bluuebunny/crossref_metadata_2025 huggingface dataset:
The Microbial Quality of Commercial Chopped Romaine Lettuce Before and After the “Use By” Date
Authors: Liao Chao , Wang Luxin
Published: April 2022

In the United States, due to the limited information about the microbial quality and safety of fresh produce after the labeled open dates, unnecessary discarding of fresh produce in good conditions and food loss have been caused. The aim of this study was to address this knowledge gap and evaluate the microbial quality of commercial chopped Romaine lettuce (RL) on the “Use By” dates (UBD) and 5 days after the “Use By” dates (UBD5). The microbial quality was evaluated using culture-dependent and culture-independent methods. Three brands of RL samples, from early and late harvest seasons, were purchased from local grocery stores and stored at 4°C until 5 days after their UBD. On the UBD and UBD5, bagged lettuce was opened, homogenized, diluted, and plated onto plate count agar and anaerobic agar to obtain total aerobic plate counts (APC) and total anaerobic plate counts (AnPC). For the culture-independent method, DNA was extracted from each sample homogenate and used for 16S rRNA gene sequencing. The culture-dependent results showed that there was no significant change in APC or AnPC between UBD and UBD5 samples. The APC and AnPC ranged from 5.71 ± 0.74 to 7.89 ± 0.10 Log CFU/g and 1.75 ± 0.08 to 7.32 ± 0.61 Log CFU/g, respectively. No significant difference in alpha diversity, based on observed features and Shannon index values, was detected between UBD and UBD5 samples using 16S rRNA sequencing. Similarly, no difference was observed in beta diversity based on the Jaccard distance matrixes and the weighted Unifrac distance matrixes. Taxonomic analysis revealed 128 genera in all RL samples. The top five genera were Pseudomonas (with relative abundance ranging from 16.47 to 92.72%), Serratia (0–52.35%), Weissella (0–42.42%), Pantoea (0.17–21.33%), and Lactococcus (0–24.30%). The differential abundance analysis based on the ANCOM test showed that no bacteria were detected to have significantly differential abundance in RL between UBD and UBD5. In summary, both the culture-dependent and culture-independent results showed that there was no significant difference in the microbial quality of RL before and shortly after the UBD.
Outbreak of Severe Acute Respiratory Syndrome Coronavirus-2 B.1.620 Lineage in the General Hospital of Jeju Island, Republic of Korea
Authors: Ha Young-Ran , Shin Een-suk , Kim Hyun-Jeong , Hyeon Eun-Hwa , Park Jae-Sung , Chung Yoon-Seok
Published: April 2022

The number of coronavirus disease (COVID-19)-positive cases has increased in Jeju Island, Republic of Korea. Identification and monitoring of new mutations in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are extremely important to fighting the global pandemic. We report a breakout of the B.1.620 lineage, harboring the E484 mutation in the virus spike protein in a general hospital on Jeju Island. A cluster of cases was detected between August 4 and September 10, 2021, involving 20 patients positive for COVID-19 of 286 individuals exposed to the virus, comprising hospital patients, staff, and caregivers. We analyzed the epidemiological characteristics and spike proteins mutation sites using Sanger sequencing and phylogenetic analysis on these 20 patients. By analyzing genomic variance, it was confirmed that 12 of the confirmed patients harbored the SARS-CoV-2 B.1.620 lineage. The breakthrough rate of infection was 2% in fully vaccinated individuals among these patients. Next clade analysis revealed that these SARS-CoV-2 genomes belong to clade 20A. This is the first reported case of SARS-CoV-2 sub-lineage B.1.620, although the B.1.617.2 lineage has prevailed in August and September in Jeju, which has a geographical advantage of being an island. We reaffirm that monitoring the spread of SARS-CoV-2 variants with characteristic features is indispensable for controlling COVID-19 outbreaks.
Highly Selenite-Tolerant Strain Proteus mirabilis QZB-2 Rapidly Reduces Selenite to Selenium Nanoparticles in the Cell Membrane
Authors: Huang JinLan , Jiang DaiHua , Wang MingShi , Huang XueJiao
Published: April 2022

The application of biosynthesized nano-selenium fertilizers to crops can improve their nutrient levels by increasing their selenium content. However, microorganisms with a high selenite tolerance and rapid reduction rate accompanied with the production of selenium nanoparticles (SeNPs) at the same time have seldom been reported. In this study, a bacterial strain showing high selenite resistance (up to 300 mM) was isolated from a lateritic red soil and identified as Proteus mirabilis QZB-2. This strain reduced nearly 100% of 1.0 and 2.0 mM selenite within 12 and 18 h, respectively, to produce SeNPs. QZB-2 isolate reduced SeO32– to Se0 in the cell membrane with NADPH or NADH as electron donors. Se0 was then released outside of the cell, where it formed spherical SeNPs with an average hydrodynamic diameter of 152.0 ± 10.2 nm. P. mirabilis QZB-2 could be used for SeNPs synthesis owing to its simultaneously high SeO32– tolerance and rapid reduction rate.
Response of Plant-Associated Microbiome to Plant Root Colonization by Exogenous Bacterial Endophyte in Perennial Crops
Authors: Yurgel Svetlana N. , Ajeethan Nivethika , Smertenko Andrei
Published: April 2022

The application of bacterial inoculums for improving plant growth and production is an important component of sustainable agriculture. However, the efficiency of perennial crop inoculums depends on the ability of the introduced endophytes to exert an impact on the host-plant over an extended period of time. This impact might be evaluated by the response of plant-associated microbiome to the inoculation. In this study, we monitored the effect of a single bacterial strain inoculation on the diversity, structure, and cooperation in plant-associated microbiome over 1-year period. An endophyte (RF67) isolated fromVaccinium angustifolium(wild blueberry) roots and annotated asRhizobiumwas used for the inoculation of 1-year-oldLonicera caerulea(Haskap) plants. A significant level of bacterial community perturbation was detected in plant roots after 3 months post-inoculation. About 23% of root-associated community variation was correlated with an application of the inoculant, which was accompanied by increased cooperation between taxa belonging to Proteobacteria and Actinobacteriota phyla and decreased cooperation between Firmicutes in plant roots. Additionally, a decrease in bacterial Shannon diversity and an increase in the relative abundances ofRhizobiaceaeandEnterobacteriaceaewere detected in the roots of inoculated plants relative to the non-inoculated control. A strong effect of the inoculation on the bacterial cooperation was also detected after 1 year of plant field growth, whereas no differences in bacterial community composition and also alpha and beta diversities were detected between bacterial communities from inoculated and non-inoculated roots. These findings suggest that while exogenous endophytes might have a short-term effect on the root microbiome structure and composition, they can boost cooperation between plant-growth-promoting endophytes, which can exist for the extended period of time providing the host-plant with long-lasting beneficial effects.
Aspartate Transaminase AST2 Involved in Sporulation and Necrotrophic Pathogenesis in the Hemibiotrophs Magnaporthe oryzae and Colletotrichum graminicola
Authors: Zhang Penghui , Fang Zhenyu , Song Yanyue , Wang Shaowei , Bao Lina , Liu Mingyu , Dang Yuejia , Wei Yi , Zhang Shi-Hong
Published: April 2022

Aspartate family includes five additional amino acids other than aspartate, among which most except aspartate have been reported for their action in pathogenesis by amino acid biosynthesis. However, how aspartate, the initial substrate of this family metabolic pathway, is involved in pathogenesis remains unknown. Here, we focused on aspartate transaminase (AST) that catalyzes transamination reaction between glutamate-aspartate in Magnaporthe oryzae. Three MoAST genes were bioinformatically analyzed, of which MoAST2 was uniquely upregulated when invasive hyphae switched to necrotrophic pathogenesis. MoAST2 deletion (ΔMoast2) caused a drastic reduction in conidiogenesis and appressorium formation. Particularly, ΔMoast2 was observed to be proliferated at the biotrophic phase but inhibited at the necrotrophic stage, and with invisible symptoms detected, suggesting a critical role in necrotrophic phase. Glutamate family restored the ΔMoast2 defects but aspartate family did not, inferring that transamination occurs from aspartate to glutamine. MoAST2 is cytosolic and possessed H2O2 stress tolerance. In parallel, Colletotrichum graminicola AST2, CgAST2 was proven to be a player in necrotrophic anthracnose development. Therefore, conserved AST2 is qualified to be a drug target for disease control.
The RNA Chaperone Protein Hfq Regulates the Characteristic Sporulation and Insecticidal Activity of Bacillus thuringiensis
Authors: Yu Zhaoqing , Fu Yang , Zhang Wei , Zhu Li , Yin Wen , Chou Shan-Ho , He Jin
Published: April 2022

Bacillus thuringiensis (Bt) is one of the most widely used bio-insecticides at present. It can produce many virulence factors and insecticidal crystal proteins during growth and sporulation. Hfq, on the other hand, is a bacterial RNA chaperone that can regulate the function of different kinds of RNAs, thereby affecting various bacterial phenotypes. To further explore the physiological functions of Hfq in Bt, we took BMB171 as the starting strain, knocked out one, two, or three hfq genes in its genome in different combinations, and compared the phenotypic differences between the deletion mutant strains and the starting strain. We did observe significant changes in several phenotypes, including motility, biofilm formation, sporulation, and insecticidal activity against cotton bollworm, among others. Afterward, we found through transcriptome studies that when all hfq genes were deleted, 32.5% of the genes in Bt were differentially transcribed, with particular changes in the sporulation-related and virulence-related genes. The above data demonstrated that Hfq plays a pivotal role in Bt and can regulate its various physiological functions. Our study on the regulatory mechanism of Hfq in Bt, especially the mining of the regulatory network of its sporulation and insecticidal activity, could lay a theoretical foundation for the better utilization of Bt as an effective insecticide.
Serum Proteomic Analysis by Tandem Mass Tag-Based Quantitative Proteomics in Pediatric Obstructive Sleep Apnea
Authors: Cheng Hanrong , Jin Shoumei , Huang Simin , Hu Tianyong , Zhao Miao , Li Dongcai , Wu Benqing
Published: April 2022

Pediatric obstructive sleep apnea (OSA) is a frequent respiratory disorder with an estimated prevalence of 3–6% in the general population. However, the underlying pathophysiology of OSA remains unclear. Recently, proteomic analysis using high-resolution and high-throughput mass spectrometry has been widely used in the field of medical sciences. In the present study, tandem mass tag (TMT)-based proteomic analysis was performed in the serum of patients with OSA. The proteomic analysis revealed a set of differentially expressed proteins that may be associated with the pathophysiology of OSA. The differentially expressed proteins in patients with OSA were enriched in pathways including phagosome and glycan synthesis/degradation, immune response, and the hedgehog signaling pathway, indicating that such functions are key targets of OSA. Moreover, the experimental validation studies revealed that four proteins including ANTXR1, COLEC10, NCAM1, and VNN1 were reduced in the serum from patients with moderate and severe OSA, while MAN1A1 and CSPG4 protein levels were elevated in the serum from patients with severe OSA. The protein levels of ANTXR1, COLEC10, NCAM1, and VNN1 were inversely correlated with apnea-hypopnea index (AHI) in the recruited subjects, while the protein level of MAN1A1 was positively correlated with AHI, and no significant correlation was detected between CSPG4 protein and AHI. In summary, the present study for the first time identified differentially expressed proteins in the serum from OSA patients with different severities by using TMT-based proteomic analysis. The functional enrichment studies suggested that several signaling pathways may be associated with the pathophysiology of OSA. The experimental validation results indicated that six proteins including ANTXR1, COLEC10, NCAM1, VNN1, CGPG4, and MAN1A1 may play important roles in the pathophysiology of OSA, which requires further mechanistic investigation.
Building Biological Relevance Into Integrative Modelling of Macromolecular Assemblies
Authors: Molza Anne-Elisabeth , Westermaier Yvonne , Moutte Magali , Ducrot Pierre , Danilowicz Claudia , Godoy-Carter Veronica , Prentiss Mara , Robert Charles H. , Baaden Marc , Prévost Chantal
Published: April 2022

Recent advances in structural biophysics and integrative modelling methods now allow us to decipher the structures of large macromolecular assemblies. Understanding the dynamics and mechanisms involved in their biological function requires rigorous integration of all available data. We have developed a complete modelling pipeline that includes analyses to extract biologically significant information by consistently combining automated and interactive human-guided steps. We illustrate this idea with two examples. First, we describe the ryanodine receptor, an ion channel that controls ion flux across the cell membrane through transitions between open and closed states. The conformational changes associated with the transitions are small compared to the considerable system size of the receptor; it is challenging to consistently track these states with the available cryo-EM structures. The second example involves homologous recombination, in which long filaments of a recombinase protein and DNA catalyse the exchange of homologous DNA strands to reliably repair DNA double-strand breaks. The nucleoprotein filament reaction intermediates in this process are short-lived and heterogeneous, making their structures particularly elusive. The pipeline we describe, which incorporates experimental and theoretical knowledge combined with state-of-the-art interactive and immersive modelling tools, can help overcome these challenges. In both examples, we point to new insights into biological processes that arise from such interdisciplinary approaches.
From the PnTx2-6 Toxin to the PnPP-19 Engineered Peptide: Therapeutic Potential in Erectile Dysfunction, Nociception, and Glaucoma
Authors: Silva Carolina Nunes da , Nunes Kenia Pedrosa , Dourado Lays Fernanda Nunes , Vieira Thayllon Oliveira , Mariano Xavier Maia , Cunha Junior Armando da Silva , de Lima Maria Elena
Published: April 2022

The venom of the “armed” spider Phoneutria nigriventer comprises several potent toxins. One of the most toxic components from this venom is the neurotoxin PnTx2-6 (LD50 = ∼ 0.7 μg/mouse, 48 residues, five disulfide bridges, MW = 5,289.31 Da), which slows down the inactivation of various Na+ channels. In mice and rats, this toxin causes priapism, an involuntary and painful erection, similar to what is observed in humans bitten by P. nigriventer. While not completely elucidated, it is clear that PnTx2-6 potentiates erectile function via NO/cGMP signaling, but it has many off-target effects. Seeking to obtain a simpler and less toxic molecule able to retain the pharmacological properties of this toxin, we designed and synthesized the peptide PnPP-19 (19 residues, MW = 2,485.6 Da), representing a discontinuous epitope of PnTx2-6. This synthetic peptide also potentiates erectile function via NO/cGMP, but it does not target Na+ channels, and therefore, it displays nontoxic properties in animals even at high doses. PnPP-19 effectively potentiates erectile function not only after subcutaneous or intravenous administration but also following topical application. Surprisingly, PnPP-19 showed central and peripheral antinociceptive activity involving the opioid and cannabinoid systems, suggesting applicability in nociception. Furthermore, considering that PnPP-19 increases NO availability in the corpus cavernosum, this peptide was also tested in a model of induced intraocular hypertension, characterized by low NO levels, and it showed promising results by decreasing the intraocular pressure which prevents retinal damage. Herein, we discuss how was engineered this smaller active non-toxic peptide with promising results in the treatment of erectile dysfunction, nociception, and glaucoma from the noxious PnTx2-6, as well as the pitfalls of this ongoing journey.
Paternal High-Fat Diet Altered Sperm 5'tsRNA-Gly-GCC Is Associated With Enhanced Gluconeogenesis in the Offspring
Authors: Wang Bin , Xia Lin , Zhu Dan , Zeng Hongtao , Wei Bin , Lu Likui , Li Weisheng , Shi Yajun , Liu Jingliu , Zhang Yunfang , Sun Miao
Published: April 2022

Background: Paternal lifestyle, stress and environmental exposures play a crucial role in the health of offspring and are associated with non-genetic inheritance of acquired traits, however the underlying mechanisms are unclear. In this study, we aimed to find out how the sperm tsRNA involved in paternal high-fat diet induced abnormal gluconeogenesis of F1 offspring, and explore the underlying molecular mechanism of its regulation.

Method: We generated a paternal high fat diet (42% kcal fat) model to investigate the mechanism by which paternal diet affects offspring metabolism. Four-week-old C57BL/6J male mice were randomly assigned into two groups to receive either a control diet (CD; 10% kcal fat) or a high-fat (HFD; 42% kcal fat) diet for 10 weeks, and mice from each group were then mated with 8-week-old females with control diet in a 1:2 ratio to generate F1. F0 sperms were isolated and small RNAs was sequenced by high-throughput sequencing. Metabolic phenotypes were examined with both F0 and F1.

Results: A significant increase in body weight was observed with HFD-F0 mice at 8 weeks of age as compared to CD mice at the same age. F0 mice showed impaired glucose tolerance (GTT), resistance to insulin tolerance (ITT) and increased pyruvate tolerance (PTT) at 14 weeks. HFD-F1 male mice showed no significant difference in body weight. An increase in PTT was found at 13 weeks of age and no significant changes in GTT and ITT. PEPCK and G6Pase that related to gluconeogenesis increased significantly in the liver of HFD-F1 male mice. Sperm sequencing results showed that 5′tsRNA-Gly-GCC derived from tRNA-Gly-GCC-2 specifically was remarkably upregulated in sperm of HFD F0 mice. Q-PCR further showed that this tsRNA was also increased in the liver of HFD-F1 comparison with CD-F1 mice. In addition, we found that 5′tsRNA-Gly-GCC can regulate Sirt6-FoxO1 pathway and be involved in the gluconeogenesis pathway in liver.

Conclusion: 5′tsRNA-Gly-GCC that increased in HFD mice mature sperms can promote gluconeogenesis in liver by regulating Sirt6-FoxO1 pathway, which might represent a potential paternal epigenetic factor mediating the intergenerational inheritance of diet-induced metabolic alteration.
Total Cerebral Small Vessel Disease Score and Cerebral Bleeding Risk in Patients With Acute Stroke Treated With Intravenous Thrombolysis
Authors: Du Houwei , Wu Sangru , Lei Hanhan , Ambler Gareth , Werring David J. , Li Hangfeng , Chen Yangui , Chen Dongping , Yuan Qilin , Fang Shuangfang , Chen Ronghua , Zhang Yixian , Wei Jin , Chen Guangliang , Chen Jianhua , Liu Nan
Published: April 2022

Objective

The aim of this study was to investigate the association of total cerebral small vessel disease (cSVD) score with the risk of intracerebral hemorrhage (ICH) in patients with acute ischemic stroke who received intravenous thrombolysis (IVT) using recombinant tissue-plasminogen activator (rt-PA).

Methods

We retrospectively reviewed clinical data from two stroke registries of patients with acute ischemic stroke treated with IVT. We assessed the baseline magnetic resonance (MR) visible cSVD markers and total cSVD score (ranging from 0 to 4) between patients with and without ICH after IVT. Logistic regression analysis was used to determine the association of total cSVD score with the risk of ICH after IVT, adjusted for cofounders selected by least absolute shrinkage and selection operator (LASSO). We additionally performed an E-value analysis to fully explain away a specific exposure-outcome association. Receiver operating characteristic (ROC) curve analysis was used to quantify the predictive potential of the total cSVD score for any ICH after IVT.

Results

Among 271 eligible patients, 55 (20.3%) patients experienced any ICH, 16 (5.9%) patients experienced a symptomatic ICH (sICH), and 5 (1.85%) patients had remote intracranial parenchymal hemorrhage (rPH). Logistic regression analysis showed that the risk of any ICH increased with increasing cSVD score [per unit increase, adjusted odds ratio (OR) 2.03, 95% CI 1.22–3.41, P = 0.007]. Sensitivity analyses using E-value revealed that it would need moderately robust unobserved confounding to render the exposure-outcome (cSVD-any ICH) association null. ROC analysis showed that compared with the National Institutes of Health Stroke Scale (NIHSS) score alone, a combination of cSVD and NIHSS score had a larger area under the curve for any ICH (0.811, 95% CI 0.756–0.866 vs. 0.784, 95% CI 0.723–0.846, P = 0.0004).

Conclusion

The total cSVD score is associated with an increased risk of any ICH after IVT and improves prediction for any ICH compared with NIHSS alone.
The Top-Cited Original Articles on the Role of Microglia in Neurodegenerative Diseases: A Bibliometric and Visualized Study
Authors: Sun Mengjiao , Li Xiaoling , Sun Jing , Wang Hongxia , Xie Qinfang , Wang Manxia
Published: April 2022

Background

Microglia participants to neuronal loss during brain development, inflammation, ischemia, and neurodegeneration. This bibliometric and visualized study aimed to confirm the top 100 cited original research in the field and to analyze their characteristics.

Methods

The Web of Science database (WOS) was retrieved using the specific search strategy. The top 100 cited original articles that focused on the role of microglia in neurodegenerative diseases (NDs) were filtered by two researchers independently. The trend of yearly publications and citations, citation densities, languages, and global contributions were analyzed. The highly cited countries, authors, institutions, and journals were visualized by bibliographic coupling analysis. The highly cited authors and journals in the references were visualized by co-citation analysis. The research hotspots were revealed by co-occurrence analysis and burst detection of author keywords.

Results

The top 100 cited articles were published during the period 1988 to 2019. The peak of publication occurred in 2005 and 2006. The yearly total citations presented a rising trend. The highly cited articles were contributed by 26 countries, the United States was the country with the overwhelming number of publications and cited times. Stevens, Beth was the author with the largest number of cited times. Mcgeer PL was the author most frequently cited in the references. Harvard University was the institution with the greatest number of cited times and publications. Nature was the journal with the largest number of cited times. Journal of neuroscience was both the most often published and most frequently cited journal in the references. “Microglia”, “inflammation”, “Alzheimer’s disease” were the most frequently used keywords, and their average occurred time was around 2005. “Dementia,” “delirium,” “priming” were keywords that averagely occurred around 2010. The burst detection revealed that “TNF-beta,” “macrophage,” and “inflammation” were keywords that frequently burst in recent years.

Conclusion

This bibliometric and visualized study revealed the top 100 cited original research that discussed the role of microglia in NDs. The United States was the biggest contributor, Harford University was the most influential institution. Journal of Neuroscience was the most often published and cited journal. Alzheimer’s disease was the hotspot in microglia and NDs. Recent research mainly focused on inflammation.
Effects of Immediate Aversive Stimulation on Haloperidol-Induced Catalepsy in Rats
Authors: Waku Isabelle , Reimer Adriano E. , de Oliveira Amanda R.
Published: April 2022

In animal models, the administration of the dopaminergic D2 antagonist haloperidol affects the nigrostriatal pathway, inducing catalepsy, a state of immobility similar to Parkinson’s disease (PD) bradykinesia and akinesia. In PD, the motor impairments are due to difficulties in selecting and executing motor actions, associated with dopamine loss in basal ganglia and cortical targets. Motor and affective limbic networks seem to be integrated via a striato-nigro-striatal network, therefore, it is not surprising that the motor impairments in PD can be influenced by the patient’s emotional state. Indeed, when exposed to aversive stimuli or life-threatening events, immobile patients are capable of performing sudden movements, a phenomenon known as paradoxical kinesia. Thus, the present study investigated the effects of unconditioned and conditioned aversive stimulation on haloperidol-induced catalepsy in rats. First, male Wistar rats received intraperitoneal administration of saline or haloperidol (1 or 2 mg/kg) and were evaluated in the catalepsy bar test to assess the cataleptic state induced by the different doses of haloperidol over time. Next, we evaluated the effects of two types of unconditioned aversive stimuli–100 lux light (1 and 20 s) or 0.6 mA footshock (1 s)–on the catalepsy. Finally, we evaluated the effects of light conditioned stimuli (Light-CS), previously paired with footshocks, on the cataleptic state. Catalepsy was observed following haloperidol 1 and 2 mg/kg administration. Exposure to footshocks, but not to light, significantly reduced step-down latency during the catalepsy test. Although unconditioned light did not affect catalepsy, paired Light-CS did reduce step-down latency. Here, we have provided evidence of face validity for the study of paradoxical kinesia. In addition to demonstrating that immediate exposure to an aversive stimulus is capable of disrupting the cataleptic state, our findings show that haloperidol-induced catalepsy seems to be differently influenced depending on the modality of aversive stimulation. Our data suggest that the selective recruitment of threat response systems may bypass the dysfunctional motor circuit leading to the activation of alternative routes to drive movement.
Progresses and Prospects of Neuroprotective Agents-Loaded Nanoparticles and Biomimetic Material in Ischemic Stroke
Authors: Chen Junfa , Jin Jing , Li Kaiqiang , Shi Lin , Wen Xuehua , Fang Fuquan
Published: April 2022

Ischemic stroke remains the leading cause of death and disability, while the main mechanisms of dominant neurological damage in stroke contain excitotoxicity, oxidative stress, and inflammation. The clinical application of many neuroprotective agents is limited mainly due to their inability to cross the blood-brain barrier (BBB), short half-life and low bioavailability. These disadvantages can be better eliminated/reduced by nanoparticle as the carrier of these drugs. This review expounded the currently hot researched nanomedicines from the perspective of the mechanism of ischemic stroke. In addition, this review describes the bionic nanomedicine delivery strategies containing cells, cell membrane vesicles and exosomes that can effectively avoid the risk of clearance by the reticuloendothelial system. The potential challenges and application prospect for clinical translation of these delivery platforms were also discussed.
U-RISC: An Annotated Ultra-High-Resolution Electron Microscopy Dataset Challenging the Existing Deep Learning Algorithms
Authors: Shi Ruohua , Wang Wenyao , Li Zhixuan , He Liuyuan , Sheng Kaiwen , Ma Lei , Du Kai , Jiang Tingting , Huang Tiejun
Published: April 2022

Connectomics is a developing field aiming at reconstructing the connection of the neural system at the nanometer scale. Computer vision technology, especially deep learning methods used in image processing, has promoted connectomic data analysis to a new era. However, the performance of the state-of-the-art (SOTA) methods still falls behind the demand of scientific research. Inspired by the success of ImageNet, we present an annotated ultra-high resolution image segmentation dataset for cell membrane (U-RISC), which is the largest cell membrane-annotated electron microscopy (EM) dataset with a resolution of 2.18 nm/pixel. Multiple iterative annotations ensured the quality of the dataset. Through an open competition, we reveal that the performance of current deep learning methods still has a considerable gap from the human level, different from ISBI 2012, on which the performance of deep learning is closer to the human level. To explore the causes of this discrepancy, we analyze the neural networks with a visualization method, which is an attribution analysis. We find that the U-RISC requires a larger area around a pixel to predict whether the pixel belongs to the cell membrane or not. Finally, we integrate the currently available methods to provide a new benchmark (0.67, 10% higher than the leader of the competition, 0.61) for cell membrane segmentation on the U-RISC and propose some suggestions in developing deep learning algorithms. The U-RISC dataset and the deep learning codes used in this study are publicly available.
Sleep: The Tip of the Iceberg in the Bidirectional Link Between Alzheimer's Disease and Epilepsy
Authors: B. Szabo Anna , Cretin Benjamin , Gérard Fleur , Curot Jonathan , J. Barbeau Emmanuel , Pariente Jérémie , Dahan Lionel , Valton Luc
Published: April 2022

The observation that a pathophysiological link might exist between Alzheimer's disease (AD) and epilepsy dates back to the identification of the first cases of the pathology itself and is now strongly supported by an ever-increasing mountain of literature. An overwhelming majority of data suggests not only a higher prevalence of epilepsy in Alzheimer's disease compared to healthy aging, but also that AD patients with a comorbid epileptic syndrome, even subclinical, have a steeper cognitive decline. Moreover, clinical and preclinical investigations have revealed a marked sleep-related increase in the frequency of epileptic activities. This characteristic might provide clues to the pathophysiological pathways underlying this comorbidity. Furthermore, the preferential sleep-related occurrence of epileptic events opens up the possibility that they might hasten cognitive decline by interfering with the delicately orchestrated synchrony of oscillatory activities implicated in sleep-related memory consolidation. Therefore, we scrutinized the literature for mechanisms that might promote sleep-related epileptic activity in AD and, possibly dementia onset in epilepsy, and we also aimed to determine to what degree and through which processes such events might alter the progression of AD. Finally, we discuss the implications for patient care and try to identify a common basis for methodological considerations for future research and clinical practice.
Endoscopic Endonasal Transsphenoidal Surgery for Recurrent Craniopharyngiomas
Authors: Feng Zhenguang , Li Chuzhong , Cao Lei , Qiao Ning , Wu Wentao , Bai Jiwei , Zhao Peng , Gui Songbai
Published: April 2022

Object

Although revision surgery for recurrent craniopharyngiomas is more challenging than primary surgery and often accompanies a higher risk of death and complications, endoscopic endonasal transsphenoidal surgery (EETS) is sometimes still an effective and reliable treatment option. In this study, we introduced the surgical outcomes of EETS for recurrent craniopharyngiomas and summarized the surgical experiences.

Methods

Between 2014 and 2018, 28 patients with recurrent craniopharyngiomas underwent 29 EETS in our department. We regarded the patient undergoing two EETS as two independent patients in statistical analysis. Of the 29 patients, 16 had undergone 1 previous surgery, 10 had undergone 2 previous surgeries, and the remaining 3 patients had undergone 3 surgeries. The extent of resection, visual and endocrine outcomes, and complications of all the patients were collected and analyzed.

Results

Gross total resection was accomplished in 16 patients (55.17%), subtotal resection in 11 patients (37.93%), and partial resection in 2 patients (6.9%). Among the 22 patients with preoperative visual acuity and visual field impairment, some degree of vision improvement was observed in 18 patients, 3 patients were without visual change, and perpetual deterioration of vision occurred in one patient. The remaining six patients had normal vision before and after surgery. Postoperative endocrine tests showed that, among five patients with normal preoperative pituitary hormone function, only one patient still had normal pituitary hormone function and the other four patients had one or more hypothalamic-pituitary axes involved. None of the patients with preoperative endocrine dysfunction had endocrine function improved. Diabetes insipidus was observed in six new cases postoperatively. Cerebrospinal fluid (CSF) leakage occurred in 1 patient. One patient had bacterial meningitis, which was cured with antibiotics and a lumbar drain. No serious morbidity and mortality occurred in all patients.

Conclusions

For recurrent craniopharyngiomas, a personalized treatment plan should be developed according to the tumor characteristics and the patient's situation. There is no omnipotent method to be used for all patients. The EETS still is a safe and effective way to treat recurrent craniopharyngiomas in appropriate patients.
hsa-miR-518-5p/hsa-miR-3135b Regulates the REL/SOD2 Pathway in Ischemic Cerebral Infarction
Authors: Zhao Boyan , Jiang Xiaofan
Published: April 2022

Objectives

Ischemic cerebral infarction (ICI) is a fatal neurovascular disorder. A bioinformatics approach based on single-cell and bulk RNA-seq analyses was applied to investigate the pathways and genes involved in ICI and study the expression profile of these genes.

Methods

First, the aberrantly regulated “small-molecule ribonucleic acids” [microRNA (miRNAs)] and messenger RNAs (mRNAs) were analyzed using transcriptome data from the ischemic brain infarction dataset of the Gene Expression Omnibus (GEO) database. In mouse cerebrovascular monocytes, the single-cell regulatory network inference and clustering (SCENIC) workflow was used to identify key transcription factors (TFs). Then, the two miRNA-TF-mRNA interaction networks were constructed. Moreover, the molecular complex detection (MCODE) extracted the core sub-networks and identified the important TFs within these sub-networks. Finally, whole blood samples were collected for validation of the expression of critical molecules in ICI.

Results

We identified four cell types and 266 regulons in mouse cerebrovascular monocytes using SCENIC analysis. Moreover, 112 differently expressed miRNAs and 3,780 differentially expressed mRNAs were identified. We discovered potential biomarkers in ICI by building a miRNA-TF-mRNA interaction network. The hsa-miR-518-5p/hsa-miR-3135b/REL/SOD2 was found to play a potential role in ICI progression. The expression of REL and superoxide dismutase 2 (SOD2) was significantly elevated in the ICI group in the clinical cohort (P < 0.05). Furthermore, a REL expression was elevated in endothelial cells and fibroblasts at the single-cell level, indicating that REL is a cell-specific regulon. Functional enrichment analyses revealed that REL is primarily engaged in neurotransmitter activity and oxidative phosphorylation.

Conclusions

Our research uncovered novel biomarkers for ICI of neurovascular disease. The hsa-miR-518-5p/hsa-miR-3135b may regulate the REL/SOD2 pathway in ICI progression.
Advances in the Role of Endothelial Cells in Cerebral Small Vessel Disease
Authors: Bai Tao , Yu Shijia , Feng Juan
Published: April 2022

Cerebral small vessel disease (CSVD) poses a serious socio-economic burden due to its high prevalence and severe impact on the quality of life of elderly patients. Pathological changes in CSVD mainly influence small cerebral arteries, microarteries, capillaries, and small veins, which are usually caused by multiple vascular risk factors. CSVD is often identified on brain magnetic resonance imaging (MRI) by recent small subcortical infarcts, white matter hyperintensities, lacune, cerebral microbleeds (CMBs), enlarged perivascular spaces (ePVSs), and brain atrophy. Endothelial cell (EC) dysfunction is earlier than clinical symptoms. Immune activation, inflammation, and oxidative stress may be potential mechanisms of EC injury. ECs of the blood–brain–barrier (BBB) are the most important part of the neurovascular unit (NVU) that ensures constant blood flow to the brain. Impaired cerebral vascular autoregulation and disrupted BBB cause cumulative brain damage. This review will focus on the role of EC injury in CSVD. Furthermore, several specific biomarkers will be discussed, which may be useful for us to assess the endothelial dysfunction and explore new therapeutic directions.
Construction and Evaluation of Multiple Radiomics Models for Identifying the Instability of Intracranial Aneurysms Based on CTA
Authors: Li Ran , Zhou Pengyu , Chen Xinyue , Mossa-Basha Mahmud , Zhu Chengcheng , Wang Yuting
Published: April 2022

Background and Aims

Identifying unruptured intracranial aneurysm instability is crucial for therapeutic decision-making. This study aims to evaluate the role of Radiomics and traditional morphological features in identifying aneurysm instability by constructing and comparing multiple models.

Materials and Methods

A total of 227 patients with 254 intracranial aneurysms evaluated by CTA were included. Aneurysms were divided into unstable and stable groups using comprehensive criteria: the unstable group was defined as aneurysms with near-term rupture, growth during follow-up, or caused compressive symptoms; those without the aforementioned conditions were grouped as stable aneurysms. Aneurysms were randomly divided into training and test sets at a 1:1 ratio. Radiomics and traditional morphological features (maximum diameter, irregular shape, aspect ratio, size ratio, location, etc.) were extracted. Three basic models and two integrated models were constructed after corresponding statistical analysis. Model A used traditional morphological parameters. Model B used Radiomics features. Model C used the Radiomics features related to aneurysm morphology. Furthermore, integrated models of traditional and Radiomics features were built (model A+B, model A+C). The area under curves (AUC) of each model was calculated and compared.

Results

There were 31 (13.7%) patients harboring 36 (14.2%) unstable aneurysms, 15 of which ruptured post-imaging, 16 with growth on serial imaging, and 5 with compressive symptoms, respectively. Four traditional morphological features, six Radiomics features, and three Radiomics-derived morphological features were identified. The classification of aneurysm stability was as follows: the AUC of the training set and test set in models A, B, and C are 0.888 (95% CI 0.808–0.967) and 0.818 (95% CI 0.705–0.932), 0.865 (95% CI 0.777–0.952) and 0.739 (95% CI 0.636–0.841), 0.605(95% CI 0.470–0.740) and 0.552 (95% CI 0.401–0.703), respectively. The AUC of integrated Model A+B was numerically slightly higher than any single model, whereas Model A+C was not.

Conclusions

A radiomics and traditional morphology integrated model seems to be an effective tool for identifying intracranial aneurysm instability, whereas the use of Radiomics-derived morphological features alone is not recommended. Radiomics-based models were not superior to the traditional morphological features model.
Ferroptosis—A Novel Mechanism With Multifaceted Actions on Stroke
Authors: Fang Xiao-Ling , Ding Shao-Yun , Du Xiao-Zheng , Wang Jin-Hai , Li Xing-Lan
Published: April 2022

As a neurological disease with high morbidity, disability, and mortality, the pathological mechanism underlying stroke involves complex processes such as neuroinflammation, oxidative stress, apoptosis, autophagy, and excitotoxicity; but the related research on these molecular mechanisms has not been effectively applied in clinical practice. As a form of iron-dependent regulated cell death, ferroptosis was first discovered in the pathological process of cancer, but recent studies have shown that ferroptosis is closely related to the onset and development of stroke. Therefore, a deeper understanding of the relationship between ferroptosis and stroke may lead to more effective treatment strategies. Herein, we reviewed the mechanism(s) underlying the onset of ferroptosis in stroke, the potential role of ferroptosis in stroke, and the crosstalk between ferroptosis and other pathological mechanisms. This will further deepen our understanding of ferroptosis and provide new approaches to the treatment of stroke.
A Virtual Navigation Training Promotes the Remapping of Space in Allocentric Coordinates: Evidence From Behavioral and Neuroimaging Data
Authors: Sacco Katiuscia , Ronga Irene , Perna Pasqualina , Cicerale Alessandro , Del Fante Elena , Sarasso Pietro , Geminiani Giuliano Carlo
Published: April 2022

Allocentric space representations demonstrated to be crucial to improve visuo-spatial skills, pivotal in every-day life activities and for the development and maintenance of other cognitive abilities, such as memory and reasoning. Here, we present a series of three different experiments: Experiment 1, Discovery sample (23 young male participants); Experiment 2, Neuroimaging and replicating sample (23 young male participants); and Experiment 3 (14 young male participants). In the experiments, we investigated whether virtual navigation stimulates the ability to form spatial allocentric representations. With this aim, we used a novel 3D videogame (MindTheCity!), focused on the navigation of a virtual town. We verified whether playing at MindTheCity! enhanced the performance on spatial representational tasks (pointing to a specific location in space) and on a spatial memory test (asking participant to remember the location of specific objects). Furthermore, to uncover the neural mechanisms underlying the observed effects, we performed a preliminary fMRI investigation before and after the training with MindTheCity!. Results show that our virtual training enhances the ability to form allocentric representations and spatial memory (Experiment 1). Experiments 2 and 3 confirmed the behavioral results of Experiment 1. Furthermore, our preliminary neuroimaging and behavioral results suggest that the training activates brain circuits involved in higher-order mechanisms of information encoding, triggering the activation of broader cognitive processes and reducing the working load on memory circuits (Experiments 2 and 3).
Somatosensory Cortex Repetitive Transcranial Magnetic Stimulation and Associative Sensory Stimulation of Peripheral Nerves Could Assist Motor and Sensory Recovery After Stroke
Authors: de Freitas Zanona Aristela , Romeiro da Silva Andressa Claudia , do Rego Maciel Adriana Baltar , Gomes do Nascimento Livia Shirahige , Bezerra da Silva Amanda , Bolognini Nadia , Monte-Silva Katia
Published: April 2022

Background

We investigated whether transcranial magnetic stimulation (rTMS) over the primary somatosensory cortex (S1) and sensory stimulation (SS) could promote upper limb recovery in participants with subacute stroke.

Methods

Participants were randomized into four groups: rTMS/Sham SS, Sham rTMS/SS, rTMS/SS, and control group (Sham rTMS/Sham SS). Participants underwent ten sessions of sham or active rTMS over S1 (10 Hz, 1,500 pulses, 120% of resting motor threshold, 20 min), followed by sham or active SS. The SS involved active sensory training (exploring features of objects and graphesthesia, proprioception exercises), mirror therapy, and Transcutaneous electrical nerve stimulation (TENS) in the region of the median nerve in the wrist (stimulation intensity as the minimum intensity at which the participants reported paresthesia; five electrical pulses of 1 ms duration each at 10 Hz were delivered every second over 45 min). Sham stimulations occurred as follows: Sham rTMS, coil was held while disconnected from the stimulator, and rTMS noise was presented with computer loudspeakers with recorded sound from a real stimulation. The Sham SS received therapy in the unaffected upper limb, did not use the mirror and received TENS stimulation for only 60 seconds. The primary outcome was the Body Structure/Function: Fugl-Meyer Assessment (FMA) and Nottingham Sensory Assessment (NSA); the secondary outcome was the Activity/Participation domains, assessed with Box and Block Test, Motor Activity Log scale, Jebsen-Taylor Test, and Functional Independence Measure.

Results

Forty participants with stroke ischemic (n= 38) and hemorrhagic (n= 2), men (n= 19) and women (n= 21), in the subacute stage (10.6 ± 6 weeks) had a mean age of 62.2 ± 9.6 years, were equally divided into four groups (10 participants in each group). Significant somatosensory improvements were found in participants receiving active rTMS and active SS, compared with those in the control group (sham rTMS with sham SS). Motor function improved only in participants who received active rTMS, with greater effects when active rTMS was combined with active SS.

Conclusion

The combined use of SS with rTMS over S1 represents a more effective therapy for increasing sensory and motor recovery, as well as functional independence, in participants with subacute stroke.

Clinical Trial Registration

[clinicaltrials.gov], identifier [NCT03329807].
MONETA: A Processing-In-Memory-Based Hardware Platform for the Hybrid Convolutional Spiking Neural Network With Online Learning
Authors: Kim Daehyun , Chakraborty Biswadeep , She Xueyuan , Lee Edward , Kang Beomseok , Mukhopadhyay Saibal
Published: April 2022

We present a processing-in-memory (PIM)-based hardware platform, referred to as MONETA, for on-chip acceleration of inference and learning in hybrid convolutional spiking neural network. MONETAuses 8T static random-access memory (SRAM)-based PIM cores for vector matrix multiplication (VMM) augmented with spike-time-dependent-plasticity (STDP) based weight update. The spiking neural network (SNN)-focused data flow is presented to minimize data movement in MONETAwhile ensuring learning accuracy. MONETAsupports on-line and on-chip training on PIM architecture. The STDP-trained convolutional neural network within SNN (ConvSNN) with the proposed data flow, 4-bit input precision, and 8-bit weight precision shows only 1.63% lower accuracy in CIFAR-10 compared to the STDP accuracy implemented by the software. Further, the proposed architecture is used to accelerate a hybrid SNN architecture that couples off-chip supervised (back propagation through time) and on-chip unsupervised (STDP) training. We also evaluate the hybrid network architecture with the proposed data flow. The accuracy of this hybrid network is 10.84% higher than STDP trained accuracy result and 1.4% higher compared to the backpropagated training-based ConvSNN result with the CIFAR-10 dataset. Physical design of MONETAin 65 nm complementary metal-oxide-semiconductor (CMOS) shows 18.69 tera operation per second (TOPS)/W, 7.25 TOPS/W and 10.41 TOPS/W power efficiencies for the inference mode, learning mode, and hybrid learning mode, respectively.