bluuebunny/crossref_metadata_2025 huggingface dataset:
Cold Shock Proteins Promote Nisin Tolerance in Listeria monocytogenes Through Modulation of Cell Envelope Modification Responses
Authors: Muchaamba Francis , Wambui Joseph , Stephan Roger , Tasara Taurai
Published: December 2021

Listeria monocytogenes continues to be a food safety challenge owing to its stress tolerance and virulence traits. Several listeriosis outbreaks have been linked to the consumption of contaminated ready-to-eat food products. Numerous interventions, including nisin application, are presently employed to mitigate against L. monocytogenes risk in food products. In response, L. monocytogenes deploys several defense mechanisms, reducing nisin efficacy, that are not yet fully understood. Cold shock proteins (Csps) are small, highly conserved nucleic acid-binding proteins involved in several gene regulatory processes to mediate various stress responses in bacteria. L. monocytogenes possesses three csp gene paralogs; cspA, cspB, and cspD. Using a panel of single, double, and triple csp gene deletion mutants, the role of Csps in L. monocytogenes nisin tolerance was examined, demonstrating their importance in nisin stress responses of this bacterium. Without csp genes, a L. monocytogenes ΔcspABD mutant displayed severely compromised growth under nisin stress. Characterizing single (ΔcspA, ΔcspB, and ΔcspD) and double (ΔcspBD, ΔcspAD, and ΔcspAB) csp gene deletion mutants revealed a hierarchy (cspD > cspB > cspA) of importance in csp gene contributions toward the L. monocytogenes nisin tolerance phenotype. Individual eliminations of either cspA or cspB improved the nisin stress tolerance phenotype, suggesting that their expression has a curbing effect on the expression of nisin resistance functions through CspD. Gene expression analysis revealed that Csp deficiency altered the expression of DltA, MprF, and penicillin-binding protein-encoding genes. Furthermore, the ΔcspABD mutation induced an overall more electronegative cell surface, enhancing sensitivity to nisin and other cationic antimicrobials as well as the quaternary ammonium compound disinfectant benzalkonium chloride. These observations demonstrate that the molecular functions of Csps regulate systems important for enabling the constitution and maintenance of an optimal composed cell envelope that protects against cell-envelope-targeting stressors, including nisin. Overall, our data show an important contribution of Csps for L. monocytogenes stress protection in food environments where antimicrobial peptides are used. Such knowledge can be harnessed in the development of better L. monocytogenes control strategies. Furthermore, the potential that Csps have in inducing cross-protection must be considered when combining hurdle techniques or using them in a series.
Immune Signature-Based Risk Stratification and Prediction of Immunotherapy Efficacy for Bladder Urothelial Carcinoma
Authors: Liang Fangfang , Xu Yansong , Chen Yi , Zhong Huage , Wang Zhen , Nong Tianwen , Zhong Jincai
Published: December 2021

Immune-related genes (IRGs) are closely related to tumor progression and the immune microenvironment. Few studies have investigated the effect of tumor immune microenvironment on the survival and response to immune checkpoint inhibitors of patients with bladder urothelial carcinoma (BLCA). We constructed two IRG-related prognostic signatures based on gene–immune interaction for predicting risk stratification and immunotherapeutic responses. We also verified their predictive ability on internal and overall data sets. Patients with BLCA were divided into high- and low-risk groups. The high-risk group had poor survival, enriched innate immune-related cell subtypes, low tumor mutation burden, and poor response to anti-PD-L1 therapy. Our prognostic signatures can be used as reliable prognostic biomarkers, which may be helpful to screen the people who will benefit from immunotherapy and guide the clinical decision-making of patients with BLCA.
New Born Calf Serum Can Induce Spheroid Formation in Breast Cancer KAIMRC1 Cell Line
Authors: Ali Rizwan , Huwaizi Sarah , Alhallaj Alshaimaa , Al Subait Arwa , Barhoumi Tlili , Al Zahrani Hajar , Al Anazi Abdullah , Latif Khan Abdul , Boudjelal Mohamed
Published: December 2021

Three-dimensional (3D) cell culture systems have become very popular in the field of drug screening and discovery. There is an immense demand for highly efficient and easy methods to produce 3D spheroids in any cell format. We have developed a novel and easy method to produce spheroids from the newly isolated KAIMRC1 cell line in vitro. It can be used as a 3D model to study proliferation, differentiation, cell death, and drug response of cancer cells. Our procedure requires growth media supplemented with 10% new born calf serum (NBCS) and regular cell culture plates to generate KAIMRC1 spheroids without the need for any specialized 3D cell culture system. This procedure generates multiple spheroids within a 12–24-h culture. KAIMRC1 spheroids are compact, homogeneous in size and morphology with a mean size of 55.8 µm (±3.5). High content imaging (HCI) of KAIMRC1 spheroids treated with a panel of 240 compounds resulted in the identification of several highly specific compounds towards spheroids. Immunophenotyping of KAIMRC1 spheroids revealed phosphorylation of FAK, cJUN, and E-cadherin, which suggests the involvement of JNK/JUN pathway in the KAIMRC1 spheroids formation. Gene expression analysis showed upregulation of cell junction genes, GJB3, DSC1, CLDN5, CLDN8, and PLAU. Furthermore, co-culture of KAIMRC1 cells with primary cancer-associated-fibroblasts (CAFs) showcased the potential of these cells in drug discovery application.
Identification of Novel Tumor Microenvironment-Related Long Noncoding RNAs to Determine the Prognosis and Response to Immunotherapy of Hepatocellular Carcinoma Patients
Authors: Huang Shenglan , Zhang Jian , Lai Xiaolan , Zhuang Lingling , Wu Jianbing
Published: December 2021

Introduction: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with poor prognosis. The tumor microenvironment (TME) plays a vital role in HCC progression. Thus, this research was designed to analyze the correlation between the TME and the prognosis of HCC patients and to construct a TME-related long noncoding RNA (lncRNA) signature to determine HCC patients’ prognosis and response to immunotherapy.

Methods: We assessed the stromal–immune–estimate scores within the HCC microenvironment using the ESTIMATE (Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression Data) algorithm based on The Cancer Genome Atlas database, and their associations with survival and clinicopathological parameters were also analyzed. Thereafter, differentially expressed lncRNAs were filtered out according to the immune and stromal scores. Cox regression analysis was performed to build a TME-related lncRNA risk signature. Kaplan–Meier analysis was used to explore the prognostic value of the risk signature. Furthermore, we explored the biological functions and immune microenvironment features in the high- and low-risk groups. Lastly, we probed the association of the risk model with treatment responses to immune checkpoint inhibitors (ICIs) in HCC.

Results: The stromal, immune, and estimate scores were obtained utilizing the ESTIMATE algorithm for patients with HCC. Kaplan–Meier analysis showed that high scores were significantly correlated with better prognosis in HCC patients. Six TME-related lncRNAs were screened to construct the prognostic model. The Kaplan–Meier curves suggested that HCC patients with low risk had better prognosis than those with high risk. Receiver operating characteristic (ROC) curve and Cox regression analyses indicated that the risk model could predict HCC survival exactly and independently. Functional enrichment analysis revealed that some tumor- and immune-related pathways were activated in the high-risk group. We also revealed that some immune cells, which were important in enhancing immune responses toward cancer, were significantly increased in the low-risk group. In addition, there was a close correlation between ICIs and the risk signature, which can be used to predict the treatment responses of HCC patients.

Conclusion: We analyzed the influence of the stromal, immune, and estimate scores on the prognosis of HCC patients. A novel TME-related lncRNA risk model was established, which could be effectively applied as an independent prognostic biomarker and predictor of ICIs for HCC patients.
Lipidomic Profiling Reveals the Reducing Lipid Accumulation Effect of Dietary Taurine in Groupers (Epinephelus coioides)
Authors: Bai Fakai , Wang Xuexi , Niu Xingjian , Shen Guiping , Ye Jidan
Published: December 2021

A lipidomic analysis was conducted to provide the first detailed overview of lipid molecule profiles in response to dietary lipid and taurine and associations of liver lipid-lowering effects of dietary taurine with lipid molecular species and the positional distributions of fatty acids in the liver of juvenile orange-spotted groupers (Epinephelus coioides). The results indicated that the liver was more sensitive to varied dietary lipid and taurine contents than the muscle with regard to lipid molecules. A total of 131 differential lipid molecules (DLMs) were observed in the liver of groupers when dietary taurine was increased from 0 to 1% at 15% lipid, among which all the up and down-regulated DLMs are phospholipids (PLs) and triglycerides (TGs), respectively. The liver content of TGs containing 18:2n-6 attached at the sn-2 and sn-3 positions on the glycerol backbone increased with increasing dietary lipid from 10 to 15% but decreased with increasing dietary taurine from 0 to 1%. Therefore, dietary taurine can not only reduce lipid accumulation through decreasing the contents of TGs containing 18:2n-6 at the sn-2 and sn-3 positions but also enhance the anti-inflammatory capacity and health status of groupers. This study will also provide a new insight into the function of taurine in farmed fish.
Classification of Cognitive Impairment and Healthy Controls Based on Transcranial Magnetic Stimulation Evoked Potentials
Authors: Zhang Jiahao , Lu Haifeng , Zhu Lin , Ren Huixia , Dang Ge , Su Xiaolin , Lan Xiaoyong , Jiang Xin , Zhang Xu , Feng Jiansong , Shi Xue , Wang Taihong , Hu Xiping , Guo Yi
Published: December 2021

Backgrounds: Nowadays, risks of Cognitive Impairment (CI) [highly suspected Alzheimer's disease (AD) in this study] threaten the quality of life for more older adults as the population ages. The emergence of Transcranial Magnetic Stimulation-Electroencephalogram (TMS-EEG) enables noninvasive neurophysiological investi-gation of the human cortex, which might be potentially used for CI detection.

Objectives: The aim of this study is to explore whether the spatiotemporal features of TMS Evoked Potentials (TEPs) could classify CI from healthy controls (HC).

Methods: Twenty-one patients with CI and 22 HC underwent a single-pulse TMS-EEG stimulus in which the pulses were delivered to the left dorsolateral prefrontal cortex (left DLPFC). After preprocessing, seven regions of interest (ROIs) and two most reliable TEPs' components: N100 and P200 were selected. Next, seven simple and interpretable linear features of TEPs were extracted for each region, three common machine learning algorithms including Support Vector Machine (SVM), Random Forest (RF), and K-Nearest Neighbor (KNN) were used to detect CI. Meanwhile, data augmentation and voting strategy were used for a more robust model. Finally, the performance differences of features in classifiers and their contributions were investigated.

Results: 1. In the time domain, the features of N100 had the best performance in the SVM classifier, with an accuracy of 88.37%. 2. In the aspect of spatiality, the features of the right frontal region and left parietal region had the best performance in the SVM classifier, with an accuracy of 83.72%. 3. The Local Mean Field Power (LMFP), Average Value (AVG), Latency and Amplitude contributed most in classification.

Conclusions: The TEPs induced by TMS over the left DLPFC has significant differences spatially and temporally between CI and HC. Machine learning based on the spatiotemporal features of TEPs have the ability to separate the CI and HC which suggest that TEPs has potential as non-invasive biomarkers for CI diagnosis.
Axonal Projection Patterns of the Dorsal Interneuron Populations in the Embryonic Hindbrain
Authors: Hirsch Dana , Kohl Ayelet , Wang Yuan , Sela-Donenfeld Dalit
Published: December 2021

Unraveling the inner workings of neural circuits entails understanding the cellular origin and axonal pathfinding of various neuronal groups during development. In the embryonic hindbrain, different subtypes of dorsal interneurons (dINs) evolve along the dorsal-ventral (DV) axis of rhombomeres and are imperative for the assembly of central brainstem circuits. dINs are divided into two classes, class A and class B, each containing four neuronal subgroups (dA1-4 and dB1-4) that are born in well-defined DV positions. While all interneurons belonging to class A express the transcription factor Olig3 and become excitatory, all class B interneurons express the transcription factor Lbx1 but are diverse in their excitatory or inhibitory fate. Moreover, within every class, each interneuron subtype displays its own specification genes and axonal projection patterns which are required to govern the stage-by-stage assembly of their connectivity toward their target sites. Remarkably, despite the similar genetic landmark of each dINs subgroup along the anterior-posterior (AP) axis of the hindbrain, genetic fate maps of some dA/dB neuronal subtypes uncovered their contribution to different nuclei centers in relation to their rhombomeric origin. Thus, DV and AP positional information has to be orchestrated in each dA/dB subpopulation to form distinct neuronal circuits in the hindbrain. Over the span of several decades, different axonal routes have been well-documented to dynamically emerge and grow throughout the hindbrain DV and AP positions. Yet, the genetic link between these distinct axonal bundles and their neuronal origin is not fully clear. In this study, we reviewed the available data regarding the association between the specification of early-born dorsal interneuron subpopulations in the hindbrain and their axonal circuitry development and fate, as well as the present existing knowledge on molecular effectors underlying the process of axonal growth.
Anatomical and Functional Characterization of Central Amygdala Glucagon-Like Peptide 1 Receptor Expressing Neurons
Authors: Zeng Ningxiang , Cutts Elam J. , Lopez Christian B. , Kaur Simran , Duran Miguel , Virkus Sonja A. , Hardaway J. Andrew
Published: December 2021

Glucagon-like peptide 1 receptors (GLP-1Rs) are highly expressed in the brain and are responsible for mediating the acute anorexigenic actions of widely prescribed GLP-1R agonists. Neurobiological efforts to localize the hypophagic effects of GLP-1R agonists in the brain have mainly focused on the hypothalamus and hindbrain. In this study, we performed a deep anatomical and neurophysiological characterization of GLP-1Rs in the central nucleus of the amygdala (CeA). At an mRNA level, we found that Glp1r is diffusely coexpressed in known CeA subpopulations like protein kinase c δ (Prkcd), somatostatin (Sst), or tachykinin2 (Tac2). At a cellular level, we used Glp1r-Cre mice and viral Cre-dependent tracing to map the anatomical positions of GLP-1R cells across the rostral-caudal axis of the CeA and in CeA subdivisions. We found that Glp1rCeA cells are highly enriched in the medial subdivision of the CeA (CeM). Using whole cell patch clamp electrophysiology, we found that Glp1rCeA neurons are characterized by the presence of Ih-like currents and resemble a low threshold bursting neuronal subtype in response to hyperpolarizing and depolarizing current injections. We observed sex differences in the magnitude of Ih-like currents and membrane capacitance. At rest, we observed that nearly half of Glp1rCeA neurons are spontaneously active. We observed that active and inactive neurons display significant differences in excitability even when normalized to an identical holding potential. Our data are the first to deeply characterize the pattern of Glp1r in the CeA and study the neurophysiological characteristics of CeA neurons expressing Glp1r. Future studies leveraging these data will be important to understanding the impact of GLP-1R agonists on feeding and motivation.
Non-thermal Electroporation Ablation of Epileptogenic Zones Stops Seizures in Mice While Providing Reduced Vascular Damage and Accelerated Tissue Recovery
Authors: Acerbo Emma , Safieddine Sawssan , Weber Pascal , Botzanowski Boris , Missey Florian , Carrère Marcel , Gross Robert E. , Bartolomei Fabrice , Carron Romain , Jirsa Viktor , Vanzetta Ivo , Trébuchon Agnès , Williamson Adam
Published: December 2021

In epilepsy, the most frequent surgical procedure is the resection of brain tissue in the temporal lobe, with seizure-free outcomes in approximately two-thirds of cases. However, consequences of surgery can vary strongly depending on the brain region targeted for removal, as surgical morbidity and collateral damage can lead to significant complications, particularly when bleeding and swelling are located near delicate functional cortical regions. Although focal thermal ablations are well-explored in epilepsy as a minimally invasive approach, hemorrhage and edema can be a consequence as the blood-brain barrier is still disrupted. Non-thermal irreversible electroporation (NTIRE), common in many other medical tissue ablations outside the brain, is a relatively unexplored method for the ablation of neural tissue, and has never been reported as a means for ablation of brain tissue in the context of epilepsy. Here, we present a detailed visualization of non-thermal ablation of neural tissue in mice and report that NTIRE successfully ablates epileptic foci in mice, resulting in seizure-freedom, while causing significantly less hemorrhage and edema compared to conventional thermal ablation. The NTIRE approach to ablation preserves the blood-brain barrier while pathological circuits in the same region are destroyed. Additionally, we see the reinnervation of fibers into ablated brain regions from neighboring areas as early as day 3 after ablation. Our evidence demonstrates that NTIRE could be utilized as a precise tool for the ablation of surgically challenging epileptogenic zones in patients where the risk of complications and hemorrhage is high, allowing not only reduced tissue damage but potentially accelerated recovery as vessels and extracellular matrix remain intact at the point of ablation.
Cordycepin Ameliorates Synaptic Dysfunction and Dendrite Morphology Damage of Hippocampal CA1 via A1R in Cerebral Ischemia
Authors: Chen Zhao-Hui , Han Yuan-Yuan , Shang Ying-Jie , Zhuang Si-Yi , Huang Jun-Ni , Wu Bao-Yan , Li Chu-Hua
Published: December 2021

Cordycepin exerted significant neuroprotective effects and protected against cerebral ischemic damage. Learning and memory impairments after cerebral ischemia are common. Cordycepin has been proved to improve memory impairments induced by cerebral ischemia, but its underlying mechanism has not been revealed yet. The plasticity of synaptic structure and function is considered to be one of the neural mechanisms of learning and memory. Therefore, we investigated how cordycepin benefits dendritic morphology and synaptic transmission after cerebral ischemia and traced the related molecular mechanisms. The effects of cordycepin on the protection against ischemia were studied by using global cerebral ischemia (GCI) and oxygen-glucose deprivation (OGD) models. Behavioral long-term potentiation (LTP) and synaptic transmission were observed with electrophysiological recordings. The dendritic morphology and histological assessment were assessed by Golgi staining and hematoxylin-eosin (HE) staining, respectively. Adenosine A1 receptors (A1R) and adenosine A2A receptors (A2AR) were evaluated with western blotting. The results showed that cordycepin reduced the GCI-induced dendritic morphology scathing and behavioral LTP impairment in the hippocampal CA1 area, improved the learning and memory abilities, and up-regulated the level of A1R but not A2AR. In thein vitroexperiments, cordycepin pre-perfusion could alleviate the hippocampal slices injury and synaptic transmission cripple induced by OGD, accompanied by increased adenosine content. In addition, the protective effect of cordycepin on OGD-induced synaptic transmission damage was eliminated by using an A1R antagonist instead of A2AR. These findings revealed that cordycepin alleviated synaptic dysfunction and dendritic injury in ischemic models by modulating A1R, which provides new insights into the pharmacological mechanisms of cordycepin for ameliorating cognitive impairment induced by cerebral ischemia.
Astrocyte and Oligodendrocyte Responses From the Subventricular Zone After Injury
Authors: David-Bercholz Jennifer , Kuo Chay T. , Deneen Benjamin
Published: December 2021

Under normal conditions, neural stem cells (NSCs or B cells) in the adult subventricular zone (SVZ) give rise to amplifying neural progenitor cells (NPCs or C cells), which can produce neuroblasts (or A cells) that migrate to the olfactory bulb and differentiate into new neurons. However, following brain injury, these cells migrate toward the injury site where they differentiate into astrocytes and oligodendrocytes. In this review, we will focus on recent findings that chronicle how astrocytes and oligodendrocytes derived from SVZ-NSCs respond to different types of injury. We will also discuss molecular regulators of SVZ-NSC proliferation and their differentiation into astrocytes and oligodendrocytes. Overall, the goal of this review is to highlight how SVZ-NSCs respond to injury and to summarize the regulatory mechanisms that oversee their glial response. These molecular and cellular processes will provide critical insights needed to develop strategies to promote brain repair following injury using SVZ-NSCs.
High-Resolution MR for Follow-Up of Intracranial Steno-Occlusive Disease Treated by Endovascular Treatment
Authors: Wang Junjie , Zhang Shun , Lu Jun , Qi Peng , Hu Shen , Yang Ximeng , Chen Kunpeng , Wang Daming
Published: December 2021

Background and Purpose: An endovascular recanalization is an alternative option for symptomatic intracranial atherosclerotic steno-occlusive disease (ICAD). Accurate non-invasive alternatives to digital subtraction angiography (DSA) for follow-up imaging after endovascular treatment are desirable. We aimed to evaluate the image quality and diagnostic performance of high-resolution magnetic imaging in follow-up using DSA as a reference.

Materials and Methods: From January 2017 to June 2021, data from 35 patients with 40 intracranial steno-occlusive lesions who underwent endovascular recanalization and received high-resolution magnetic resonance (HR-MR) follow-up were retrospectively collected in our prospective database. Studies were evaluated for the quality of visualization of the vessel lumen, restenosis rate, and accuracy of high-resolution magnetic resonance (HR-MR) with DSA used as the reference standard. Intraclass correlation coefficient (ICC) analyses were performed to assess the agreement between the two different readers.

Results: In total, 40 intracranial steno-occlusive lesions in 35 patients, with 34 lesions undergoing balloon angioplasty [including 16 drug-coated balloons (DCBs)] and 8 lesions undergoing stenting were enrolled. The median age was 63.6 years (IQR 58.5–70.0 years), and the mean imaging follow-up time was 9.5 months (IQR 4.8–12.5 months). The median degrees of preprocedural and residual stenosis were 85.0% (IQR 75.0–99.0%) and 32.8% (IQR 15.0–50.0%), respectively. Intracranial periprocedural complications occurred in 1 (3.6%) patient. In the case of a stainless-steel stent (n = 1), there was a signal drop at the level of the vessel, which did not allow evaluation of the vessel lumen. However, this was visible in the case of nitinol stents (n = 7) and angioplasty (n = 34). The overall restenosis rate was 25.8% (n = 9). The DCB subgroup showed a lower rate of restenosis than the percutaneous transluminal angioplasty (PTA) subgroup [5.3% (2/13) vs. 35.7% (5/14)].

Conclusion: High-resolution magnetic resonance may be a reliable non-invasive method for demonstrating the vessel lumen and diagnostic follow-up after endovascular recanalization for ICAD. Compared with MR angiography (MRA), HR-MR showed a higher inter-reader agreement and could provide more information after endovascular recanalization, such as enhancement of the vessel wall.
Sonographic Measurement of Brainstem Through the Foramen Magnum in Premature Neonates Can Predict Neurodevelopment Outcome?
Authors: Chen Shyi-Jou , Hu Chih-Fen , Tien Chiung-Hsi , Chen Cheng-Yu
Published: December 2021

Background: To investigate whether serial morphometric measurements of the brainstem using high resolution trans-foramen-magnum ultrasound (US) in premature neonates correlate with neurological outcomes.

Methods: Serial brain ultrasound scans were performed in 36 consecutive preterm infants born at <34 weeks of gestation from birth until term-equivalent age. Two-dimensional brainstem measurements of the pons and medulla oblongata were compared with those in a cohort of 67 healthy full-term newborns. Neurologic assessment of the premature infants was assessed at 5 years of age.

Results: Of the 36 preterm infants born between 25 and 34 weeks of gestation, eight had significantly delayed growth profiles in both the pons and medulla and developed neurological sequelae by 5 years of age.

Conclusions: Morphometric measurements of the developing brainstem using high resolution trans-foramen-magnum ultrasound (US) may help predict neurological outcome in high-risk neonates, particularly in those who are born extremely premature.
Evaluation of the Quantitative Myasthenia Gravis Score and Grip Strength in Chinese Patients With Myasthenia Gravis: An Observational Study
Authors: Li Jinghao , Weng Senhui , Lin Sen , Huang Linwen , Yang Xiaojun , Liang Bo , Lu Jiaxin , Jiang Qilong
Published: December 2021

Introduction: The quantitative myasthenia gravis score is a commonly used scale for evaluating muscle weakness associated with myasthenia gravis (MG). It has been reported that some items used in the scale have low discriminative properties. However, there has been no research investigating the applicability of the quantitative MG score (QMGS) in Chinese patients with MG. In addition, the scoring method and ranges of grip strength items in QMGS need to be further evaluated.

Methods: This study included 106 Chinese patients with MG, enrolled between September 2020 and February 2021, who were evaluated using the QMGS. Each item in the QMGS was analyzed for distribution. Three methods of evaluating grip strength, grip strength decrement, maximum grip strength, and relative grip strength, were compared. The correlation between the QMG total score minus grip strength score, and three evaluating methods, was analyzed.

Results: The grip strength, swallowing, speech, diplopia, ptosis, and facial muscles items showed a clustered distribution. Most patients (94%) presented their maximum grip strength in the first four grip strength measurements. The QMG total score minus the grip strength score had a weak correlation with grip strength decrement (R grip r = 0.276; L grip r = 0.353, both p < 0.05) and moderate correlations with maximum grip strength (R grip r = −0.508; L grip r = −0.507; both p < 0.001) and relative grip strength (R grip r = −0.494; L grip r = −0.497, both p < 0.001).

Conclusions: This study suggested that partial items in the QMGS have low discriminative properties for Chinese populations and the maximum grip strength value is the better method to evaluate grip strength compared to the other two scoring methods. Based on the quartiles of maximum grip strength, we propose new scoring ranges for the grip strength items.
Persistent Postural-Perceptual Dizziness: Precipitating Conditions, Co-morbidities and Treatment With Cognitive Behavioral Therapy
Authors: Waterston John , Chen Luke , Mahony Kate , Gencarelli Jamila , Stuart Geoff
Published: December 2021

Persistent postural perceptual dizziness (PPPD) is a common chronic vestibular disorder characterized by persistent vestibular symptoms, including postural instability and non-spinning vertigo, which is aggravated by motion, upright posture and moving or complex visual stimuli. In our review of 198 cases seen over a 5 year period, we have confirmed a number of common precipitating conditions for PPPD, including anxiety disorders and vestibular migraine. Vestibular abnormalities, including a unilateral loss of vestibular hypofunction and isolated otolith abnormalities, were found on investigation in just under half the cases. The use of cognitive behavioral therapy (CBT) as a treatment for PPPD resulted in impressive reductions in anxiety and measures of dizziness over follow up periods of up to 6 months.
Investigation of Altered Spontaneous Brain Activities in Patients With Moyamoya Disease Using Percent Amplitude of Fluctuation Method: A Resting-State Functional MRI Study
Authors: Li Chu-Qi , Ge Qian-Min , Shu Hui-Ye , Liao Xu-Lin , Pan Yi-Cong , Wu Jie-Li , Su Ting , Zhang Li-Juan , Liang Rong-Bin , Shao Yi , Zeng Er-Ming
Published: December 2021

Background: Moyamoya disease (MMD) is a chronic progressive cerebrovascular abnormality characterized by chronic occlusion of large intracranial vessels with smoky vascular development at the base of the skull. In patients with MMD, abnormal spontaneous brain activity would be expected.

Purpose: To assess the brain activity changes in patients with MMD by resting-state functional MRI (rs-fMRI), using the percent amplitude of fluctuation (PerAF) analysis method.

Materials and Methods: A total of 17 patients with MMD (3 males and 14 females) and 17 healthy control (HC) subjects with matched gender and age were recruited for this study. We used rs-fMRI to scan all the patients with MMD. Spontaneous neural activity was evaluated using the PerAF approach. The receiver operating characteristic (ROC) curve analysis was used to assess the ability of the PerAF to distinguish patients with MMD from HCs. The Hospital Anxiety and Depression Scale (HADS) tests were performed to assess the emotional status of patients with MMD and retinal nerve fiber layer thickness (RNFLT) was measured using high-resolution optical coherence tomography (hr-OCT). The relationship between the HADS scores, RNFLT values, and the PerAF signals was assessed using the Pearson's correlation analysis.

Results: Compared with HCs, the PerAF signals in patients with MMD were decreased in the Frontal_Sup_Medial_R and Precentral_L, whereas those in the Caudate_L were increased. The areas under the ROC curves indicated that signals in these brain regions could distinguish between patients with MMD and HCs. The PerAF value of Frontal_Sup_Medial_R was positively correlated with the left and right eye RNFLT values and negatively correlated with the HADS scores.

Conclusion: In patients with MMD, reduced PerAF signals in the Frontal_Sup_Medial_R, Precentral_L, and Caudate_L may be associated with psychiatric diseases including anxiety and depression and decreased RNFLT may be associated with ophthalmic complications due to the compression of terminal branches of the internal carotid artery in the retinal fiber layer. The PerAF can be used as an effective indicator of ocular complications of MMD and to study the neural mechanism underpinning emotional complications in patients with MMD.
VEGF Modulates Neurogenesis and Microvascular Remodeling in Epileptogenesis After Status Epilepticus in Immature Rats
Authors: Han Wei , Jiang Li , Song Xiaojie , Li Tianyi , Chen Hengsheng , Cheng Li
Published: December 2021

Neurogenesis and angiogenesis are widely recognized to occur during epileptogenesis and important in brain development. Because vascular endothelial growth factor (VEGF) is a critical neurovascular target in neurological diseases, its effect on neurogenesis, microvascular remodeling and epileptogenesis in the immature brain after lithium-pilocarpine-induced status epilepticus (SE) was investigated. The dynamic changes in and the correlation between hippocampal neurogenesis and microvascular remodeling after SE and the influence of VEGF or SU5416 injection into the lateral ventricles at different stages after SE on neurogenesis and microvascular remodeling through regulation of VEGF expression were assessed by immunofluorescence and immunohistochemistry. Western blot analysis revealed that the VEGFR2 signaling pathway promotes phosphorylated ERK and phosphorylated AKT expression. The effects of VEGF expression regulation at different stages after SE on pathological changes in hippocampal structure and spontaneous recurrent seizures (SRS) were evaluated by Nissl staining and electroencephalography (EEG). The results showed that hippocampal neurogenesis after SE is related to microvascular regeneration. VEGF promotion in the acute period and inhibition in the latent period after SE alleviates loss of hippocampal neuron, abnormal vascular regeneration and inhibits neural stem cells (NSCs) ectopic migration, which may effectively alleviate SRS severity. Interfering with VEGF via the AKT and ERK pathways in different phases after SE may be a promising strategy for treating and preventing epilepsy in children.
Simultaneous Damage of the Cingulate Cortex Zone II and Fronto-Striatal Circuit Causes Prolonged Selective Attentional Deficits
Authors: Nakajima Riho , Kinoshita Masashi , Nakada Mitsutoshi
Published: December 2021

Selective attention is essential for successful cognitive performance. Although several brain areas are known to be involved in selective attention, damage to some of these areas does not necessarily cause attentional deficits. In the current study, we hypothesized that damage to specific parts of the right cerebral hemisphere, especially the cingulate cortex (CC), causes prolonged selective attentional deficits, and examined the influence of focal brain damage on selective attention. We recruited 36 patients with right cerebral hemispheric WHO grade 2 and 3 brain tumors who underwent surgery. We assessed selective attention over time from pre-operation to 3 months postoperatively using the cancelation test and color Stroop test, and calculated the percentage of deficit. Additionally, two types of imaging analyses were performed: voxel-based lesion symptom mapping (VLSM) and multiple logistic regression analysis, to reveal related brain regions for selective attention. Consequently, we found that the CC and deep part of the middle frontal gyrus were associated with deficits in selective attention via VLSM. Using multiple logistic regression analysis, the CC zone II at the cortical level (p < 0.0001) and the fronto-striatal tract (FST) at the subcortical level (p = 0.0079) were associated with attentional deficit among several regions identified in the VLSM. At 3 months postoperatively, selective attention was impaired in patients who underwent resection of these regions. Moreover, only patients with simultaneous damage of the CC zone II and FST had prolonged attentional deficits until the chronic phase. Our results suggest that the right CC zone II and FST are critical areas for the selective attentional networks.
Dysfunctional Interaction Between the Dorsal Attention Network and the Default Mode Network in Patients With Type 2 Diabetes Mellitus
Authors: Lei Yumeng , Zhang Dongsheng , Qi Fei , Gao Jie , Tang Min , Ai Kai , Yan Xuejiao , Lei Xiaoyan , Shao Zhirong , Su Yu , Zhang Xiaoling
Published: December 2021

The risk of cognitive impairment in patients with type 2 diabetes mellitus (T2DM) is significantly higher than that in the general population, but the exact neurophysiological mechanism underlying this is still unclear. An abnormal change in the intrinsic anticorrelation of the dorsal attention network (DAN) and the default mode network (DMN) is thought to be the mechanism underlying cognitive deficits that occur in many psychiatric disorders, but this association has rarely been tested in T2DM. This study explored the relationship between the interaction patterns of the DAN-DMN and clinical/cognitive variables in patients with T2DM. Forty-four patients with T2DM and 47 sex-, age-, and education-matched healthy controls (HCs) underwent neuropsychological assessments, independent component analysis (ICA), and functional network connection analysis (FNC). The relationship of DAN-DMN anticorrelation with the results of a battery of neuropsychological tests was also assessed. Relative to the HC group, the DMN showed decreased functional connectivity (FC) in the right precuneus, and the DAN showed decreased FC in the left inferior parietal lobule (IPL) in patients with T2DM. Subsequent FNC analysis revealed that, compared with the HC group, the T2DM patients displayed significantly increased inter-network connectivity between the DAN and DMN. These abnormal changes were correlated with the scores of multiple neuropsychological assessments (P < 0.05). These findings indicate abnormal changes in the interaction patterns of the DAN-DMN may be involved in the neuropathology of attention and general cognitive dysfunction in T2DM patients.
The Critical Modulatory Role of Spiny Stellate Cells in Seizure Onset Based on Dynamic Analysis of a Neural Mass Model
Authors: Tabatabaee Saba , Bahrami Fariba , Janahmadi Mahyar
Published: December 2021

Growing evidence suggests that excitatory neurons in the brain play a significant role in seizure generation. Nonetheless, spiny stellate cells are cortical excitatory non-pyramidal neurons in the brain, whose basic role in seizure occurrence is not well understood. In the present research, we study the critical role of spiny stellate cells or the excitatory interneurons (EI), for the first time, in epileptic seizure generation using an extended neural mass model inspired by a thalamocortical model originally introduced by another research group. Applying bifurcation analysis on this modified model, we investigated the rich dynamics corresponding to the epileptic seizure onset and transition between interictal and ictal states caused by EI connectivity to other cell types. Our results indicate that the transition between interictal and ictal states (preictal signal) corresponds to a supercritical Hopf bifurcation, and thus, the extended model suggests that before seizure onset, the amplitude and frequency of neural activities gradually increase. Moreover, we showed that (1) the altered function of GABAergic and glutamatergic receptors of EI can cause seizure, and (2) the pathway between the thalamic relay nucleus and EI facilitates the transition from interictal to ictal activity by decreasing the preictal period. Thereafter, we considered both sensory and cortical periodic inputs to study model responses to various harmonic stimulations. Bifurcation analysis of the model, in this case, suggests that the initial state of the model might be the main cause for the transition between interictal and ictal states as the stimulus frequency changes. The extended thalamocortical model shows also that the amplitude jump phenomenon and non-linear resonance behavior result from the preictal state of the modified model. These results can be considered as a step forward to a deeper understanding of the mechanisms underlying the transition from normal activities to epileptic activities.
Dynamical Characteristics of Recurrent Neuronal Networks Are Robust Against Low Synaptic Weight Resolution
Authors: Dasbach Stefan , Tetzlaff Tom , Diesmann Markus , Senk Johanna
Published: December 2021

The representation of the natural-density, heterogeneous connectivity of neuronal network models at relevant spatial scales remains a challenge for Computational Neuroscience and Neuromorphic Computing. In particular, the memory demands imposed by the vast number of synapses in brain-scale network simulations constitute a major obstacle. Limiting the number resolution of synaptic weights appears to be a natural strategy to reduce memory and compute load. In this study, we investigate the effects of a limited synaptic-weight resolution on the dynamics of recurrent spiking neuronal networks resembling local cortical circuits and develop strategies for minimizing deviations from the dynamics of networks with high-resolution synaptic weights. We mimic the effect of a limited synaptic weight resolution by replacing normally distributed synaptic weights with weights drawn from a discrete distribution, and compare the resulting statistics characterizing firing rates, spike-train irregularity, and correlation coefficients with the reference solution. We show that a naive discretization of synaptic weights generally leads to a distortion of the spike-train statistics. If the weights are discretized such that the mean and the variance of the total synaptic input currents are preserved, the firing statistics remain unaffected for the types of networks considered in this study. For networks with sufficiently heterogeneous in-degrees, the firing statistics can be preserved even if all synaptic weights are replaced by the mean of the weight distribution. We conclude that even for simple networks with non-plastic neurons and synapses, a discretization of synaptic weights can lead to substantial deviations in the firing statistics unless the discretization is performed with care and guided by a rigorous validation process. For the network model used in this study, the synaptic weights can be replaced by low-resolution weights without affecting its macroscopic dynamical characteristics, thereby saving substantial amounts of memory.
Learning Cortical Parcellations Using Graph Neural Networks
Authors: Eschenburg Kristian M. , Grabowski Thomas J. , Haynor David R.
Published: December 2021

Deep learning has been applied to magnetic resonance imaging (MRI) for a variety of purposes, ranging from the acceleration of image acquisition and image denoising to tissue segmentation and disease diagnosis. Convolutional neural networks have been particularly useful for analyzing MRI data due to the regularly sampled spatial and temporal nature of the data. However, advances in the field of brain imaging have led to network- and surface-based analyses that are often better represented in the graph domain. In this analysis, we propose a general purpose cortical segmentation method that, given resting-state connectivity features readily computed during conventional MRI pre-processing and a set of corresponding training labels, can generate cortical parcellations for new MRI data. We applied recent advances in the field of graph neural networks to the problem of cortical surface segmentation, using resting-state connectivity to learn discrete maps of the human neocortex. We found that graph neural networks accurately learn low-dimensional representations of functional brain connectivity that can be naturally extended to map the cortices of new datasets. After optimizing over algorithm type, network architecture, and training features, our approach yielded mean classification accuracies of 79.91% relative to a previously published parcellation. We describe how some hyperparameter choices including training and testing data duration, network architecture, and algorithm choice affect model performance.
Neuropeptide S Attenuates the Alarm Pheromone-Evoked Defensive and Risk Assessment Behaviors Through Activation of Cognate Receptor-Expressing Neurons in the Posterior Medial Amygdala
Authors: Shao Yu-Feng , Wang Can , Rao Xiao-Ping , Wang Hua-Dong , Ren Yan-Li , Li Jing , Dong Chao-Yu , Xie Jun-Fan , Yang Xing-Wen , Xu Fu-Qiang , Hou Yi-Ping
Published: December 2021

Neuropeptide S (NPS) acts by activating its cognate receptor (NPSR). High level expression of NPSR in the posterior medial amygdala suggests that NPS-NPSR system should be involved in regulation of social behaviors induced by social pheromones. The present study was undertaken to investigate the effects of central administration of NPS or with NPSR antagonist on the alarm pheromone (AP)-evoked defensive and risk assessment behaviors in mice. Furthermore, H129-H8, a novel high-brightness anterograde multiple trans-synaptic virus, c-Fos and NPSR immunostaining were employed to reveal the involved neurocircuits and targets of NPS action. The mice exposed to AP displayed an enhancement in defensive and risk assessment behaviors. NPS (0.1–1 nmol) intracerebroventricular (i.c.v.) injection significantly attenuated the AP-evoked defensive and risk assessment behaviors. NPSR antagonist [D-Val5]NPS at the dose of 40 nmol completely blocked the effect of 0.5 nmol of NPS which showed the best effective among dose range. The H129-H8-labeled neurons were observed in the bilateral posterodorsal medial amygdala (MePD) and posteroventral medial amygdala (MePV) 72 h after the virus injection into the unilateral olfactory bulb (OB), suggesting that the MePD and MePV receive olfactory information inputs from the OB. The percentage of H129-H8-labeled neurons that also express NPSR were 90.27 ± 3.56% and 91.67 ± 2.46% in the MePD and MePV, respectively. NPS (0.5 nmol, i.c.v.) remarkably increased the number of Fos immunoreactive (-ir) neurons in the MePD and MePV, and the majority of NPS-induced Fos-ir neurons also expressed NPSR. The behavior characteristic of NPS or with [D-Val5]NPS can be better replicated in MePD/MePV local injection within lower dose. The present findings demonstrated that NPS, via selective activation of the neurons bearing NPSR in the posterior medial amygdala, attenuates the AP-evoked defensive and risk assessment behaviors in mice.
Is the Imitative Competence an Asymmetrically Distributed Function?
Authors: Fabri Mara , Pierpaoli Chiara , Foschi Nicoletta , Polonara Gabriele
Published: December 2021

This study reconsiders behavioral and functional data from studies investigating the anatomical imitation (AI) and the related mental rotation (MR) competence, carried out by our group in healthy subjects, with intact interhemispheric connections, and in split-brain patients, completely or partially lacking callosal connections. The results strongly point to the conclusion that AI and MR competence requires interhemispheric communication, mainly occurring through the corpus callosum, which is the largest white matter structure in the human brain. The results are discussed in light of previous studies and of future implications.