventions or no treatment. We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) for randomized controlled trials that compared lorcaserin with other interventions or no treatment in adults. We performed descriptive synthesis of all included studies and conducted meta‐analysis of trials that reported new cases of cancer. From 11 trials, comprising 21,299 individuals, four studies were included in the meta‐analysis and reported 476 cases of cancer in 10,342 subjects in the lorcaserin group and 438 among 9429 individuals randomized to placebo (relative risk [RR]: 1.08; 95% confidence interval [95% CI]: 0.96–1.23). The result was heavily influenced by the CAMELLIA‐TIMI 61 trial. In this study, the lorcaserin group had a higher risk of lung and pancreatic but not colon cancer. Overall risk of bias was low, and quality of evidence was moderate. The current evidence does not confirm the increased risk of cancer with lorcaserin but suggests a trend in this direction, with a greater incidence of some subtypes such as lung and pancreas.
LED-based light sources optimised for high colour rendition from an end users’ perspective

Abstract Light emitting diode (LED) technology is continuously developing, leading to the current transition from simple phosphor-converted LED lamps to LED lamps optimised for high colour rendition in residential lighting. To assess whether such optimised phosphor-converted LED lamps may fulfil the end users’ needs better than simple phosphor-converted LED lamps we asked participants to rank two particular brands of phosphor-converted LED lamps optimised for high colour rendition, a typical simple phosphor-converted LED lamp and a halogen lamp for pleasantness, naturalness and purchase preference. The results of two experiments suggest that phosphor-converted LED lamps optimised for high colour rendition have the potential to outperform simple phosphor-converted LED lamps and even to measure up to traditional halogen lighting in terms of user preference. However, this is not the case for all phosphor-converted LED lamps optimised for high colour rendition. From the end users’ perspective, unfortunately, it is currently difficult if not impossible to choose the LED light source that one would prefer most. Practitioner Summary: Considering innovations in LED technology, we assessed the potential of LED lamps optimised for high colour rendition to outperform their predecessors regarding user preference. In one of two conditions, these optimised LED lamps outperformed a simple phosphor-converted LED lamp and measured up to halogen lighting. Abbreviations: LED: light emitting diode; CCT: correlated colour temperature; CRI: colour rendering index; CIE: Commission Internationale de l’Éclairage; CRI Ra: CIE General Colour Rendering Index; K: kelvin; lx: lux; GFC: goodness of fit coefficient; BLED80: simple blue-pumped phosphor-converted LED with a CRI Ra of 80; BLED96: blue-pumped phosphor-converted LED optimised for high colour rendition with a CRI Ra of 96; VLED97: violet-pumped phosphor-converted LED optimised for high colour rendition with a CRI Ra of 97; R9: CIE Special Colour Rendering Index for red; ANSI: American National Standards Institute; IES: Illuminating Engineering Society; Rf: IES Fidelity Index; Rg: IES Gamut Index; CC: chromaticity coordinates
Assessing Rolling Abilities in Primary School Children: Physical Education Specialists vs. Generalists

Teaching physical education requires competencies to conduct the classes and to assess the motor skills of practitioners. Specialists (physical education professionals) and generalists (primary school teachers) differently experienced motor tasks during their academic education. This study aimed to compare the teachers’ ability in assessing the children’s forward and backward rolls from the analysis of the reliability of an evaluation grid of rolling abilities (Information Scale for Agility on the Soil, InfoSAS), which was investigated in a first study with teachers. A second study in young children explored the responsiveness of the InfoSAS to discriminate by skill level or by training effects. When administered by specialists, the InfoSAS resulted in being reliable (forward: p = 0.087 and p = 0.908; backward: p = 0.926 and p = 0.910; intra- and inter-rater reliability, respectively) and responsive in detecting differences due to expertise (gymnasts vs. primary school children; forward: p = 0.003, backward: p = 0.016) or improvements after specific training in rolling (pre- vs. post-children’s training; forward: p = 0.005, backward: p = 0.001). The results support the conclusion that specialists exhibit higher competence than generalists, which allows proper application of the InfoSAS, possibly because of the practice of skills and reflective teaching styles in physical activity they experienced, along with their academic education in sport sciences.
Anti-Tumor Effects of Sodium Meta-Arsenite in Glioblastoma Cells with Higher Akt Activities

Glioblastoma is a type of aggressive brain tumor that grows very fast and evades surrounding normal brain, lead to treatment failure. Glioblastomas are associated with Akt activation due to somatic alterations in PI3 kinase/Akt pathway and/or PTEN tumor suppressor. Sodium meta-arsenite, KML001 is an orally bioavailable, water-soluble, and trivalent arsenical and it shows antitumoral effects in several solid tumor cells via inhibiting oncogenic signaling, including Akt and MAPK. Here, we evaluated the effect of sodium meta-arsenite, KML001, on the growth of human glioblastoma cell lines with different PTEN expression status and Akt activation, including PTEN-deficient cells (U87-MG and U251) and PTEN-positive cells (LN229). The growth-inhibitory effect of KML001 was stronger in U87-MG and U251 cells, which exhibited higher Akt activity than LN229 cells. KML001 deactivated Akt and decreased its protein levels via proteasomal degradation in U87-MG cells. KML001 upregulated mutant PTEN levels via inhibition of its proteasomal degradation. KML001 inhibited cell growth more effectively in active Akt-overexpressing LN229 cells than in mock-expressing LN229 cells. Consistent with these results, KML001 sensitized PTEN-deficient cells more strongly to growth inhibition than it did PTEN-positive cells in prostate and breast cancer cell lines. Finally, we illustrated in vivo anti-tumor effects of KML001 using an intracranial xenograft mouse model. These results suggest that KML001 could be an effective chemotherapeutic drug for the treatment of glioblastoma cancer patients with higher Akt activity and PTEN loss.
Druggability assessment of precursor membrane protein as a target for inhibiting the Zika virus

Abstract The Zika virus (ZIKV), a significant zoonotic flavivirus, was neglected as a human pathogen until the recent epidemic. The rapid geographic spread of the virus and association with neurological disorders has created a global public health concern pressing the need for anti-ZIKV drugs. Previous ZIKV drug discovery research has focused on three primary targets, RNA-dependent RNA polymerase, envelope protein, and viral proteases, and none has yet resulted in a commercially viable inhibitor. In the quest for finding effective inhibitors, it is important to expand the number of targets available for drug discovery research. To this end, the ZIKV precursor membrane protein (prM) comes to the forefront as a potential target due to its critical role in virus infectivity and pathogenicity. prM acts as a chaperone for envelope protein folding and prevents premature fusion of virions to the host membrane and has not been attempted as a drug target before. One critical requirement for a protein to be an effective target is the ability of the protein to be druggable, i.e. having active sites that can bind to specific ligands. In this work, the druggability of prM was assessed via molecular docking combined molecular dynamics simulations followed binding affinity kinetics studies. Compounds that had a high affinity to the prM protein were screened in silico and ligand-binding free energies were computed using molecular mechanics with generalized Born and surface area continuum solvation (MM-GBSA) method. In vitro binding kinetics via biolayer interferometry (BLI) and interaction analysis confirmed that prM could be targeted for drug discovery to combat ZIKV infection. Communicated by Ramaswamy H. Sarma
A Kalman Filter for Nonlinear Attitude Estimation Using Time Variable Matrices and Quaternions

The nonlinear problem of sensing the attitude of a solid body is solved by a novel implementation of the Kalman Filter. This implementation combines the use of quaternions to represent attitudes, time-varying matrices to model the dynamic behavior of the process and a particular state vector. This vector was explicitly created from measurable physical quantities, which can be estimated from the filter input and output. The specifically designed arrangement of these three elements and the way they are combined allow the proposed attitude estimator to be formulated following a classical Kalman Filter approach. The result is a novel estimator that preserves the simplicity of the original Kalman formulation and avoids the explicit calculation of Jacobian matrices in each iteration or the evaluation of augmented state vectors.
Constriction of endoplasmic reticulum tubules by the viral movement protein BMB2 is associated with local BMB2 anchorage at constriction sites

ABSTRACT Plant virus-encoded movement proteins (MPs) interact with endoplasmic reticulum (ER) membranes, the cytoskeleton, and plasmodesmata (PD) to mediate intracellular delivery of the virus genome to PD and its further transport through PD from infected to healthy cells. The Hibiscus green spot virus MP termed BMB2 has been shown to induce constrictions of ER tubules and to occur at highly curved membranes, thus showing properties similar to those of reticulons, a class of cellular proteins inducing membrane curvature and shaping the ER tubules. Consistent with this BMB2 function, mRFP-BMB2 localizes to discrete, constricted regions scattered along the ER tubules. Here, using BMB2-mRFP fusion protein as a BMB2 derivative with partially disabled functionality, we demonstrate that the focal localization of BMB2 to discrete sites along the ER tubules is insufficient to induce local tubule constrictions at these sites, suggesting that the formation of ER tubule constrictions represents a specific BMB2 function and is not simply a mechanistic consequence of its localization to the ER. The presented data suggest that the formation of ER-residing BMB2-containing distinct small aggregates, or protein platforms, can be uncoupled from BMB2-induced ER tubule constrictions, whereas the anchoring of platforms at particular ER sites appears to be linked to the constriction of ER tubules at these sites.
Autophagy Activation Protects Ocular Surface from Inflammation in a Dry Eye Model In Vitro

Inflammation is the main pathophysiology of dry eye, characterized by tear film instability and hyperosmolarity. The aim of this study was to investigate the association of inflammation and cellular autophagy using an in vitro dry eye model with primary cultured human corneal epithelial cells (HCECs). Primary HCECs cultured with fresh limbal explants from donors were switched to a hyperosmotic medium (450 mOsM) by adding sodium chloride into the culture medium. We observed the stimulated inflammatory mediators, TNF-α, IL-1β, IL-6 and IL-8, as well as the increased expression of autophagy related genes, Ulk1, Beclin1, Atg5 and LC3B, as evaluated by RT-qPCR and ELISA. The immunofluorescent staining of LC3B and Western blotting revealed the activated autophagosome formation and autophagic flux, as evidenced by the increased LC3B autophagic cells with activated Beclin1, Atg5, Atg7 and LC3B proteins, and the decreased levels of P62 protein in HCECs. Interestingly, the autophagy activation was later at 24 h than inflammation induced at 4 h in HCECs exposed to 450 mOsM. Furthermore, application of rapamycin enhanced autophagy activation also reduced the inflammatory mediators and restored cell viability in HCECs exposed to the hyperosmotic medium. Our findings for the first time demonstrate that the autophagy activation is a late phase response to hyperosmotic stress, and is enhanced by rapamycin, which protects HCECs by suppressing inflammation and promoting cells survival, suggesting a new therapeutic potential to treat dry eye diseases.
Autophagy and Its Regulators in Response to Stress in Plants

To survive in stressful conditions, plants have developed multiple strategies to relieve damage. One of the strategies is to clear the damaged protein and organelles. Autophagy is a highly conservative degradation process, which refers to the recycling of damaged protein and organelles. Over the past decades, increasing evidence has revealed the important roles of autophagy in response to stress conditions, and many factors have been revealed involved in the sophisticated regulation of the autophagy signaling pathway. However, the accurate regulation pathway of the autophagy pathway is largely unknown. The current review proposes how stress-response factors respond to stress conditions involved in regulating the autophagy signaling pathway. In short, clarifying the regulating pathway of autophagy in response to stress conditions is beneficial to plant breeding.