bluuebunny/crossref_metadata_2025 huggingface dataset:
A Neuro-Computational Model for Discrete-Continuous Dual-Task Process
Authors: Sadeghi Talarposhti Maryam , Ahmadi-Pajouh Mohammad Ali , Towhidkhah Farzad
Published: March 2022

Studies on dual-task (DT) procedures in human behavior are important, as they can offer great insight into the cognitive control system. Accordingly, a discrete-continuous auditory-tracking DT experiment was conducted in this study with different difficulty conditions, including a continuous mouse-tracking task concurrent with a discrete auditory task (AT). Behavioral results of 25 participants were investigated via different factors, such as response time (RT), errors, and hesitations (pauses in tracking tasks). In DT, synchronization of different target neuron units was observed in corresponding brain regions; consequently, a computational model of the stimulus process was proposed to investigate the DT interference procedure during the stimulus process. This generally relates to the bottom-up attention system that a neural resource allocates for various ongoing stimuli. We proposed a black-box model based on interactions and mesoscopic behaviors of neural units. Model structure was implemented based on neurological studies and oscillator units to represent neural activities. Each unit represents one stimulus feature of task concept. Comparing the model's output behavior with the experiment results (RT) validates the model. Evaluation of the proposed model and data on RT implies that the stimulus of the AT affects the DT procedure in the model output (84% correlation). However, the continuous task is not significantly changed (26% correlation). The continuous task simulation results were inconsistent with the experiment, suggesting that continuous interference occurs in higher cognitive processing regions and is controlled by the top-down attentional system. However, this is consistent with the psychological research finding of DT interference occurring in response preparation rather than the stimulus process stage. Furthermore, we developed the proposed model by adding qualitative interpretation and saving the model's generality to address various types of discrete continuous DT procedures. The model predicts a justification method for brain rhythm interactions by synchronization, and manipulating parameters would produce different behaviors. The decrement of coupling parameter and strength factor would predict a similar pattern as in Parkinson's disease and ADHD disorder, respectively. Also, by increasing the similarity factor among the features, the model's result shows automatic task performance in each task.
Cannabis-Based Products in a Neurological Setting: A Clinical and Pharmacokinetic Survey
Authors: Mohamed Susan , Lopane Giovanna , Sabattini Loredana , Scandellari Cinzia , Zardi Diletta , Donadio Vincenzo , Rizzo Giovanni , Perrone Alessandro , Lugaresi Alessandra , Contin Manuela
Published: March 2022

Background and Aim

Limited data are available in clinical settings on the pharmacokinetics of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). We investigated the use of cannabis-based products in neurological practice, monitoring patients' steady-state cannabinoids (CBs) plasma concentrations matched with different preparations.

Methods

This was a prospective, single-center, observational study. Patients underwent venous blood withdrawal before the CBs' morning dose and then 2.5 h post-dosing. Spasticity or pain were patient self-assessed by the Numeric Rating Scale (NRS) before the morning CB's administration and 2.5 h post-dosing.

Results

Thirty-three patients were enrolled. Main indications for CBs were spasticity and chronic pain. Sixteen patients were treated with oromucosal spray formulation Sativex® and 17 with oil-based solutions. Both CBs trough plasma concentrations were ≤ limit of detection (0.1 ng/ml) in 45% of patients. Intrasubject CB's plasma levels significantly increased over baseline values in patients treated with Bediol® oil (p < 0.05) and Sativex® (p < 0.01). Post-dosing CB's bioavailability did not significantly differ between oral oil and oromucosal spray. NRS scores decreased (p < 0.01), matching the increase (p < 0.01) in CB's plasma concentrations.

Conclusion

This is the first study investigating CB's plasma concentrations of oral and oromucosal preparations in real-world neurological practice. Findings of similar bioavailability for both CBD and THC after galenic oil compared with oromucosal spray dosing may be clinically relevant and deserve additional research in larger cohorts.
Comparison of the Gait Biomechanical Constraints in Three Different Type of Neuromotor Damages
Authors: Minosse Silvia , Favetta Martina , Romano Alberto , Pisano Alessandra , Summa Susanna , Schirinzi Tommaso , Vasco Gessica , Castelli Enrico , Petrarca Maurizio
Published: March 2022

Background and Objective

Absolute angle represents the inclination of a body segment relative to a fixed reference in space. This work compares the absolute and relative angles for exploring biomechanical gait constraints.

Methods

Gait patterns of different neuromotor conditions were analyzed using 3D gait analysis: normal gait (healthy, H), Cerebral Palsy (CP), Charcot Marie Tooth (CMT) and Duchenne Muscular Dystrophy (DMD), representing central and peripheral nervous system and muscular disorders, respectively. Forty-two children underwent gait analysis: 10 children affected by CP, 10 children by CMT, 10 children by DMD and 12 healthy children. The kinematic and kinetic parameters were collected to describe the biomechanical pattern of participants’ lower limbs. The absolute angles of thigh, leg and foot were calculated using the trigonometric relationship of the tangent. For each absolute series, the mean, range, maximum, minimum and initial contact were calculated. Kinematic and kinetic gait data were studied, and the results were compared with the literature.

Results

Statistical analysis of the absolute angles showed how, at the local level, the single segments (thigh, leg and foot) behave differently depending on the pathology. However, if the lower limb is studied globally (sum of the kinematics of the three segments: thigh, leg and foot), a biomechanical constraint emerges.

Conclusion

Each segment compensates separately for the disease deficit so as to maintain a global biomechanical invariance. Using a model of inter-joint co-variation could improve the interpretation of the clinical gait pattern.
Brain Network Topology and Structural–Functional Connectivity Coupling Mediate the Association Between Gut Microbiota and Cognition
Authors: Zhang Shujun , Xu Xiaotao , Li Qian , Chen Jingyao , Liu Siyu , Zhao Wenming , Cai Huanhuan , Zhu Jiajia , Yu Yongqiang
Published: March 2022

Increasing evidence indicates that gut microbiota can influence cognition via the gut–brain axis, and brain networks play a critical role during the process. However, little is known about how brain network topology and structural–functional connectivity (SC–FC) coupling contribute to gut microbiota-related cognition. Fecal samples were collected from 157 healthy young adults, and 16S amplicon sequencing was used to assess gut diversity and enterotypes. Topological properties of brain structural and functional networks were acquired by diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (fMRI data), and SC–FC coupling was further calculated. 3-Back, digit span, and Go/No-Go tasks were employed to assess cognition. Then, we tested for potential associations between gut microbiota, complex brain networks, and cognition. The results showed that gut microbiota could affect the global and regional topological properties of structural networks as well as node properties of functional networks. It is worthy of note that causal mediation analysis further validated that gut microbial diversity and enterotypes indirectly influence cognitive performance by mediating the small-worldness (Gamma and Sigma) of structural networks and some nodal metrics of functional networks (mainly distributed in the cingulate gyri and temporal lobe). Moreover, gut microbes could affect the degree of SC–FC coupling in the inferior occipital gyrus, fusiform gyrus, and medial superior frontal gyrus, which in turn influence cognition. Our findings revealed novel insights, which are essential to provide the foundation for previously unexplored network mechanisms in understanding cognitive impairment, particularly with respect to how brain connectivity participates in the complex crosstalk between gut microbiota and cognition.
Case Report: Response to Immunotherapy and Anti-Androgen Therapy in Male Occult Triple-Negative Breast Cancer
Authors: Wang Xin-Hua , Zhang Jing , Wu Jie , He Xiao-Han , Shen Yan-Ru , Peng Yong-Gang , An Yu-Zhi
Published: March 2022

Male occult triple-negative breast cancer (TNBC) is an exceedingly rare form of breast cancer, and prospective information regarding its management is therefore lacking. Current treatment strategies are largely extrapolated from clinical trials of female breast cancer, leading to substantial knowledge gaps concerning the optimal management of male breast cancer. Here, we present a male patient with occult TNBC who responded to immunotherapy, with an obvious reduction in his tumor burden following antiandrogen therapy, after heavy treatment with several lines of chemotherapy. This case highlights the potential efficacy of immunotherapy in cases of male TNBC and suggests a role for antiandrogen therapy in managing patients with luminal androgen receptor-positive TNBC.
Impact of Virtual Imaging Technology on Film and Television Production Education of College Students Based on Deep Learning and Internet of Things
Authors: Du Chengye , Yu Chijiang , Wang Tingting , Zhang Fengrui
Published: March 2022

More and more schools begin to design simulation technology based on virtual imaging technology (VIT) and virtual reality (VR) in their course contents. In particular, among these technical courses, there is a need to first strengthen the Film and Television Production (FTP) education in higher institutions. This article aims to study the impact of VRT, VR, and Internet of things (IoT) technology on FTP courses and audience psychology in higher institutions under the era of intelligent multimedia. How to use emerging VR technology to promote the psychological wellbeing of students or patients has become a new research direction, the exploration of which has a far-reaching significance for the applications of the related technologies. First, the principle and applications of VR and IoT technology are described. Thereon, the deep learning (DL)-based training model is used to analyze the postproduction (PP) of VR-based Sand Table game, and the function and effect of the designed game model are discussed. Subsequently, VR-based Sand Play Therapy (SPT) is applied to mentally ill patients to obtain its therapeutic effect. The results show that the designed VR-based Sand Table game model can be used to treat mentally ill patients and alleviate their negative psychological states. Meanwhile, the Test Anxiety Scale (TAS) scores prove the significant therapeutic effect of the designed game model on the mental problems of patients. Therefore, VR-based psychological SPT can be applied in the stress relief of students and the treatment of mentally ill patients, as well as alleviate their mental health problems. This research provides a new direction and some theoretical support for the application field of VR technology.
Analysis of Efficacy and Safety of Modified Transfrontal Puncture Drainage in Hypertensive Basal Ganglia Hemorrhage Patients
Authors: Wang Wenxin , Lv Wei , Yang Jianquan
Published: March 2022

Objective

The study aimed to explore the efficacy and safety of modified transfrontal puncture drainage in patients with hypertensive basal ganglia hemorrhage.

Methods

The study enrolled 102 patients with hypertensive basal ganglia hemorrhage who received treatment at our hospital between April 2020 and June 2020. They were divided into a control group (51 cases, burr hole evacuation of intracranial hematoma) and a study group (51 cases, modified transfrontal puncture drainage) using the random number table method. The operative time, hematoma evacuation rate, time to recovery of consciousness, postoperative Glasgow coma scales (GOS), and the length of hospital stay were compared between the two groups. The postoperative recovery of neurological function in the two groups was observed, and activities of daily living at 3 months postoperatively in the two groups were statistically analyzed. The postoperative complications and recurrent bleeding, as well as prognosis in the two groups, were recorded.

Results

The operative time, hematoma evacuation rate, time to recovery of consciousness, postoperative GOS scores, time to extubation, and the length of hospital stay of the two groups were compared postoperatively, and the difference was statistically significant (p < 0.05). The preoperative neurological function of the two groups was compared, and the difference was statistically insignificant (P > 0.05). The postoperative neurological function of the study group was lower than that of the control group, and the difference was statistically significant (P < 0.05). The postoperative incidence of stress ulcer, renal failure, and recurrent bleeding in the two groups was compared, and the difference was statistically insignificant (p > 0.05). The rate of pulmonary infections and gastrointestinal bleeding in the study group was lower than that of the control group, and the difference was statistically significant (P < 0.05). The mortality rate of the study group was 1.96% (1/51) and that of the control group was 3.92% (2/51), and the difference was statistically insignificant (p > 0.05). The activities of daily living in the two groups were compared and the difference was statistically insignificant (p > 0.05).

Conclusion

Modified transfrontal puncture drainage can effectively treat hypertensive basal ganglia hemorrhage patients and has relatively good safety.
Naturalising Agent Causation
Authors: Potter Henry D. , Mitchell Kevin J.
Published: March 2022

The idea of agent causation—that a system such as a living organism can be a cause of things in the world—is often seen as mysterious and deemed to be at odds with the physicalist thesis that is now commonly embraced in science and philosophy. Instead, the causal power of organisms is attributed to mechanistic components within the system or derived from the causal activity at the lowest level of physical description. In either case, the ‘agent’ itself (i.e., the system as a whole) is left out of the picture entirely, and agent causation is explained away. We argue that this is not the right way to think about causation in biology or in systems more generally. We present a framework of eight criteria that we argue, collectively, describe a system that overcomes the challenges concerning agent causality in an entirely naturalistic and non-mysterious way. They are: (1) thermodynamic autonomy, (2) persistence, (3) endogenous activity, (4) holistic integration, (5) low-level indeterminacy, (6) multiple realisability, (7) historicity, (8) agent-level normativity. Each criterion is taken to be dimensional rather than categorical, and thus we conclude with a short discussion on how researchers working on quantifying agency may use this multidimensional framework to situate and guide their research.
Application of Convolutional Neural Network for Fingerprint-Based Prediction of Gender, Finger Position, and Height
Authors: Hsiao Chung-Ting , Lin Chun-Yi , Wang Po-Shan , Wu Yu-Te
Published: March 2022

Fingerprints are the most common personal identification feature and key evidence for crime scene investigators. The prediction of fingerprints features include gender, height range (tall or short), left or right hand, and finger position can effectively narrow down the list of suspects, increase the speed of comparison, and greatly improve the effectiveness of criminal investigations. In this study, we used three commonly used CNNs (VGG16, Inception-v3, and Resnet50) to perform biometric prediction on 1000 samples, and the results showed that VGG16 achieved the highest accuracy in identifying gender (79.2%), left- and right-hand fingerprints (94.4%), finger position (84.8%), and height range (69.8%, using the ring finger of male participants). In addition, we visualized the CNN classification basis by the Grad-CAM technique and compared the results with those predicted by experts and found that the CNN model outperformed experts in terms of classification accuracy and speed, and provided good reference for fingerprints that were difficult to determine manually.
Epistemic Communities under Active Inference
Authors: Albarracin Mahault , Demekas Daphne , Ramstead Maxwell J. D. , Heins Conor
Published: March 2022

The spread of ideas is a fundamental concern of today’s news ecology. Understanding the dynamics of the spread of information and its co-option by interested parties is of critical importance. Research on this topic has shown that individuals tend to cluster in echo-chambers and are driven by confirmation bias. In this paper, we leverage the active inference framework to provide an in silico model of confirmation bias and its effect on echo-chamber formation. We build a model based on active inference, where agents tend to sample information in order to justify their own view of reality, which eventually leads to them to have a high degree of certainty about their own beliefs. We show that, once agents have reached a certain level of certainty about their beliefs, it becomes very difficult to get them to change their views. This system of self-confirming beliefs is upheld and reinforced by the evolving relationship between an agent’s beliefs and observations, which over time will continue to provide evidence for their ingrained ideas about the world. The epistemic communities that are consolidated by these shared beliefs, in turn, tend to produce perceptions of reality that reinforce those shared beliefs. We provide an active inference account of this community formation mechanism. We postulate that agents are driven by the epistemic value that they obtain from sampling or observing the behaviours of other agents. Inspired by digital social networks like Twitter, we build a generative model in which agents generate observable social claims or posts (e.g., ‘tweets’) while reading the socially observable claims of other agents that lend support to one of two mutually exclusive abstract topics. Agents can choose which other agent they pay attention to at each timestep, and crucially who they attend to and what they choose to read influences their beliefs about the world. Agents also assess their local network’s perspective, influencing which kinds of posts they expect to see other agents making. The model was built and simulated using the freely available Python package pymdp. The proposed active inference model can reproduce the formation of echo-chambers over social networks, and gives us insight into the cognitive processes that lead to this phenomenon.
Numerical Study on Liquid-Return Characteristics in the Accumulator of the R290 Rotary Compressor
Authors: Lin Jie , Guo Nini , Wu Jianhua , Hong Liangkun , Jiang Jianjiang
Published: March 2022

Liquid often exists in the accumulator of the rotary compressor during the process of startup or defrost of air-conditioning systems. Too much liquid entering the compressor cylinder would result in excessive pressure caused by the liquid compression, which is a great threat to the compressor. The liquid return through the liquid-return hole is the key to ensure the stable operation of the compressor. In this paper, the liquid-return characteristics in the liquid-return holes of the accumulator, including the mass-flow rate, liquid velocity and pressure difference between the liquid-return holes, during the startup process of the R290 rotary compressor are numerically investigated. The numerical simulation using the fluent volume of fluid (VOF) method was experimentally validated with the error of 1.55%. The comparison of liquid-return characteristics using different refrigerants is conducted. Effects of refrigerant solubility in the oil, refrigerant/oil-mixture type, liquid-return-hole diameter and compressor frequency on the liquid-return characteristics and liquid shape trough the liquid-return hole are discussed. The results show that the surface tension and viscosity of the liquid are the main factors affecting the liquid-return speed. The liquid-return rate of the refrigerant R290 is slower than that of other refrigerants R22 and R410A. The liquid-return rate increases with the increase in the compressor frequency. We conclude that for air-conditioning systems using R290 as refrigerant, increasing the number of return holes or the hole diameter is necessary to improve the liquid-return characteristics of the compressor. This research will provide theoretical guidance for the optimization of liquid return of rotary compressors using new refrigerants.
Verification of the Parallel Transport Codes Parafish and AZTRAN with the TAKEDA Benchmarks
Authors: Duran-Gonzalez Julian , Sanchez-Espinoza Victor Hugo , Mercatali Luigi , Gomez-Torres Armando , Valle-Gallegos Edmundo del
Published: March 2022

With the increase in computational resources, parallel computation in neutron transport codes is inherent since it allows simulations with high spatial-angular resolution. Among the different methodologies available for the solution of the neutron transport equation, spherical harmonics (PN) and discrete-ordinates (SN) approximations have been widely used, as they are established classical methods for performing nuclear reactor calculations. This work focuses on describing and verifying two parallel deterministic neutron transport codes under development. The first one is the Parafish code that is based on the finite-element method and PN approximation. The second one is the AZTRAN code, based on the RTN-0 nodal method and SN approximation. The capabilities of these two codes have been tested on the TAKEDA benchmarks and the results obtained show good behavior and accuracy compared to the Monte Carlo reference solutions. Additionally, the speedup obtained by each code in the parallel execution is acceptable. In general, the results encourage further improvement in the codes to be comparable to other well-validated deterministic transport codes.
Guide Vane for Thermal Enhancement of a LED Heat Sink
Authors: Byun Sungjoon , Hyeon Seounghwan , Lee Kwan-Soo
Published: March 2022

A guide vane was installed on a heat sink to enhance the cooling effect of light-emitting diode (LED) lights. The validity of the numerical analysis was verified against the experimental results and the result of the previous studies. The effect of the guide vane on the heat dissipation performance of the heat sink was identified. The effect of the guide vane on the heat sink was qualitatively studied using the streamline and temperature contour. The cooling effect of the heat sink was enhanced by increased air supplement to the center-bottom part. A parametric study was conducted to determine the thermal resistance according to the guide vane angle, installation height, and vane length. Optimization was performed to minimize the thermal resistance using the Kriging model and micro-genetic algorithm (MGA). The cooling performance of the heat sink was enhanced by a maximum of 17.2% when the guide vane was installed.
Streaming Electrification of C60 Fullerene Doped Insulating Liquids for Power Transformers Applications
Authors: Zdanowski Maciej
Published: March 2022

Long-term and fault-free operation of power transformers depends on the electrical strength of the insulation system and effective heat dissipation. Forced circulation of the insulating liquid is used to increase the cooling capacity. A negative effect of such a solution is the creation of the phenomenon of streaming electrification, which in unfavorable conditions may lead to damage to the insulating system of the transformer. This paper presents results of research confirming the possibility of using fullerene C60 to reduce the phenomenon of streaming electrification generated by the flow of liquid dielectrics. The volume charge density qw was used as a material indicator to determine the electrostatic charging tendency (ECT) of nanofluids. This parameter was determined from the Abedian-Sonin electrification model on the basis of electrification current measurements and selected physicochemical and electrical properties of the liquid. The electrification current was measured in a flow system with an aluminum pipe of 4 mm diameter and 400 mm length. All measurements were carried out at a temperature of 20 °C. The influence of flow velocity (from 0.34 m/s to 1.75 m/s) and C60 concentration (25 mg/L, 50 mg/L, 100 mg/L, 200 mg/L and 350 mg/L) was analyzed on the electrification of fresh and aged Trafo En mineral oil, as well as Midel 1204 natural ester and Midel 7131 synthetic ester. The density, kinematic viscosity, dielectric constant, and conductivity were also determined. A negative effect of the C60 doping on the electrostatic properties of fresh mineral oil was demonstrated. For other liquids, fullerene C60 can be used as an inhibitor of the streaming electrification process. Based on the analysis of the qw parameter, the optimum concentration of C60 (from 100 mg/L to 200 mg/L) resulting in the highest reduction of the electrification phenomenon in nanofluids was identified.
Machine Learning Methods Modeling Carbohydrate-Enriched Cyanobacteria Biomass Production in Wastewater Treatment Systems
Authors: Rodríguez-Rángel Héctor , Arias Dulce María , Morales-Rosales Luis Alberto , Gonzalez-Huitron Victor , Valenzuela Partida Mario , García Joan
Published: March 2022

One-stage production of carbohydrate-enriched microalgae biomass in wastewater is a promising option to obtain biofuels. Understanding the interaction of water quality parameters such as nutrients, carbon, internal carbohydrates, and microbial composition in the culture is crucial for efficient operation and viable large-scale cultivation. Bioprocess models are an essential tool for studying the simultaneous effect of complex factors on carbohydrate accumulation, optimizing the process, and reducing operational costs. In this sense, we use a dataset obtained from an empirical model that analyzed the accumulation of carbohydrates in a single process (simultaneous growth and accumulation) from real wastewater. In this experiment, there were no ideal conditions (limiting nutrient conditions), but rather these limitations are guaranteed by the operating conditions (hydraulic retention times/nutrient or carbon loads). Thus, the model integrates 18 variables that are affected and not only carbohydrates. The effect of these variables directly influences the accumulation of carbohydrates. Therefore, this paper analyzes artificial intelligence (AI) algorithms to develop a model to forecast biomass production in wastewater treatment systems. Carbohydrates were modeled using five artificial intelligence methods: (1) Artificial Neural Networks (ANNs), (2) Convolutional Neural Networks (CNN), (3) Long Short-Term Memory Network (LSTMs), (4) K-Nearest Neighbors (kNN), and (5) Random Forest (RF)). The AI methods allow learning how several components interact and if their combinations work faster than building the physical experiments over the same period of time. After comparing the five learning models, the CNN-1D model obtained the best results with an MSE (Mean Squared Error) = 0.0028. This result shows that the model adequately approximates the system’s dynamics.
Assortment of Frontiers in Protein Science
Authors: Simon István , Magyar Csaba
Published: March 2022

Recent decades have brought significant changes to the protein structure research field [...]
Metazoans and Intrinsic Apoptosis: An Evolutionary Analysis of the Bcl-2 Family
Authors: Suraweera Chathura D. , Banjara Suresh , Hinds Mark G. , Kvansakul Marc
Published: March 2022

The B-cell lymphoma-2 (Bcl-2) family is a group of genes regulating intrinsic apoptosis, a process controlling events such as development, homeostasis and the innate and adaptive immune responses in metazoans. In higher organisms, Bcl-2 proteins coordinate intrinsic apoptosis through their regulation of the integrity of the mitochondrial outer membrane; this function appears to have originated in the basal metazoans. Bcl-2 genes predate the cnidarian-bilaterian split and have been identified in porifera, placozoans and cnidarians but not ctenophores and some nematodes. The Bcl-2 family is composed of two groups of proteins, one with an α-helical Bcl-2 fold that has been identified in porifera, placozoans, cnidarians, and almost all higher bilaterians. The second group of proteins, the BH3-only group, has little sequence conservation and less well-defined structures and is found in cnidarians and most bilaterians, but not porifera or placozoans. Here we examine the evolutionary relationships between Bcl-2 proteins. We show that the structures of the Bcl-2-fold proteins are highly conserved over evolutionary time. Some metazoans such as the urochordate Oikopleura dioica have lost all Bcl-2 family members. This gene loss indicates that Bcl-2 regulated apoptosis is not an absolute requirement in metazoans, a finding mirrored in recent gene deletion studies in mice. Sequence analysis suggests that at least some Bcl-2 proteins lack the ability to bind BH3-only antagonists and therefore potentially have other non-apoptotic functions. By examining the foundations of the Bcl-2 regulated apoptosis, functional relationships may be clarified that allow us to understand the role of specific Bcl-2 proteins in evolution and disease.
Biogenesis, Functions, Interactions, and Resources of Non-Coding RNAs in Plants
Authors: Chao Haoyu , Hu Yueming , Zhao Liang , Xin Saige , Ni Qingyang , Zhang Peijing , Chen Ming
Published: March 2022

Plant transcriptomes encompass a large number of functional non-coding RNAs (ncRNAs), only some of which have protein-coding capacity. Since their initial discovery, ncRNAs have been classified into two broad categories based on their biogenesis and mechanisms of action, housekeeping ncRNAs and regulatory ncRNAs. With advances in RNA sequencing technology and computational methods, bioinformatics resources continue to emerge and update rapidly, including workflow for in silico ncRNA analysis, up-to-date platforms, databases, and tools dedicated to ncRNA identification and functional annotation. In this review, we aim to describe the biogenesis, biological functions, and interactions with DNA, RNA, protein, and microorganism of five major regulatory ncRNAs (miRNA, siRNA, tsRNA, circRNA, lncRNA) in plants. Then, we systematically summarize tools for analysis and prediction of plant ncRNAs, as well as databases. Furthermore, we discuss the silico analysis process of these ncRNAs and present a protocol for step-by-step computational analysis of ncRNAs. In general, this review will help researchers better understand the world of ncRNAs at multiple levels.
7-Ketocholesterol-Induced Micro-RNA-107-5p Increases Number and Activity of Osteoclasts by Targeting MKP1
Authors: Li Guoen , Sul Ok-Joo , Yu Rina , Choi Hye-Seon
Published: March 2022

Osteoclasts (OCs), which are responsible for bone resorption, play a critical role in cholesterol-induced bone loss and recent studies have suggested that various micro-RNAs (miRs) contribute to modulating OCs. We hypothesized that 7-ketocholesterol (7-KC), a metabolite responsible for cholesterol-induced bone loss, induces miR-107-5p, which affects OCs. Overexpression and knock-down of miR-107-5p were performed using miR-107-5p mimic and anti-miR-107-5p, respectively. The effects of miR-107-5p on OCs were analyzed by tartrate-resistant alkaline phosphatase staining, qPCR, and Western blot. MiR-107-5p was upregulated after 7-KC exposure in receptor activator of nuclear factor kappa-Β ligand-stimulated OCs. Furthermore, miR-107-5p upregulation was also observed in tibiae from an atherogenic diet-fed mice compared with mice fed with a normal diet. MiR-107-5p overexpression enhanced the area and number of OCs, whereas inhibiting the endogenous expression of miR-107-5p generated by 7-KC had the opposite effect. Among the possible candidates, mitogen-activated protein kinase phosphatase-1, a stress-responsive dual-specificity phosphatase that inactivates mitogen-activated protein kinase (MKP1), has been proven to be a target gene of miR-107-5p, as demonstrated by the direct interaction between miR-107-5p and the 3′-untranslated region of MKP1. Collectively, our findings demonstrate that 7-KC-induced miR-107-5p promotes differentiation and function of OCs by downregulating MKP1.
Generative Adversarial Networks for Creating Synthetic Nucleic Acid Sequences of Cat Genome
Authors: Hazra Debapriya , Kim Mi-Ryung , Byun Yung-Cheol
Published: March 2022

Nucleic acids are the basic units of deoxyribonucleic acid (DNA) sequencing. Every organism demonstrates different DNA sequences with specific nucleotides. It reveals the genetic information carried by a particular DNA segment. Nucleic acid sequencing expresses the evolutionary changes among organisms and revolutionizes disease diagnosis in animals. This paper proposes a generative adversarial networks (GAN) model to create synthetic nucleic acid sequences of the cat genome tuned to exhibit specific desired properties. We obtained the raw sequence data from Illumina next generation sequencing. Various data preprocessing steps were performed using Cutadapt and DADA2 tools. The processed data were fed to the GAN model that was designed following the architecture of Wasserstein GAN with gradient penalty (WGAN-GP). We introduced a predictor and an evaluator in our proposed GAN model to tune the synthetic sequences to acquire certain realistic properties. The predictor was built for extracting samples with a promoter sequence, and the evaluator was built for filtering samples that scored high for motif-matching. The filtered samples were then passed to the discriminator. We evaluated our model based on multiple metrics and demonstrated outputs for latent interpolation, latent complementation, and motif-matching. Evaluation results showed our proposed GAN model achieved 93.7% correlation with the original data and produced significant outcomes as compared to existing models for sequence generation.
Small-Molecule RAS Inhibitors as Anticancer Agents: Discovery, Development, and Mechanistic Studies
Authors: Shetu Shaila A. , Bandyopadhyay Debasish
Published: March 2022

Mutations of RAS oncogenes are responsible for about 30% of all human cancer types, including pancreatic, lung, and colorectal cancers. While KRAS1 is a pseudogene, mutation of KRAS2 (commonly known as KRAS oncogene) is directly or indirectly associated with human cancers. Among the RAS family, KRAS is the most abundant oncogene related to uncontrolled cellular proliferation to generate solid tumors in many types of cancer such as pancreatic carcinoma (over 80%), colon carcinoma (40–50%), lung carcinoma (30–50%), and other types of cancer. Once described as ‘undruggable’, RAS proteins have become ‘druggable’, at least to a certain extent, due to the continuous efforts made during the past four decades. In this account, we discuss the chemistry and biology (wherever available) of the small-molecule inhibitors (synthetic, semi-synthetic, and natural) of KRAS proteins that were published in the past decades. Commercial drugs, as well as investigational molecules from preliminary stages to clinical trials, are categorized and discussed in this study. In summary, this study presents an in-depth discussion of RAS proteins, classifies the RAS superfamily, and describes the molecular mechanism of small-molecule RAS inhibitors
In Vitro and In Vivo Effects of the Urokinase Plasminogen Activator Inhibitor WX-340 on Anaplastic Thyroid Cancer Cell Lines
Authors: Baldini Enke , Presutti Dario , Favoriti Pasqualino , Santini Simonetta , Papoff Giuliana , Tuccilli Chiara , Carletti Raffaella , Di Gioia Cira , Lori Eleonora , Ferent Iulia Catalina , Gagliardi Federica , Catania Antonio , Pironi Daniele , Tripodi Domenico , D’Andrea Vito , Sorrenti Salvatore , Ruberti Giovina , Ulisse Salvatore
Published: March 2022

Increased expression of the urokinase-type plasminogen activator (uPA) system is associated with tumor invasion, neo-angiogenesis, and metastatic spread, and has been shown to positively correlate with a poor prognosis in several cancer types, including thyroid carcinomas. In recent years, several uPA inhibitors were found to have anticancer effects in preclinical studies and in some phase II clinical trials, which prompted us to evaluate uPA as a potential therapeutic target for the treatment of patients affected by the most aggressive form of thyroid cancer, the anaplastic thyroid carcinoma (ATC). In this study, we evaluated the in vitro and in vivo effects of WX-340, a highly specific and selective uPA inhibitor, on two ATC-derived cell lines, CAL-62 and BHT-101. The results obtained indicated that WX-340 was able to reduce cell adhesion and invasiveness in a dose-dependent manner in both cell lines. In addition, WX-340 increased uPA receptor (uPAR) protein levels without affecting its plasma membrane concentration. However, this compound was unable to significantly reduce ATC growth in a xenograft model, indicating that uPA inhibition alone may not have the expected therapeutic effects.
SOAT1: A Suitable Target for Therapy in High-Grade Astrocytic Glioma?
Authors: Löhr Mario , Härtig Wolfgang , Schulze Almut , Kroiß Matthias , Sbiera Silviu , Lapa Constantin , Mages Bianca , Strobel Sabrina , Hundt Jennifer Elisabeth , Bohnert Simone , Kircher Stefan , Janaki-Raman Sudha , Monoranu Camelia-Maria
Published: March 2022

Targeting molecular alterations as an effective treatment for isocitrate dehydrogenase-wildtype glioblastoma (GBM) patients has not yet been established. Sterol-O-Acyl Transferase 1 (SOAT1), a key enzyme in the conversion of endoplasmic reticulum cholesterol to esters for storage in lipid droplets (LD), serves as a target for the orphan drug mitotane to treat adrenocortical carcinoma. Inhibition of SOAT1 also suppresses GBM growth. Here, we refined SOAT1-expression in GBM and IDH-mutant astrocytoma, CNS WHO grade 4 (HGA), and assessed the distribution of LD in these tumors. Twenty-seven GBM and three HGA specimens were evaluated by multiple GFAP, Iba1, IDH1 R132H, and SOAT1 immunofluorescence labeling as well as Oil Red O staining. To a small extent SOAT1 was expressed by tumor cells in both tumor entities. In contrast, strong expression was observed in glioma-associated macrophages. Triple immunofluorescence labeling revealed, for the first time, evidence for SOAT1 colocalization with Iba1 and IDH1 R132H, respectively. Furthermore, a notable difference in the amount of LD between GBM and HGA was observed. Therefore, SOAT1 suppression might be a therapeutic option to target GBM and HGA growth and invasiveness. In addition, the high expression in cells related to neuroinflammation could be beneficial for a concomitant suppression of protumoral microglia/macrophages.
Sirt3 Pharmacologically Promotes Insulin Sensitivity through PI3/AKT/mTOR and Their Downstream Pathway in Adipocytes
Authors: Lee Alexandra Yatine , Christensen Sabrina Marie , Duong Nhi , Tran Quoc-Anh , Xiong Hou Mai , Huang Jennifer , James Sarah , Vallabh Dimple , Talbott George , Rose Melanie , Ho Linh
Published: March 2022

Sirtuin-3 (Sirt3) is a major mitochondrial deacetylase enzyme that regulates multiple metabolic pathways, and its expression is decreased in diabetes type 1 and type 2 diabetes. This study aimed to elucidate Sirt3′s molecular mechanism in regulating insulin sensitivity in adipocytes that can contribute to the effort of targeting Sirt3 for the treatment of obesity and type 2 diabetes. We found that the Sirt3 activator honokiol (HNK) induced adipogenesis compared to the control, in contrast to Sirt3 inhibitor, 3-TYP. Accordingly, HNK increased expression of adipocyte gene markers, gene-involved lipolysis and glucose transport (GLUT4), while 3-TYP reduced expression of those genes. Interestingly, 3-TYP caused an increase in gene expression of adipocyte-specific cytokines including IL6, resistin, and TNF-α. However, changes in adipocyte-specific cytokines in HNK treated cells were not significant. In addition, HNK stimulated insulin pathway by promoting insulin receptor beta (IRβ) and PI3K/AKT/mTOR pathways, resulting in an increase in phosphorylation of the forkhead family FoxO1/FoxO3a/FoxO4 and glycogen synthase kinase-3 (GSK-3β), opposing 3-TYP. In line with these findings, HNK increased free fatty acid and glucose uptake, contrary to 3-TYP. In conclusion, Sirt3 activator-HNK induced adipogenesis and lipolysis reduced adipocytes specific cytokines. Intriguingly, HNK activated insulin signaling pathway and increased free fatty acid as well as glucose uptake and transport, in sharp contrast to 3-TYP. These results indicate that, via insulin signaling regulation, Sirt3 activation by HNK improves insulin resistance, while Sirt3 inhibition by 3-TYP might precipitate insulin resistance.
Innate Lymphoid Cells: Emerging Players in Pancreatic Disease
Authors: Shi Saimeng , Ye Longyun , Jin Kaizhou , Xiao Zhiwen , Yu Xianjun , Wu Weiding
Published: March 2022

Common pancreatic diseases have caused significant economic and social burdens worldwide. The interstitial microenvironment is involved in and plays a crucial part in the occurrence and progression of pancreatic diseases. Innate lymphoid cells (ILCs), an innate population of immune cells which have only gradually entered our visual field in the last 10 years, play an important role in maintaining tissue homeostasis, regulating metabolism, and participating in regeneration and repair. Recent evidence indicates that ILCs in the pancreas, as well as in other tissues, are also key players in pancreatic disease and health. Herein, we examined the possible functions of different ILC subsets in common pancreatic diseases, including diabetes mellitus, pancreatitis and pancreatic cancer, and discussed the potential practical implications of the relevant findings for future further treatment of these pancreatic diseases.
BRCA1/2 Serves as a Biomarker for Poor Prognosis in Breast Carcinoma
Authors: Jin Tong Yi , Park Kyoung Sik , Nam Sang Eun , Yoo Young Bum , Park Won Seo , Yun Ik Jin
Published: March 2022

BRCA1/2 are breast cancer susceptibility genes that are involved in DNA repair and transcriptional control. They are dysregulated in breast cancer, making them attractive therapeutic targets. Here, we performed a systematic multiomics analysis to expound BRCA1/2 functions as prognostic biomarkers in breast cancer. First, using different web-based bioinformatics platforms (Oncomine, TIMER 2.0, UALCAN, and cBioportal), the expression of BRCA1/2 was assessed. Then, the R package was used to analyze the diagnostic value of BRCA1/2 in patients. Next, we determined the relationship between BRCA1/2 mRNA expression and prognosis in patients (PrognoScan Database, R2: Kaplan Meier Scanner and Kaplan–Meier Plotter). Subsequently, the association of BRCA1/2 with mutation frequency alteration and copy number alterations in breast cancer was investigated using the cBioportal platform. After that, we identified known and predicted structural genes and proteins essential for BRCA1/2 functions using GeneMania and STRING db. Finally, GO and KEGG pathway enrichment analyses were performed to elucidate the potential biological functions of the co-expression genes of BRCA1/2. The BRCA1/2 mRNA level in breast cancer tissues was considerably higher than in normal tissues, with AUCs of 0.766 and 0.829, respectively. Overexpression of BRCA1/2 was significantly related to the worse overall survival (p < 0.001) and was correlated to clinicopathological characteristics including lymph nodes, estrogen receptors, and progesterone receptors (p < 0.01). The alteration frequencies of both the gens have been checked, and the results show that BRCA1 and BRCA2 show different alteration frequencies. Their mutation sites differ from each other. GO and KEGG showed that BRCA1/2 was mainly enriched in catalytic activity, acting on DNA, chromosomal region, organelle fission, cell cycle, etc. The 20 most frequently changed genes were closely related to BRCA1/2, including PALB2 and RAD51 relatively. Our study provides suggestive evidence of the prognostic role of BRCA1/2 in breast cancer and the therapeutic target for breast cancer. Furthermore, BRCA1/2 may influence BRCA prognosis through catalytic activity, acting on DNA, chromosomal regions, organelle fission, and the cell cycle. Nevertheless, further validation is warranted.
Multi-Omics Techniques for Analysis Antifungal Mechanisms of Lipopeptides Produced by Bacillus velezensis GS-1 against Magnaporthe oryzae In Vitro
Authors: Zhang Yanhua , Zhao Meixi , Chen Wei , Yu Huilin , Jia Wantong , Pan Hongyu , Zhang Xianghui
Published: March 2022

Magnaporthe oryzae is a fungal pathogen that causes rice blast, a highly destructive disease. In the present study, the bacteria strain GS-1 was isolated from the rhizosphere soil of ginseng and identified as Bacillus velezensis through 16S rRNA gene sequencing, whole genome assembly, and average nucleotide identity analysis. B. velezensis strain GS-1 exhibited significant antagonistic activity to several plant fungal pathogens. Through whole genome sequencing, 92 Carbohydrate-Active Enzymes and 13 gene clusters that encoded for secondary metabolites were identified. In addition, strain GS-1 was able to produce the lipopeptide compounds, surfactin, fengycin, and plantazolicin. The inhibitory effects of lipopeptide compounds on M. oryzae were confirmed, and the antagonistic mechanism was explored using transcriptomics and metabolomics analysis. Differential expressed genes (DEGs) and differential accumulated metabolites (DAMs) revealed that the inhibition of M. oryzae by lipopeptide produced by GS-1 downregulated the expression of genes involved in amino acid metabolism, sugar metabolism, oxidative phosphorylation, and autophagy. These results may explain why GS-1 has antagonistic activity to fungal pathogens and revealed the mechanisms underlying the inhibitory effects of lipopeptides produced by GS-1 on fungal growth, which may provide a theoretical basis for the potential application of B. velezensis GS-1 in future plant protection.