bluuebunny/crossref_metadata_2025 huggingface dataset:
Mini-Review: Regenerating the Corneal Epithelium With Simple Limbal Epithelial Transplantation
Authors: Singh Aastha , Sangwan Virender S.
Published: May 2021

Simple limbal epithelial transplantation (SLET) is an ingenious, low cost and effective technique of limbal stem cell transplantation (LSCT) that is increasingly being undertaken in practice across the world. Since it was first described a decade ago, the technique has been performed in a variety of cases of limbal stem cell deficiency (LSCD) and has underwent several innovative modifications. Published literature on SLET has progressively increased over time and successful outcomes in various clinical scenarios have been reported. This concise review attempts to present a crisp account of SLET covering the indications and contraindications of performing the procedure; detailed account of pre-operative work up and preparation; surgical technique and its modifications; post-operative course, care and possible complications as well as published outcomes of surgery from across the world. Comparative analysis of various techniques of LSCT have been discussed and common concerns of surgeons practising or those who are planning to start practising SLET have been addressed. The authors hope that the pragmatic insights and pearls given at the end of the review will aid the surgeons in performing this technique to provide maximum benefit to patients suffering from the potentially blinding condition of LSCD.
Evaluation of Eight-Item Vancomycin Prescribing Confidence Questionnaire Among Junior Doctors
Authors: Liu Lu , Jiang Zhehan , Xie Ana , Wang Weimin
Published: May 2021

Background: Assessing the preparedness of junior doctors to use vancomycin is important in medical education. Preparedness is typically evaluated by self-reported confidence surveys.

Materials and Methods: An eight-item vancomycin prescribing confidence questionnaire was developed, piloted, and evaluated. The questionnaire responses were collected from 195 junior doctors and a series of statistical techniques, such as principal component analysis and confirmatory factor analysis, and were implemented to examine the validity and reliability.

Results: The principal component analysis supported a one-factor structure, which was fed into a confirmatory factor analysis model resulting in a good fit [comparative fit index (CFI) = 0.99, Tucker–Lewis index (TLI) = 0.99, root mean square error of approximation (RMSEA) = 0.08, standardized root mean square residual (SRMR) = 0.04]. Ordinal-based α was 0.95, and various ωs were all above 0.93, indicating a high reliability level. The questionnaire responses were further proved to be robust to extreme response patterns via item response tree modeling. Jonckheere–Terpstra test results (z = 6.5237, p = 3.429e−11) showed that vancomycin prescribing confidence differed based on the experience in order (i.e., four ordinal independent groups: “≤10 times,” “11–20 times,” “21–30 times,” and “≥31 times”) and therefore provided external validity evidences for the questionnaire.

Conclusions: The questionnaire is valid and reliable such that teaching hospitals can consider using it to assess junior doctors' vancomycin prescribing confidence. Further investigation of the questionnaire can point to the relationship between the prescribing confidence and the actual performance.
Characterization of the Complete Mitochondrial Genome of Basidiomycete Yeast Hannaella oryzae: Intron Evolution, Gene Rearrangement, and Its Phylogeny
Authors: Li Qiang , Li Lijiao , Feng Huiyu , Tu Wenying , Bao Zhijie , Xiong Chuan , Wang Xu , Qing Yuan , Huang Wenli
Published: May 2021

In this study, the mitogenome of Hannaella oryzae was sequenced by next-generation sequencing (NGS) and successfully assembled. The H. oryzae mitogenome comprised circular DNA molecules with a total size of 26,444 bp. We found that the mitogenome of H. oryzae partially deleted the tRNA gene transferring cysteine. Comparative mitogenomic analyses showed that intronic regions were the main factors contributing to the size variations of mitogenomes in Tremellales. Introns of the cox1 gene in Tremellales species were found to have undergone intron loss/gain events, and introns of the H. oryzae cox1 gene may have different origins. Gene arrangement analysis revealed that H. oryzae contained a unique gene order different from other Tremellales species. Phylogenetic analysis based on a combined mitochondrial gene set resulted in identical and well-supported topologies, wherein H. oryzae was closely related to Tremella fuciformis. This study represents the first report of mitogenome for the Hannaella genus, which will allow further study of the population genetics, taxonomy, and evolutionary biology of this important phylloplane yeast and other related species.
Decentralized Investigation of Bacterial Outbreaks Based on Hashed cgMLST
Authors: Deneke Carlus , Uelze Laura , Brendebach Holger , Tausch Simon H. , Malorny Burkhard
Published: May 2021

Whole-genome sequencing (WGS)-based outbreak investigation has proven to be a valuable method for the surveillance of bacterial pathogens. Its utility has been successfully demonstrated using both gene-by-gene (cgMLST or wgMLST) and single-nucleotide polymorphism (SNP)-based approaches. Among the obstacles of implementing a WGS-based routine surveillance is the need for an exchange of large volumes of sequencing data, as well as a widespread reluctance to share sequence and metadata in public repositories, together with a lacking standardization of suitable bioinformatic tools and workflows. To address these issues, we present chewieSnake, an intuitive and simple-to-use cgMLST workflow. ChewieSnake builds on the allele calling software chewBBACA and extends it by the concept of allele hashing. The resulting hashed allele profiles can be readily compared between laboratories without the need of a central allele nomenclature. The workflow fully automates the computation of the allele distance matrix, cluster membership, and phylogeny and summarizes all important findings in an interactive HTML report. Furthermore, chewieSnake can join allele profiles generated at different laboratories and identify shared clusters, including a stable and intercommunicable cluster nomenclature, thus facilitating a joint outbreak investigation. We demonstrate the feasibility of the proposed approach with a thorough method comparison using publically available sequencing data for Salmonella enterica. However, chewieSnake is readily applicable to all bacterial taxa, provided that a suitable cgMLST scheme is available. The workflow is freely available as an open-source tool and can be easily installed via conda or docker.
Differential Impacts of Water Table and Temperature on Bacterial Communities in Pore Water From a Subalpine Peatland, Central China
Authors: Tian Wen , Xiang Xing , Wang Hongmei
Published: May 2021

The level of water table and temperature are two environmental variables shaping soil bacterial communities, particularly in peatland ecosystems. However, discerning the specific impact of these two factors on bacterial communities in natural ecosystems is challenging. To address this issue, we collected pore water samples across different months (August and November in 2017 and May 2018) with a gradient of water table changes and temperatures at the Dajiuhu peatland, Central China. The samples were analyzed with 16S rRNA high-throughput sequencing and Biolog EcoMicroplates. Bacterial communities varied in the relative abundances of dominant taxa and harbored exclusive indicator operational taxonomic units across the different months. Despite these differences, bacterial communities showed high similarities in carbon utilization, with preferences for esters (pyruvic acid methyl ester, Tween 40, Tween 80, and D-galactonic acid γ-lactone), amino acids (L-arginine and L-threonine), and amines (phenylethylamine and putrescine). However, rates of carbon utilization (as indicated by average well-color development) and metabolic diversity (McIntosh and Shannon index) in May and August were higher than those in November. Redundancy analysis revealed that the seasonal variations in bacterial communities were significantly impacted by the level of the water table, whereas the temperature had a fundamental role in bacterial carbon utilization rate. Co-occurrence analysis identified Sphingomonas, Mucilaginibacter, Novosphingobium, Lacunisphaera, Herminiimonas, and Bradyrhizobium as keystone species, which may involve in the utilization of organic compounds such as amino acids, phenols, and others. Our findings suggest that bacterial community functions were more stable than their compositions in the context of water table changes. These findings significantly expand our current understanding of the variations of bacterial community structures and metabolic functions in peatland ecosystems in the context of global warming and fluctuation of the water table.
The Challenge of CRISPR-Cas Toward Bioethics
Authors: Gonzalez-Avila Luis Uriel , Vega-López Juan Manuel , Pelcastre-Rodríguez Leda Ivonne , Cabrero-Martínez Omar Alejandro , Hernández-Cortez Cecilia , Castro-Escarpulli Graciela
Published: May 2021

Since determining the structure of the DNA double helix, the study of genes and genomes has revolutionized contemporary science; with the decoding of the human genome, new findings have been achieved, including the ability that humans have developed to modify genetic sequences in vitro. The discovery of gene modification mechanisms, such as the CRISPR-Cas system (Clustered Regularly Interspaced Short Palindromic Repeats) and Cas (CRISPR associated). Derived from the latest discoveries in genetics, the idea that science has no limits has exploded. However, improvements in genetic engineering allowed access to new possibilities to save lives or generate new treatment options for diseases that are not treatable by using genes and their modification in the genome. With this greater knowledge, the immediate question is who governs the limits of genetic science? The first answer would be the intervention of a legislative branch, with adequate scientific advice, from which the logical answer, bioethics, should result. This term was introduced for the first time by Van Rensselaer Potter, who in 1970 combined the Greek words bios and ethos, Bio-Ethik, which determined the study of the morality of human behavior in science. The approach to this term was introduced to avoid the natural tension that results from the scientific technical development and the ethics of limits. Therefore, associating the use of biotechnology through the CRISPR-Cas system and the regulation through bioethics, aims to monitor the use of techniques and technology, with benefits for humanity, without altering fundamental rights, acting with moral and ethical principles.
Differential Impact of Plant Secondary Metabolites on the Soil Microbiota
Authors: Schütz Vadim , Frindte Katharina , Cui Jiaxin , Zhang Pengfan , Hacquard Stéphane , Schulze-Lefert Paul , Knief Claudia , Schulz Margot , Dörmann Peter
Published: May 2021

Plant metabolites can shape the microbial community composition in the soil. Two indole metabolites, benzoxazolinone (BOA) and gramine, produced by different Gramineae species, and quercetin, a flavonoid synthesized by many dicot species, were studied for their impacts on the community structure of field soil bacteria. The three plant metabolites were directly added to agricultural soil over a period of 28 days. Alterations in bacterial composition were monitored by next generation sequencing of 16S rRNA gene PCR products and phospholipid fatty acid analysis. Treatment of the soil with the plant metabolites altered the community composition from phylum to amplicon sequence variant (ASV) level. Alpha diversity was significantly reduced by BOA or quercetin, but not by gramine. BOA treatment caused a decrease of the relative abundance of 11 ASVs, while only 10 ASVs were increased. Gramine or quercetin treatment resulted in the increase in relative abundance of many more ASVs (33 or 38, respectively), most of them belonging to the Proteobacteria. Isolation and characterization of cultivable bacteria indicated an enrichment in Pseudarthrobacter or Pseudomonas strains under BOA/quercetin or BOA/gramine treatments, respectively. Therefore, the effects of the treatments on soil bacteria were characteristic for each metabolite, with BOA exerting a predominantly inhibitory effect, with only few genera being able to proliferate, while gramine and quercetin caused the proliferation of many potentially beneficial strains. As a consequence, BOA or gramine biosynthesis, which have evolved in different barley species, is accompanied with the association of distinct bacterial communities in the soil, presumably after mutual adaptation during evolution.
CD8+ T-Cell Mediated Control of HIV-1 in a Unique Cohort With Low Viral Loads
Authors: Jones Amber D. , Khakhina Svetlana , Jaison Tara , Santos Erin , Smith Stephen , Klase Zachary A.
Published: May 2021

A unique population of HIV-1 infected individuals can control infection without antiretroviral therapy. These individuals fall into a myriad of categories based on the degree of control (low or undetectable viral load), the durability of control over time and the underlying mechanism (i.e., possession of protective HLA alleles or the absence of critical cell surface receptors). In this study, we examine a cohort of HIV-1 infected individuals with a documented history of sustained low viral loads in the absence of therapy. Throughin vitroanalyses of cells from these individuals, we have determined that infected individuals with naturally low viral loads are capable of controlling spreading infectionin vitroin a CD8+T-cell dependent manner. This control is lost when viral load is suppressed by antiretroviral therapy and correlates with a clinical CD4:CD8 ratio of <1. Our results support the conclusion that HIV-1 controllers with low, but detectable viral loads may be controlling the virus due to an effective CD8+T-cell response. Understanding the mechanisms of control in these subjects may provide valuable understanding that could be applied to induce a functional cure in standard progressors.
Rhizosphere Bacterial Networks, but Not Diversity, Are Impacted by Pea-Wheat Intercropping
Authors: Pivato Barbara , Semblat Amélie , Guégan Thibault , Jacquiod Samuel , Martin Juliette , Deau Florence , Moutier Nathalie , Lecomte Christophe , Burstin Judith , Lemanceau Philippe
Published: May 2021

Plant-plant associations, notably cereal-legume intercropping, have been proposed in agroecology to better value resources and thus reduce the use of chemical inputs in agriculture. Wheat-pea intercropping allows to decreasing the use of nitrogen fertilization through ecological processes such as niche complementarity and facilitation. Rhizosphere microbial communities may account for these processes, since they play a major role in biogeochemical cycles and impact plant nutrition. Still, knowledge on the effect of intecropping on the rhizosphere microbiota remains scarce. Especially, it is an open question whether rhizosphere microbial communities in cereal-legume intercropping are the sum or not of the microbiota of each plant species cultivated in sole cropping. In the present study, we assessed the impact of wheat and pea in IC on the diversity and structure of their respective rhizosphere microbiota. For this purpose, several cultivars of wheat and pea were cultivated in sole and intercropping. Roots of wheat and pea were collected separately in intercropping for microbiota analyses to allow deciphering the effect of IC on the bacterial community of each plant species/cultivar tested. Our data confirmed the well-known specificity of the rhizosphere effect and further stress the differentiation of bacterial communities between pea genotypes (Hr and hr). As regards the intercropping effect, diversity and structure of the rhizosphere microbiota were comparable to sole cropping. However, a specific co-occurrence pattern in each crop rhizosphere due to intercropping was revealed through network analysis. Bacterial co-occurrence network of wheat rhizosphere in IC was dominated by OTUs belonging to Alphaproteobacteria, Bacteroidetes and Gammaproteobacteria. We also evidenced a common network found in both rhizosphere under IC, indicating the interaction between the plant species; this common network was dominated by Acidobacteria, Alphaproteobacteria, and Bacteroidetes, with three OTUs belonging to Acidobacteria, Betaproteobacteria and Chloroflexi that were identified as keystone taxa. These findings indicate more complex rhizosphere bacterial networks in intercropping. Possible implications of these conclusions are discussed in relation with the functioning of rhizosphere microbiota in intercropping accounting for its beneficial effects.
Genomics-Enabled Novel Insight Into the Pathovar-Specific Population Structure of the Bacterial Leaf Streak Pathogen Xanthomonas translucens in Small Grain Cereals
Authors: Shah Syed Mashab Ali , Khojasteh Moein , Wang Qi , Taghavi S. Mohsen , Xu Zhengyin , Khodaygan Pejman , Zou Lifang , Mohammadikhah Sedighe , Chen Gongyou , Osdaghi Ebrahim
Published: May 2021

The Gram-negative bacterium Xanthomonas translucens infects a wide range of gramineous plants with a notable impact on small grain cereals. However, genomics-informed intra-species population structure and virulence repertories of the pathogen have rarely been investigated. In this study, the complete genome sequences of seven X. translucens strains representing an entire set of genetic diversity of two pathovars X. translucens pv. undulosa and X. translucens pv. translucens is provided and compared with those of seven publicly available complete genomes of the pathogen. Organization of the 25 type III secretion system genes in all the 14 X. translucens strains was exactly the same, while TAL effector genes localized singly or in clusters across four loci in X. translucens pv. translucens and five to six loci in X. translucens pv. undulosa. Beside two previously unreported endogenous plasmids in X. translucens pv. undulosa, and variations in repeat variable diresidue (RVD) of the 14 strains, tal1a of X. translucens pv. translucens strain XtKm8 encode the new RVDs HE and YI which have not previously been reported in xanthomonads. Further, a number of truncated tal genes were predicted among the 14 genomes lacking conserved BamHI site at N-terminus and SphI site at C-terminus. Our data have doubled the number of complete genomes of X. translucens clarifying the population structure and genomics of the pathogen to pave the way in the small grain cereals industry for disease resistance breeding in the 21st century’s agriculture.
Altered Glycosylation in the Aging Heart
Authors: Franzka Patricia , Krüger Lynn , Schurig Mona K. , Olecka Maja , Hoffmann Steve , Blanchard Véronique , Hübner Christian A.
Published: May 2021

Cardiovascular disease is one of the leading causes of death in developed countries. Because the incidence increases exponentially in the aging population, aging is a major risk factor for cardiovascular disease. Cardiac hypertrophy, fibrosis and inflammation are typical hallmarks of the aged heart. The molecular mechanisms, however, are poorly understood. Because glycosylation is one of the most common post-translational protein modifications and can affect biological properties and functions of proteins, we here provide the first analysis of the cardiac glycoproteome of mice at different ages. Western blot as well as MALDI-TOF based glycome analysis suggest that high-mannose N-glycans increase with age. In agreement, we found an age-related regulation of GMPPB, the enzyme, which facilitates the supply of the sugar-donor GDP-mannose. Glycoprotein pull-downs from heart lysates of young, middle-aged and old mice in combination with quantitative mass spectrometry bolster widespread alterations of the cardiac glycoproteome. Major hits are glycoproteins related to the extracellular matrix and Ca2+-binding proteins of the endoplasmic reticulum. We propose that changes in the heart glycoproteome likely contribute to the age-related functional decline of the cardiovascular system.
Visualizing the Growth and Division of Rat Gut Bacteria by D-Amino Acid-Based in vivo Labeling and FISH Staining
Authors: Chen Ru , Song Jia , Lin Liyuan , Liu Jie , Yang Chaoyong , Wang Wei
Published: May 2021

Rat is a widely used mammalian model for gut microbiota research. However, due to the difficulties of individual in vitro culture of many of the gut bacteria, much information about the microbial behaviors in the rat gut remains largely unknown. Here, to characterize the in situ growth and division of rat gut bacteria, we apply a chemical strategy that integrates the use of sequential tagging with D-amino acid-based metabolic probes (STAMP) with fluorescence in situ hybridization (FISH) to rat gut microbiota. Following sequential gavages of two different fluorescent D-amino acid probes to rats, the resulting dually labeled gut bacteria provides chronological information of their in situ cell wall synthesis. After taxonomical labeling with FISH probes, most of which are newly designed in this study, we successfully identify the growth patterns of 15 bacterial species, including two that have not been cultured separately in the laboratory. Furthermore, using our labeling protocol, we record Butyrivibrio fibrisolvens cells growing at different growth stages of a complete cell division cycle, which offers a new scope for understanding basic microbial activities in the gut of mammalian hosts.
Decreased Exosomal Acetylcholinesterase Activity in the Plasma of Patients With Parkinson’s Disease
Authors: Shim Kyu Hwan , Go Han Gyeol , Bae Heewon , Jeong Da-Eun , Kim Danyeong , Youn Young Chul , Kim SangYun , An Seong Soo A. , Kang Min Ju
Published: May 2021

Exosomes, which are small extracellular vesicles produced from various cell types, contain a variety of molecular constituents, such as proteins, lipids, and RNA. Recently, exosomal biomarkers have been investigated to probe the understanding and diagnosis of neurodegenerative disorders. Previous reports have demonstrated increased exosomal α-synuclein (α-syn) in patients with Parkinson’s disease (PD) in comparison to healthy controls (HC). Interestingly, the cholinergic loss was revealed in the central and peripheral nervous systems in histopathology and molecular neuroimaging. Thereby, we simultaneously examined acetylcholinesterase (AChE) with α-syn as exosomal markers. Exosomes were isolated from the plasma of 34 FP-CIT PET proven patients with PD and 29 HC. Exosomal α-syn and AChE activity were quantified andthe relationship with clinical parameters was analyzed. Remarkably, exosomal AChE activity was significantly decreased in PD compared to HC (P = 0.002). Moreover, exosomal AChE activity in PD revealed a strong negative correlation with disease severity, including H&Y (P = 0.007) and UPDRS part III (P = 0.047) scores. By contrast, no significant difference in exosomal α-syn concentration was observed between groups. These results support the occurrence of cholinergic dysfunction in PD, and they could be implicated with disease progression, especially motor deficits. Exosomal AChE activity with advanced exosome isolation techniques may be a reliable biomarker for the early diagnosis and prognosis of PD.
Prediction of Hemorrhagic Transformation After Ischemic Stroke: Development and Validation Study of a Novel Multi-biomarker Model
Authors: Liu Junfeng , Wang Yanan , Jin Yuxi , Guo Wen , Song Quhong , Wei Chenchen , Li Jing , Zhang Shanshan , Liu Ming
Published: May 2021

Objectives: We aimed to develop and validate a novel multi-biomarker model for predicting hemorrhagic transformation (HT) risk after acute ischemic stroke (AIS).

Methods: We prospectively included patients with AIS admitted within 24 h of stroke from January 1st 2016 to January 31st 2019. A panel of 17 circulating biomarkers was measured and analyzed in this cohort. We assessed the ability of individual circulating biomarkers and the combination of multiple biomarkers to predict any HT, symptomatic HT (sHT) and parenchymal hematoma (PH) after AIS. The strategy of multiple biomarkers in combination was then externally validated in an independent cohort of 288 Chinese patients.

Results: A total of 1207 patients with AIS (727 males; mean age, 67.2 ± 13.9 years) were included as a derivation cohort, of whom 179 patients (14.8%) developed HT. The final multi-biomarker model included three biomarkers [platelets, neutrophil-to-lymphocyte ratios (NLR), and high-density lipoprotein (HDL)] from different pathways, showing a good performance for predicting HT in both the derivation cohort (c statistic = 0·64, 95% CI 0·60–0·69), and validation cohort (c statistic = 0·70, 95% CI 0·58–0·82). Adding these three biomarkers simultaneously to the basic model with conventional risk factors improved the ability of HT reclassification [net reclassification improvement (NRI) 65.6%, P < 0.001], PH (NRI 64.7%, P < 0.001), and sHT (NRI 71.3%, P < 0.001).

Conclusion: This easily applied multi-biomarker model had a good performance for predicting HT in both the derivation and external validation cohorts. Incorporation of biomarkers into clinical decision making may help to identify patients at high risk of HT after AIS and warrants further consideration.
Expression of Urea Transporter B in Normal and Injured Brain
Authors: Huang Boyue , Wang Hongkai , Zhong Dandan , Meng Jia , Li Min , Yang Baoxue , Ran Jianhua
Published: May 2021

Urea transporter B (UT-B) is a membrane channel protein widely distributed in mammals, and plays a significant physiological role by regulating urea and water transportation in different tissues. More and more studies have found that UT-B is related to neurological diseases, including myelinopathy and depression. When urea accumulates in the brains of UT-B knockout mice, the synaptic plasticity of neurons is reduced, and the morphology and function of glial cells are also changed. However, the distribution and expression change of UT-B remain unclear. The purpose of this study is to determine the expression characteristics of UT-B in the brain. Through single-cell RNA sequencing, UT-B was found to express universally and substantially throughout the various cells in the central nervous system except for endothelial and smooth muscle cells. UT-B was detected in the third cerebral ventricular wall, granule cell layer of the dentate gyrus, and other parts of the hippocampal, cerebral cortex, substantia nigra, habenular, and lateral hypothalamic nucleus by immunohistochemistry. Compared with the membrane expression of UT-B in glial cells, the subcellular localization of UT-B is in the Golgi apparatus of neurons. Further, the expression of UT-B was regulated by osmotic pressure in vitro. In the experimental traumatic brain injury model (TBI), the number of UT-B positive neurons near the ipsilateral cerebral cortex increased first and then decreased over time, peaking at the 24 h. We inferred that change in UT-B expression after the TBI was an adaptation to changed urea levels. The experimental data suggest that the UT-B may be a potential target for the treatment of TBI and white matter edema.
Early Sensory Deprivation Leads to Differential Inhibitory Changes in the Striatum During Learning
Authors: Paraouty Nihaad , Mowery Todd M.
Published: May 2021

The corticostriatal circuit has been identified as a vital pathway for associative learning. However, how learning is implemented when the sensory striatum is permanently impaired remains unclear. Using chemogenetic techniques to suppress layer five auditory cortex (AC) input to the auditory striatum, learning of a sound discrimination task was significantly impacted in freely moving Mongolian gerbils, in particular when this suppression occurs early on during learning. Whole-cell recordings sampled throughout learning revealed a transient reduction in postsynaptic (GABAA) inhibition in both striatal D1 and D2 cells in normal-hearing gerbils during task acquisition. In contrast, when the baseline striatal inhibitory strengths and firing rates were permanently reduced by a transient period of developmental sensory deprivation, learning was accompanied by augmented inhibition and increased firing rates. Direct manipulation of striatal inhibition in vivo and in vitro revealed a key role of the transient inhibitory changes in task acquisition. Together, these results reveal a flexible corticostriatal inhibitory synaptic plasticity mechanism that accompanies associative auditory learning.
The Role of Neuroinflammation in Post-traumatic Epilepsy
Authors: Sun Lei , Shan Wei , Yang Huajun , Liu Ru , Wu Jianping , Wang Qun
Published: May 2021

Post-traumatic epilepsy (PTE) is one of the consequences after traumatic brain injury (TBI), which increases the morbidity and mortality of survivors. About 20% of patients with TBI will develop PTE, and at least one-third of them are resistant to conventional antiepileptic drugs (AEDs). Therefore, it is of utmost importance to explore the mechanisms underlying PTE from a new perspective. More recently, neuroinflammation has been proposed to play a significant role in epileptogenesis. This review focuses particularly on glial cells activation, peripheral leukocytes infiltration, inflammatory cytokines release and chronic neuroinflammation occurrence post-TBI. Although the immune response to TBI appears to be primarily pro-epileptogenic, further research is needed to clarify the causal relationships. A better understanding of how neuroinflammation contributes to the development of PTE is of vital importance. Novel prevention and treatment strategies based on the neuroinflammatory mechanisms underlying epileptogenesis are evidently needed.

Search Strategy

Search MeSH Terms in pubmed: “[“Epilepsy”(Mesh)] AND “Brain Injuries, Traumatic”[Mesh]”. Published in last 30 years. 160 results were founded. Full text available:145 results. Record screened manually related to Neuroinflammation and Post-traumatic epilepsy. Then finally 123 records were included.
Alteration of Vestibular Function in Pediatric Cochlear Implant Recipients
Authors: Koyama Hajime , Kashio Akinori , Fujimoto Chisato , Uranaka Tsukasa , Matsumoto Yu , Kamogashira Teru , Kinoshita Makoto , Iwasaki Shinichi , Yamasoba Tatsuya
Published: May 2021

Background:Vestibular dysfunction is a complication of cochlear implantation (CI). Reports on the evaluation of vestibular function before and after CI are limited, especially in children. We investigated the effect of CI on vestibular function in pediatric patients.

Patients and Methods:We routinely evaluated vestibular function before but not immediately after CI. Therefore, patients who underwent sequential bilateral CI were enrolled in this study. Seventy-three children who underwent sequential CI from 2003 to 2020 at our hospital were included. Since the vestibular function of the first implanted ear was evaluated before the second surgery for the contralateral ear, post-CI evaluation timing differed among the cases. The evaluation included a caloric test, a cervical vestibular-evoked myogenic potential (cVEMP) test, and a damped rotation test. The objective variables included the results of these tests, and the explanatory variables included the age at surgery, cause of hearing loss, electrode type, and surgical approach used. The associations of these tests were analyzed.

Results:cVEMP was the most affected after CI (36.1%), followed by the caloric test (23.6%), and damped rotation test (7.8%). Cochleostomy was significantly more harmful than a round window (RW) approach or an extended RW approach based on the results of the caloric test (p= 0.035) and damped rotation test (p= 0.029). Perimodiolar electrodes affected the caloric test results greater than straight electrodes (p= 0.041). There were no significant associations among these tests' results.

Conclusions:Minimally invasive surgery in children using a round window approach or an extended round window approach with straight electrodes is desirable to preserve vestibular function after CI.
Phenotypes of GNAO1 Variants in a Chinese Cohort
Authors: Yang Xiaoling , Niu Xueyang , Yang Ying , Cheng Miaomiao , Zhang Jing , Chen Jiaoyang , Yang Zhixian , Zhang Yuehua
Published: May 2021

This study aimed to analyze the genotypes and phenotypes of GNAO1 variants in a Chinese cohort. Seven male and four female patients with GNAO1 variants were enrolled, including siblings of brothers. Ten different GNAO1 variants (nine missense and one splicing site) were identified, among which six were novel. All the variants were confirmed to be de novo in peripheral blood DNA. Eight (73%, 8/11) patients had epilepsy; the seizure onset age ranged from 6 h after birth to 4 months (median age, 2.5 months). Focal seizures were observed in all eight patients, epileptic spasms occurred in six (75%, 6/8), tonic spasm in four (50%, 4/8), tonic seizures in two, atypical absence in one, and generalized tonic–clonic seizures in one. Seven patients had multiple seizure types. Eight (73%, 8/11) patients had movement disorders, seven of them having only dystonia, and one having dystonia with choreoathetosis. Varying degrees of developmental delay (DD) were present in all 11 patients. The phenotypes were diagnosed as early infantile epileptic encephalopathy (EIEE) in two (18%) patients, which were further diagnosed as West syndrome. Movement disorders (MD) with developmental delay were diagnosed in two (18%) brothers. EIEE and MD were overlapped in six (55%) patients, among which two were diagnosed with West syndrome, one with Ohtahara syndrome, and the other three with non-specific EIEE. One (9%) patient was diagnosed as DD alone. The onset age of GNAO1-related disorders was early infancy. The phenotypic spectrum of GNAO1 included EIEE, MD with DD, and DD alone.
Endovascular Treatment of Intracranial Aneurysms in Small Peripheral Vessel Segments—Efficacy and Intermediate Follow-Up Results of Flow Diversion With the Silk Vista Baby Low-Profile Flow Diverter
Authors: Schüngel Marie-Sophie , Quäschling Ulf , Weber Erik , Struck Manuel Florian , Maybaum Jens , Bailis Nikolaos , Arlt Felix , Richter Cindy , Hoffmann Karl-Titus , Scherlach Cordula , Schob Stefan
Published: May 2021

Background and Purpose: Low-profile flow diverter stents (FDS) quite recently amended peripheral segments as targets for hemodynamic aneurysm treatment; however, reports on outcomes, especially later than 3 months, are scarce. This study therefore reports our experience with the novel silk vista baby (SVB) FDS and respective outcomes after 8 and 11 months with special respect to specific adverse events.

Materials and Methods: Forty-four patients (mean age, 53 years) harboring 47 aneurysms treated with the SVB between June 2018 and December 2019 were included in our study. Clinical, procedural, and angiographic data were collected. Follow-ups were performed on average after 3, 8, and 11 months, respectively. Treatment effect was assessed using the O'Kelly Marotta (OKM) grading system.

Results: Overall, angiographic follow-ups were available for 41 patients/45 aneurysms. Occlusion or significant reduction in aneurysmal perfusion (OKM: D1, B1–B3 and A2–A3) was observed in 98% of all aneurysms after 8 months. Only 2% of the treated aneurysms remained morphologically unaltered and without an apparent change in perfusion (OKM A1). Adverse events in the early post-interventional course occurred in seven patients; out of them, mRS-relevant morbidity at 90 days related to FDS treatment was observable in two patients. One death occurred in the context of severe SAH related to an acutely ruptured dissecting aneurysm of the vertebral artery.

Conclusion: The SVB achieves sufficient occlusion rates of intracranial aneurysms originating from peripheral segments, which are comparable to prior established conventional FDS with acceptably low complication rates. However, alteration of a hemodynamic equilibrium in distal localizations requires special attention to prevent ischemic events.
A Survey on Deep Learning-Based Short/Zero-Calibration Approaches for EEG-Based Brain–Computer Interfaces
Authors: Ko Wonjun , Jeon Eunjin , Jeong Seungwoo , Phyo Jaeun , Suk Heung-Il
Published: May 2021

Brain–computer interfaces (BCIs) utilizing machine learning techniques are an emerging technology that enables a communication pathway between a user and an external system, such as a computer. Owing to its practicality, electroencephalography (EEG) is one of the most widely used measurements for BCI. However, EEG has complex patterns and EEG-based BCIs mostly involve a cost/time-consuming calibration phase; thus, acquiring sufficient EEG data is rarely possible. Recently, deep learning (DL) has had a theoretical/practical impact on BCI research because of its use in learning representations of complex patterns inherent in EEG. Moreover, algorithmic advances in DL facilitate short/zero-calibration in BCI, thereby suppressing the data acquisition phase. Those advancements include data augmentation (DA), increasing the number of training samples without acquiring additional data, and transfer learning (TL), taking advantage of representative knowledge obtained from one dataset to address the so-called data insufficiency problem in other datasets. In this study, we review DL-based short/zero-calibration methods for BCI. Further, we elaborate methodological/algorithmic trends, highlight intriguing approaches in the literature, and discuss directions for further research. In particular, we search forgenerative model-based andgeometric manipulation-based DA methods. Additionally, we categorize TL techniques in DL-based BCIs intoexplicitandimplicitmethods. Our systematization reveals advances in the DA and TL methods. Among the studies reviewed herein, ~45% of DA studies used generative model-based techniques, whereas ~45% of TL studies used explicit knowledge transferring strategy. Moreover, based on our literature review, we recommend an appropriate DA strategy for DL-based BCIs and discuss trends of TLs used in DL-based BCIs.
The Interaction Between Microglia and Macroglia in Glaucoma
Authors: Zhao Xiaohuan , Sun Rou , Luo Xueting , Wang Feng , Sun Xiaodong
Published: May 2021

Glaucoma, a neurodegenerative disease that leads to irreversible vision loss, is characterized by progressive loss of retinal ganglion cells (RGCs) and optic axons. To date, elevated intraocular pressure (IOP) has been recognized as the main phenotypic factor associated with glaucoma. However, some patients with normal IOP also have glaucomatous visual impairment and RGC loss. Unfortunately, the underlying mechanisms behind such cases remain unclear. Recent studies have suggested that retinal glia play significant roles in the initiation and progression of glaucoma. Multiple types of glial cells are activated in glaucoma. Microglia, for example, act as critical mediators that orchestrate the progression of neuroinflammation through pro-inflammatory cytokines. In contrast, macroglia (astrocytes and Müller cells) participate in retinal inflammatory responses as modulators and contribute to neuroprotection through the secretion of neurotrophic factors. Notably, research results have indicated that intricate interactions between microglia and macroglia might provide potential therapeutic targets for the prevention and treatment of glaucoma. In this review, we examine the specific roles of microglia and macroglia in open-angle glaucoma, including glaucoma in animal models, and analyze the interaction between these two cell types. In addition, we discuss potential treatment options based on the relationship between glial cells and neurons.
Dynamics of Long-Range Temporal Correlations in Broadband EEG During Different Motor Execution and Imagery Tasks
Authors: Wairagkar Maitreyee , Hayashi Yoshikatsu , Nasuto Slawomir J.
Published: May 2021

Brain activity is composed of oscillatory and broadband arrhythmic components; however, there is more focus on oscillatory sensorimotor rhythms to study movement, but temporal dynamics of broadband arrhythmic electroencephalography (EEG) remain unexplored. We have previously demonstrated that broadband arrhythmic EEG contains both short- and long-range temporal correlations that change significantly during movement. In this study, we build upon our previous work to gain a deeper understanding of these changes in the long-range temporal correlation (LRTC) in broadband EEG and contrast them with the well-known LRTC in alpha oscillation amplitude typically found in the literature. We investigate and validate changes in LRTCs during five different types of movements and motor imagery tasks using two independent EEG datasets recorded with two different paradigms—our finger tapping dataset with single self-initiated asynchronous finger taps and publicly available EEG dataset containing cued continuous movement and motor imagery of fists and feet. We quantified instantaneous changes in broadband LRTCs by detrended fluctuation analysis on single trial 2 s EEG sliding windows. The broadband LRTC increased significantly (p < 0.05) during all motor tasks as compared to the resting state. In contrast, the alpha oscillation LRTC, which had to be computed on longer stitched EEG segments, decreased significantly (p < 0.05) consistently with the literature. This suggests the complementarity of underlying fast and slow neuronal scale-free dynamics during movement and motor imagery. The single trial broadband LRTC gave high average binary classification accuracy in the range of 70.54±10.03% to 76.07±6.40% for all motor execution and imagery tasks and hence can be used in brain–computer interface (BCI). Thus, we demonstrate generalizability, robustness, and reproducibility of novel motor neural correlate, the single trial broadband LRTC, during different motor execution and imagery tasks in single asynchronous and cued continuous motor-BCI paradigms and its contrasting behavior with LRTC in alpha oscillation amplitude.
Inborn Errors of Metabolism Associated With Autism Spectrum Disorders: Approaches to Intervention
Authors: Žigman Tamara , Petković Ramadža Danijela , Šimić Goran , Barić Ivo
Published: May 2021

Increasing evidence suggests that the autism spectrum disorder (ASD) may be associated with inborn errors of metabolism, such as disorders of amino acid metabolism and transport [phenylketonuria, homocystinuria, S-adenosylhomocysteine hydrolase deficiency, branched-chain α-keto acid dehydrogenase kinase deficiency, urea cycle disorders (UCD), Hartnup disease], organic acidurias (propionic aciduria, L-2 hydroxyglutaric aciduria), cholesterol biosynthesis defects (Smith-Lemli-Opitz syndrome), mitochondrial disorders (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes—MELAS syndrome), neurotransmitter disorders (succinic semialdehyde dehydrogenase deficiency), disorders of purine metabolism [adenylosuccinate lyase (ADSL) deficiency, Lesch-Nyhan syndrome], cerebral creatine deficiency syndromes (CCDSs), disorders of folate transport and metabolism (cerebral folate deficiency, methylenetetrahydrofolate reductase deficiency), lysosomal storage disorders [Sanfilippo syndrome, neuronal ceroid lipofuscinoses (NCL), Niemann-Pick disease type C], cerebrotendinous xanthomatosis (CTX), disorders of copper metabolism (Wilson disease), disorders of haem biosynthesis [acute intermittent porphyria (AIP)] and brain iron accumulation diseases. In this review, we briefly describe etiology, clinical presentation, and therapeutic principles, if they exist, for these conditions. Additionally, we suggest the primary and elective laboratory work-up for their successful early diagnosis.
Brain Tumor MR Image Classification Using Convolutional Dictionary Learning With Local Constraint
Authors: Gu Xiaoqing , Shen Zongxuan , Xue Jing , Fan Yiqing , Ni Tongguang
Published: May 2021

Brain tumor image classification is an important part of medical image processing. It assists doctors to make accurate diagnosis and treatment plans. Magnetic resonance (MR) imaging is one of the main imaging tools to study brain tissue. In this article, we propose a brain tumor MR image classification method using convolutional dictionary learning with local constraint (CDLLC). Our method integrates the multi-layer dictionary learning into a convolutional neural network (CNN) structure to explore the discriminative information. Encoding a vector on a dictionary can be considered as multiple projections into new spaces, and the obtained coding vector is sparse. Meanwhile, in order to preserve the geometric structure of data and utilize the supervised information, we construct the local constraint of atoms through a supervised k-nearest neighbor graph, so that the discrimination of the obtained dictionary is strong. To solve the proposed problem, an efficient iterative optimization scheme is designed. In the experiment, two clinically relevant multi-class classification tasks on the Cheng and REMBRANDT datasets are designed. The evaluation results demonstrate that our method is effective for brain tumor MR image classification, and it could outperform other comparisons.
Post-stroke Delivery of Valproic Acid Promotes Functional Recovery and Differentially Modifies Responses of Peri-Infarct Microglia
Authors: Kuo Tung-Tai , Wang Vicki , Wu Jui-Sheng , Chen Yuan-Hao , Tseng Kuan-Yin
Published: May 2021

The specific role of peri-infarct microglia and the timing of its morphological changes following ischemic stroke are not well understood. Valproic acid (VPA) can protect against ischemic damage and promote recovery. In this study, we first determined whether a single dose of VPA after stroke could decrease infarction area or improve functional recovery. Next, we investigated the number and morphological characteristic of peri-infarct microglia at different time points and elucidated the mechanism of microglial response by VPA treatment. Male Sprague-Dawley rats were subjected to distal middle cerebral artery occlusion (dMCAo) for 90 min, followed by reperfusion. Some received a single injection of VPA (200 mg/kg) 90 min after the induction of ischemia, while vehicle-treated animals underwent the same procedure with physiological saline. Infarction volume was calculated at 48 h after reperfusion, and neurological symptoms were evaluated. VPA didn’t significantly reduce infarct volume but did ameliorate neurological deficit at least partially compared with vehicle. Meanwhile, VPA reduced dMCAo-induced elevation of IL-6 at 24 h post-stroke and significantly decreased the number of CD11b-positive microglia within peri-infarct cortex at 7 days. Morphological analysis revealed that VPA therapy leads to higher fractal dimensions, smaller soma size and lower circularity index of CD11b-positive cells within peri-infarct cortex at both 2 and 7 days, suggesting that VPA has core effects on microglial morphology. The modulation of microglia morphology caused by VPA might involve HDAC inhibition-mediated suppression of galectin-3 production. Furthermore, qPCR analysis of CD11b-positive cells at 3 days post-stroke suggested that VPA could partially enhance M2 subset polarization of microglia in peri-infarct cortex. Analysis of VPA-induced changes to gene expressions at 3 days post-stroke implies that these alternations of the biomarkers and microglial responses are implicated in the upregulation of wound healing, collagen trimmer, and extracellular matrix genes within peri-infarct cortex. Our results are the first to show that a low dose of VPA promotes short-term functional recovery but does not alter infarct volume. The decreases in the expression of both IL-6 and galectin-3 might influence the morphological characteristics and transcriptional profiles of microglia and extracellular matrix remodeling, which could contribute to the improved recovery.