Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical Utility of Exome Sequencing and Reinterpreting Genetic Test Results in Children and Adults With Epilepsy

The clinical utility of genetic testing for epilepsy has been enhanced with the advancement of next-generation sequencing (NGS) technology along with the rapid updating of publicly available databases. The aim of this study was to evaluate the diagnostic yield of NGS and assess the value of reinterpreting genetic test results in children and adults with epilepsy. We performed genetic testing on 200 patients, including 82 children and 118 adults. The results were classified into three categories: positive, inconclusive, or negative. The reinterpretation of inconclusive results was conducted in April 2020. Overall, we identified disease-causing variants in 12% of the patients in the original analysis, and 14.5% at reinterpretation. The diagnostic yield for adults with epilepsy was similar to that for children (11 vs. 19.5%, p = 0.145). After reinterpretation, 9 of the 86 patients who initially had inconclusive results obtained a clinically significant change in diagnosis. Among these nine revised cases, five obtained positive diagnoses, representing a diagnosis rate of 5.8% (5/86). Manual searches for additional evidence of pathogenicity for candidate variants and updated patient clinical information were the main reasons for diagnostic reclassification. This study emphasizes the diagnostic potential of combining NGS and reinterpretation of inconclusive genetic test reports in children and adults with epilepsy.
No Population Genetic Structure of Skipjack Tuna (Katsuwonus pelamis) in the Tropical Western and Central Pacific Assessed Using Single Nucleotide Polymorphisms

Skipjack tuna (Katsuwonus pelamis) has historically been considered panmictic at the ocean basin scale because of the species’ life history and substantial absolute population size. However, recent advances in population genomics have enabled scientists to demonstrate population structure in other species that were likewise traditionally assumed to be panmictic. Accordingly, we used DArTseq, a proprietary platform of reduced-representation genome sequencing developed by Diversity Arrays Technology (DArTech) to genotype 222 skipjack tuna from 9 sample groups collected across 6 exclusive economic zones (EEZs) and over 6 years in the tropical Western and Central Pacific Ocean. This is one of the most fine-scale population genetics assessments of skipjack tuna to date. We found several statistically significant pairwise FST comparisons using purportedly neutral loci, but very little indication of structure based on observed and expected heterozygosity, effective population size, a Mantel test, AMOVA, numerous genetic clustering and population assignment tests, and exploration of correlation with oceanographic features. Significant pairwise FST values were often shallow and resulted in uncertainty about their biological significance. Furthermore, a test of the hypothesis that the geographic and temporal distribution of the potentially adaptive genetic diversity may depict cryptic fine scale structure using two different outlier detection methods, could not reject panmixia based on estimates of fixation indices and two clustering software. Our results support the presence of a single population of skipjack tuna in the tropical Western and Central Pacific Ocean, but highly recommend the expansion of the study area, in latitude, longitude, and seasonality, before drawing any global conclusions.
Micro-Rheological Changes of Red Blood Cells in the Presence of an Arterio-Venous Fistula or a Loop-Shaped Venous Graft in the Rat

Introduction: In case of kidney failure, hemodialysis is the primary kidney replacement technique. Several vascular access methods used for the therapy, one of which is the arterio-venous fistula (AVF). In the AVF, the blood flow is altered, which can elevate the mechanical stress on the red blood cells (RBCs). This can affect the RBC hemorheological properties, and it can further cause systemic changes. To lower the turbulence and shear stress, we performed a loop-shaped arterio-arterial venous interposition graft (loop-shaped graft) to compare its effect to the conventional AVF. Materials and Methods: Thirty male Wistar were used (permission registration Nr.: 25/2016/UDCAW). The animals were randomly divided into sham-operated, AVF, and loop groups (n = 10/each). The superficial inferior epigastric vein (SIEV) was used to create the AVF and the loop-shaped graft. Blood samples were taken before/after the surgery and at the 1st, 3rd, and 5th postoperative weeks. We measured hemorhelogical, hematological, and blood gas parameters. The microcirculation of the hind limbs was also monitored using Laser Doppler fluxmetry. Results: Hematocrit, RBC count, and hemoglobin decreased by the 1st postoperative week. The erythrocyte aggregation values significantly increased in the fistula group by the 5th week (6.43 ± 2.31 vs. 13.60; p < 0.0001; vs. before operation). At the postoperative 1st week in the loop group, the values showed a significant decrease in RBC deformability. During the maturation period, dominantly at the 5th week, all values were normalized. The operated hind limb’s skin microcirculation significantly increased in the sham and loop group by the 1st week (39 ± 10.57 vs. 73.93 ± 1.97 BFU, p < 0.01). This increase wasn’t observed in the fistula group probably due to a steal-effect. Conclusion: Unlike in the loop group, in the presence of the fistula, several rheological parameters have changed. The loop-shaped graft had only minimal impact on micro-rheological parameters.
The T Cell Receptor Immune Repertoire Protects the Liver From Reconsitution

Aberrant immune cell infiltrates and microcircumstances represent characteristic features of liver fibrosis. In this study, we profiled the transcriptomes of intrahepatic CD45+ immune cells, from mice, using single-cell RNA sequencing (scRNA-seq) technology to understand the landscape of intrahepatic immune cells during the pathogenesis of fibrosis. Analysis of approximately 10,000 single-cell transcriptomes revealed an increase in dendritic cells (DCs), macrophages, and neutrophils and a decrease in T and natural killer T (NKT) cells. In addition, we report changes in the transcriptomes of diverse immune cell types, implying a deteriorating intrahepatic immune microcircumstance. Furthermore, we uncovered a novel fibrosis-associated CD8 T (Ccl5+, Ccl4+) and CD4 T (mt-Co1+) cell subpopulation, which infiltrates fibrotic liver and is characterized by abnormal activation or inactivation as well as a TCR decline. The results from scRNA-seq and bulk immune repertoire sequencing (IR-seq) revealed an obvious decline in T cell receptor (TCR) clonotypes combined with shrinking VJ and VDJ segment usage, as well as lower complementarity-determining region 3 (CDR3) amino acid (AA) diversity from fibrotic liver. Interestingly, a deficiency of TCR IR (TcrbKO mice) led to a deterioration of liver fibrosis, coupled with activation of hepatic stellate cells (HSCs) induced by the upregulation of macrophage and γδ T cell distribution in fibrotic TcrbKO livers. Our findings reveal the landscape and dynamics of single immune cells in liver fibrosis, and clarify the protective role of TCR IR in response to chronic liver injury.
The Effect of Bilingualism on Cue-Based vs. Memory-Based Task Switching in Older Adults

Findings suggest a positive impact of bilingualism on cognition, including the later onset of dementia. However, it is not clear to what extent these effects are influenced by variations in attentional control demands in response to specific task requirements. In this study, 20 bilingual and 20 monolingual older adults performed a task-switching task under explicit task-cuing vs. memory-based switching conditions. In the cued condition, task switches occurred in random order and a visual cue signaled the next task to be performed. In the memory-based condition, the task alternated after every second trial in a predictable sequence without presenting a cue. The performance of bilinguals did not vary across experimental conditions, whereas monolinguals experienced a pronounced increase in response latencies and error rates in the cued condition. Both groups produced similar switch costs (difference in performance on switch trials as opposed to repeating trials within the mixed-task block) and mixing costs (difference in performance on repeat trials of a mixed-task block as opposed to trials of a single-task block), but bilinguals produced them with lower response latencies. The cognitive benefits of bilingualism seem not to apply to executive functions per se but to affect specific cognitive processes that involve task-relevant context processing. The present results suggest that lifelong bilingualism could promote in older adults a flexible adjustment to environmental cues, but only with increased task demands. However, due to the small sample size, the results should be interpreted with caution.
Quality Markers for Astragali Radix and Its Products Based on Process Analysis

Due to the complex nature of traditional medicines, quality control methods need to cover two aspects: compliance of raw materials with quality standards and process control. Astragali radix (AR), the roots of Astragalus mongholicus Bunge, was selected in this study as an example of a widely used traditional medicine in various formulations. Astragaloside IV (AG IV) and calycosin 7-O-β-D-glucoside (CG) are used as the markers for the quality control of AR and its products in the Chinese Pharmacopoeia. However, in the raw materials, malic acid esters of the CG and acetate esters of the astragaloside are easily decomposed into CG and AG IV during storage and processing of AR to make extracts for various preparations. The thermal stability of the isoflavonoids and astragalosides in decoction was studied. The level of CG and astragalosides (AG I/AG II/AG IV) was strongly affected by prolonged heat during processing, while calycosin was stable in the conditions. Also the major astragalosides in AR could fully converted into AG IV which eventually reaches a stable level under certain conditions. With calycosin and AG IV as marker components, practical, reproducible, and precise methods were established and applied to the quality analysis of AR from its raw materials to its intermediates and products. This study demonstrates that a full chemical profiles analysis of the whole manufacturing process (from “raw materials—intermediates/extracts—final product”) is important to identify quality markers (Q-markers) and even to establish proper analysis methods for traditional Chinese medicine products.
Perspective: The Lung, Particles, Fibers, Nanomaterials, and Autoimmunity

Studies have shown that a wide range of factors including drugs, chemicals, microbes, and other environmental agents can induce pre-clinical autoimmunity. However, only a few have been confidently linked to autoimmune diseases. Among these are exposures to inhaled particulates that are known to be associated with autoimmune diseases such as lupus and rheumatoid arthritis. In this article, the potential of particle, fiber, and nanomaterial exposures to induce autoimmunity is discussed. It is hypothesized that inhalation of particulate material known to be associated with human autoimmune diseases, such as cigarette smoke and crystalline silica, results in a complex interplay of a number of pathological processes, including, toxicity, oxidative stress, cell and tissue damage, chronic inflammation, post-translational modification of self-antigens, and the formation of lymphoid follicles that provide a milieu for the accumulation of autoreactive B and T cells necessary for the development and persistence of autoimmune responses, leading to disease. Although experimental studies show nanomaterials are capable of inducing several of the above features, there is no evidence that this matures to autoimmune disease. The procession of events hypothesized here provides a foundation from which to pursue experimental studies to determine the potential of other environmental exposures to induce autoimmunity and autoimmune disease.
Microwave-Assisted Synthesis of Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) Complexes of Tridentate Schiff Base N-(2-hydroxyphenyl) 2-hydroxy-5-bromobenzaldimine: Characterization, DNA Interaction, Antioxidant, and In Vitro Antimicrobial Studies

Five mononuclear complexes of Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) with the Schiff base N-(2-hydroxyphenyl) 2-hydroxy-5-bromobenzaldimine were synthesized under microwave irradiation. The microwave irradiation method was found remarkably successful and gave higher yield at a less reaction time. The complexes were fully characterized by elemental analyses, FT-IR, 1H NMR, EPR, FAB mass spectra, electronic spectra, molar conductivity, magnetic susceptibility measurements, and thermogravimetric analyses (TGA). Structural compositions were assigned by mass spectral studies. Four-coordinate geometry has been assigned to these complexes tentatively. The interaction of the complexes with calf thymus DNA (CT-DNA) was investigated by absorption spectroscopy, emission spectroscopy, and viscosity measurements. The experimental evidences indicated that the binding strength follow the order Cu(II) > Mn(II) > Co(II) > Ni(II) >Zn (II). Moreover, the complexes were examined for their antioxidant activities against r.
Prognostic Performance of Albumin–Bilirubin Grade With Artificial Intelligence for Hepatocellular Carcinoma Treated With Transarterial Chemoembolization Combined With Sorafenib

Purpose To establish albumin-bilirubin (ALBI) grade-based and Child-Turcotte-Pugh (CTP) grade-based nomograms, as well as to develop an artificial neural network (ANN) model to compare the prognostic performance and discrimination of these two grades for hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) combined with sorafenib as an initial treatment. Methods This multicenter retrospective study included patients from three hospitals between January 2013 and August 2018. In the training cohort, independent risk factors associated with overall survival (OS) were identified by univariate and multivariate analyses. The nomograms and ANN were established and then validated in two validation cohorts. Results A total of 504 patients (319, 61, and 124 patients from hospitals A, B, and C, respectively) were included. The median OS was 15.2, 26.9, and 14.8 months in the training cohort and validation cohorts 1 and 2, respectively (P = 0.218). In the training cohort, both ALBI grade and CTP grade were identified as independent risk factors. The ALBI grade-based and CTP grade-based nomograms were established separately and showed similar prognostic performance and discrimination when validated in the validation cohorts (C-index in validation cohort 1: 0.799 vs. 0.779, P = 0.762; in validation cohort 2: 0.700 vs. 0.693, P = 0.803). The ANN model showed that the ALBI grade had higher importance in survival prediction than the CTP grade. Conclusions The ALBI grade and CTP grade have comparable prognostic performance for HCC patients treated with TACE combined with sorafenib. ALBI grades 1 and 2 have the potential to act as a stratification factor for clinical trials on the combination therapy of TACE and systemic therapy.
The Ion Channel and GPCR Toolkit of Brain Capillary Pericytes

Brain pericytes reside on the abluminal surface of capillaries, and their processes cover ~90% of the length of the capillary bed. These cells were first described almost 150 years ago (Eberth, 1871; Rouget, 1873) and have been the subject of intense experimental scrutiny in recent years, but their physiological roles remain uncertain and little is known of the complement of signaling elements that they employ to carry out their functions. In this review, we synthesize functional data with single-cell RNAseq screens to explore the ion channel and G protein-coupled receptor (GPCR) toolkit of mesh and thin-strand pericytes of the brain, with the aim of providing a framework for deeper explorations of the molecular mechanisms that govern pericyte physiology. We argue that their complement of channels and receptors ideally positions capillary pericytes to play a central role in adapting blood flow to meet the challenge of satisfying neuronal energy requirements from deep within the capillary bed, by enabling dynamic regulation of their membrane potential to influence the electrical output of the cell. In particular, we outline how genetic and functional evidence suggest an important role for Gs-coupled GPCRs and ATP-sensitive potassium (KATP) channels in this context. We put forth a predictive model for long-range hyperpolarizing electrical signaling from pericytes to upstream arterioles, and detail the TRP and Ca2+ channels and Gq, Gi/o, and G12/13 signaling processes that counterbalance this. We underscore critical questions that need to be addressed to further advance our understanding of the signaling topology of capillary pericytes, and how this contributes to their physiological roles and their dysfunction in disease.
CVD deposition of cobalt oxide (Co3O4) from Co(acac)2

Cobalt oxides are interesting materials for catalytic applications. Their deposition by CVD methods, however, have been rarely studied to date. In this work, cobalt(Il)-acetylacetonate, Co(acac)(2), Was used as metalorganic precursor together with oxygen, to deposit Co3O4 on steel and silicon dioxide substrates in an atmospheric cold-wall CVD reactor. The morphology and growth rate as a function of temperature, flow rate and oxygen partial pressure was studied. Growth was found between 200 and 500 degreesC. The samples were analysed by SEM, UV-Vis spectroscopy and XRD. The morphology as well as the growth rate may be varied in a wide parameter range from smooth films to dendritic growth. Some samples were also tested for their catalytic activity in propane oxidation.
Cooperation of Neural Networks for Spoken Digit Classification

Notably, all neural network models are trained by using gradient descent, and by far, the most successful approach for machine learning is to use gradient descent. However, this is a greedy algorithm and hits some of the biggest open problems in the neural networks. By using gradient descent, it is not guaranteed that a better solution cannot be found. Here, this article has presented an empirical study of the performance of two hidden layers’ neural networks. It gives practical methods to improve the accuracy of neural networks: cooperation method of neural network. In this study, our group applied the data augmentation method by adding noise into the training data set and compared 3 kinds of training methods: batch gradient descent (BGD), stochastic gradient descent (SGD), and batch stochastic gradient descent (BSGD). According to cooperating the neural networks, the performance of these neural networks has improved compared to baseline neural networks by 47% (PEG (generalization classification error probability) of 9 neural networks in cooperation is 0.071). Finally, the real-time classification using a cooperation method which has PEG equals 0.04 (single neural networks’ PEG is 0.104), further proves the results that cooperation improves the performance of neural networks.
Patterns in Hydrogen Bonding: Functionality and Graph Set Analysis in Crystals

Whereas much of organic chemistry has classically dealt with the preparation and study of the properties of individual molecules, an increasingly significant portion of the activity in chemical research involves understanding and utilizing the nature of the interactions between molecules. Two representative areas of this evolution are supramolecular chemistry and molecular recognition. The interactions between molecules are governed by intermolecular forces whose energetic and geometric properties are much less well understood than those of classical chemical bonds between atoms. Among the strongest of these interactions, however, are hydrogen bonds, whose directional properties are better understood on the local level (that is, for a single hydrogen bond) than many other types of non-bonded interactions. Nevertheless, the means by which to characterize, understand, and predict the consequences of many hydrogen bonds among molecules, and the resulting formation of molecular aggregates (on the microscopic scale) or crystals (on the macroscopic scale) has remained largely enigmatic. One of the most promising systematic approaches to resolving this enigma was initially developed by the late M. C. Etter, who applied graph theory to recognize, and then utilize, patterns of hydrogen bonding for the understanding and design of molecular crystals. In working with Etter's original ideas the power and potential utility of this approach on one hand, and on the other, the need to develop and extend the initial Etter formalism was generally recognized. It with that latter purpose that we originally undertook the present review.
Improved Secure Lightweight RFID Authentication Protocol

In order to improve the computing performance and security of RFID authentication protocol, an improved lightweight RFID two-way authentication protocol is proposed. With the authorization of a small amount of additional information, the two-way authentication between the reader and the tag can be completed quickly, without the need to communicate with the backend server frequently, which avoids increasing the security risks and communication costs caused by additional communication. Compared with the existing RFID authentication protocol, the improved protocol has meet requirements of backward security, mutual authentication, synchronization and non-denial of service. The improved protocol is suitable to be deployed in mobile RFID environment and applied in low-cost RFID tags.
Battery Day

Tesla held its first Battery Day on September 22, 2020. The Tesla team didn't just look at one angle but all the angles: cell design, manufacturing, vehicle integration, and materials. If Tesla were to achieve 400 watt-hours per kilogram, a zero-emissions jet just might be on the horizon.