Mapping the global research landscape and trends of autoimmune encephalitis: A bibliometric analysis.

Background: Autoimmune encephalitis (AE) is a neuroautoimmune disease featured by the presence of antibodies targeting neuronal surface, synaptic, or intracellular antigens. An increasing number of articles on its clinical manifestations, treatments, and prognosis have appeared in recent years. The objectives of this study were to summarize this growing body of literature and provide an overview of hotspots and trends in AE research using bibliometric analysis. Methods: We retrieved AE-related articles published between 1999 and 2022 from the Web of Science Core Collection. Using bibliometric websites and software, we analyzed the data of AE research, including details about countries, institutions, authors, references, journals, and keywords. Results: We analyzed 3348 articles, with an average of 32.83 citations per article and an H-index of 141. The USA (1091, 32.587%), China (531, 15.860%), Germany (447, 13.351%), England (266, 7.945%), and Japan (213, 6.362%) had the greatest numbers of publications. The top five institutions by numbers of publications were Oxford (143, 4.271%), the Udice French Research Universities (135, 4.032%), the University of Pennsylvania (135, 4.032%), l'Institut National de la Sante de la Recherche Medicale Inserm (113, 3.375%), and the University of Barcelona (110, 3.286%). The most productive authors were J. Dalmau (98, 2.927%), A. Vincent (65, 2.479%), H. Pruess (64, 1.912%), C. G. Bien (43, 1.284%), and F. Graus (43, 1.284%). "autoimmune encephalitis" was the most frequently used keyword (430), followed by "antibodies" (420), "NMDA receptor encephalitis" (383), and "limbic encephalitis" (368). In recent years, research hotspots have focused on the diagnosis and immunotherapy of NMDAR encephalitis and on limbic encephalitis. Conclusion: Developed Western countries have made significant contributions to this field. China has shown a steady increase in the number of publications in recent years, but the quality and influence of these articles warrant efforts at improvement. Future directions in AE research lie in two key areas: (i) the clinical manifestations, prevalence, and prognosis of AE (enabled by advances in diagnosis); and (ii) the efficacy and safety of targeted, individualized immunotherapy.

The role of short-chain fatty acids in central nervous system diseases: A bibliometric and visualized analysis with future directions.

Background: Short-chain fatty acids (SCFAs) are thought to play a key role in the microbe-gut-brain axis and involve in the pathogenesis of a variety of neurological diseases. This study aimed to identify research hotspots and evolution trends in SCFAs in central nervous diseases (CNS) and examine current research trends. Methods: The bibliometric analysis was performed using CiteSpace, and the results were visualized via network maps. Results: From 2002 to 2022, 480 publications in the database met the criteria. On the country level, China produced the highest number of publications, while the United States had the highest centrality. On the institutional level, University College Cork contributed to the most publications, and John F. Cryan from this university was the key researcher with considerable academic influence. The article, the role of short-chain fatty acids in microbiota-gut-brain, written by Boushra Dalile et al., in 2019 was the most cited article. Furthermore, the journal Nutrients had the maximum number of publications, while Plos One was the most cited journal. "Gut microbiome", "SCFAs", and "central nervous system" were the three most frequent keywords. Among them, SCFAs had the highest centrality. "Animal model" was the keyword with the highest burst strength, with the latest burst keywords being "social behavior", "pathogenesis", and "insulin sensitive". In addition, the research topics on SCFAs in CNS diseases from 2002 to 2022 mainly focused on following aspects: SCFAs plays a key role in microbe-gut-brain crosstalk; The classification and definition of SCFAs in the field of CNS; Several CNS diseases that are closely related to SCFAs research; Mechanism and translational studies of SCFAs in the CNS diseases. And the hotspots over the past 5 years have gradually increased the attention to the therapeutic potential of SCFAs in the CNS diseases. Conclusion: The research of SCFAs in CNS diseases is attracting growing attention. However, there is a lack of cooperation between countries and institutions, and additional measures are required to promote cooperation. The current evidence for an association between SCFAs and CNS diseases is preliminary and more work is needed to pinpoint the precise mechanism. Moreover, large-scale clinical trials are needed in the future to define the therapeutic potential of SCFAs in CNS diseases.

Does Gut Microbiome have an Effect on Wilson's Disease Phenotype?

Wilson's Disease (WD), a genetic metabolic disorder, is characterized by the accumulation of copper in the liver and brain, resulting in a range of clinical symptoms. The clinical manifestations of WD vary widely. The present study introduces the distinctive features of intestinal microbiota in Chinese patients with WD, presenting diverse clinical symptoms. It shows a reduction in the diversity of gut microbiota among patients with hepatic symptoms associated with WD, particularly in the genus responsible for SCFAs production. It demonstrates an increase in the Haemophilus microorganism. This study may offer novel insights for further investigation into the mechanisms underlying the occurrence, development, and treatment of WD subtypes.

Corrigendum: Case report: early recognition, treatment, and occupational safety protection are crucial for methanol toxicity.

[This corrects the article DOI: 10.3389/fmed.2022.918812.].

A bibliometric analysis of PCSK9 inhibitors from 2007 to 2022.

Background: Since the approval of the proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies for marketing in 2015, PCSK9 inhibitors have attracted significant interest in the field of cardiovascular endocrinology. A large number of clinical trials have confirmed the efficacy and safety of PCSK9 inhibitors in reducing cholesterol and the risk of cardiovascular events. No bibliometric analysis of PCSK9 inhibitors has been performed as of yet. This study aims to analyze the research trends and hotspots of PCSK9 inhibitors through bibliometric analysis. Methods: We searched the Web of Science Core Collection (WoSCC) database for PCSK9 inhibitor-related publications from 2007 to 2022. Data visualization analysis was performed using CiteSpace software. Microsoft Excel and Graphpad software were used for the drawing of some tables and figures. Results: A total of 1072 pieces of literature were retrieved between 2007 and 2022. The number of publications concerning PCSK9 inhibitors is growing annually. The top five countries with the most articles published were the United States, England, Canada, Italy, and France. Harvard University, Amgen, Brigham & Women's Hospital, Harvard Medical School, and Imperial College London are the five institutions with the highest output. The Journal of Clinical Lipidology is the most popular journal in this field. The most frequently cited journal is the New England Journal of Medicine. As for authors, Sabatine MS and Giugliano RP from Brigham & Women's Hospital have the highest number of published articles. Amgen is the funding agency for most of the research. According to keyword analysis, "low density lipoprotein", "familial hypercholesterolemia", "PCSK9 inhibitor", "PCSK9", and "efficacy" are the five keywords with the highest frequency of co-occurrence. Conclusion: The past 15 years have witnessed a rapid and fruitful development of PCSK9 inhibitors. The research trend and focus for PCSK9 inhibitors are from the mechanism of reducing low-density lipoprotein cholesterol to related clinical trials. Developed countries such as the United States have contributed prominently in this area. Coronary artery and inflammation are currently at the forefront of research in the field and are in an explosion period.

Case report: Episodic psychosis caused by a novel SCP2 splicing mutation.

SCPx deficiency is a rare disorder of peroxisomal beta-oxidation dysfunction, and it has only been documented in two patients thus far. In the previously reported patients, both patients were primarily presented with slowly progressive dystonia or ataxia, and they both displayed symmetrical lesions in the thalamus and brainstem on magnetic resonance imaging. This study presents the third patient exhibiting a similar neuroimaging abnormality but a notably different clinical phenotype characterized by episodic psychosis. Through whole-exome sequencing, we identified a homozygous splicing mutation in SCP2 (c.674 + 1G > C), and further RNA sequencing revealed exon 8 skipping in the mature transcripts of SCP2. This study significantly expands our understanding of the genotypic and phenotypic spectrum associated with SCP2-related metabolic encephalopathy.

Corrigendum to "The 100 top-cited articles in the field of Wilson's disease from 1990 to 2022: A bibliometric study" [Heliyon 9(7) (July 2023) e17785].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e17785.].

Corrigendum: Bibliometric analysis of evolutionary trends and hotspots of super-enhancers in cancer.

[This corrects the article DOI: 10.3389/fphar.2023.1192855.].

The Tao of copper metabolism: from physiology to pathology.

As a transitional metal, copper plays a crucial role in maintaining the normal physiological activities of mammals. The intracellular copper concentration is meticulously regulated to maintain extremely low levels through homeostatic regulation. Excessive accumulation of free copper in cells can have deleterious effects, as observed in conditions such as Wilson's disease. Moreover, data accumulated over the past few decades have revealed a crucial role of copper imbalance in tumorigenesis, progression and metastasis. Recently, cuproptosis, also known as copper-induced cell death, has been proposed as a novel form of cell death. This discovery offers new prospects for treating copper-related diseases and provides a promising avenue for developing copper-responsive therapies, particularly in cancer treatment. We present a comprehensive overview of the Yin-Yang equilibrium in copper metabolism, particularly emphasising its pathophysiological alterations and their relevance to copper-related diseases and malignancies.

Bibliometric analysis of evolutionary trends and hotspots of super-enhancers in cancer.

Introduction: In the past decade, super-enhancer (SE) has become a research hotspot with increasing attention on cancer occurrence, development, and prognosis. To illustrate the hotspots of SE in cancer research and its evolutionary tendency, bibliometric analysis was carried out for this topic. Methods: Literature published before Dec 31, 2022, in WOSCC, was systematically classified, and Citespace, bibliometric.com/app, and GraphPad Prism analyzed the data. Results: After screening out inappropriate documents and duplicate data, 911 publications were selected for further bibliometric analysis. The top five research areas were Oncology (257, 28.211%), Cell Biology (210, 23.052%), Biochemistry Molecular Biology (209, 22.942%), Science Technology Other Topics (138, 15.148%), and Genetics Heredity (132, 14.490%). The United States of America (United States) has the highest number of documents (462, 50.71%), followed by China (303, 33.26%). Among the most productive institutions, four of which are from the United States and one from Singapore, the National University of Singapore. Harvard Medical School (7.68%) has the highest percentage of articles. Young, Richard A, with 32 publications, ranks first in the number of articles. The top three authors came from Whitehead Institute for Biomedical Research as a research team. More than two-thirds of the research are supported by the National Institutes of Health of the United States (337, 37.654%) and the United States Department of Health Human Services (337, 37.654%). And "super enhancer" (525), "cell identity" (258), "expression" (223), "cancer" (205), and "transcription factor" (193) account for the top 5 occurrence keywords. Discussion: Since 2013, SE and cancer related publications have shown a rapid growth trend. The United States continues to play a leading role in this field, as the top literature numbers, affiliations, funding agencies, and authors were all from the United States, followed by China and European countries. A high degree of active cooperation is evident among a multitude of countries. The role of SEs in cell identity, gene transcription, expression, and inhibition, as well as the relationship between SEs and TFs, and the selective inhibition of SEs, have received much attention, suggesting that they are hot issues for research.

The 100 top-cited articles in the field of Wilson's disease from 1990 to 2022: A bibliometric study.

Objectives: To characterize the 100 most-cited articles in the field of Wilson's Disease (WD) to provide a general overview and reveal the historical developments classical studies, and new findings. Design: WD-related articles were searched on the Web of Science database. The 100 most-cited articles were retrieved and their descriptive statistics were analyzed. Data extraction and synthesis: The 100 most-cited articles in the field of WD were selected and several parameters, including citation count, citation density, first author, corresponding author, journal, country, institution, and keywords were extracted to assess the overall quality and impact of the articles. Results: Most of the selected 100 articles were published in the 1990s and 2000s, with the highest number of articles published in 2005. Citations per paper ranged from 100 to 1,631, with a mean number of citations of 199.03. The top 100 articles were published in 38 journals, and the majority were published in the Journal of Biological Chemistry. The most prominent research themes were clinical presentations, clinical trials, copper transport mechanisms, and dysregulation of copper metabolism. Prof. Svetlana Lutsenko, Prof. Peter Ferenci, Prof. George J. Brewer, and Prof. Diane W. Cox were among the most influential researchers in this field, while Euro-American countries were the most dominant in terms of research output. Keywords network analysis identified "Transporting ATPase," "ATP7B," and "Menkes disease" as the most influential keywords. Moreover, disease management, WD clinical phenotype, ATP7B function, and copper metabolism are potential hotspots in future WD research. Conclusions: This study reveals the most influential articles in the field of WD research. In addition, the major research themes and technological innovations in the field of WD worldwide are presented.

Therapeutic effects of engineered exosome-based miR-25 and miR-181a treatment in spinocerebellar ataxia type 3 mice by silencing ATXN3.

BACKGROUND: Spinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant hereditary ataxia worldwide, which is however in a lack of effective treatment. In view of that engineered exosomes are a promising non-invasive gene therapy transporter that can overcome the traditional problem of poor drug delivery, the aim of this study was to evaluate, for the first time, the value of exosome-based microRNA therapy in SCA3 and the therapeutic effects of intravenously administrated ATXN3 targeting microRNAs in transgenic SCA3 mouse models. METHODS: The rabies virus glycoprotein (RVG) peptide-modified exosomes loaded with miR-25 or miR-181a were peripherally injected to enable targeted delivery of miRNAs to the brain of SCA3 mice. The behaviors, ATXN3 level, purkinje cell and other neuronal loss, and neuroinflammation were evaluated 4 weeks after initial treatment. RESULTS: The targeted and efficient delivery of miR-25 and miR-181a by modified exosomes substantially inhibited the mutant ATXN3 expression, reduced neuron apoptosis and induced motor improvements in SCA3 mouse models without increasing the neuroinflammatory response. CONCLUSIONS: Our study confirmed the therapeutic potential of engineered exosome-based miR-25 and miR-181a treatment in substantially reducing ATXN3 aggregation and cytotoxicity by relying on its targeted and efficient drug delivery performance in SCA3 mice. This treatment method shows a promising prospect for future clinical applications in SCA3.

A Bioinformatics Perspective on the Dysregulation of Ferroptosis and Ferroptosis-related Immune Cell Infiltration in Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent dementia worldwide, but its pathophysiology and molecular events remain unknown. Herein, we first analyzed the differential expression pattern of patients' AD hippocampus through gene expression array data from the GEO database. Notch2nl, TGFB1I1, and LTF were up-regulated in AD patients, while ARPC1A, CHGB, and MPV17 down-regulated. Second, dysregulation of ferroptosis related genes was demonstrated from our data: PCBP2 and FTL significantly up-significant in AD hippocampus, while VDAC2, LPCAT3, GSS, ACSL4, and ACSL6 significantly down-regulated. The protein-protein interactions (PPI) network revealed that FTL was involved in iron metabolism and utilization, while ACSL4 and ACSL6 were involved in a polyunsaturated fatty acids metabolism network. Gene correlation analysis on differential expressed genes (DEGs) indicated that ferroptosis regulates a series of biological processes and pathways related to AD pathogenesis. Third, ferroptosis-related DEGs regulated the immune cell infiltration pattern in the AD hippocampus, characterized by decreased memory B cells, increased memory resting CD4+ T cells, memory activated CD4+ T cells, and resting NK cells. The altered expression of ferroptosis-related DEGs affected the infiltration of specific immune cell types. The model constructed by the seven ferroptosis-related differential genes may accurately predict the outcome of AD occurrence. Finally, qPCR validation on these ferroptosis-related DEGs in APPswe/PSEN1dE9 mice confirmed the dysregulated expression of Pcbp2, FTL, GSS, and ACSL4 in the AD hippocampus and forebrain. In conclusion, our results supported the conception that the AD brain revealed dysregulated ferroptosis and immune cell infiltration.

Case Report: Early Recognition, Treatment, and Occupational Safety Protection are Crucial for Methanol Toxicity.

Background: Despite significant progress in treating methanol poisoning, the lack of training, hazard communication, and occupational safety protection education contributes to the risk of occupational exposure and methanol toxicity. In addition, early diagnosis and timely medical care are essential to reduce the risk of morbidity and mortality, yet it remains a challenging procedure. Case Report: A 35-year-old man working in a fireworks factory came to our emergency department with acute mental change and progressive disturbance of consciousness. The patient's vital signs were stable, and he presented with enlargement of both pupils with a weak reaction to light. Head computed tomography showed low signal intensities in the bilateral basal ganglia. He was admitted to the neurologic intensive care unit, where additional laboratory workup showed high anion-gap metabolic acidosis. Methanol poisoning was thus considered. Before being treated with sodium bicarbonate infusion, hemodialysis, folate, and high-dose vitamin B, the blood and urine samples were collected for toxicity tests, which turned out to be methanol poisoning. After 8 hours of hemodialysis, the patient's consciousness recovered, but he complained of a complete loss of vision in both eyes. Brain and optic nerve magnetic resonance images showed bilateral symmetric putamen lesions and optic neuropathy. Ophthalmic tests indicated visual pathway impairment and optic disc swelling but no fluorescein leakage. The right eye's vision was partially restored on the third day, but he could only count fingers at 20 cm. Unfortunately, his eyesight ceased to improve during the 6 months of follow-up. Conclusions: Early diagnosis and prompt treatment will improve the prognosis of methanol poisoning in terms of vision and patient survival. Awareness and supervision of commercial alcohol use are indispensable for similar industrial processes.

Case Report: Diagnosis of Acute Q Fever With Aseptic Meningitis in a Patient by Using Metagenomic Next-Generation Sequencing.

Query fever (Q fever) is a widespread zoonotic disease caused by the bacterium of Coxiella burnetii (C. burnetii). Its neurological complications are rarely reported. But they may lead to severe consequences. It needs a rapid and accurate detective method to diagnose acute Q fever with neurological presentations in non-epidemic areas urgently. Here, we report an acute Q fever case with aseptic meningitis. The male patient, without any contact history in the epidemic area or with animals, was indicated to exhibit fever and headache symptoms. The cultures of blood, stool, urine, and sputum were all negative. But C. burnetii was repeatedly detected in blood by metagenomic next-generation sequencing (mNGS). He received Doxycycline therapy and quickly returned to normal. Therefore, for the diagnosis and identification of Q fever in non-reporting regions, mNGS has comparative advantages. Secondly, aseptic meningitis may be a direct infection of C. burnetii to central nervous system (CNS) or inflammatory reactions to systemic infection, we recommend detecting mNGS both in blood and cerebrospinal fluid (CSF).

Clinical Presentations and Genetic Characteristics of Late-Onset MADD Due to ETFDH Mutations in Five Patients: A Case Series.

Background: Late-onset multiple acyl-CoA dehydrogenase deficiency (LO-MADD) describes a curable autosomal recessive genetic disease caused by ETFDH mutations that result in defects in ETF-ubiquinone oxidoreductase. Almost all patients are responsive to riboflavin. This study describes the clinical presentations and genetic characteristics of five LO-MADD patients. Methods: From 2018 to 2021, we collected clinical and genetic data on five patients diagnosed with LO-MADD at our hospital and retrospectively analyzed their clinical characteristics, laboratory examination, electromyography, muscle biopsy, genetic analysis, and outcome data. Results: This study included three males and two females with mean onset age of 37.8 years. Fluctuating exercise intolerance was the most common presentation. Serum creatine kinase (CK) levels were significantly elevated in all patients, and plasma acylcarnitine profiles revealed an increase in long-chain acylcarnitine species in three cases. The urinary organic acid study revealed a high level of hydroxyglutaric acid in all patients. Electrophysiology demonstrated myogenic impairment. Muscle biopsies revealed lipid storage myopathy. Molecular analysis identified nine mutations (three novels and six reported) in ETFDH. Exercise intolerance and muscle weakness were dramatically improved in all patients treated with riboflavin (100 mg) daily following diagnosis. Conclusions: LO-MADD is caused by ETFDH variants and responds well to riboflavin. Three novel ETFDH pathogenic variants were identified, expanding their spectrum in the Chinese population and facilitating future interpretation and analysis of ETFDH mutations.

Diagnostic and Therapeutic Potential of Exosomal MicroRNAs for Neurodegenerative Diseases.

Neurodegenerative disorders (NDs) are characterized by a gradual loss of neurons and functions that eventually leads to progressive neurological impairment. In view of the heavy burden on the healthcare system, efficient and reliable biomarkers for early diagnosis and therapeutic treatments to reverse the progression of NDs are in urgent need. There has been an increasing interest in using exosomal miRNAs as biomarkers or targeted therapies for neurological diseases recently. In this review, we overviewed the updated studies on exosomal miRNAs as biomarkers and potential therapeutic approaches in NDs, as well as their association with the pathophysiology of this group of disorders, especially Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). The exosomal miRNAs that are commonly dysregulated across different NDs or are commonly used as therapeutic candidates were also identified and summarized. In summary, the feasibility of exosomal miRNAs as biomarkers and potential targeted therapy for NDs has been verified. However, due to the limitations of existing studies and the discrepancies across different studies, high quality laboratory and clinical investigations are still required.

Remote clinical training practice in the neurology internship during the COVID-19 pandemic.

Background: During the current COVID-19 pandemic, offline clinical education was mandated to suspend at the neurology department of many teaching hospitals globally, yet there is insufficient evidence regarding the preferred practice and methods for online neurology intern training course.Objective: The investigation aimed to examine whether the online neurology training course based on Small Private Online Course (SPOC) and blending learning mode can achieve a good effect and cater for interns from different medical programs and whether the learning group size affects the teaching effect.Design: The subjects were 92 students enrolled in the neurology internship at the Second Xiangya Hospital of China from 9 March to 9 August 2020. After completing the online course, the final scores and evaluation results were compared among different groups of interns, and their preference to distinct contents of the course was analyzed. Statistical analysis was performed using the SPSS program (version 22.0).Results: Our online course received consistent positive recognition from the interns. Ninety-nine percent of the interns recommended incorporating the online course into the conventional offline training program after the pandemic. There was no significant difference between interns from different programs concerning the final scores and course evaluation. A smaller learning group size (<15 students) could achieve a better teaching effect than a larger group size (p < 0.05). The interns preferred interactive discussions, and course contents that they can get practice and feedback from, rather than video watching and didactic lectures.Conclusions: The online neurology intern training course based on SPOC and blending learning mode is worthy of popularization in a large student base. The teaching effect of an online intern training program may be improved by limiting the group size to less than 15 students and encouraging more interactive discussion, more practice and feedback.

Balance and coordination training for patients with genetic degenerative ataxia: a systematic review.

BACKGROUND AND PURPOSE: The group of genetic degenerative ataxias shares the same feature of gradual deterioration in balance and coordination. However, no cure is yet available for this group of disorders, while rehabilitation remains a cornerstone in the current therapy. This review aims to present a summary of the current knowledge of balance and coordination training in patients with inherited degenerative ataxia and to discuss the training effectiveness accordingly. METHODS: A comprehensive search was performed in 5 electronic databases (i.e., Cochrane Library, PEDro, EMbase, PubMed and MEDLINE) to identify the related publications from January, 1999 to January, 2020. Methodological quality was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) grading system and the PEDro scale. RESULTS: A total of 33 out of 515 studies met the eligibility criteria, and were categorized and discussed by their training methods including: (1) conventional physical/occupational therapy, (2) virtual reality/videogame-based training, and (3) adapted physical activity. Despite the substantial variation among included studies, most patients achieved significant improvement in the aspect of balance and coordination following individually-tailored rehabilitation programs. The effects of training showed a relative consistency regardless of the functional dependency level on admission. CONCLUSIONS: Balance and coordination training, especially the conventional physical/occupational therapy, is able to improve the balance and coordinative function of patients with genetic degenerative ataxia, but more high-quality studies are needed to formulate recommendations for clinical practice.

Pancreatic and duodenal homeobox-1 in pancreatic ductal adenocarcinoma and diabetes mellitus.

Diabetes mellitus and pancreatic ductal adenocarcinoma are two common diseases worldwidely which are both derived from different components of pancreas. The pancreatic and duodenal homeobox-1 (PDX1) is an essential transcription factor for the early development of pancreas that is required for the differentiation of all pancreatic cell lineages. Current evidence suggests an important role of PDX1 in both the origin and progression of pancreatic diseases. In this review, we discussed recent studies of PDX1 in diabetes mellitus and pancreatic cancer, and the therapeutic strategies derived from this transcription factor.