bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbial Communities and Physicochemical Characteristics of Traditional Dajiang and Sufu in North China Revealed by High-Throughput Sequencing of 16S rRNA
Authors: Liang Tingting , Xie Xinqiang , Ma Jun , Wu Lei , Xi Yu , Zhao Hui , Li Longyan , Li Haixin , Feng Ying , Xue Liang , Chen Moutong , Chen Xuefeng , Zhang Jumei , Ding Yu , Wu Qingping
Published: September 2021

The process of soybean fermentation has been practiced for more than 3,000 years. Although Dajiang and Sufu are two popular fermented soybean products consumed in North China, limited information is available regarding their microbial composition. Hence, the current study sought to investigate, and compare, the physicochemical indicators and microbial communities of traditional Dajiang and Sufu. Results showed that the titratable acidity (TA), and salinity, as well as the lactic acid, and malic acid contents were significantly higher in Sufu samples compared to Dajiang. Furthermore, Sufu samples contain abundant sucrose and fructose, while the acetic acid content was lower in Sufu compared to Dajiang samples. Moreover, the predominant bacterial phyla in Dajiang and Sufu samples were Firmicutes and Proteobacteria, while the major genera comprise Bacillus, Lactobacillus, Tetragenococcus, and Weissella. Moreover, Dajiang samples also contained abundant Pseudomonas, and Brevundimonas spp., while Halomonas, Staphylococcus, Lysinibacillus, Enterobacter, Streptococcus, Acinetobacter, and Halanaerobium spp. were abundant in Sufu samples. At the species level, Bacillus velezensis, Tetragenococcus halophilus, Lactobacillus rennini, Weissella cibaria, Weissella viridescens, Pseudomonas brenneri, and Lactobacillus acidipiscis represented the major species in Dajiang, while Halomonas sp., Staphylococcus equorum, and Halanaerobium praevalens were the predominant species in Sufu. Acetic acid and sucrose were found to be the primary major physicochemical factor influencing the bacterial communities in Dajiang and Sufu, respectively. Furthermore, Bacillus subtilis is strongly correlated with lactic acid levels, L. acidipiscis is positively correlated with acetic acid levels, while Staphylococcus sciuri and S. equorum are strongly, and positively, correlated with malic acid. Following analysis of carbohydrate and amino acid metabolism in all samples, cysteine and methionine metabolism, as well as fatty acid biosynthesis-related genes are upregulated in Dajiang compared to Sufu samples. However, such as the Staphylococcus, W. viridescens, and P. brenneri, as potentially foodborne pathogens, existed in Dajang and Sufu samples. Cumulatively, these results suggested that Dajiang and Sufu have unique bacterial communities that influence their specific characteristics. Hence, the current study provides insights into the microbial community composition in Dajiang and Sufu samples, which may facilitate the isolation of functional bacterial species suitable for Dajiang and Sufu production, thus improving their production efficiency.
Persistence of Hepatitis B Virus Infection: A Multi-Faceted Player for Hepatocarcinogenesis
Authors: Ghosh Suchandrima , Chakraborty Anannya , Banerjee Soma
Published: September 2021

Hepatitis B virus (HBV) infection has a multi-dimensional effect on the host, which not only alters the dynamics of immune response but also persists in the hepatocytes to predispose oncogenic factors. The virus exists in multiple forms of which the nuclear localized covalently closed circular DNA (cccDNA) is the most stable and the primary reason for viral persistence even after clearance of surface antigen and viral DNA. The second reason is the existence of pregenomic RNA (pgRNA) containing virion particles. On the other hand, the integration of the viral genome in the host chromosome also leads to persistent production of viral proteins along with the chromosomal instabilities. The interferon treatment or administration of nucleot(s)ide analogs leads to reduction in the viral DNA load, but the pgRNA and surface antigen clearance are a slow process and complete loss of serological HBsAg is rare. The prolonged exposure of immune cells to the viral antigens, particularly HBs antigen, in the blood circulation results in T-cell exhaustion, which disrupts immune clearance of the virus and virus-infected cells. In addition, it predisposes immune-tolerant microenvironment, which facilitates the tumor progression. Thus cccDNA, pgRNA, and HBsAg along with the viral DNA could be the therapeutic targets in the early disease stages that may improve the quality of life of chronic hepatitis B patients by impeding the progression of the disease toward hepatocellular carcinoma.
The Emergence of Novel Sequence Type Strains Reveals an Evolutionary Process of Intraspecies Clone Shifting in ICU-Spreading Carbapenem-Resistant Klebsiella pneumoniae
Authors: Zhao Dongdong , Shi Qiucheng , Hu Dandan , Fang Li , Mao Yihan , Lan Peng , Han Xinhong , Zhang Ping , Hu Huangdu , Wang Yanfei , Quan Jingjing , Yu Yunsong , Jiang Yan
Published: September 2021

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an urgent public health problem worldwide, and its rapid evolution in the clinical environment has been a major concern. A total of 99 CRKP isolates spreading in the intensive care unit (ICU) setting were included and subjected to whole-genome sequencing, and their sequence types (STs), serotype loci, and virulence determinants were screened based on genome data. The phylogenetic structure was reconstructed based on the core genome multilocus sequence typing method. Regions of recombination were assessed. Biofilm formation, serum resistance assays, and a Galleria mellonella infection model were used to evaluate strain virulence. A novel ST, designated ST4496, emerged in the ICU and spread for 6 months before its disappearance. ST4496 was closely related to ST11, with only a single-allele variant, and ST11 is the most dominant clinical clone in China. Recombination events occurred at capsule biosynthesis loci and divided the strains of ST11 and its derivative ST4496 into three clusters, including ST11-KL47, ST11-KL64, and ST4496-KL47. The phylogenetic structure indicated that ST11-KL47 was probably the origin of ST11-related strain evolution and presented more diversity in terms of both sequence similarity and phenotypes. ST4496-KL47 cluster strains presented less virulence than ST11-KL64, which was probably one of the factors preventing the former from spreading widely. In conclusion, ST4496-KL47 was probably derived from ST11-KL47 via intraspecies shifting but was less competitive than ST11-KL64, which also evolved from ST11-KL47 and developed increased virulence via capsule biosynthesis locus recombination. ST11-KL64 has the potential to be the predominant CRKP clone in China.
Current Methods, Common Practices, and Perspectives in Tracking and Monitoring Bioinoculants in Soil
Authors: Manfredini Andrea , Malusà Eligio , Costa Corrado , Pallottino Federico , Mocali Stefano , Pinzari Flavia , Canfora Loredana
Published: September 2021

Microorganisms promised to lead the bio-based revolution for a more sustainable agriculture. Beneficial microorganisms could be a valid alternative to the use of chemical fertilizers or pesticides. However, the increasing use of microbial inoculants is also raising several questions about their efficacy and their effects on the autochthonous soil microorganisms. There are two major issues on the application of bioinoculants to soil: (i) their detection in soil, and the analysis of their persistence and fate; (ii) the monitoring of the impact of the introduced bioinoculant on native soil microbial communities. This review explores the strategies and methods that can be applied to the detection of microbial inoculants and to soil monitoring. The discussion includes a comprehensive critical assessment of the available tools, based on morpho-phenological, molecular, and microscopic analyses. The prospects for future development of protocols for regulatory or commercial purposes are also discussed, underlining the need for a multi-method (polyphasic) approach to ensure the necessary level of discrimination required to track and monitor bioinoculants in soil.
Metagenomic Survey Reveals More Diverse and Abundant Antibiotic Resistance Genes in Municipal Wastewater Than Hospital Wastewater
Authors: Zhang Dengwei , Peng Ye , Chan Chak-Lun , On Hilda , Wai Hogan Kok-Fung , Shekhawat Sandeep Singh , Gupta Akhilendra Bhushan , Varshney Alok Kumar , Chuanchuen Rungtip , Zhou Xudong , Xia Yankai , Liang Suisha , Fukuda Keiji , Medicherla Krishna Mohan , Tun Hein M.
Published: September 2021

Alongside antibiotic resistance, co-selection of antibiotics, biocides, and metal resistance is a growing concern. While hospital wastewater is considered a hotspot for antibiotic-resistant bacteria (ARB) and genes (ARGs), the scenario in India, one of the biggest consumers of antibiotics, remains poorly described. In this study, we used metagenomic sequencing to characterize ARGs and biocide/metal resistance genes (BMRGs) in four wastewater treatment plants (WWTPs) in Jaipur City of India. We observed a significantly lower richness and abundance of ARGs in the influent of a WWTP exclusively receiving hospital wastewater when compared to other three WWTPs involving municipal wastewater treatment. Several tetracycline and macrolide-lincosamide-streptogramin resistance genes were enriched in influents of these three municipal wastewater-related treatment plants, whereas hospital wastewater had a higher abundance of genes conferring resistance to disinfectant-related compounds such as synergize and wex-cide-128, reflecting the patterns of antibiotic/disinfectant use. Of note, in the wastewater system with more chemicals, there was a strong correlation between the numbers of ARGs and BMRGs potentially harbored by common hosts. Our study highlights significant influxes of ARGs from non-hospital sources in Jaipur City, and thus more attention should be paid on the emergence of ARGs in general communities.
Highly Efficient Computationally Derived Novel Metagenome α-Amylase With Robust Stability Under Extreme Denaturing Conditions
Authors: Ariaeenejad Shohreh , Zolfaghari Behrouz , Sadeghian Motahar Seyedeh Fatemeh , Kavousi Kaveh , Maleki Morteza , Roy Swapnoneel , Hosseini Salekdeh Ghasem
Published: September 2021

α-Amylases are among the very critical enzymes used for different industrial purposes. Most α-amylases cannot accomplish the requirement of industrial conditions and easily lose their activity in harsh environments. In this study, a novel α-amylase named PersiAmy1 has been identified through the multistagein silicoscreening pipeline from the rumen metagenomic data. The long-term storage of PersiAmy1 in low and high temperatures demonstrated 82.13 and 71.01% activities after 36 days of incubation at 4 and 50°C, respectively. The stable α-amylase retained 61.09% of its activity after 180 min of incubation at 90°C and was highly stable in a broad pH range, showing 60.48 and 86.05% activities at pH 4.0 and pH 9.0 after 180 min of incubation, respectively. Also, the enzyme could resist the high-salinity condition and demonstrated 88.81% activity in the presence of 5 M NaCl. PersiAmy1 showed more than 74% activity in the presence of various metal ions. The addition of the detergents, surfactants, and organic solvents did not affect the α-amylase activity considerably. Substrate spectrum analysis showed that PersiAmy1 could act on a wide array of substrates. PersiAmy1 showed high stability in inhibitors and superb activity in downstream conditions, thus useful in detergent and baking industries. Investigating the applicability in detergent formulation, PersiAmy1 showed more than 69% activity after incubation with commercial detergents at different temperatures (30–50°C) and retained more than 56% activity after incubation with commercial detergents for 3 h at 10°C. Furthermore, the results of the wash performance analysis exhibited a good stain removal at 10°C. The power of PersiAmy1 in the bread industry revealed soft, chewable crumbs with improved volume and porosity compared with control. This study highlights the intense power of robust novel PersiAmy1 as a functional bio-additive in many industrial applications.
Comparative Study on the Antioxidant Activity of Monascus Yellow Pigments From Two Different Types of Hongqu—Functional Qu and Coloring Qu
Authors: Wu Li , Zhou Kangxi , Chen Feng , Chen Guimei , Yu Ying , Lv Xucong , Zhang Wen , Rao Pingfan , Ni Li
Published: September 2021

Graphical Abstract

Monascus yellow pigments (MYPs) in functional Qu (FQ) have a higher antioxidant potential than those in coloring Qu (CQ). The difference in antioxidant activities of MYPs is due to the critical hydroxyl group on C-3′ or C-11.
The Burden of Respiratory Viruses and Their Prevalence in Different Geographical Regions of India: 1970–2020
Authors: Waghmode Rushabh , Jadhav Sushama , Nema Vijay
Published: September 2021

As per the 2019 report of the National Health Portal of India, 41,996,260 cases and 3,740 deaths from respiratory infections were recorded across India in 2018. India contributes to 18% of the global population, with severe acute respiratory infection (SARI) as one of the prominent causes of mortality in children >5 years of age. Measures in terms of the diagnosis and surveillance of respiratory infections are taken up globally to discover their circulating types, detect outbreaks, and estimate the disease burden. Similarly, the purpose of this review was to determine the prevalence of respiratory infections in various regions of India through published reports. Understanding the pattern and prevalence of various viral entities responsible for infections and outbreaks can help in designing better strategies to combat the problem. The associated pathogens comprise respiratory syncytial virus (RSV), rhinovirus, influenza virus, parainfluenza virus, adenovirus, etc. Identification of these respiratory viruses was not given high priority until now, but the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has sensitized our system to be alert about the burden of existing infections and to have proper checks for emerging ones. Most of the studies reported to date have worked on the influenza virus as a priority. However, the data describing the prevalence of other respiratory viruses with their seasonal pattern have significant epidemiological value. A comprehensive literature search was done to gather data from all geographical regions of India comprising all states of India from 1970 to 2020. The same has been compared with the global scenario and is being presented here.
Identification and Characterization of a Novel Aminoglycoside 3''-Nucleotidyltransferase, ANT(3'')-IId, From Acinetobacter lwoffii
Authors: Liang Jialei , Zhou Kexin , Li Qiaoling , Dong Xu , Zhang Peiyao , Liu Hongmao , Lin Hailong , Zhang Xueya , Lu Junwan , Lin Xi , Li Kewei , Xu Teng , Zhang Hailin , Bao Qiyu , Zhu Mei , Hu Yunliang , Ren Ping
Published: September 2021

A novel plasmid-encoded aminoglycoside 3''-nucleotidyltransferase ANT(3")-IId, was discovered in Acinetobacter lwoffi strain H7 isolated from a chick on an animal farm in Wenzhou, China. The whole-genome of A. lwoffii H7 consisted of one chromosome and five plasmids (pH7-250, pH7-108, pH7-68, pH7-48, and pH7-11). ant(3")-IId was identified as being encoded on pH7-250, sharing the highest amino acid identity of 50.64% with a function-known resistance gene, ant(3")-IIb (KB849358.1). Susceptibility testing and enzyme kinetic parameter analysis were conducted to determine the function of the aminoglycoside 3"-nucleotidyltransferase. The ant(3")-IId gene conferred resistance to spectinomycin and streptomycin [the minimum inhibitory concentration (MIC) levels of both increased 16-fold compared with the control strain]. Consistent with the MIC data, kinetic analysis revealed a narrow substrate profile including spectinomycin and streptomycin, with Kcat/Km ratios of 4.99 and 4.45×103M−1 S−1, respectively. Sequencing analysis revealed that the ant(3")-IId gene was associated with insertion sequences (IS) element [ΔISAba14-ΔISAba14-hp-orf-orf-orf1-ant(3")-IId], and ant(3")-IId were identified in plasmids from various Acinetobacter species. This study of the novel aminoglycoside 3"-nucleotidyltranferase ANT(3")-IId helps us further understand the functional and sequence characteristics of aminoglycoside 3"-nucleotidyltranferases, highlights the risk of resistance gene transfer among Acinetobacter species and suggests that attention should be given to the emergence of new aminoglycoside 3"-nucleotidyltranferase genes.
RhoA/ROCK-YAP/TAZ Axis Regulates the Fibrotic Activity in Dexamethasone-Treated Human Trabecular Meshwork Cells
Authors: Liu Zhicheng , Li Shanshan , Qian Xiuqing , Li Lin , Zhang Haixia , Liu Zhicheng
Published: September 2021

High intraocular pressure (IOP) is a major risk factor for glaucoma, a leading cause of irreversible blindness. Abnormal fibrotic activity in the human trabecular meshwork (HTM) cells is considered to be partly responsible for the increased resistance of aqueous humor outflow and IOP. This study aimed to identify the fibrotic pathways using integrated bioinformatics and further elucidate their mechanism of regulating fibrotic activity in dexamethasone (DEX)-treated HTM cells. Microarray datasets from the GEO database were obtained and analyzed by GEO2R. Bioinformatics analyses, including GO and KEGG analyses, were performed to explore biological functions and signaling pathways of differentially expressed genes (DEGs). The fibrotic pathways and targets were determined by western blot, RT-qPCR, or immunofluorescence staining. The cellular elastic modulus was measured using an atomic force microscope. A total of 204 DEGs, partly enriched in fibrotic activity (collagen-containing ECM, fibroblast activation) and Rap1, Ras, TGF-β, and Hippo pathways, were identified. Experimental results showed that DEX induced fibrotic activity and regulated the expression of RhoA/ROCK in HTM cells. Similarly, the constitutively active RhoA (RhoAG14V) also promoted the fibrotic activity of HTM cells. Mechanistically, RhoAG14V induced the expression and nuclear translocation of YAP/TAZ to produce CTGF. Moreover, inhibition of ROCK or YAP decreased the expression of Collagen I and α-SMA proteins induced by DEX or RhoAG14V in HTM cells. In conclusion, these results indicate that RhoA/ROCK-YAP/TAZ axis plays a crucial role in regulating the fibrotic activity of DEX-treated HTM cells.
The Association Between Perivascular Spaces and Cerebral Blood Flow, Brain Volume, and Cardiovascular Risk
Authors: Liu Sirui , Hou Bo , You Hui , Zhang Yiwei , Zhu Yicheng , Ma Chao , Zuo Zhentao , Feng Feng
Published: September 2021

Background: Basal ganglia perivascular spaces are associated with cognitive decline and cardiovascular risk factors. There is a lack of studies on the cardiovascular risk burden of basal ganglia perivascular spaces (BG-PVS) and their relationship with gray matter volume (GMV) and GM cerebral blood flow (CBF) in the aging brain. Here, we investigated these two issues in a large sample of cognitively intact older adults.

Methods: A total of 734 volunteers were recruited. MRI was performed with 3.0 T using a pseudo-continuous arterial spin labeling (pCASL) sequence and a sagittal isotropic T1-weighted sequence for CBF and GMV analysis. The images obtained from 406 participants were analyzed to investigate the relationship between the severity of BG-PVS and GMV/CBF. False discovery rate-corrected P-values (PFDR) of <0.05 were considered significant. The images obtained from 254 participants were used to study the relationship between the severity of BG-PVS and cardiovascular risk burden. BG-PVS were rated using a 5-grade score. The severity of BG-PVS was classified as mild (grade <3) and severe (grade ≥3). Cardiovascular risk burden was assessed with the Framingham General Cardiovascular Risk Score (FGCRS).

Results: Severe basal ganglia perivascular spaces were associated with significantly smaller GMV and CBF in multiple cortical regions (PFDR <0.05), and were associated with significantly larger volume in the bilateral caudate nucleus, pallidum, and putamen (PFDR <0.05). The participants with severe BG-PVS were more likely to have a higher cardiovascular risk burden than the participants with mild BG-PVS (60.71% vs. 42.93%; P =0.02).

Conclusion: In cognitively intact older adults, severe BG-PVS are associated with smaller cortical GMV and CBF, larger subcortical GMV, and higher cardiovascular risk burden.
Altered Spontaneous Brain Activity in Subjects With Different Cognitive States of Biologically Defined Alzheimer's Disease: A Surface-Based Functional Brain Imaging Study
Authors: Zhu Zili , Zeng Qingze , Kong Linghan , Luo Xiao , Li Kaicheng , Xu Xiaopei , Zhang Minming , Huang Peiyu , Yang Yunjun
Published: September 2021

Background: Before the apparent cognitive decline, subjects on the course of Alzheimer's disease (AD) can have significantly altered spontaneous brain activity, which could be potentially used for early diagnosis. As previous studies investigating local brain activity may suffer from the problem of cortical signal aliasing during volume-based analysis, we aimed to investigate the cortical functional alterations in the AD continuum using a surface-based approach.

Methods: Based on biomarker profile “A/T,” we included 11 healthy controls (HC, A–T–), 22 preclinical AD (CU, A+T+), 33 prodromal AD (MCI, A+T+), and 20 AD with dementia (d-AD, A+T+) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The amplitude of low-frequency fluctuation (ALFF) method was used to evaluate the changes of spontaneous brain activity, which was performed in the classic frequency band (0.01–0.08 Hz), slow-4 (0.027–0.073 Hz) band, and slow-5 (0.01–0.027 Hz) band.

Results: Under classic frequency band and slow-4 band, analysis of covariance (ANCOVA) showed that there were significant differences of standardized ALFF (zALFF) in the left posterior cingulate cortex (PCC) among the four groups. The post-hoc analyses showed that under the classic frequency band, the AD group had significantly decreased zALFF compared with the other three groups, and the cognitively unimpaired (CU) group had decreased zALFF compared with the healthy control (HC) group. Under the slow-4 band, more group differences were detected (HC > CU/MCI > d-AD). The accuracy of classifying CU, mild cognitive impairment (MCI), and AD from HC by left PCC activity under the slow-4 band were 0.774, 0.744, and 0.920, respectively. Moreover, the zALFF values of the left PCC had significant correlations with cerebrospinal fluid (CSF) biomarkers and neuropsychological tests.

Conclusions: Spontaneous brain activity in the left PCC may decrease in preclinical AD when cognitive functions were relatively normal. The combination of a surfaced-based approach and specific frequency band analysis may increase sensitivity for the identification of preclinical AD subjects.
Modulation of Glial Function in Health, Aging, and Neurodegenerative Disease
Authors: Hanslik Kendra L. , Marino Kaitlyn M. , Ulland Tyler K.
Published: September 2021

In the central nervous system (CNS), glial cells, such as microglia and astrocytes, are normally associated with support roles including contributions to energy metabolism, synaptic plasticity, and ion homeostasis. In addition to providing support for neurons, microglia and astrocytes function as the resident immune cells in the brain. The glial function is impacted by multiple aspects including aging and local CNS changes caused by neurodegeneration. During aging, microglia and astrocytes display alterations in their homeostatic functions. For example, aged microglia and astrocytes exhibit impairments in the lysosome and mitochondrial function as well as in their regulation of synaptic plasticity. Recent evidence suggests that glia can also alter the pathology associated with many neurodegenerative disorders including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Shifts in the microbiome can impact glial function as well. Disruptions in the microbiome can lead to aberrant microglial and astrocytic reactivity, which can contribute to an exacerbation of disease and neuronal dysfunction. In this review, we will discuss the normal physiological functions of microglia and astrocytes, summarize novel findings highlighting the role of glia in aging and neurodegenerative diseases, and examine the contribution of microglia and astrocytes to disease progression.
The Role of the UPR Pathway in the Pathophysiology and Treatment of Bipolar Disorder
Authors: Suliman Mahmoud , Schmidtke Michael W. , Greenberg Miriam L.
Published: September 2021

Bipolar disorder (BD) is a mood disorder that affects millions worldwide and is associated with severe mood swings between mania and depression. The mood stabilizers valproate (VPA) and lithium (Li) are among the main drugs that are used to treat BD patients. However, these drugs are not effective for all patients and cause serious side effects. Therefore, better drugs are needed to treat BD patients. The main barrier to developing new drugs is the lack of knowledge about the therapeutic mechanism of currently available drugs. Several hypotheses have been proposed for the mechanism of action of mood stabilizers. However, it is still not known how they act to alleviate both mania and depression. The pathology of BD is characterized by mitochondrial dysfunction, oxidative stress, and abnormalities in calcium signaling. A deficiency in the unfolded protein response (UPR) pathway may be a shared mechanism that leads to these cellular dysfunctions. This is supported by reported abnormalities in the UPR pathway in lymphoblasts from BD patients. Additionally, studies have demonstrated that mood stabilizers alter the expression of several UPR target genes in mouse and human neuronal cells. In this review, we outline a new perspective wherein mood stabilizers exert their therapeutic mechanism by activating the UPR. Furthermore, we discuss UPR abnormalities in BD patients and suggest future research directions to resolve discrepancies in the literature.
Therapeutic Plasma Exchange in Myasthenia Gravis: A Systematic Literature Review and Meta-Analysis of Comparative Evidence
Authors: Ipe Tina S. , Davis Adeola R. , Raval Jay S.
Published: September 2021

Background: Patients with Myasthenia Gravis (MG) can be treated acutely with therapeutic plasma exchange (TPE) or intravenous immune globulin (IVIG). To date, there is no definitive understanding of which of the two treatments is more effective and safer. The purpose of this study was to systematically review the literature on the comparative efficacy and safety of TPE to other available treatments for MG.

Methods: A systematic literature search for studies published between 1997 and 2017 was performed per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using two database sources, MEDLINE (through the PubMed database) and Cochrane Library.

Results: The search strategy resulted in 535 articles whose abstracts were reviewed. Among these, 165 full texts articles were reviewed for eligibility and 101 articles were excluded. Of the 165 articles, 64 articles were included for a systematic literature and 11 articles for a meta-analysis.

Conclusions: This systematic literature review and meta-analysis of treatment options showed that there was a higher response rate with TPE than IVIG in acute MG patients and patients undergoing thymectomy. There was no difference in mortality between the two treatment options. Our findings highlight the need for additional randomized clinical trials in these patients with MG.
Metabolic and Structural Signatures of Speech and Language Impairment in Corticobasal Syndrome: A Multimodal PET/MRI Study
Authors: Parmera Jacy Bezerra , Almeida Isabel Junqueira de , Oliveira Marcos Castello Barbosa de , Silagi Marcela Lima , de Godoi Carneiro Camila , Studart-Neto Adalberto , Ono Carla Rachel , Reis Barbosa Egberto , Nitrini Ricardo , Buchpiguel Carlos Alberto , Brucki Sonia Maria Dozzi , Coutinho Artur Martins
Published: September 2021

Introduction: Corticobasal syndrome (CBS) is a progressive neurological disorder related to multiple underlying pathologies, including four-repeat tauopathies, such as corticobasal degeneration and progressive supranuclear palsy, and Alzheimer's disease (AD). Speech and language are commonly impaired, encompassing a broad spectrum of deficits. We aimed to investigate CBS speech and language impairment patterns in light of a multimodal imaging approach.

Materials and Methods: Thirty-one patients with probable CBS were prospectively evaluated concerning their speech–language, cognitive, and motor profiles. They underwent positron emission tomography with [18F]fluorodeoxyglucose (FDG-PET) and [11C]Pittsburgh Compound-B (PIB-PET) on a hybrid PET-MRI machine to assess their amyloid status. PIB-PET images were classified based on visual and semi-quantitative analyses. Quantitative group analyses were performed on FDG-PET data, and atrophy patterns on MRI were investigated using voxel-based morphometry (VBM). Thirty healthy participants were recruited as imaging controls.

Results: Aphasia was the second most prominent cognitive impairment, presented in 67.7% of the cases, following apraxia (96.8%). We identified a wide linguistic profile, ranging from nonfluent variant-primary progressive aphasia to lexical–semantic deficits, mostly with impaired verbal fluency. PIB-PET was classified as negative (CBS-A– group) in 18/31 (58%) and positive (CBS-A+ group) in 13/31 (42%) patients. The frequency of dysarthria was significantly higher in the CBS-A– group than in the CBS-A+ group (55.6 vs. 7.7%, p = 0.008). CBS patients with dysarthria had a left-sided hypometabolism at frontal regions, with a major cluster at the left inferior frontal gyrus and premotor cortex. They showed brain atrophy mainly at the opercular frontal gyrus and putamen. There was a positive correlation between [18F]FDG uptake and semantic verbal fluency at the left inferior (p = 0.006, R2 = 0.2326), middle (0.0054, R2 = 0.2376), and superior temporal gyri (p = 0.0066, R2 = 0.2276). Relative to the phonemic verbal fluency, we found a positive correlation at the left frontal opercular gyrus (p = 0.0003, R2 = 0.3685), the inferior (p = 0.0004, R2 = 0.3537), and the middle temporal gyri (p = 0.0001, R2 = 0.3993).

Discussion: In the spectrum of language impairment profile, dysarthria might be helpful to distinguish CBS patients not related to AD. Metabolic and structural signatures depicted from this feature provide further insights into the motor speech production network and are also helpful to differentiate CBS variants.
A Nomogram for Predicting the Need of Postoperative Tracheostomy in Patients With Aneurysmal Subarachnoid Hemorrhage
Authors: Chen Xiao-Yong , Chen Yue , Lin Ni , Chen Jin-Yuan , Ding Chen-Yu , Kang De-Zhi , Wang Deng-Liang , Fang Wen-Hua
Published: September 2021

Objective: Early identification for the need of tracheostomy (TT) in aneurysmal subarachnoid hemorrhage (aSAH) patients remains one of the main challenges in clinical practice. Our study aimed to establish and validate a nomogram model for predicting postoperative TT in aSAH patients.

Methods: Patients with aSAH receiving active treatment (interventional embolization or clipping) in our institution between June 2012 and December 2018 were retrospectively included. The effects of patients' baseline information, aneurysm features, and surgical factors on the occurrence of postoperative TT were investigated for establishing a nomogram in the training cohort with 393 patients. External validation for the nomogram was performed in the validation cohort with 242 patients.

Results: After multivariate analysis, higher age, high neutrophil-to-lymphocyte ratio (NLR), high World Federation of Neurological Surgeons Scale (WFNS), and high Barrow Neurological Institute (BNI) grade were left in the final logistic regression model. The predictive power of the model was excellent in both training cohort and validation cohort [area under the curve (AUC): 0.924, 95% confidence interval [CI]: 0.893–0.948; AUC: 0.881, 95% CI: 0.833–0.919]. A nomogram consisting of these factors had a C-index of 0.924 (95% CI: 0.869–0.979) in the training cohort and was validated in the validation cohort (C-index: 0.881, 95% CI: 0.812–0.950). The calibration curves suggested good match between prediction and observation in both training and validation cohorts.

Conclusion: Our study established and validated a nomogram model for predicting postoperative TT in aSAH patients.
Where We Mentalize: Main Cortical Areas Involved in Mentalization
Authors: Monticelli Matteo , Zeppa Pietro , Mammi Marco , Penner Federica , Melcarne Antonio , Zenga Francesco , Garbossa Diego
Published: September 2021

When discussing “mentalization,” we refer to a very special ability that only humans and few species of great apes possess: the ability to think about themselves and to represent in their mind their own mental state, attitudes, and beliefs and those of others. In this review, a summary of the main cortical areas involved in mentalization is presented. A thorough literature search using PubMed MEDLINE database was performed. The search terms “cognition,” “metacognition,” “mentalization,” “direct electrical stimulation,” “theory of mind,” and their synonyms were combined with “prefrontal cortex,” “temporo-parietal junction,” “parietal cortex,” “inferior frontal gyrus,” “cingulate gyrus,” and the names of other cortical areas to extract relevant published papers. Non-English publications were excluded. Data were extracted and analyzed in a qualitative manner. It is the authors' belief that knowledge of the neural substrate of metacognition is essential not only for the “neuroscientist” but also for the “practical neuroscientist” (i.e., the neurosurgeon), in order to better understand the pathophysiology of mentalizing dysfunctions in brain pathologies, especially those in which integrity of cortical areas or white matter connectivity is compromised. Furthermore, in the context of neuro-oncological surgery, understanding the anatomical structures involved in the theory of mind can help the neurosurgeon obtain a wider and safer resection. Though beyond of the scope of this paper, an important but unresolved issue concerns the long-range white matter connections that unify these cortical areas and that may be themselves involved in neural information processing.
Temporal Onset Focal Seizures Induced by Intermittent Photic Stimulation
Authors: Niu Yue , Gong Pan , Jiao Xianru , Yang Haipo , Yang Zhixian
Published: September 2021

The study aimed to review the clinical, radiological, and pathological findings and electroencephalogram (EEG) of pediatric epilepsy patients with temporal onset focal seizures induced by intermittent photic stimulation (IPS). Four patients with temporal onset photosensitivity focal seizures were analyzed. Three (75%) of the four patients were female. The average age of seizure-onset was 4.4 years. The interictal EEG showed both generalized and focal spike and waves in one patient and focal or multifocal spike and waves alone in three patients. Photoparoxysmal response (PPR) was evoked in all patients and showed generalized discharges (patients 2–4), both generalized and posterior discharges (patient 1). Both generalized and focal discharges could coexist in interictal discharges and PPR. The sensitive frequencies of PPR and photoconvulsive response (PCR) were 12–30 and 10–16 Hz, respectively, which were close to the occipital rhythm. In all patients, the onset of PCR was recorded, namely, the left anterior and mesial temporal lobe (TL), the left posterior TL, and the whole left TL, which showed two forms: the seizure of two patients was the onset of slow waves in the temporal area without spreading generalized discharges (patients 1 and 4), and the other one was fast rhythmic activities in the temporal area, spreading to the occipital area or gradually evolving into the generalized discharges (patients 2 and 3). During follow-up, except for patient 3 who had occasional seizures, the seizures of the remaining patients were under control. Temporal onset focal seizures could be induced by IPS. Temporal onset photosensitivity seizures were mostly easy to control with antiseizure drugs.
Fibrinogen Level Combined With Platelet Count for Predicting Hemorrhagic Transformation in Acute Ischemic Stroke Patients Treated With Mechanical Thrombectomy
Authors: Lin Changchun , Pan Hui , Qiao Yuan , Huang Peisheng , Su Jingjing , Liu Jianren
Published: September 2021

A serious complication of acute ischemic stroke (AIS) after mechanical thrombectomy (MT) is hemorrhagic transformation (HT), which is potentially associated with clinical deterioration. This study examined predictors of HT following MT in AIS patients. Patients with AIS due to large artery occlusion in the anterior circulation, treated with MT and successfully recanalized (modified Thrombolysis in Cerebral Infarction score 2b/3), were studied retrospectively. HT was evaluated by computed tomography (CT) 24 h after MT and was diagnosed and classified into parenchymal hematoma (PH) and hemorrhagic infarction (HI). Multivariate logistic regression models were used to determine the risk factors for HT. Receiver operating characteristic (ROC) curve analysis was performed to determine the predictive utility of risk factors for HT. We enrolled 135 patients: 49 in the HT group and 86 in the non-HT group. The two groups differed significantly in baseline fibrinogen levels (p = 0.003) and platelet counts (p = 0.006). Multivariate logistic regression analyses showed that lower fibrinogen levels [odds ratio (OR), 0.41; 95% CI, 0.23–0.72; p = 0.002] and platelet counts (OR, 0.58; 95% CI, 0.33–0.99; p = 0.048) were independently associated with a higher risk of HT. Together, the binary variates fibrinogen and platelets well-predicted HT (area under the curve, 0.703; specificity, 77.9%; sensitivity, 55.1%). The combination of fibrinogen <2.165 g/L and platelets <171.5 × 109/L was the strongest predictor of HT (OR, 23.17; 95% CI, 5.75–126.80; p < 0.0001). Our study suggests that lower baseline fibrinogen levels and platelet counts may be risk factors for HT in AIS patients following MT and reperfusion. Specifically, the combination of fibrinogen level and platelet count may predict the risk of HT after MT in these patients.
Intrinsic Thalamic Network in Temporal Lobe Epilepsy With Hippocampal Sclerosis According to Surgical Outcomes
Authors: Cho Kyoo Ho , Lee Ho-Joon , Heo Kyoung , Kim Sung Eun , Lee Dong Ah , Park Kang Min
Published: September 2021

Background: The aim of this study was to identify the differences of intrinsic amygdala, hippocampal, or thalamic networks according to surgical outcomes in temporal lobe epilepsy (TLE) patients with hippocampal sclerosis (HS).

Methods: We enrolled 69 pathologically confirmed TLE patients with HS. All patients had pre-operative three-dimensional T1-weighted MRI using a 3.0 T scanner. We obtained the structural volumes of the amygdala nuclei, hippocampal subfields, and thalamic nuclei. Then, we investigated the intrinsic networks based on volumes of these structures using structural covariance and graph theoretical analysis.

Results: Of the 69 TLE patients with HS, 21 patients (42.1%) had poor surgical outcomes, whereas 40 patients (57.9%) had good surgical outcomes. The volumes in the amygdala nuclei, hippocampal subfields, and thalamic nuclei were not different according to surgical outcome. In addition, the intrinsic amygdala and hippocampal networks were not different between the patients with poor and good surgical outcomes. However, there was a significant difference in the intrinsic thalamic network in the ipsilateral hemisphere between them. The eccentricity and small-worldness index were significantly increased, whereas the characteristic path length was decreased in the patients with poor surgical outcomes compared to those with good surgical outcomes.

Conclusion: We successfully demonstrated significant differences in the intrinsic thalamic network in the ipsilateral hemisphere between TLE patients with HS with poor and good surgical outcomes. This result suggests that the pre-operative intrinsic thalamic network can be related with surgical outcomes in TLE patients with HS.
Simultaneous Stenting for Symptomatic Tandem Extracranial and Intracranial Posterior Circulation Stenoses: Long-Term Outcomes and Procedural Experience
Authors: Jia Zichang , Zhao Yanqing , Wang Peng , Han Jintao , Zhao Shilu , Li Xuan
Published: September 2021

Few studies have reported on simultaneous endovascular stenting for tandem posterior circulation (PC) stenoses and its long-term outcomes. Thus, our aim was to investigate the safety and efficacy of simultaneous stenting in patients with symptomatic tandem extra- and intracranial PC stenoses. From September 2014 to June 2018, 16 such patients with symptomatic stenoses who underwent simultaneous stent placement were analyzed. The primary outcome was occurrence of any stroke, TIA, or death within 30 days after the procedure. The secondary outcomes were technical success, clinical success, and the occurrence of in-stent restenosis ≥50% during follow-up. Technical success was defined as stent coverage of all tandem lesions and residual stenosis <30%. Clinical success was determined based on any occurrence of neurological events or death within 3 months after the procedure. All stents (19 intracranial and 14 extracranial) were placed with a technical success rate of 100%. One patient experienced a pontine ischemic stroke 2 days after the procedure and had recovered well at discharge. One patient experienced a minor complication of groin hematoma. The clinical success rate was 93.75% (15/16). During a median follow-up of 36.0 ± 11.0 months, two patients developed ISR ≥50% at the 1-year follow-up. None of the patients experienced stroke, TIA, or death after discharge during follow-up. Simultaneous stenting for symptomatic tandem extra- and intracranial PC stenoses is safe and feasible. Its impact on long-term stroke prevention is promising, and further study of a larger patient population is needed.
Voxel-Wise Linearity Analysis of Increments and Decrements in BOLD Responses in Human Visual Cortex Using a Contrast Adaptation Paradigm
Authors: Lin Yun , Zhou Xi , Naya Yuji , Gardner Justin L. , Sun Pei
Published: September 2021

The linearity of BOLD responses is a fundamental presumption in most analysis procedures for BOLD fMRI studies. Previous studies have examined the linearity of BOLD signal increments, but less is known about the linearity of BOLD signal decrements. The present study assessed the linearity of both BOLD signal increments and decrements in the human primary visual cortex using a contrast adaptation paradigm. Results showed that both BOLD signal increments and decrements kept linearity to long stimuli (e.g., 3 s, 6 s), yet, deviated from linearity to transient stimuli (e.g., 1 s). Furthermore, a voxel-wise analysis showed that the deviation patterns were different for BOLD signal increments and decrements: while the BOLD signal increments demonstrated a consistent overestimation pattern, the patterns for BOLD signal decrements varied from overestimation to underestimation. Our results suggested that corrections to deviations from linearity of transient responses should consider the different effects of BOLD signal increments and decrements.
Continuous Theta Burst Stimulation to the Secondary Visual Cortex at 80% Active Motor Threshold Does Not Impair Central Vision in Humans During a Simple Detection Task
Authors: Lasagna Carly A. , Taylor Stephan F. , Lee Taraz G. , Rutherford Saige , Greathouse Tristan , Gu Pan , Tso Ivy F.
Published: September 2021

Continuous theta burst stimulation (cTBS) is a powerful form of repetitive transcranial magnetic stimulation capable of suppressing cortical excitability for up to 50 min. A growing number of studies have applied cTBS to the visual cortex in human subjects to investigate the neural dynamics of visual processing, but few have specifically examined its effects on central vision, which has crucial implications for safety and inference on downstream cognitive effects. The present study assessed the safety of offline, neuronavigated cTBS to V2 by examining its effects on central vision performance. In this single-blind, randomized sham-controlled, crossover study, 17 healthy adults received cTBS (at 80% active motor threshold) and sham to V2 1–2 weeks apart. Their central vision (≤8°) was tested at 1-min (T1) and again at 50-min (T50) post-stimulation. Effects of condition (cTBS vs. sham) and time (T1 vs. T50) on accuracy and reaction time were examined using Bayes factor. Bayes factor results suggested that cTBS did not impair stimulus detection over the entire central visual field nor subfields at T1 or T50. Our results offer the first explicit evidence supporting that cTBS applied to V2 does not create blind spots in the central visual field in humans during a simple detection task. Any subtler changes to vision and downstream visual perception should be investigated in future studies.
Retinal Diseases and Parkinson Disease: A Population-Based Study
Authors: Chen Po-Chih , Chung Chen-Chih , Cheng Yun-Yung , Chen Wan-Ting , Hong Chien-Tai , Chan Lung , Chien Li-Nien
Published: September 2021

Introduction

Patients with Parkinson disease (PD) tend to have ophthalmic symptoms. Retinal diseases are associated with central nervous system diseases, especially neurodegenerative diseases. Here, we investigated the association of retinal diseases with PD, especially the temporal relationship before and after PD diagnosis.

Methods

Data were obtained from the National Health Insurance Research Database of Taiwan. In total, 21,845 patients with newly diagnosed PD were matched with four controls each on the basis of propensity score. This study was bidirectional. A case–control study evaluated the adjusted odds ratio (aOR) of retinal disease before PD diagnosis by using conditional logistic regression. Furthermore, a cohort study evaluated the adjusted subdistribution hazard ratio (aSHR) for new-onset retinal and optic nerve diseases after PD diagnosis by using competing risk analysis. The association between PD with optic nerve diseases and glaucoma (another common ophthalmic diseases with the consequence of retinal dysfunction) were also analyzed as reference.

Results

In the case–control study, PD was found to be significantly comorbid with recent and remote retinal disease [recent: ≤ 5 years, aOR: 1.12, 95% confidence interval (CI): 1.03–1.23; remote: > 5 years, aOR: 1.18, 95% CI: 1.04–1.34]. No similar association was identified between optic nerve disease or glaucoma with PD. In the cohort study, patients with PD were found to have a low risk of retinal disease in short-term (≤ 5 years, aSHR: 0.81, 95% CI: 0.71–0.93) and long-term (> 5 years, aSHR: 0.82, 95% CI: 0.72–0.93) follow-up.

Conclusion

The study findings demonstrated that patients with prediagnostic PD were at greater risk of retinal disease than non-PD participants, but the risk reversed afterward. Thus, retinal disease may be a premotor manifestation of PD, and there may be some possible effect of dopamine supplements on retina.