bluuebunny/crossref_metadata_2025 huggingface dataset:
Liquid Biopsy in Pre-Metastatic Niche: From Molecular Mechanism to Clinical Application
Authors: Liu Zaoqu , Kong Ying , Dang Qin , Weng Siyuan , Zheng Youyang , Ren Yuqing , Lv Jinxiang , Li Na , Han Yilin , Han Xinwei
Published: July 2022

Metastatic dissemination represents a hallmark of cancer that is responsible for the high mortality rate. Recently, emerging evidence demonstrates a time-series event—pre-metastatic niche (PMN) has a profound impact on cancer metastasis. Exosomes, cell-free DNA (cfDNA), circulating tumor cells (CTC), and tumor microenvironment components, as critical components in PMN establishment, could be monitored by liquid biopsy. Intensive studies based on the molecular profile of liquid biopsy have made it a viable alternative to tissue biopsy. Meanwhile, the complex molecular mechanism and intercellular interaction are great challenges for applying liquid biopsy in clinical practice. This article reviews the cellular and molecular components involved in the establishment of the PMN and the promotion of metastasis, as well as the mechanisms of their interactions. Better knowledge of the characteristics of the PMN may facilitate the application of liquid biopsy for clinical diagnosis, prognosis, and treatment.
Cardiac Mast Cells: A Two-Head Regulator in Cardiac Homeostasis and Pathogenesis Following Injury
Authors: Jin Jing , Jiang Yuanyuan , Chakrabarti Subrata , Su Zhaoliang
Published: July 2022

Cardiac mast cells (CMCs) are multifarious immune cells with complex roles both in cardiac physiological and pathological conditions, especially in cardiac fibrosis. Little is known about the physiological importance of CMCs in cardiac homeostasis and inflammatory process. Therefore, the present review will summarize the recent progress of CMCs on origin, development and replenishment in the heart, including their effects on cardiac development, function and ageing under physiological conditions as well as the roles of CMCs in inflammatory progression and resolution. The present review will shed a light on scientists to understand cardioimmunology and to develop immune treatments targeting on CMCs following cardiac injury.
Influence of the Order Exchange of the Node Connection in the Force Analysis of Steel Structures
Authors: Luo Shuai , Song Dehai , Shen Kangli , Fang Rui , Wang Wei
Published: July 2022

In the mechanical analysis of steel structures, whether it is static analysis or dynamic analysis, it is necessary to establish the structural stiffness matrix first. In the process of building the structural stiffness matrix, the same element usually has different node code connection orders, and it has never been argued whether the different connection orders of the same element will have an effect on the building of the stiffness matrix. In this study, the influence of the difference in the node connection order on the construction of the element stiffness matrix is studied. First, the structural element stiffness matrix in the global coordinate system is established when the node connection order is different. It is found that the element stiffness matrix in the global coordinate system is indeed inconsistent for the same element with different connection orders. In this study, the elements of the established element stiffness matrix are extracted into the global stiffness matrix of the structural system based on the law of energy conservation; it is found that the global stiffness matrix finally established by using two different connection relationships is the same. The research results of the example show that in the stress analysis of steel structures, selecting different node connection sequences to establish the structural stiffness matrix will obtain the element stiffness matrix under different global coordinate systems. However, through the aggregation process of the global stiffness matrix of the structural system, the global stiffness matrix obtained is consistent, so the different connection sequences of nodes will not affect the stress analysis of steel structures. The example further analyzes the static stress and dynamic responses of the steel structure. The conclusions of this study provide a reliable theoretical basis for the situation that the order of node connections need not be consistent in the finite element modeling of steel structures and are of reference value for the finite element modeling of steel structures.
Clinical evaluation of metagenomic next-generation sequencing for detecting pathogens in bronchoalveolar lavage fluid collected from children with community-acquired pneumonia
Authors: Guo Wei , Cui Xiaojian , Wang Qiushi , Wei Yupeng , Guo Yanqing , Zhang Tongqiang , Zhan Jianghua
Published: July 2022

This study is to evaluate the usefulness of pathogen detection using metagenomic next-generation sequencing (mNGS) on bronchoalveolar lavage fluid (BALF) specimens from children with community-acquired pneumonia (CAP). We retrospectively collected BALF specimens from 121 children with CAP at Tianjin Children's Hospital from February 2021 to December 2021. The diagnostic performances of mNGS and conventional tests (CT) (culture and targeted polymerase chain reaction tests) were compared, using composite diagnosis as the reference standard. The results of mNGS and CT were compared based on pathogenic and non-pathogenic organisms. Pathogen profiles and co-infections between the mild CAP and severe CAP groups were also analyzed. The overall positive coincidence rate was 86.78% (105/121) for mNGS and 66.94% (81/121) for CT. The proportion of patients diagnosed using mNGS plus CT increased to 99.18%. Among the patients, 17.36% were confirmed only by mNGS; Streptococcus pneumoniae accounted for 52.38% and 23.8% of the patients were co-infected. Moreover, Bordetella pertussis and Human bocavirus (HBoV) were detected only using mNGS. Mycoplasma pneumoniae, which was identified in 89 (73.55%) of 121 children with CAP, was the most frequent pathogen detected using mNGS. The infection rate of M. pneumoniae in the severe CAP group was significantly higher than that in the mild CAP group (P = 0.007). The symptoms of single bacterial infections (except for mycoplasma) were milder than those of mycoplasma infections. mNGS identified more bacterial infections when compared to the CT methods and was able to identify co-infections which were initially missed on CT. Additionally, it was able to identify pathogens that were beyond the scope of the CT methods. The mNGS method is a powerful supplement to clinical diagnostic tools in respiratory infections, as it can increase the precision of diagnosis and guide the use of antibiotics.
The Landscape of Virus-Host Protein–Protein Interaction Databases
Authors: Valiente Gabriel
Published: July 2022

Knowledge of virus-host interactomes has advanced exponentially in the last decade by the use of high-throughput screening technologies to obtain a more comprehensive landscape of virus-host protein–protein interactions. In this article, we present a systematic review of the available virus-host protein–protein interaction database resources. The resources covered in this review are both generic virus-host protein–protein interaction databases and databases of protein–protein interactions for a specific virus or for those viruses that infect a particular host. The databases are reviewed on the basis of the specificity for a particular virus or host, the number of virus-host protein–protein interactions included, and the functionality in terms of browse, search, visualization, and download. Further, we also analyze the overlap of the databases, that is, the number of virus-host protein–protein interactions shared by the various databases, as well as the structure of the virus-host protein–protein interaction network, across viruses and hosts.
Bartonella taylorii: A Model Organism for Studying Bartonella Infection in vitro and in vivo
Authors: Fromm Katja , Boegli Alexandra , Ortelli Monica , Wagner Alexander , Bohn Erwin , Malmsheimer Silke , Wagner Samuel , Dehio Christoph
Published: July 2022

Bartonella spp. are Gram-negative facultative intracellular pathogens that infect diverse mammals and cause a long-lasting intra-erythrocytic bacteremia in their natural host. These bacteria translocate Bartonella effector proteins (Beps) into host cells via their VirB/VirD4 type 4 secretion system (T4SS) in order to subvert host cellular functions, thereby leading to the downregulation of innate immune responses. Most studies on the functional analysis of the VirB/VirD4 T4SS and the Beps were performed with the major zoonotic pathogen Bartonella henselae for which efficient in vitro infection protocols have been established. However, its natural host, the cat, is unsuitable as an experimental infection model. In vivo studies were mostly confined to rodent models using rodent-specific Bartonella species, while the in vitro infection protocols devised for B. henselae are not transferable for those pathogens. The disparities of in vitro and in vivo studies in different species have hampered progress in our understanding of Bartonella pathogenesis. Here we describe the murine-specific strain Bartonella taylorii IBS296 as a new model organism facilitating the study of bacterial pathogenesis both in vitro in cell cultures and in vivo in laboratory mice. We implemented the split NanoLuc luciferase-based translocation assay to study BepD translocation through the VirB/VirD4 T4SS. We found increased effector-translocation into host cells if the bacteria were grown on tryptic soy agar (TSA) plates and experienced a temperature shift immediately before infection. The improved infectivity in vitro was correlating to an upregulation of the VirB/VirD4 T4SS. Using our adapted infection protocols, we showed BepD-dependent immunomodulatory phenotypes in vitro. In mice, the implemented growth conditions enabled infection by a massively reduced inoculum without having an impact on the course of the intra-erythrocytic bacteremia. The established model opens new avenues to study the role of the VirB/VirD4 T4SS and the translocated Bep effectors in vitro and in vivo.
Microbial volatile organic compounds: Antifungal mechanisms, applications, and challenges
Authors: Zhao Xixi , Zhou Jingyi , Tian Ruofei , Liu Yanlin
Published: July 2022

The fungal decay of fresh fruits and vegetables annually generates substantial global economic losses. The utilization of conventional synthetic fungicides is damaging to the environment and human health. Recently, the biological control of post-harvest fruit and vegetable diseases via antagonistic microorganisms has become an attractive possible substitution for synthetic fungicides. Numerous studies have confirmed the potential of volatile organic compounds (VOCs) for post-harvest disease management. Moreover, VOC emission is a predominant antifungal mechanism of antagonistic microorganisms. As such, it is of great significance to discuss and explore the antifungal mechanisms of microbial VOCs for commercial application. This review summarizes the main sources of microbial VOCs in the post-harvest treatment and control of fruit and vegetable diseases. Recent advances in the elucidation of antifungal VOC mechanisms are emphasized, and the applications of VOCs produced from antagonistic microorganisms are described. Finally, the current prospects and challenges associated with microbial VOCs are considered.
An Assay Combining Droplet Digital PCR With Propidium Monoazide Treatment for the Accurate Detection of Live Cells of Vibrio vulnificus in Plasma Samples
Authors: Hu Ling , Fu Yidong , Zhang Shun , Pan Zhilei , Xia Jiang , Zhu Peng , Guo Jing
Published: July 2022

Vibrio vulnificus (V. vulnificus) is one of the most common pathogenic Vibrio species to humans; therefore, the establishment of timely and credible detection methods has become an urgent requirement for V. vulnificus illness surveillance. In this study, an assay combining droplet digital PCR (ddPCR) with propidium monoazide (PMA) treatment was developed for detecting V. vulnificus. The primers/probes targeting the V. vulnificus hemolysin A (vvhA) gene, amplification procedures, and PMA processing conditions involved in the assay were optimized. Then, we analyzed the specificity, sensitivity, and ability to detect live cell DNA while testing the performance of PMA-ddPCR in clinical samples. The optimal concentrations of primers and probes were 1.0 and 0.3 μM, respectively. The annealing temperature achieving the highest accuracy in ddPCR assay was 60°C. With an initial V. vulnificus cell concentration of 108 CFU/mL (colony-forming units per milliliter), the optimal strategy to distinguish live cells from dead cells was to treat samples with 100 μM PMA for 15 min in the dark and expose them to LED light with an output wavelength of 465 nm for 10 min. The specificity of the PMA-ddPCR assay was tested on 27 strains, including seven V. vulnificus strains and 20 other bacterial strains. Only the seven V. vulnificus strains were observed with positive signals in specificity analysis. Comparative experiments on the detection ability of PMA-ddPCR and PMA-qPCR in pure cultures and plasma samples were performed. The limit of detection (LOD) and the limit of quantitation (LOQ) in pure culture solutions of V. vulnificus were 29.33 and 53.64 CFU/mL in PMA-ddPCR, respectively. For artificially clinical sample tests in PMA-ddPCR, V. vulnificus could be detected at concentrations as low as 65.20 CFU/mL. The sensitivity of the PMA-ddPCR assay was 15- to 40-fold more sensitive than the PMA-qPCR in this study. The PMA-ddPCR assay we developed provides a new insight to accurately detect live cells of V. vulnificus in clinical samples, which is of great significance to enhance public health safety and security capability and improve the emergency response level for V. vulnificus infection.
Design and application of an efficient cellulose-degrading microbial consortium and carboxymethyl cellulase production optimization
Authors: Zhang Guoyan , Dong Yuanjie
Published: July 2022

Microbial consortia with high cellulase activities can speed up the composting of agricultural wastes with high cellulose contents and promote the beneficial utilization of agricultural wastes. In this paper, rabbit feces and sesame oil cake were used as feedstocks for compost production. Cellulose-degrading microbial strains were isolated from compost samples taken at the different composting stages and screened via Congo red staining and filter paper degradation test. Seven strains, Trichoderma reesei, Escherichia fergusonii, Proteus vulgaris, Aspergillus glaucus, Bacillus mycoides, Corynebacterium glutamicum, and Serratia marcescens, with high activities of carboxymethyl cellulase (CMCase), filter paper cellulase (FPase), and β-glucosidase (β-Gase) were identified and selected for consortium design. Six microbial consortia were designed with these strains. Compared with the other five consortia, consortium VI composed of all seven strains displayed the highest cellulase activities, 141.89, 104.56, and 131.18 U/ml of CMCase, FPase, and β-Gase, respectively. The single factor approach and response surface method were employed to optimize CMCase production of consortium VI. The optimized conditions were: culture time 4.25 days, culture temperature 35.5°C, pH 6.6, and inoculum volume 5% (v/v). Under these optimized conditions, the CMCase activity of consortium VI was up to 170.83 U/ml. Fermentation experiment of rabbit feces was carried out by using the consortium VI cultured under the optimal conditions. It was found that the application effect was better than other treatments, and the fermentation efficiency and nutrient content of the pile were significantly improved. This study provides a basis for the design of microbial consortia for the composting of agricultural wastes with high cellulose contents and provides a support for beneficial utilization of agricultural wastes.
Toward a Topology-Based Therapeutic Design of Membrane Proteins: Validation of NaPi2b Topology in Live Ovarian Cancer Cells
Authors: Bulatova Leisan , Savenkova Daria , Nurgalieva Alsina , Reshetnikova Daria , Timonina Arina , Skripova Vera , Bogdanov Mikhail , Kiyamova Ramziya
Published: July 2022

NaPi2b is a sodium-dependent phosphate transporter that belongs to the SLC34 family of transporters which is mainly responsible for phosphate homeostasis in humans. Although NaPi2b is widely expressed in normal tissues, its overexpression has been demonstrated in ovarian, lung, and other cancers. A valuable set of antibodies, including L2 (20/3) and MX35, and its humanized versions react strongly with an antigen on the surface of ovarian and other carcinoma cells. Although the topology of NaPi2b was predicted in silico, no direct experimental data are available for the orientation of NaPi2b extracellular domains in cancer cells. The presented results of antibody mapping of untagged NaPi2b in live ovarian carcinoma cells OVCAR-4 provide a platform for current and future epitope-based cancer therapies and serological diagnostics.
Prediction of Prognosis in Patients With Endometrial Carcinoma and Immune Microenvironment Estimation Based on Ferroptosis-Related Genes
Authors: Liu Shouze , Zhang Qianqian , Liu Wenhua , Huang Xianghua
Published: July 2022

Background: Ferroptosis, a form of non-apoptotic cell death, has aroused worldwide interest in cancer researchers. However, the current study about the correlation between ferroptosis-related genes (FRGs) and endometrial cancer (EC) remains limited.

Methods: First, the transcriptome profiling and clinical data of EC patients were downloaded from The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) program as the training group and testing group, respectively. FRGs were acquired through literature mining. Then, we used R 4.1.1 software to screen the differently expressed FRGs from TCGA, which was also connected with the prognosis of EC patients. Subsequently, the risk score of each tumor sample was identified by LASSO regression analysis, and we classified these samples into the high- and low-risk groups in the light of the median risk score. Receiver operating characteristic (ROC) curve analysis and Kaplan-Meier analysis were performed to assess the accuracy of this signature. Significantly, the data from CPTAC was used to validate the prediction model externally. Furthermore, we evaluated the immune microenvironment in this model via single-sample gene set enrichment analysis (ssGSEA).

Results: Among the 150 FRGs, 6 differentially expressed genes (DEGs) based on TCGA had a relationship with the prognosis of EC patients, namely, TP53, AIFM2, ATG7, TLR4, PANX1 and MDM2. The survival curve indicated a higher survival probability in the low-risk group. Moreover, the FRGs-based signature acted well in the prediction of overall survival (OS). The results of external verification confirmed the prediction model we established. Finally, ssGSEA revealed significant differences in the abundance of 16 immune cells infiltration and the activity of 13 immune functions between different risk groups.

Conclusion: We identified a novel ferroptosis-related gene signature which could concisely predict the prognosis and immunotherapy in EC patients.
Application of Nanoparticles in Tumour Targeted Drug Delivery and Vaccine
Authors: Tu Yuhan , Yao Zhiang , Yang Wenjing , Tao Shanhui , Li Bin , Wang Yun , Su Zhijian , Li Shijun
Published: July 2022

Cancer is a major cause of death worldwide, and nearly 1 in 6 deaths each year is caused by cancer. Traditional cancer treatment strategies cannot completely solve cancer recurrence and metastasis. With the development of nanotechnology, the study of nanoparticles (NPs) has gradually become a hotspot of medical research. NPs have various advantages. NPs exploit the enhanced permeability and retention (EPR) of tumour cells to achieve targeted drug delivery and can be retained in tumours long-term. NPs can be used as a powerful design platform for vaccines as well as immunization enhancers. Liposomes, as organic nanomaterials, are widely used in the preparation of nanodrugs and vaccines. Currently, most of the anticancer drugs that have been approved and entered clinical practice are prepared from lipid materials. However, the current clinical conversion rate of NPs is still extremely low, and the transition of NPs from the laboratory to clinical practice is still a substantial challenge. In this paper, we review the in vivo targeted delivery methods, material characteristics of NPs and the application of NPs in vaccine preparation. The application of nanoliposomes is also emphasized. Furthermore, the challenges and limitations of NPs are briefly discussed.
Abnormal spontaneous neural activity in hippocampal–cortical system of patients with obsessive–compulsive disorder and its potential for diagnosis and prediction of early treatment response
Authors: Yan Haohao , Shan Xiaoxiao , Li Huabing , Liu Feng , Guo Wenbin
Published: July 2022

Early brain functional changes induced by pharmacotherapy in patients with obsessive–compulsive disorder (OCD) in relation to drugs per se or because of the impact of such drugs on the improvement of OCD remain unclear. Moreover, no neuroimaging biomarkers are available for diagnosis of OCD and prediction of early treatment response. We performed a longitudinal study involving 34 patients with OCD and 36 healthy controls (HCs). Patients with OCD received 5-week treatment with paroxetine (40 mg/d). Resting-state functional magnetic resonance imaging (fMRI), regional homogeneity (ReHo), support vector machine (SVM), and support vector regression (SVR) were applied to acquire and analyze the imaging data. Compared with HCs, patients with OCD had higher ReHo values in the right superior temporal gyrus and bilateral hippocampus/parahippocampus/fusiform gyrus/cerebellum at baseline. ReHo values in the left hippocampus and parahippocampus decreased significantly after treatment. The reduction rate (RR) of ReHo values was positively correlated with the RRs of the scores of Yale–Brown Obsessive–Compulsive Scale (Y-BOCS) and obsession. Abnormal ReHo values at baseline could serve as potential neuroimaging biomarkers for OCD diagnosis and prediction of early therapeutic response. This study highlighted the important role of the hippocampal–cortical system in the neuropsychological mechanism underlying OCD, pharmacological mechanism underlying OCD treatment, and the possibility of building models for diagnosis and prediction of early treatment response based on spontaneous activity in the hippocampal–cortical system.
Chemogenetic Silencing of Differentiating Cortical Neurons Impairs Dendritic and Axonal Growth
Authors: Gasterstädt Ina , Schröder Max , Cronin Lukas , Kusch Julian , Rennau Lisa-Marie , Mücher Brix , Herlitze Stefan , Jack Alexander , Wahle Petra
Published: July 2022

Electrical activity is considered a key driver for the neurochemical and morphological maturation of neurons and the formation of neuronal networks. Designer receptors exclusively activated by designer drugs (DREADDs) are tools for controlling neuronal activity at the single cell level by triggering specific G protein signaling. Our objective was to investigate if prolonged silencing of differentiating cortical neurons can influence dendritic and axonal maturation. The DREADD hM4Di couples to Gi/o signaling and evokes hyperpolarization via GIRK channels. HM4Di was biolistically transfected into neurons in organotypic slice cultures of rat visual cortex, and activated by clozapine-N-oxide (CNO) dissolved in H2O; controls expressed hM4Di, but were mock-stimulated with H2O. Neurons were analyzed after treatment for two postnatal time periods, DIV 5-10 and 10-20. We found that CNO treatment delays the maturation of apical dendrites of L2/3 pyramidal cells. Further, the number of collaterals arising from the main axon was significantly lower, as was the number of bouton terminaux along pyramidal cell and basket cell axons. The dendritic maturation of L5/6 pyramidal cells and of multipolar interneurons (basket cells and bitufted cells) was not altered by CNO treatment. Returning CNO-treated cultures to CNO-free medium for 7 days was sufficient to recover dendritic and axonal complexity. Our findings add to the view that activity is a key driver in particular of postnatal L2/3 pyramidal cell maturation. Our results further suggest that inhibitory G protein signaling may represent a factor balancing the strong driving force of neurotrophic factors, electrical activity and calcium signaling.
Neurodevelopment in Down syndrome: Concordance in humans and models
Authors: Klein Jenny A. , Haydar Tarik F.
Published: July 2022

Great strides have been made over the past 30 years in understanding the neurodevelopmental changes underlying the intellectual disability (ID) in Down syndrome (DS). Detailed studies of human tissue coupled with findings from rodent and induced pluripotent stem cells (iPSCs) model systems have uncovered the changes in neurogenesis, synaptic connectivity, and myelination that drive the anatomical and physiological changes resulting in the disability. However, there remain significant conflicting data between human studies and the models. To fully understand the development of ID in DS, these inconsistencies need to be reconciled. Here, we review the well documented neurodevelopmental phenotypes found in individuals with DS and examine the degree to which widely used models recapitulate these phenotypes. Resolving these areas of discord will further research on the molecular underpinnings and identify potential treatments to improve the independence and quality of life of people with DS.
Type-I Interferons in Alzheimer's Disease and Other Tauopathies
Authors: Sanford Sophie A. I. , McEwan William A.
Published: July 2022

The detection of pathogen-associated molecular patterns can elicit the production of type-I interferons (IFNs), soluble cytokines that induce a transcriptional state inhibitory to viral replication. Signatures of type-I IFN-driven gene expression, and type-I IFNs themselves, are observed in the central nervous system during neurodegenerative diseases including Alzheimer's disease and other tauopathies, the umbrella term for diseases that feature aggregation of the cytosolic protein tau. The contribution of the type-I IFN response to pathological progression of these diseases, however, is not well-understood. The wholesale transcriptional changes that ensue from type-I IFN production can both promote protective effects and lead to damage dependent on the context and duration of the response. The type-I IFN system therefore represents a signaling pathway with a potential disease-modifying role in the progression of neurodegenerative disease. In this review we summarize the evidence for a type-I IFN signature in AD and other tauopathies and examine the role of aggregated proteins as inflammatory stimuli. We explore both the protective role of IFN against protein pathologies as well as their downstream toxic consequences, which include the exacerbation of protein pathology as a potentially destructive feed-forward loop. Given the involvement of type-I IFNs in other neurogenerative diseases, we draw comparisons with other categories of homotypic protein aggregation. Understanding how type-I IFN influences progression of AD and other tauopathies may yield important insight to neurodegeneration and identify new targets in an area currently lacking disease-modifying therapies.
Profiling morphologic MRI features of motor neuron disease caused by TARDBP mutations
Authors: Spinelli Edoardo Gioele , Ghirelli Alma , Riva Nilo , Canu Elisa , Castelnovo Veronica , Domi Teuta , Pozzi Laura , Carrera Paola , Silani Vincenzo , Chiò Adriano , Filippi Massimo , Agosta Federica
Published: July 2022

Objective

Mutations in the TARDBP gene are a rare cause of genetic motor neuron disease (MND). Morphologic MRI characteristics of MND patients carrying this mutation have been poorly described. Our objective was to investigate distinctive clinical and MRI features of a relatively large sample of MND patients carrying TARDBP mutations.

Methods

Eleven MND patients carrying a TARDBP mutation were enrolled. Eleven patients with sporadic MND (sMND) and no genetic mutations were also selected and individually matched by age, sex, clinical presentation and disease severity, along with 22 healthy controls. Patients underwent clinical and cognitive evaluations, as well as 3D T1-weighted and diffusion tensor (DT) MRI on a 3 Tesla scanner. Gray matter (GM) atrophy was first investigated at a whole-brain level using voxel-based morphometry (VBM). GM volumes and DT MRI metrics of the main white matter (WM) tracts were also obtained. Clinical, cognitive and MRI features were compared between groups.

Results

MND with TARDBP mutations was associated with all possible clinical phenotypes, including isolated upper/lower motor neuron involvement, with no predilection for bulbar or limb involvement at presentation. Greater impairment at naming tasks was found in TARDBP mutation carriers compared with sMND. VBM analysis showed significant atrophy of the right lateral parietal cortex in TARDBP patients, compared with controls. A distinctive reduction of GM volumes was found in the left precuneus and right angular gyrus of TARDBP patients compared to controls. WM microstructural damage of the corticospinal tract (CST) and inferior longitudinal fasciculi (ILF) was found in both sMND and TARDBP patients, compared with controls, although decreased fractional anisotropy of the right CST and increased axial diffusivity of the left ILF (p = 0.017) was detected only in TARDBP mutation carriers.

Conclusions

TARDBP patients showed a distinctive parietal pattern of cortical atrophy and greater damage of motor and extra-motor WM tracts compared with controls, which sMND patients matched for disease severity and clinical presentation were lacking. Our findings suggest that TDP-43 pathology due to TARDBP mutations may cause deeper morphologic alterations in both GM and WM.
Multi-View Feature Enhancement Based on Self-Attention Mechanism Graph Convolutional Network for Autism Spectrum Disorder Diagnosis
Authors: Zhao Feng , Li Na , Pan Hongxin , Chen Xiaobo , Li Yuan , Zhang Haicheng , Mao Ning , Cheng Dapeng
Published: July 2022

Functional connectivity (FC) network based on resting-state functional magnetic resonance imaging (rs-fMRI) has become an important tool to explore and understand the brain, which can provide objective basis for the diagnosis of neurodegenerative diseases, such as autism spectrum disorder (ASD). However, most functional connectivity (FC) networks only consider the unilateral features of nodes or edges, and the interaction between them is ignored. In fact, their integration can provide more comprehensive and crucial information in the diagnosis. To address this issue, a new multi-view brain network feature enhancement method based on self-attention mechanism graph convolutional network (SA-GCN) is proposed in this article, which can enhance node features through the connection relationship among different nodes, and then extract deep-seated and more discriminative features. Specifically, we first plug the pooling operation of self-attention mechanism into graph convolutional network (GCN), which can consider the node features and topology of graph network at the same time and then capture more discriminative features. In addition, the sample size is augmented by a “sliding window” strategy, which is beneficial to avoid overfitting and enhance the generalization ability. Furthermore, to fully explore the complex connection relationship among brain regions, we constructed the low-order functional graph network (Lo-FGN) and the high-order functional graph network (Ho-FGN) and enhance the features of the two functional graph networks (FGNs) based on SA-GCN. The experimental results on benchmark datasets show that: (1) SA-GCN can play a role in feature enhancement and can effectively extract more discriminative features, and (2) the integration of Lo-FGN and Ho-FGN can achieve the best ASD classification accuracy (79.9%), which reveals the information complementarity between them.
Distinct Kinematic and Neuromuscular Activation Strategies During Quiet Stance and in Response to Postural Perturbations in Healthy Individuals Fitted With and Without a Lower-Limb Exoskeleton
Authors: Layne Charles S. , Malaya Christopher A. , Ravindran Akshay S. , John Isaac , Francisco Gerard E. , Contreras-Vidal Jose Luis
Published: July 2022

Many individuals with disabling conditions have difficulty with gait and balance control that may result in a fall. Exoskeletons are becoming an increasingly popular technology to aid in walking. Despite being a significant aid in increasing mobility, little attention has been paid to exoskeleton features to mitigate falls. To develop improved exoskeleton stability, quantitative information regarding how a user reacts to postural challenges while wearing the exoskeleton is needed. Assessing the unique responses of individuals to postural perturbations while wearing an exoskeleton provides critical information necessary to effectively accommodate a variety of individual response patterns. This report provides kinematic and neuromuscular data obtained from seven healthy, college-aged individuals during posterior support surface translations with and without wearing a lower limb exoskeleton. A 2-min, static baseline standing trial was also obtained. Outcome measures included a variety of 0 dimensional (OD) measures such as center of pressure (COP) RMS, peak amplitude, velocities, pathlength, and electromyographic (EMG) RMS, and peak amplitudes. These measures were obtained during epochs associated with the response to the perturbations: baseline, response, and recovery. T-tests were used to explore potential statistical differences between the exoskeleton and no exoskeleton conditions. Time series waveforms (1D) of the COP and EMG data were also analyzed. Statistical parametric mapping (SPM) was used to evaluate the 1D COP and EMG waveforms obtained during the epochs with and without wearing the exoskeleton. The results indicated that during quiet stance, COP velocity was increased while wearing the exoskeleton, but the magnitude of sway was unchanged. The OD COP measures revealed that wearing the exoskeleton significantly reduced the sway magnitude and velocity in response to the perturbations. There were no systematic effects of wearing the exoskeleton on EMG. SPM analysis revealed that there was a range of individual responses; both behaviorally (COP) and among neuromuscular activation patterns (EMG). Using both the OD and 1D measures provided a more comprehensive representation of how wearing the exoskeleton impacts the responses to posterior perturbations. This study supports a growing body of evidence that exoskeletons must be personalized to meet the specific capabilities and needs of each individual end-user.
Research trends of the neuroimaging in aphasia: A bibliometric analysis and visualization analysis from 2004 to 2021
Authors: Huang Jiaqin , Cao Yun , Zhang Danli , Lei Xiaojing , Chang Jingling
Published: July 2022

Objectives

To review the current research status of the neuroimaging of aphasia, and reveal the hotspots and frontiers of research in this field.

Methods

We searched articles related to the neuroimaging research on aphasia since Web of Science (WOS) database construction and extracted the data. CiteSpace and VOSviewer were used for the country/institution analysis, journal analysis, discipline analysis, burst keyword analysis and cited-reference cluster analysis.

Results

Of the studies retrieved from WOS, 2922 studies that related to the neuroimaging of aphasia were screened and finally included 2799 articles for research. The United States of America and University of California San Francisco were the main countries and institutions in this field. Brain had the highest impact factor in both published and cited journals. Through the discipline and topic analysis of this field, the most common category was Neurosciences and Neurology. The keyword with the strongest citation strength was “functional connectivity,” and the recent burst keywords were “functional connectivity” and “network.” The co-citation network showed seven clusters greater than 100. Among the top 5 clusters, the most recently formed cluster, Cluster #2 (progressive supranuclear palsy), had an average year of 2017. The literature in the top 5 clusters mainly focused on 3 aspects, specifically, the discovery of language processing models, injury and recovery mechanisms of post-stroke aphasia (PSA), and diagnosis of primary progressive aphasia (PPA) variants.

Conclusion

The results of this bibliometric study revealed the following three research hotspots in the neuroimaging of aphasia: clarifying the connotation of the most recognized language processing model, the dual-stream model, exploring the injury mechanism based on the dual-stream model and the recovery mechanism involving the left and right hemispheres of PSA, and determining the diagnostic criteria for PPA variants. A major research trend is to combine new neuroimaging technology, such as PET tracer technology, to realize the visual presentation of disease-specific proteins to improve the pathological diagnostic criteria of PPA variants. Accordingly, a visualized analysis of literature that uses CiteSpace provides a more rapid, repeatable and flexible method, which is more conducive to capturing research hotspots and emerging trends.
Identification of cortical interneuron cell markers in mouse embryos based on machine learning analysis of single-cell transcriptomics
Authors: Li Zhandong , Wang Deling , Guo Wei , Zhang Shiqi , Chen Lei , Zhang Yu-Hang , Lu Lin , Pan XiaoYong , Huang Tao , Cai Yu-Dong
Published: July 2022

Mammalian cortical interneurons (CINs) could be classified into more than two dozen cell types that possess diverse electrophysiological and molecular characteristics, and participate in various essential biological processes in the human neural system. However, the mechanism to generate diversity in CINs remains controversial. This study aims to predict CIN diversity in mouse embryo by using single-cell transcriptomics and the machine learning methods. Data of 2,669 single-cell transcriptome sequencing results are employed. The 2,669 cells are classified into three categories, caudal ganglionic eminence (CGE) cells, dorsal medial ganglionic eminence (dMGE) cells, and ventral medial ganglionic eminence (vMGE) cells, corresponding to the three regions in the mouse subpallium where the cells are collected. Such transcriptomic profiles were first analyzed by the minimum redundancy and maximum relevance method. A feature list was obtained, which was further fed into the incremental feature selection, incorporating two classification algorithms (random forest and repeated incremental pruning to produce error reduction), to extract key genes and construct powerful classifiers and classification rules. The optimal classifier could achieve an MCC of 0.725, and category-specified prediction accuracies of 0.958, 0.760, and 0.737 for the CGE, dMGE, and vMGE cells, respectively. The related genes and rules may provide helpful information for deepening the understanding of CIN diversity.
Effects and Mechanisms of Acupuncture on Diarrhea-Predominant Irritable Bowel Syndrome: A Systematic Review
Authors: Zhang Gezhi , Zhang Tao , Cao Zeng , Tao Zijing , Wan Tianhao , Yao Mengxi , Su Xiaolan , Wei Wei
Published: July 2022

Background

Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction with challenging treatment. According to evidence-based studies, acupuncture is likely to be a promising therapy and subservient adjunct for IBS. Mechanism study of acupuncture based on related clinical trials of high quality, nevertheless, is still vacant.

Aim

This study aims to assess the results and qualities of current clinical evidence and conclude the relevant pathophysiological mechanisms and therapeutic effects of acupuncture on IBS with diarrhea (IBS-D).

Methods

Literature from four databases, namely, PubMed, Cochrane Library, EMBASE, and Web of Science, was systematically searched to obtain eligible randomized controlled trials (RCTs), which contained mechanism research of acupuncture treatment in IBS-D patients. Two independent reviewers completed data extraction and quality evaluation using the RevMan 5.4.1 software.

Results

Ten trials that covered 19 items related to mechanism research were included in this review. Acupuncture was reported to improve IBS-D symptoms and quality of life, with positive effects in regulating brain-gut peptides, cerebral activities, neuroendocrine functions, psychological state, and inflammatory GI and hypersensitive intestinal tracts.

Conclusion

Acupuncture has potential influence on pathophysiology alterations such as regulating brain-gut peptides, altering cerebral connectivity and activity, promoting neuroendocrine functions and mental state, and mitigating inflammation as well as hypersensitivity of bowels in IBS-D patients, but further studies of high quality are still necessary.

Systematic Review Registration

[https://www.crd.york.ac.uk/PROSPERO], identifier [CRD42022320331].
Combining magnetic resonance imaging with readout and/or perturbation of neural activity in animal models: Advantages and pitfalls
Authors: Kosten Lauren , Emmi Serena Alexa , Missault Stephan , Keliris Georgios A.
Published: July 2022

One of the main challenges in brain research is to link all aspects of brain function: on a cellular, systemic, and functional level. Multimodal neuroimaging methodology provides a continuously evolving platform. Being able to combine calcium imaging, optogenetics, electrophysiology, chemogenetics, and functional magnetic resonance imaging (fMRI) as part of the numerous efforts on brain functional mapping, we have a unique opportunity to better understand brain function. This review will focus on the developments in application of these tools within fMRI studies and highlight the challenges and choices neurosciences face when designing multimodal experiments.
Evaluation of the Dangerous Decibels Brazil Program in Workers Exposed to Noise
Authors: Bramati Luciana , Marques Jair Mendes , Gonçalves Claudia Giglio Oliveira , Welch David , Reddy Ravi , Lacerda Adriana Bender de Moreira
Published: July 2022

Introduction

Noise-induced hearing loss can be avoided by taking preventive measures.

Objective

To assess the effectiveness of the Brazilian version of the Dangerous Decibels® program for noise-exposed workers, using the ecological model as an educational intervention plan.

Method

Non-randomized interventional study with a quantitative, experimental trial design, conducted at a meatpacking company. The participants were divided into two groups—the first one (n = 132, divided into 6 subgroups) received the Dangerous Decibels® Brazil educational intervention (DDBEI) adapted to workers while the second group (n = 138, divided into 5 subgroups) received a conventional educational intervention (CEI). The interventions lasted 50 min. The Hearing Protection Assessment Questionnaire (HPA-5) was administered before and after the interventions. The five dimensions (attitude, behavior, knowledge, supports, and barriers) were compared using the Student’s t-test for paired data (<0.05).

Results

After both the DDBEI and CEI training, workers improved significantly in barriers, supports, knowledge, attitudes, and behavior around noise. By chance, the CEI group scored lower in all measures than the DDBEI group before training, and though both groups improved, the difference was maintained after training.

Conclusion

The Brazilian version of the Dangerous Decibels® program for noise-exposed workers was effective, influencing positively the factors at different levels of the ecological model. Though the DDBEI was no more effective than the CEI, the CEI participants began at much lower levels, so the effectiveness of the DDBEI may have been underestimated.
Prognostic values of serum alkaline phosphatase and globulin levels in patients undergoing intravenous thrombolysis
Authors: Zhu Hong-Jing , Sun Xin , Guo Zhen-Ni , Qu Yang , Sun Ying-Ying , Jin Hang , Wang Mei-Qi , Xu Bao-Feng , Yang Yi
Published: July 2022

Background

In previous studies, alkaline phosphatase (ALP) level was a prognostic factor for patients with ischemic stroke, and globulin level was associated with hemorrhagic transformation (HT) after intravenous thrombolysis (IVT). However, the association between these serum biomarkers and prognosis in patients with acute ischemic stroke (AIS) who undergo IVT remains unclear. This study aimed to investigate the characteristics of serum ALP and globulin levels after IVT and to assess the relationship between these serum biomarkers and prognosis.

Materials and methods

This retrospective study used a prospectively collected database. We included patients with AIS who received recombinant tissue plasminogen activator (rt-PA) IVT. Demographic information, vascular risk factors, laboratory test results, and other stroke-related data were collected for analysis. Clinical outcomes included HT and 3-month poor outcome (modified Rankin Scale scores ≥ 2) after IVT. The association of ALP and globulin levels with HT and poor outcome was investigated using multivariate logistic regression analysis. An individualized prediction model based on ALP and globulin levels for functional outcomes was established.

Results

We enrolled 750 patients in this study; 452 patients (60.3%) had poor outcome, and 117 patients (15.6%) had HT after IVT. After adjusting for all confounders, serum globulin level [OR = 1.055; 95% confidence intervals (CI): 1.006–1.107; P = 0.028] was independently associated with HT in patients with IVT. Serum ALP (OR = 1.009; 95% CI: 1.002–1.016; P = 0.010) and globulin levels (OR = 1.062; 95% CI: 1.020–1.107; P = 0.004) were associated with 3-month poor outcome in these patients. The constructed individualized prediction model for the 3-month poor outcome comprised the National Institutes of Health Stroke Scale (NIHSS) score, Trial of Org 10172 in Acute Stroke Treatment (TOAST), history of antihypertensive therapy, ALP and globulin levels. The area under the curve of the training and validation sets were 0.726 and 0.706, respectively, revealing that the model had good discriminating power. The P-values for the Hosmer-Lemeshow test in the training and validation sets were 0.978 and 0.148, respectively, indicating the model had good calibration.

Conclusion

This study found that higher serum globulin levels were independently associated with HT. Additionally, higher serum ALP and globulin levels were independently associated with a poor outcome in patients after IVT.