Signal alignment for cross-datasets in P300 brain-computer interfaces.

OBJECTIVE: Transfer learning has become an important issue in the brain-computer interface (BCI) field, and studies on subject-to-subject transfer within the same dataset have been performed. However, few studies have been performed on dataset-to-dataset transfer, including paradigm-to-paradigm transfer. In this study, we propose a signal alignment for P300 event-related potential (ERP) signals that is intuitive, simple, computationally less expensive, and can be used for cross-dataset transfer learning. Approach. We proposed a linear signal alignment that uses the P300's latency, amplitude scale, and reverse factor to transform signals. For evaluation, four datasets were introduced (two from conventional P300 Speller BCIs, one from a P300 Speller with face stimuli, and the last from a standard auditory oddball paradigm). Results. Although the standard approach without signal alignment had an average precision score of 25.5%, the approach demonstrated a 35.8% average precision score, and we observed that the number of subjects showing improvement was 36.0% on average. Particularly, we confirmed that the Speller dataset with face stimuli was more comparable with other datasets. Significance. We proposed a simple and intuitive way to align ERP signals that uses the characteristics of ERP signals. The results demonstrated the feasibility of cross-dataset transfer learning even between datasets with different paradigms.

An updated review on animal models to study attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is a neuropsychiatric disorder affecting both children and adolescents. Individuals with ADHD experience heterogeneous problems, such as difficulty in attention, behavioral hyperactivity, and impulsivity. Recent studies have shown that complex genetic factors play a role in attention-deficit hyperactivity disorders. Animal models with clear hereditary traits are crucial for studying the molecular, biological, and brain circuit mechanisms underlying ADHD. Owing to their well-managed genetic origins and the relative simplicity with which the function of neuronal circuits is clearly established, models of mice can help learn the mechanisms involved in ADHD. Therefore, in this review, we highlighting the important genetic animal models that can be used to study ADHD.

Effects of a Diabetic Microenvironment on Neurodegeneration: Special Focus on Neurological Cells.

Diabetes is a chronic metabolic condition associated with high levels of blood glucose which leads to serious damage to the heart, kidney, eyes, and nerves. Elevated blood glucose levels damage brain function and cognitive abilities. They also lead to various neurological and neuropsychiatric disorders, including chronic neurodegeneration and cognitive decline. High neuronal glucose levels can cause drastic neuronal damage due to glucose neurotoxicity. Astrocytes, a type of glial cell, play a vital role in maintaining brain glucose levels through neuron-astrocyte coupling. Hyperglycemia leads to progressive decline in neuronal networks and cognitive impairment, contributing to neuronal dysfunction and fostering a neurodegenerative environment. In this review, we summarize the various connections, functions, and impairments of glial cells due to metabolic dysfunction in the diabetic brain. We also summarize the effects of hyperglycemia on various neuronal functions in the diabetic brain.

Investigating Bacopa monnieri L. Therapeutic Potential for the Treatment of Neurological Diseases.

The popular perennial creeping plant known as Bacopa monnieri (also known as Brahmi) is being utilized in the Indian Ayurvedic medicine practice. It has a variety of bioactive phytoconstituents that have been used therapeutically to treat a number of serious illnesses. Ancient Vedic scholars used this herb because of its pharmacological effects, particularly as a nerve booster and nootropic supporter. However, it is vital to comprehend the active phytochemical components of Bacopa monnieri extract (BME) and their molecular mechanisms in order to better grasp the effect of BME on neurological illnesses and diseases. Understanding its active phytochemical constituents and their molecular processes is essential. Numerous clinical investigations indicated that BME may have neuroprotective benefits, so it is worthwhile to re-evaluate this wellknown plant. Here, we focused on neurological problems as we examined the pharmacological and phytochemical characteristics of BME. For their effective usage in neuroprotection and cognition, many clinical concerns and the synergistic potential of Bacopa extract have been investigated. Alzheimer's disease is a neurological condition caused by the production of reactive oxygen species, which also causes amyloid-beta (A) and tau protein aggregation and increases neuro-inflammation and neurotoxicity. Our review offers a more indepth molecular understanding of the neuroprotective functions of BME, which can also be connected to its therapeutic management of neurological illnesses and cognitive-improving effects.

Mature microRNA-binding protein QKI promotes microRNA-mediated gene silencing.

Although Argonaute (AGO) proteins have been the focus of microRNA (miRNA) studies, we observed AGO-free mature miRNAs directly interacting with RNA-binding proteins, implying the sophisticated nature of fine-tuning gene regulation by miRNAs. To investigate microRNA-binding proteins (miRBPs) globally, we analyzed PAR-CLIP data sets to identify RBP quaking (QKI) as a novel miRBP for let-7b. Potential existence of AGO-free miRNAs were further verified by measuring miRNA levels in genetically engineered AGO-depleted human and mouse cells. We have shown that QKI regulates miRNA-mediated gene silencing at multiple steps, and collectively serves as an auxiliary factor empowering AGO2/let-7b-mediated gene silencing. Depletion of QKI decreases interaction of AGO2 with let-7b and target mRNA, consequently controlling target mRNA decay. This finding indicates that QKI is a complementary factor in miRNA-mediated mRNA decay. QKI, however, also suppresses the dissociation of let-7b from AGO2, and slows the assembly of AGO2/miRNA/target mRNA complexes at the single-molecule level. We also revealed that QKI overexpression suppresses cMYC expression at post-transcriptional level, and decreases proliferation and migration of HeLa cells, demonstrating that QKI is a tumour suppressor gene by in part augmenting let-7b activity. Our data show that QKI is a new type of RBP implicated in the versatile regulation of miRNA-mediated gene silencing.

Synaptic plasticity via receptor tyrosine kinase/G-protein-coupled receptor crosstalk.

Cellular signaling involves a large repertoire of membrane receptors operating in overlapping spatiotemporal regimes and targeting many common intracellular effectors. However, both the molecular mechanisms and the physiological roles of crosstalk between receptors, especially those from different superfamilies, are poorly understood. We find that the receptor tyrosine kinase (RTK) TrkB and the G-protein-coupled receptor (GPCR) metabotropic glutamate receptor 5 (mGluR5) together mediate hippocampal synaptic plasticity in response to brain-derived neurotrophic factor (BDNF). Activated TrkB enhances constitutive mGluR5 activity to initiate a mode switch that drives BDNF-dependent sustained, oscillatory Ca2+ signaling and enhanced MAP kinase activation. This crosstalk is mediated, in part, by synergy between Gßγ, released by TrkB, and Gαq-GTP, released by mGluR5, to enable physiologically relevant RTK/GPCR crosstalk.

Epidemiology, Molecular Pathogenesis, Immuno-Pathogenesis, Immune Escape Mechanisms and Vaccine Evaluation for HPV-Associated Carcinogenesis.

Human papillomavirus (HPV) is implicated in over 90% of cervical cancer cases, with factors like regional variability, HPV genotype, the population studied, HPV vaccination status, and anatomical sample collection location influencing the prevalence and pathology of HPV-induced cancer. HPV-16 and -18 are mainly responsible for the progression of several cancers, including cervix, anus, vagina, penis, vulva, and oropharynx. The oncogenic ability of HPV is not only sufficient for the progression of malignancy, but also for other tumor-generating steps required for the production of invasive cancer, such as coinfection with other viruses, lifestyle factors such as high parity, smoking, tobacco chewing, use of contraceptives for a long time, and immune responses such as stimulation of chronic stromal inflammation and immune deviation in the tumor microenvironment. Viral evasion from immunosurveillance also supports viral persistence, and virus-like particle-based prophylactic vaccines have been licensed, which are effective against high-risk HPV types. In addition, vaccination awareness programs and preventive strategies could help reduce the rate and incidence of HPV infection. In this review, we emphasize HPV infection and its role in cancer progression, molecular and immunopathogenesis, host immune response, immune evasion by HPV, vaccination, and preventive schemes battling HPV infection and HPV-related cancers.

Insight into Early Diagnosis of Multiple Sclerosis by Targeting Prognostic Biomarkers.

Multiple sclerosis (MS) is a central nervous system (CNS) immune-mediated disease that mainly strikes young adults and leaves them disabled. MS is an autoimmune illness that causes the immune system to attack the brain and spinal cord. The myelin sheaths, which insulate the nerve fibers, are harmed by our own immune cells, and this interferes with brain signal transmission. Numbness, tingling, mood swings, memory problems, exhaustion, agony, vision problems, and/or paralysis are just a few of the symptoms. Despite technological advancements and significant research efforts in recent years, diagnosing MS can still be difficult. Each patient's MS is distinct due to a heterogeneous and complex pathophysiology with diverse types of disease courses. There is a pressing need to identify markers that will allow for more rapid and accurate diagnosis and prognosis assessments to choose the best course of treatment for each MS patient. The cerebrospinal fluid (CSF) is an excellent source of particular indicators associated with MS pathology. CSF contains molecules that represent pathological processes such as inflammation, cellular damage, and loss of blood-brain barrier integrity. Oligoclonal bands, neurofilaments, MS-specific miRNA, lncRNA, IgG-index, and anti-aquaporin 4 antibodies are all clinically utilised indicators for CSF in MS diagnosis. In recent years, a slew of new possible biomarkers have been presented. In this review, we look at what we know about CSF molecular markers and how they can aid in the diagnosis and differentiation of different MS forms and treatment options, and monitoring and predicting disease progression, therapy response, and consequences during such opportunistic infections.

A Review on the Use of Gold Nanoparticles in Cancer Treatment.

According to a 2020 WHO study, cancer is responsible for one in every six fatalities. One in four patients die due to side effects and intolerance to chemotherapy, making it a leading cause of patient death. Compared to traditional tumor therapy, emerging treatment methods, including immunotherapy, gene therapy, photothermal therapy, and photodynamic therapy, have proven to be more effective. The aim of this review is to highlight the role of gold nanoparticles in advanced cancer treatment. A systematic and extensive literature review was conducted using the Web of Science, PubMed, EMBASE, Google Scholar, NCBI, and various websites. Highly relevant literature from 141 references was chosen for inclusion in this review. Recently, the synergistic benefits of nano therapy and cancer immunotherapy have been shown, which could allow earlier diagnosis, more focused cancer treatment, and improved disease control. Compared to other nanoparticles, the physical and optical characteristics of gold nanoparticles appear to have significantly greater effects on the target. It has a crucial role in acting as a drug carrier, biomarker, anti-angiogenesis agent, diagnostic agent, radiosensitizer, cancer immunotherapy, photodynamic therapy, and photothermal therapy. Gold nanoparticle-based cancer treatments can greatly reduce current drug and chemotherapy dosages.

Synaptic plasticity via receptor tyrosine kinase/G protein-coupled receptor crosstalk.

Cellular signaling involves a large repertoire of membrane receptors operating in overlapping spatiotemporal regimes and targeting many common intracellular effectors. However, both the molecular mechanisms and physiological roles of crosstalk between receptors, especially those from different superfamilies, are poorly understood. We find that the receptor tyrosine kinase (RTK), TrkB, and the G protein-coupled receptor (GPCR), metabotropic glutamate receptor 5 (mGluR5), together mediate a novel form of hippocampal synaptic plasticity in response to brain-derived neurotrophic factor (BDNF). Activated TrkB enhances constitutive mGluR5 activity to initiate a mode-switch that drives BDNF-dependent sustained, oscillatory Ca 2+ signaling and enhanced MAP kinase activation. This crosstalk is mediated, in part, by synergy between Gßγ, released by TrkB, and Gα q -GTP, released by mGluR5, to enable a previously unidentified form of physiologically relevant RTK/GPCR crosstalk.

Advancements in the Application of Nanomedicine in Alzheimer's Disease: A Therapeutic Perspective.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that affects most people worldwide. AD is a complex central nervous system disorder. Several drugs have been designed to cure AD, but with low success rates. Because the blood-brain and blood-cerebrospinal fluid barriers are two barriers that protect the central nervous system, their presence has severely restricted the efficacy of many treatments that have been studied for AD diagnosis and/or therapy. The use of nanoparticles for the diagnosis and treatment of AD is the focus of an established and rapidly developing field of nanomedicine. Recent developments in nanomedicine have made it possible to effectively transport drugs to the brain. However, numerous obstacles remain to the successful use of nanomedicines in clinical settings for AD treatment. Furthermore, given the rapid advancement in nanomedicine therapeutics, better outcomes for patients with AD can be anticipated. This article provides an overview of recent developments in nanomedicine using different types of nanoparticles for the management and treatment of AD.

Corrigendum: Review of public motor imagery and execution datasets in brain-computer interfaces.

[This corrects the article DOI: 10.3389/fnhum.2023.1134869.].

City 5.0: Citizen involvement in the design of future cities.

A citizen-centric view is key to channeling technological affordances into the development of future cities in which improvements are made with the quality of citizens' life in mind. This paper proposes City 5.0 as a new citizen-centric design paradigm for future cities, in which cities can be seen as markets connecting service providers with citizens as consumers. City 5.0 is dedicated to eliminating restrictions that citizens face when utilizing city services. Our design paradigm focuses on smart consumption and extends the technology-centric concept of smart city with a stronger view on citizens' roadblocks to service usage. Through a series of design workshops, we conceptualized the City 5.0 paradigm and formalized it in a semi-formal model. The applicability of the model is demonstrated using the case of a telemedical service offered by a Spanish public healthcare service provider. The usefulness of the model is validated by qualitative interviews with public organizations involved in the development of technology-based city solutions. Our contribution lies in the advancement of citizen-centric analysis and the development of city solutions for both academic and professional communities.

Mercaptoamine-assisted Post-encapsulation of Metal Nanoparticles within Preformed Zeolites and their Analogues for Hydroisomerization and Methane Decomposition.

We report a general synthetic strategy for post-encapsulation of metal nanoparticles within preformed zeolites using post-synthetic modification. Both anionic and cationic precursors to metal nanoparticle are supported on 8- and 10-membered ring zeolites and analogues during wet impregnation using 2-aminoethanethiol (AET) as a bi-grafting agent. Thiol groups are coordinated to metal centers, whereas amine moieties are dynamically attached to micropore walls via acid-base interactions. The dynamic acid-base interactions cause the even distribution of the metal-AET complex throughout the zeolite matrix. These processes encapsulate Au, Rh, and Ni precursors within the CHA, *MRE, MFI zeolite, and SAPO-34 zeolite analogues, for which small channel apertures preclude the post-synthesis impregnation of metal precursors. Sequential activation forms small and uniform nanoparticles (1-2.5 nm in diameter), as confirmed through electron microscopy and X-ray absorption spectroscopy. Containment within the small micropores protected the nanoparticles against harsh thermal sintering conditions and prevented the fouling of the metal surface by coke, thus resulting in a high catalytic performance in n-dodecane hydroisomerization and methane decomposition. The remarkable specificity of the thiol to metal precursors and the dynamic acid-base interaction make these protocols extendable to various metal-zeolite systems, suitable for shape-selective catalysts in challenging chemical environments.

Review of public motor imagery and execution datasets in brain-computer interfaces.

The demand for public datasets has increased as data-driven methodologies have been introduced in the field of brain-computer interfaces (BCIs). Indeed, many BCI datasets are available in various platforms or repositories on the web, and the studies that have employed these datasets appear to be increasing. Motor imagery is one of the significant control paradigms in the BCI field, and many datasets related to motor tasks are open to the public already. However, to the best of our knowledge, these studies have yet to investigate and evaluate the datasets, although data quality is essential for reliable results and the design of subject- or system-independent BCIs. In this study, we conducted a thorough investigation of motor imagery/execution EEG datasets recorded from healthy participants published over the past 13 years. The 25 datasets were collected from six repositories and subjected to a meta-analysis. In particular, we reviewed the specifications of the recording settings and experimental design, and evaluated the data quality measured by classification accuracy from standard algorithms such as Common Spatial Pattern (CSP) and Linear Discriminant Analysis (LDA) for comparison and compatibility across the datasets. As a result, we found that various stimulation types, such as text, figure, or arrow, were used to instruct subjects what to imagine and the length of each trial also differed, ranging from 2.5 to 29 s with a mean of 9.8 s. Typically, each trial consisted of multiple sections: pre-rest (2.38 s), imagination ready (1.64 s), imagination (4.26 s, ranging from 1 to 10 s), the post-rest (3.38 s). In a meta-analysis of the total of 861 sessions from all datasets, the mean classification accuracy of the two-class (left-hand vs. right-hand motor imagery) problem was 66.53%, and the population of the BCI poor performers, those who are unable to reach proficiency in using a BCI system, was 36.27% according to the estimated accuracy distribution. Further, we analyzed the CSP features and found that each dataset forms a cluster, and some datasets overlap in the feature space, indicating a greater similarity among them. Finally, we checked the minimal essential information (continuous signals, event type/latency, and channel information) that should be included in the datasets for convenient use, and found that only 71% of the datasets met those criteria. Our attempts to evaluate and compare the public datasets are timely, and these results will contribute to understanding the dataset's quality and recording settings as well as the use of using public datasets for future work on BCIs.

Phytochemicals: A Promising Alternative for the Prevention of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurological condition that worsens with ageing and affects memory and cognitive function. Presently more than 55 million individuals are affected by AD all over the world, and it is a leading cause of death in old age. The main purpose of this paper is to review the phytochemical constituents of different plants that are used for the treatment of AD. A thorough and organized review of the existing literature was conducted, and the data under the different sections were found using a computerized bibliographic search through the use of databases such as PubMed, Web of Science, Google Scholar, Scopus, CAB Abstracts, MEDLINE, EMBASE, INMEDPLAN, NATTS, and numerous other websites. Around 360 papers were screened, and, out of that, 258 papers were selected on the basis of keywords and relevant information that needed to be included in this review. A total of 55 plants belonging to different families have been reported to possess different bioactive compounds (galantamine, curcumin, silymarin, and many more) that play a significant role in the treatment of AD. These plants possess anti-inflammatory, antioxidant, anticholinesterase, and anti-amyloid properties and are safe for consumption. This paper focuses on the taxonomic details of the plants, the mode of action of their phytochemicals, their safety, future prospects, limitations, and sustainability criteria for the effective treatment of AD.

Exploring the potential of OMOP common data model for process mining in healthcare.

BACKGROUND AND OBJECTIVE: Recently, Electronic Health Records (EHR) are increasingly being converted to Common Data Models (CDMs), a database schema designed to provide standardized vocabularies to facilitate collaborative observational research. To date, however, rare attempts exist to leverage CDM data for healthcare process mining, a technique to derive process-related knowledge (e.g., process model) from event logs. This paper presents a method to extract, construct, and analyze event logs from the Observational Medical Outcomes Partnership (OMOP) CDM for process mining and demonstrates CDM-based healthcare process mining with several real-life study cases while answering frequently posed questions in process mining, in the CDM environment. METHODS: We propose a method to extract, construct, and analyze event logs from the OMOP CDM for process types including inpatient, outpatient, emergency room processes, and patient journey. Using the proposed method, we extract the retrospective data of several surgical procedure cases (i.e., Total Laparoscopic Hysterectomy (TLH), Total Hip Replacement (THR), Coronary Bypass (CB), Transcatheter Aortic Valve Implantation (TAVI), Pancreaticoduodenectomy (PD)) from the CDM of a Korean tertiary hospital. Patient data are extracted for each of the operations and analyzed using several process mining techniques. RESULTS: Using process mining, the clinical pathways, outpatient process models, emergency room process models, and patient journeys are demonstrated using the extracted logs. The result shows CDM's usability as a novel and valuable data source for healthcare process analysis, yet with a few considerations. We found that CDM should be complemented by different internal and external data sources to address the administrative and operational aspects of healthcare processes, particularly for outpatient and ER process analyses. CONCLUSION: To the best of our knowledge, we are the first to exploit CDM for healthcare process mining. Specifically, we provide a step-by-step guidance by demonstrating process analysis from locating relevant CDM tables to visualizing results using process mining tools. The proposed method can be widely applicable across different institutions. This work can contribute to bringing a process mining perspective to the existing CDM users in the changing Hospital Information Systems (HIS) environment and also to facilitating CDM-based studies in the process mining research community.

Stress Granules in Cancer.

The capacity of cells to organize complex biochemical reactions in intracellular space is a fundamental organizational principle of life. Key to this organization is the compartmentalization of the cytoplasm into distinct organelles, which is frequently achieved through intracellular membranes. Recent evidence, however, has added a new layer of flexibility to cellular compartmentalization. As such, in response to specific stimuli, liquid-liquid phase separations can lead to the rapid rearrangements of the cytoplasm to form membraneless organelles. Stress granules (SGs) are one such type of organelle that form specifically when cells are faced with stress stimuli, to aid cells in coping with stress. Inherently, altered SG formation has been linked to the pathogenesis of diseases associated with stress and inflammatory conditions, including cancer. Exciting discoveries have indicated an intimate link between SGs and tumorigenesis. Several pro-tumorigenic signaling molecules including the RAS oncogene, mTOR, and histone deacetylase 6 (HDAC6) have been shown to upregulate SG formation. Based on these studies, SGs have emerged as structures that can integrate oncogenic signaling and tumor-associated stress stimuli to enhance cancer cell fitness. In addition, growing evidence over the past decade suggests that SGs function not only to regulate the switch between survival and cell death, but also contribute to cancer cell proliferation, invasion, metastasis, and drug resistance. Although much remains to be learned about the role of SGs in tumorigenesis, these studies highlight SGs as a key regulatory hub in cancer and a promising therapeutic target.

A Review on the Protective Effects of Probiotics against Alzheimer's Disease.

This review summarizes the protective effects of probiotics against Alzheimer's disease (AD), one of the most common neurodegenerative disorders affecting older adults. This disease is characterized by the deposition of tau and amyloid ß peptide (Aß) in different parts of the brain. Symptoms observed in patients with AD include struggles with writing, speech, memory, and knowledge. The gut microbiota reportedly plays an important role in brain functioning due to its bidirectional communication with the gut via the gut-brain axis. The emotional and cognitive centers in the brain are linked to the functions of the peripheral intestinal system via this gut-brain axis. Dysbiosis has been linked to neurodegenerative disorders, indicating the significance of gut homeostasis for proper brain function. Probiotics play an important role in protecting against the symptoms of AD as they restore gut-brain homeostasis to a great extent. This review summarizes the characteristics, status of gut-brain axis, and significance of gut microbiota in AD. Review and research articles related to the role of probiotics in the treatment of AD were searched in the PubMed database. Recent studies conducted using animal models were given preference. Recent clinical trials were searched for separately. Several studies conducted on animal and human models clearly explain the benefits of probiotics in improving cognition and memory in experimental subjects. Based on these studies, novel therapeutic approaches can be designed for the treatment of patients with AD.

Therapeutic Applications of Fucoidans and their Potential to Act Against COVID-19.

In this review article, we present the updated evidence of therapeutic applications of fucoidan (a seaweed polysaccharide) and its novel potential to treat infectious diseases such as coronavirus disease (COVID-19). Because of their many biological activities, seaweeds have been identified as a rich and useful source of bioactive chemicals. Sulfated polysaccharides from the sea are considered a source of physiologically active chemicals that might be used in medication development. Antitumor, antiviral, antioxidant, antibacterial, anticoagulant, and immune-inflammatory properties have all been described for these compounds. By interfering at various phases of viral infection, marine sulfated polysaccharide has a virucidal effect. As a result, it opens the door to the development of antiviral treatments. Virus entry into host cells is an initial process, avoiding this type of entry makes any precautionary measure effective. The inhibitory action of certain marine sulfated polysaccharides against coronavirus was tested, and fucoidan, iota-carrageenan, and sea cucumber sulfated polysaccharides all showed a substantial antiviral impact. Fucoidan is one of the useful sulfated polysaccharides that has been widely studied and explored in various research. There are different sources of fucoidans, which have been used in the treatment of viral infection. Additionally, we highlight the mechanism of action of fuocidan against COVID-19. Hence, we could suggest that COVID-19 might be prevented and treated using these sulfated polysaccharides. This review thus highlights ample evidence to support the hypothesis that a large number of drugs have been developed from powerful compounds isolated from marine seaweeds.