bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Mootral Application Impacts Methane Production and the Microbial Community in the Rumen Simulation Technique System
Authors: Brede Johanna , Peukert Manuela , Egert Björn , Breves Gerhard , Brede Melanie
Published: October 2021

Methane emissions by ruminants contribute to global warming and result in a loss of dietary energy for the animals. One possibility of reducing methane emissions is by dietary strategies. In the present trial, we investigated the long-term effects of Mootral, a feed additive consisting of garlic powder (Allium sativum) and bitter orange extracts (Citrus aurantium), on fermentation parameters and the microbial community in the rumen simulation technique (RUSITEC) system. The experiment lasted 38 days and was divided into three phases: an equilibration period of 7 days, a baseline period (BL) of 3 days, and experimental period (EP) of 28 days. Twelve fermentation vessels were divided into three groups (n = 4): control (CON), short-term (ST), and long-term (LT) application. From day 11 to day 27, 1.7 g of Mootral was added to the ST vessels; LT vessels received 1.7 g of Mootral daily for the entire EP. With the onset of Mootral application, methane production was significantly reduced in both groups until day 18. Thereafter, the production rate returned to the initial quantity. Furthermore, the short chain fatty acid fermentation profile was significantly altered by Mootral application; the molar proportion of acetate decreased, while the proportions of propionate and butyrate increased. Metabolomic analysis revealed further changes in metabolite concentrations associated with the Mootral supplementation period. The methyl coenzyme-M reductase gene copy number was reduced in the liquid and solid phase, whereas the treatment did not affect the abundance of bacteria. At the end of the BL, Methanomicrobia was the most abundant archaeal class. Mootral supplementation induced an increase in the relative abundance of Methanomassiliicoccales and a reduction in the relative abundance of Methanomicrobia, however, this effect was transient. Abundances of bacterial families were only marginally altered by the treatment. In conclusion, Mootral has the transient ability to reduce methane production significantly due to a selective effect on archaea numbers and archaeal community composition with little effect on the bacterial community.
Variations in the SDN Loop of Class A Beta-Lactamases: A Study of the Molecular Mechanism of BlaC (Mycobacterium tuberculosis) to Alter the Stability and Catalytic Activity Towards Antibiotic Resistance of MBIs
Authors: Bhattacharya Sourya , Junghare Vivek , Pandey Niteesh Kumar , Baidya Subhecchha , Agarwal Harsha , Das Neeladrisingha , Banerjee Ayan , Ghosh Debashish , Roy Partha , Patra Hirak K. , Hazra Saugata
Published: October 2021

The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis calls for an immediate search for novel treatment strategies. Recently, BlaC, the principal beta-lactamase of Mycobacterium tuberculosis, was recognized as a potential therapeutic target. BlaC belongs to Ambler class A, which is generally susceptible to the beta-lactamase inhibitors currently used in clinics: tazobactam, sulbactam, and clavulanate. Alterations at Ser130 in conserved SDN loop confer resistance to mechanism-based inhibitors (MBIs) commonly observed in various clinical isolates. The absence of clinical evidence of S130G conversion in M. tuberculosis draws our attention to build laboratory mutants of S130G and S130A of BlaC. The study involving steady state, inhibition kinetics, and fluorescence microscopy shows the emergence of resistance against MBIs to the mutants expressing S130G and S130A. To understand the molecular reasoning behind the unavailability of such mutation in real life, we have used circular dichroism (CD) spectroscopy, differential scanning calorimetry (DSC), molecular dynamics (MD) simulation, and stability-based enzyme activity to compare the stability and dynamic behaviors of native and S130G/A mutant form of BlaC. A significant decrease in melting temperature (BlaC TM 60°C, S130A TM 50°C, and S130G TM 45°C), kinetic instability at higher temperature, and comparative dynamic instability correlate the fact that resistance to beta-lactam/beta-lactamase inhibitor combinations will likely not arise from the structural alteration of BlaC, therefore establishing confidence that this therapeutic modality can be potentially applied as a part of a successful treatment regimen against M. tuberculosis.
Aminoglycoside Resistance and Possible Mechanisms in Campylobacter Spp. Isolated From Chicken and Swine in Jiangsu, China
Authors: Zhang Xiaoyan , Zhou Qian , Tang Mengjun , Pu Junhua , Zhang Jing , Lu Junxian , Zhang Yunzeng , Gao Yushi
Published: October 2021

Campylobacter is a major food-borne pathogen in humans, and previous studies reported a high prevalence of gentamicin-resistant Campylobacter isolates from food-producing animals in China. This study aimed to investigate the aminoglycoside resistance of Campylobacter isolated from chicken and swine in Jiangsu province, China and understand the possible mechanisms responsible for aminoglycoside resistance. One hundred and eighty-five Campylobacter isolates of chicken and swine origins in 2017 and 2018 were analyzed for gentamicin and kanamycin resistance. Some aminoglycoside resistance genes were selected for PCR detection in all strains. The genomic DNAs of two strains with high resistance to gentamicin were used as donors to subject C. jejuni NCTC11168 to natural transformation. The transformants were investigated by whole-genome sequencing and analyzed comparatively with C. jejuni NCTC11168. In total, 30.5% (29/95) of C. jejuni isolates and 42.2% (38/90) of C. coli isolates were resistant to gentamicin and kanamycin. The prevalence of the aph(2")-If gene and aac(6')-Ie/aph(2")-Ia gene was 65.4% (121/185) and 36.2% (67/185) in Campylobacter isolates, respectively. The aadE-sat4-aphA-3 cluster was identified in 8.7% (8/92) and 20.4% (19/93) of all Campylobacter isolates in each year. With each donor DNA, aminoglycoside-resistant transformants were obtained. The transformants showed ≥128-fold increases in the MICs of gentamicin, kanamycin, and tobramycin. A 5200-bp segment was found to be inserted between the highly conserved genes Cj0299 and panB of Campylobacter. A total of 9.7% (18/185) strains showing high resistance to aminoglycosides had this segment by PCR detection. The genetic diversity of the insertion-fragment positive strains was determined by MLST, and seven sequence types were identified for these strains.
Phenotypic Antimicrobial Susceptibility and Genotypic Characterization of Clinical Ureaplasma Isolates Circulating in Shanghai, China
Authors: Ma Hongxia , Zhang Xuemei , Shi Xiaoxing , Zhang Jun , Zhou Yunheng
Published: October 2021

There is a growing global concern regarding the rise of antimicrobial resistance among Ureaplasma spp. isolates. However, studies on the antimicrobial susceptibility profiles, resistance mechanisms, and clonality of Ureaplasma spp. clinical isolates are still limited and cover only some geographic regions. Firstly, Ureaplasma species from the urogenital tracts of patients in Shanghai, China, were isolated by using the culture medium (A8 and 10B broth), and identified the genotype by polymerase chain reaction (PCR). Secondly, the antimicrobial susceptibility tests were determined by using broth microdilution assay. Then, the resistance genetic determinants to fluoroquinolones (FQs), macrolides, and tetracyclines were investigated through PCR/DNA sequencing. Finally, the molecular epidemiology of Ureaplasma species was studied by multilocus sequence typing (MLST). Among 258 isolates, Ureaplasma parvum (UPA) and Ureaplasma urealyticum (UUR) were found in 226 (87.60%) and 32 (12.40%) isolates, respectively. The minimum inhibitory concentrations (MICs) of 258 Ureaplasma spp. strains ranged from 0.015 to 64μg/ml for all 11 kinds of antimicrobials. Regardless of species, the isolates were most sensitive to AZI (1.94%), JOS (3.49%), and CLA (4.23%). Among them, there were 39 (15.12%) multidrug-resistant (MDR) strains, including 32 UPA isolates. The resistance rates of UPA to CIP (91.59%), and ROX (36.28%) were significantly higher than those of UUR. Twenty six FQ-resistant isolates had amino acid substitutions in gyrA and in parC (Ser83Leu). Mutations were detected in genes encoding ribosomal proteins L4 (Thr84Ile) and L22 (Ser81Pro) in macrolide-resistant isolates. Tet(M) was found in four UPA isolates. These mutations were mainly found in UPA isolates. Sequence type 1 (ST1) was the predominant ST, which contained 18 isolates. In conclusion, this study showed a higher resistance rate (especially to ROX and CIP), higher substitution rate, and higher MDR rate among UPA strains. The most active antimicrobial agents were AZI, JOS, and CLA. Identifying UPA or UUR in clinical isolates could help clinicians to choose appropriate drugs for treatment. The main resistance mechanisms may involve gene substitution of Ser83Leu in parC and Ser81Pro in L22. ST1 was the predominant ST of Ureaplasma isolates with MDR to FQs and macrolides in Shanghai, China.
Full-Length Galectin-3 Is Required for High Affinity Microbial Interactions and Antimicrobial Activity
Authors: Wu Shang-Chuen , Ho Alex D. , Kamili Nourine A. , Wang Jianmei , Murdock Kaleb L. , Cummings Richard D. , Arthur Connie M. , Stowell Sean R.
Published: October 2021

While adaptive immunity enables the recognition of a wide range of microbial antigens, immunological tolerance limits reactively toward self to reduce autoimmunity. Some bacteria decorate themselves with self-like antigens as a form of molecular mimicry to limit recognition by adaptive immunity. Recent studies suggest that galectin-4 (Gal-4) and galectin-8 (Gal-8) may provide a unique form of innate immunity against molecular mimicry by specifically targeting microbes that decorate themselves in self-like antigens. However, the binding specificity and antimicrobial activity of many human galectins remain incompletely explored. In this study, we defined the binding specificity of galectin-3 (Gal-3), the first galectin shown to engage microbial glycans. Gal-3 exhibited high binding toward mammalian blood group A, B, and αGal antigens in a glycan microarray format. In the absence of the N-terminal domain, the C-terminal domain of Gal-3 (Gal-3C) alone exhibited a similar overall binding pattern, but failed to display the same level of binding for glycans over a range of concentrations. Similar to the recognition of mammalian glycans, Gal-3 and Gal-3C also specifically engaged distinct microbial glycans isolated and printed in a microarray format, with Gal-3 exhibiting higher binding at lower concentrations toward microbial glycans than Gal-3C. Importantly, Gal-3 and Gal-3C interactions on the microbial microarray accurately predicted actual interactions toward intact microbes, with Gal-3 and Gal-3C displaying carbohydrate-dependent binding toward distinct strains ofProvidentia alcalifaciensandKlebsiella pneumoniaethat express mammalian-like antigens, while failing to recognize similar strains that express unrelated antigens. While both Gal-3 and Gal-3C recognized specific strains ofP. alcalifaciensandK. pneumoniae, only Gal-3 was able to exhibit antimicrobial activity even when evaluated at higher concentrations. These results demonstrate that while Gal-3 and Gal-3C specifically engage distinct mammalian and microbial glycans, Gal-3C alone does not possess antimicrobial activity.
The Unmet Needs of Hepatitis E Virus Diagnosis in Suspected Drug-Induced Liver Injury in Limited Resource Setting
Authors: El-Mokhtar Mohamed A. , Ramadan Haidi Karam-Allah , Thabet Marwa M. , Abd-Elkader Alaa S. , Fouad Magdy , Sallam Mohammad M. , Elgohary Elsayed A. , Abd El-Hafeez Amer Ali , Mohamed Mona Embarek , Sayed Ibrahim M.
Published: October 2021

Background: Currently, there are no specific biomarkers for drug-induced liver injury (DILI), and the diagnosis of DILI is based mainly on the exclusion of other causes of liver dysfunction and the recognition of potential causative drugs. Hepatitis E virus (HEV) diagnosis is not routinely enrolled in many countries, and HEV infection could be misdiagnosed as DILI.

Methodology: We retrospectively analyzed plasma samples (n = 80) collected from suspected DILI for HEV markers such as anti-HEV IgM, anti-HEV IgG, and HEV RNA. Anti-HEV antibodies were assessed using commercial ELISA kits. HEV RNA was tested by RT-qPCR targeting HEV ORF2/3, the receiver operating characteristic (ROC) curve was plotted, and a putative threshold for liver function parameters was determined.

Results: Out of 80 samples, 12 samples were positive for anti-HEV IgM and anti-HEV IgG, and HEV RNA was detected in seven samples. The median viral load was 3.46 × 103 IU/ml, and the isolated viruses belonged to HEV genotype 1. The level of liver enzymes such as alanine transaminase (ALT) and aspartate transaminase (AST), but not alkaline phosphatase (ALP), was significantly higher in HEV confirmed cases than in non-HEV confirmed cases. We identified a plasma ALT level of at least 415.5 U/L and AST level of at least 332 U/L; ALT/ALP ratio of at least 5.08 could be used as a guide for the patients diagnosed as DILI to be tested for HEV infection. The previous liver function parameters showed high sensitivity and good specificity.

Conclusion: Hepatitis E virus was detected in suspected DILI cases. The diagnosis of DILI is not secure until HEV testing is done. Liver function parameters can be used as a guide for HEV testing in suspected DILI cases in countries with limited resources.
Global Analysis of the Zinc Homeostasis Network in Pseudomonas aeruginosa and Its Gene Expression Dynamics
Authors: Ducret Verena , Abdou Melina , Goncalves Milho Catarina , Leoni Sara , Martin--Pelaud Oriane , Sandoz Antoine , Segovia Campos Inés , Tercier-Waeber Mary-Lou , Valentini Martina , Perron Karl
Published: October 2021

Zinc is one of the most important trace elements for life and its deficiency, like its excess, can be fatal. In the bacterial opportunistic pathogen Pseudomonas aeruginosa, Zn homeostasis is not only required for survival, but also for virulence and antibiotic resistance. Thus, the bacterium possesses multiple Zn import/export/storage systems. In this work, we determine the expression dynamics of the entire P. aeruginosa Zn homeostasis network at both transcript and protein levels. Precisely, we followed the switch from a Zn-deficient environment, mimicking the initial immune strategy to counteract bacterial infections, to a Zn-rich environment, representing the phagocyte metal boost used to eliminate an engulfed pathogen. Thanks to the use of the NanoString technology, we timed the global silencing of Zn import systems and the orchestrated induction of Zn export systems. We show that the induction of Zn export systems is hierarchically organized as a function of their impact on Zn homeostasis. Moreover, we identify PA2807 as a novel Zn resistance component in P. aeruginosa and highlight new regulatory links among Zn-homeostasis systems. Altogether, this work unveils a sophisticated and adaptive homeostasis network, which complexity is key in determining a pathogen spread in the environment and during host-colonization.
Transcriptomic Response Analysis of Escherichia coli to Palladium Stress
Authors: Joudeh Nadeem , Saragliadis Athanasios , Schulz Christian , Voigt André , Almaas Eivind , Linke Dirk
Published: October 2021

Palladium (Pd), due to its unique catalytic properties, is an industrially important heavy metal especially in the form of nanoparticles. It has a wide range of applications from automobile catalytic converters to the pharmaceutical production of morphine. Bacteria have been used to biologically produce Pd nanoparticles as a new environmentally friendly alternative to the currently used energy-intensive and toxic physicochemical methods. Heavy metals, including Pd, are toxic to bacterial cells and cause general and oxidative stress that hinders the use of bacteria to produce Pd nanoparticles efficiently. In this study, we show in detail the Pd stress-related effects on E. coli. Pd stress effects were measured as changes in the transcriptome through RNA-Seq after 10 min of exposure to 100 μM sodium tetrachloropalladate (II). We found that 709 out of 3,898 genes were differentially expressed, with 58% of them being up-regulated and 42% of them being down-regulated. Pd was found to induce several common heavy metal stress-related effects but interestingly, Pd causes unique effects too. Our data suggests that Pd disrupts the homeostasis of Fe, Zn, and Cu cellular pools. In addition, the expression of inorganic ion transporters in E. coli was found to be massively modulated due to Pd intoxication, with 17 out of 31 systems being affected. Moreover, the expression of several carbohydrate, amino acid, and nucleotide transport and metabolism genes was vastly changed. These results bring us one step closer to the generation of genetically engineered E. coli strains with enhanced capabilities for Pd nanoparticles synthesis.
Quantifying the Importance of Abiotic and Biotic Factors Governing the Succession of Gut Microbiota Over Shrimp Ontogeny
Authors: Zhang Wenqian , Zhu Zidong , Chen Jiong , Qiu Qiongfen , Xiong Jinbo
Published: October 2021

Intensive studies have evaluated abiotic factors in shaping host gut microbiota. In contrast, little is known on how and to what extent abiotic (geochemical variables) and biotic (i.e., surrounding microbes, younger shrimp, and age) factors assemble the gut microbiota over shrimp ontogeny. Considering the functional importance of gut microbiota in improving host fitness, this knowledge is fundamental to sustain a desirable gut microbiota for a healthy aquaculture. Here, we characterized the successional rules of both the shrimp gut and rearing water bacterial communities over the entire shrimp farming. Both the gut and rearing water bacterial communities exhibited the time decay of similarity relationship, with significantly lower temporal turnover rate for the gut microbiota, which were primarily governed by shrimp age (days postlarval inoculation) and water pH. Gut commensals were primary sourced (averaged 60.3%) from their younger host, rather than surrounding bacterioplankton (19.1%). A structural equation model revealed that water salinity, pH, total phosphorus, and dissolve oxygen directly governed bacterioplankton communities but not for the gut microbiota. In addition, shrimp gut microbiota did not simply mirror the rearing bacterioplankton communities. The gut microbiota tended to be governed by variable selection over shrimp ontogeny, while the rearing bacterioplankton community was shaped by homogeneous selection. However, the determinism of rare and stochasticity of abundant subcommunities were consistent between shrimp gut and rearing water. These findings highlight the importance of independently interpreting host-associated and free-living communities, as well as their rare and abundant subcommunities for a comprehensive understanding of the ecological processes that govern microbial successions.
Connectomics in Brain Aging and Dementia – The Background and Design of a Study of a Connectome Related to Human Disease
Authors: Cohen Ann D. , Bruña Ricardo , Chang Yue-Fang , Cheng Yu , Doman Jack , Huppert Ted , Kim Tae , Maestu Fernando , Roush Rebecca E. , Snitz Beth E. , Becker James T.
Published: October 2021

The natural history of Alzheimer’s Disease (AD) includes significant alterations in the human connectome, and this disconnection results in the dementia of AD. The organizing principle of our research project is the idea that the expression of cognitive dysfunction in the elderly is the result of two independent processes — the neuropathology associated with AD, and second the neuropathological changes of cerebrovascular disease. Synaptic loss, senile plaques, and neurofibrillary tangles are the functional and diagnostic hallmarks of AD, but it is the structural changes as a consequence of vascular disease that reduce brain reserve and compensation, resulting in an earlier expression of the clinical dementia syndrome. This work is being completed under the auspices of the Human Connectome Project (HCP). We have achieved an equal representation of Black individuals (vs. White individuals) and enrolled 60% Women. Each of the participants contributes demographic, behavioral and laboratory data. We acquire data relative to vascular risk, and the participants also undergo in vivo amyloid imaging, and magnetoencephalography (MEG). All of the data are publicly available under the HCP guidelines using the Connectome Coordinating Facility and the NIMH Data Archive. Locally, we use these data to address specific questions related to structure, function, AD, aging and vascular disease in multi-modality studies leveraging the differential advantages of magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), MEG, and in vivo beta amyloid imaging.
A Systematic Review of Transcranial Direct Current Stimulation in Primary Progressive Aphasia: Methodological Considerations
Authors: Coemans Silke , Struys Esli , Vandenborre Dorien , Wilssens Ineke , Engelborghs Sebastiaan , Paquier Philippe , Tsapkini Kyrana , Keulen Stefanie
Published: October 2021

A variety of tDCS approaches has been used to investigate the potential of tDCS to improve language outcomes, or slow down the decay of language competences caused by Primary Progressive Aphasia (PPA). The employed stimulation protocols and study designs in PPA are generally speaking similar to those deployed in post-stroke aphasic populations. These two etiologies of aphasia however differ substantially in their pathophysiology, and for both conditions the optimal stimulation paradigm still needs to be established. A systematic review was done and after applying inclusion and exclusion criteria, 15 articles were analyzed focusing on differences and similarities across studies especially focusing on PPA patient characteristics (age, PPA variant, language background), tDCS stimulation protocols (intensity, frequency, combined therapy, electrode configuration) and study design as recent reviews and group outcomes for individual studies suggest tDCS is an effective tool to improve language outcomes, while methodological approach and patient characteristics are mentioned as moderators that may influence treatment effects. We found that studies of tDCS in PPA have clinical and methodological and heterogeneity regarding patient populations, stimulation protocols and study design. While positive group results are usually found irrespective of these differences, the magnitude, duration and generalization of these outcomes differ when comparing stimulation locations, and when results are stratified according to the clinical variant of PPA. We interpret the results of included studies in light of patient characteristics and methodological decisions. Further, we highlight the role neuroimaging can play in study protocols and interpreting results and make recommendations for future work.
The Relationship Between ADAMTS13 Activity and Overall Cerebral Small Vessel Disease Burden: A Cross-Sectional Study Based on CSVD
Authors: Sun Wenbo , Luo Yufan , Zhang Shufan , Lu Wenmei , Liu Luqiong , Yang Xiaoli , Wu Danhong
Published: October 2021

Objectives: This study aimed to investigate the association between plasma von Willebrand factor (VWF) level, ADAMTS13 activity, and neuroimaging features of cerebral small vessel disease (CSVD), including the CSVD neuroimaging markers and the overall CSVD burden.

Methods: CSVD patients admitted to our hospital from 2016 to 2020 were recruited. Plasma VWF level and ADAMTS13 activity were measured. The overall effect of CSVD on the brain was described as a validated CSVD score. We evaluated the association between VWF levels, ADAMTS13 activity, and the increasing severity of CSVD score by the logistic regression model.

Results: We enrolled 296 patients into this study. The mean age of the sample was 69.0 years (SD 7.0). The mean VWF level was 1.31 IU/mL, and the ADAMTS13 activity was 88.01 (SD 10.57). In multivariate regression analysis, lower ADAMTS13 activity and higher VWF level was related to white matter hyperintensity (WMH) [β = −7.31; 95% confidence interval (CI) (−9.40, −4.93); p<0.01; β = 0.17; 95% confidence interval (0.11, 0.23); p<0.01], subcortical infarction (SI) [(β = −9.22; 95% CI (−11.37, −7.06); p<0.01); β = 0.21; 95% confidence interval (0.15, 0.27); p<0.01] independently, but not cerebral microbleed (CMB) [(β = −2.3; 95% CI (−4.95, 0.05); p = 0.22); β = 0.02; 95% confidence interval (−0.05, 0.08); p = 0.63]. Furthermore, ADAMTS13 activity was independently negatively correlated with the overall CSVD burden (odd ratio = 21.33; 95% CI (17.46, 54.60); p < 0.01) after adjustment for age, history of hypertension, and current smoking.

Conclusions: Reducing ADAMTS13 activity change is related to white matter hyperintensity, subcortical infarction, but not with cerebral microhemorrhage. In addition, ADAMTS13 may have played an essential role in the progression of CSVD.
Fabrication of Silver Nanoparticles Against Fungal Pathogens
Authors: Mansoor Sheikh , Zahoor Irfana , Baba Tawseef Rehman , Padder Shahid A. , Bhat Z. A. , Koul Aabid Mustafa , Jiang Linghuo
Published: October 2021

The use of silver nanoparticles (AgNPs) against various pathogens is now being well recognized in the agriculture and health sector. Nanoparticles have been shown to exhibit various novel properties and these properties, on other hand, rely upon the size, shape, and morphology of these particles. Moreover, these physical characteristics enable them to interact with microbes, plants, and animals. Smaller-sized particles have shown more toxicity than larger-sized nanoparticles. AgNPs have shown growth inhibition of many fungi likeAspergillus fumigates,A. niger,A. flavus,Trichophyton rubrum,Candida albicans, andPenicilliumspecies. According to the current hypothesis, AgNPs act by producing reactive oxygen species and free radicals, which cause protein denaturation, nucleic acid and proton pump damage, lipid peroxidation, and cell wall damage. Therefore, they alter the cell membrane permeability, causing cell death. This mini-review summarizes the use of silver nanoparticles against fungal pathogens and fungal biofilm in the agricultural sector.
Unraveling the Role of Dopaminergic and Calretinin Interneurons in the Olfactory Bulb
Authors: Capsoni Simona , Fogli Iseppe Alex , Casciano Fabio , Pignatelli Angela
Published: October 2021

The perception and discriminating of odors are sensory activities that are an integral part of our daily life. The first brain region where odors are processed is the olfactory bulb (OB). Among the different cell populations that make up this brain area, interneurons play an essential role in this sensory activity. Moreover, probably because of their activity, they represent an exception compared to other parts of the brain, since OB interneurons are continuously generated in the postnatal and adult period. In this review, we will focus on periglomerular (PG) cells which are a class of interneurons found in the glomerular layer of the OB. These interneurons can be classified into distinct subtypes based on their neurochemical nature, based on the neurotransmitter and calcium-binding proteins expressed by these cells. Dopaminergic (DA) periglomerular cells and calretinin (CR) cells are among the newly generated interneurons and play an important role in the physiology of OB. In the OB, DA cells are involved in the processing of odors and the adaptation of the bulbar network to external conditions. The main role of DA cells in OB appears to be the inhibition of glutamate release from olfactory sensory fibers. Calretinin cells are probably the best morphologically characterized interneurons among PG cells in OB, but little is known about their function except for their inhibitory effect on noisy random excitatory signals arriving at the main neurons. In this review, we will mainly describe the electrophysiological properties related to the excitability profiles of DA and CR cells, with a particular view on the differences that characterize DA mature interneurons from cells in different stages of adult neurogenesis.
Trigonal-Sparing vs. Trigonal-Involved OnabotulinumtoxinA Injection for the Treatment of Overactive Bladder: A Systematic Review and Meta-Analysis
Authors: Cui Yuanshan , Cai Tong , Dong Tiantian , Zhang Xiaoyi , Zhou Zhongbao , Lu Youyi , Zhang Yong , Wu Jitao , Gao Zhenli , Wang Yongqiang , Dong Liying
Published: October 2021

Objective: Overactive bladder (OAB) is a disease characterized by the presence of urinary urgency. We carried out a meta-analysis to assess the effectiveness and safety of trigonal-involved injection of onabotulinumtoxinA (BoNT-A) in comparison with the trigonal-sparing technique in cases with OAB [neurogenic detrusor overactivity (NDO) and idiopathic detrusor overactivity (IDO)].

Methods: Randomized controlled trials (RCTs) of BoNT-A injection for OAB were searched systematically by using EMBASE, MEDLINE, and the Cochrane Controlled Trials Register. The datum was calculated by RevMan version 5.3.0. The original references of relating articles were also reviewed.

Results: In total, six RCTs involving 437 patients were included in our analysis. For OAB, the trigone-including group showed a different patient symptom score (p = 0.03), complete dryness rate (p = 0.002), frequency of incontinence episodes (p = 0.01), detrusor pressure at maximum flow rate (p = 0.01), and volume at the first desire to void (p = 0.0004) compared with the trigone-sparing group. Also, a trigone-including intradetrusor injection demonstrated a significant improvement in the patient symptom score (p = 0.0004), complete dryness rate (p = 0.0002), frequency of incontinence episodes (p = 0.0003), detrusor pressure at maximum flow rate (p = 0.01), and volume at the first desire to void (p = 0.00006) compared with the trigone-sparing group for treatment of NDO. The adverse events rates were similar in both groups.

Conclusions: The meta-analysis has demonstrated that trigone-including BoNT-A injection was more effective compared with the trigone-sparing injection for the treatment of OAB, especially for NDO.
Increase in Brain Volume After Aneurysmal Subarachnoid Hemorrhage Leads to Unfavorable Outcome: A Retrospective Study Quantified by CT Scan
Authors: Qin Bin , Xiang Yi , Zheng Jianfeng , Xu Rui , Guo Zongduo , Cheng Chongjie , Jiang Li , Wu Yue , Sun Xiaochuan , Huang Zhijian
Published: October 2021

Background and Purpose: Primary brain swelling occurs in aneurysmal subarachnoid hemorrhage (aSAH) patients. The absence of a dynamic quantitative method restricts further study of primary brain swelling. This study compared differences in the change rate of brain volume (CRBV) between patients with and without primary brain swelling in the early stage of aSAH. Moreover, the relationship between CRBV and clinical outcomes was evaluated.

Methods: Patients hospitalized within 24 h after aSAH were included in this retrospective study. Utilizing a qualitative standard established before the study to recognize primary brain swelling through brain CT after aSAH, clinical outcomes after 3 months of SAH were evaluated with a modified Rankin scale (mRS). The brain volume (BV) of each patient was calculated with a semiautomatic threshold algorithm of 3D-slicer, and the change in brain volume (CIBV) was obtained by subtracting the two extreme values (CIBV = BVmax – BVmin). The CRBV was obtained by CIBV/BVmin × 100%. The CRBV values that predicted unfavorable prognoses were estimated.

Results: In total, 130 subjects were enrolled in the study. The mean CRBV in the non-swelling group and swelling group were 4.37% (±4.77) and 11.87% (±6.84), respectively (p < 0.05). CRBV was positively correlated with the length of hospital stay, blood in the ambient cistern, blood in the lateral ventricle, and lateral ventricular volume (Spearman ρ = 0.334; p < 0.001; Pearson ρ = 0.269, p = 0.002; Pearson ρ = 0.278, p = 0.001; Pearson ρ = 0.233, p = 0.008, respectively). Analysis of variance showed significant differences in CIBV, CRBV, blood in the ambient cistern, blood in the lateral ventricle, and lateral ventricular volume among varying modified Fisher scale (mFisher), with higher admission mFisher scale, indicating larger values of these variables. After adjusting for risk factors, the model showed that for every 1% increase in the CRBV, the probability of poor clinical prognosis increased by a factor of 1.236 (95% CI = 1.056–1.446). In the stratified analysis, the odds of worse clinical outcomes increased with increases in the CRBV. Receiver operating characteristic curve analysis showed that HH grade, mFisher scale, and score of CRBV (SCRBV) had diagnostic performance for predicting unfavorable clinical outcomes.

Conclusion: Primary brain swelling increases brain volume after aSAH. The CRBV quantified by 3D-Slicer can be used as a volumetric representation of the degree of brain swelling. A larger CRBV in the early stage of aSAH is associated with poor prognosis. The CRBV can be used as a neuroimaging biomarker of early brain injury after bleeding and may be an effective predictor of patients' clinical prognoses.
Identification and Therapeutic Outcome Prediction of Cervical Spondylotic Myelopathy Based on the Functional Connectivity From Resting-State Functional MRI Data: A Preliminary Machine Learning Study
Authors: Su Qian , Zhao Rui , Wang ShuoWen , Tu HaoYang , Guo Xing , Yang Fan
Published: October 2021

Currently, strategies to diagnose patients and predict neurological recovery in cervical spondylotic myelopathy (CSM) using MR images of the cervical spine are urgently required. In light of this, this study aimed at exploring potential preoperative brain biomarkers that can be used to diagnose and predict neurological recovery in CSM patients using functional connectivity (FC) analysis of a resting-state functional MRI (rs-fMRI) data. Two independent datasets, including total of 53 patients with CSM and 47 age- and sex-matched healthy controls (HCs), underwent the preoperative rs-fMRI procedure. The FC was calculated from the automated anatomical labeling (AAL) template and used as features for machine learning analysis. After that, three analyses were used, namely, the classification of CSM patients from healthy adults using the support vector machine (SVM) within and across datasets, the prediction of preoperative neurological function in CSM patients via support vector regression (SVR) within and across datasets, and the prediction of neurological recovery in CSM patients via SVR within and across datasets. The results showed that CSM patients could be successfully identified from HCs with high classification accuracies (84.2% for dataset 1, 95.2% for dataset 2, and 73.0% for cross-site validation). Furthermore, the rs-FC combined with SVR could successfully predict the neurological recovery in CSM patients. Additionally, our results from cross-site validation analyses exhibited good reproducibility and generalization across the two datasets. Therefore, our findings provide preliminary evidence toward the development of novel strategies to predict neurological recovery in CSM patients using rs-fMRI and machine learning technique.
Clinical Analysis of Pediatric Opsoclonus-Myoclonus Syndrome in One of the National Children's Medical Center in China
Authors: Zhu Haixia , Wu Wenlin , Chen Lianfeng , Hou Chi , Zeng Yiru , Tian Yang , Shen Huiling , Gao Yuanyuan , Zhang Yani , Peng Bingwei , Chen Wen-Xiong , Li Xiaojing
Published: October 2021

Objective: To study the clinical characteristics and treatment of pediatric opsoclonus-myoclonus syndrome (OMS).

Methods: We analyzed the clinical data of nine children OMS between June 2017 and Nov 2020.

Results: Nine children (M/F = 3:6, median onset age was 18 months) diagnosed with OMS were included in the study. Before onset, human rhinovirus and respiratory syncytial virus were seen in one patient, respectively. And one patient received Japanese encephalitis vaccination. Three patients had neuroblastoma, and one patient had ganglioneuroblastoma. All patients' symptoms were improved after receiving surgery (for four patients with tumor), intravenous human immunoglobulin and pulsed methylprednisolone. However, four patients without mass relapsed and became relapse free after rituximab treatment. The relapse rate was 44.4% (4/9). The OMS severity score at the last follow-up was significantly lower than the OMS severity score at onset (3.0 ± 1.0 vs. 11.0 ± 2.2, paired-samples t-test, P < 0.001). All patients had at least one item of neurological symptoms or neuropsychological disturbances.

Conclusion: For pediatric OMS, human rhinovirus infection and respiratory syncytial virus infection can be seen before onset. Rituximab is effective in reducing relapse. Improving recognition and long-term prognosis in OMS is urgent.
Study of Auditory Brain Cognition Laws-Based Recognition Method of Automobile Sound Quality
Authors: Xie Liping , Lu Chihua , Liu Zhien , Yan Lirong , Xu Tao
Published: October 2021

The research shows that subjective feelings of people, such as emotions and fatigue, can be objectively reflected by electroencephalography (EEG) physiological signals Thus, an evaluation method based on EEG, which is used to explore auditory brain cognition laws, is introduced in this study. The brain cognition laws are summarized by analyzing the EEG power topographic map under the stimulation of three kinds of automobile sound, namely, quality of comfort, powerfulness, and acceleration. Then, the EEG features of the subjects are classified through a machine learning algorithm, by which the recognition of diversified automobile sound is realized. In addition, the Kalman smoothing and minimal redundancy maximal relevance (mRMR) algorithm is used to improve the recognition accuracy. The results show that there are differences in the neural characteristics of diversified automobile sound quality, with a positive correlation between EEG energy and sound intensity. Furthermore, by using the Kalman smoothing and mRMR algorithm, recognition accuracy is improved, and the amount of calculation is reduced. The novel idea and method to explore the cognitive laws of automobile sound quality from the field of brain-computer interface technology are provided in this study.
Abnormal Low-Frequency Oscillations Reflect Abnormal Eye Movement and Stereovision in Patients With Comitant Exotropia
Authors: Chen Juan , Jin Han , Zhong Yu-Lin , Huang Xin
Published: October 2021

Background: Patients with comitant exotropia (CE) are accompanied by abnormal eye movements and stereovision. However, the neurophysiological mechanism of impaired eye movements and stereovision in patient with CE is still unclear.

Purpose: The purpose of this study is to investigate spontaneous neural activity changes in patients with CE using the amplitude of low-frequency fluctuation (ALFF) method and the machine learning method.

Materials and Methods: A total of 21 patients with CE and 21 healthy controls (HCs) underwent resting-state magnetic resonance imaging scans. The ALFF and fractional amplitude of low-frequency fluctuation (fALFF) values were chosen as classification features using a machine learning method.

Results: Compared with the HC group, patients with CE had significantly decreased ALFF values in the right angular (ANG)/middle occipital gyrus (MOG)/middle temporal gyrus (MTG) and bilateral supplementary motor area (SMA)/precentral gyrus (PreCG). Meanwhile, patients with CE showed significantly increased fALFF values in the left putamen (PUT) and decreased fALFF values in the right ANG/MOG. Moreover, patients with CE showed a decreased functional connectivity (FC) between the right ANG/MOG/MTG and the bilateral calcarine (CAL)/lingual (LING) and increased FC between the left PUT and the bilateral cerebellum 8/9 (CER 8/9). The support vector machine (SVM) classification reaches a total accuracy of 93 and 90% and the area under the curve (AUC) of 0.93 and 0.90 based on ALFF and fALFF values, respectively.

Conclusion: Our result highlights that patients with CE had abnormal brain neural activities including MOG and supplementary motor area/PreCG, which might reflect the neural mechanism of eye movements and stereovision dysfunction in patients with CE. Moreover, ALFF and fALFF could be sensitive biomarkers for distinguishing patients with CE from HCs.
MF-Net: Multi-Scale Information Fusion Network for CNV Segmentation in Retinal OCT Images
Authors: Meng Qingquan , Wang Lianyu , Wang Tingting , Wang Meng , Zhu Weifang , Shi Fei , Chen Zhongyue , Chen Xinjian
Published: October 2021

Choroid neovascularization (CNV) is one of the blinding ophthalmologic diseases. It is mainly caused by new blood vessels growing in choroid and penetrating Bruch's membrane. Accurate segmentation of CNV is essential for ophthalmologists to analyze the condition of the patient and specify treatment plan. Although many deep learning-based methods have achieved promising results in many medical image segmentation tasks, CNV segmentation in retinal optical coherence tomography (OCT) images is still very challenging as the blur boundary of CNV, large morphological differences, speckle noise, and other similar diseases interference. In addition, the lack of pixel-level annotation data is also one of the factors that affect the further improvement of CNV segmentation accuracy. To improve the accuracy of CNV segmentation, a novel multi-scale information fusion network (MF-Net) based on U-Shape architecture is proposed for CNV segmentation in retinal OCT images. A novel multi-scale adaptive-aware deformation module (MAD) is designed and inserted into the top of the encoder path, aiming at guiding the model to focus on multi-scale deformation of the targets, and aggregates the contextual information. Meanwhile, to improve the ability of the network to learn to supplement low-level local high-resolution semantic information to high-level feature maps, a novel semantics-details aggregation module (SDA) between encoder and decoder is proposed. In addition, to leverage unlabeled data to further improve the CNV segmentation, a semi-supervised version of MF-Net is designed based on pseudo-label data augmentation strategy, which can leverage unlabeled data to further improve CNV segmentation accuracy. Finally, comprehensive experiments are conducted to validate the performance of the proposed MF-Net and SemiMF-Net. The experiment results show that both proposed MF-Net and SemiMF-Net outperforms other state-of-the-art algorithms.
Comorbidity Trajectories Associated With Alzheimer’s Disease: A Matched Case-Control Study in a United States Claims Database
Authors: Butler Lesley M. , Houghton Richard , Abraham Anup , Vassilaki Maria , Durán-Pacheco Gonzalo
Published: October 2021

Background: Trajectories of comorbidities among individuals at risk of Alzheimer’s disease (AD) may differ from those aging without AD clinical syndrome. Therefore, characterizing the comorbidity burden and pattern associated with AD risk may facilitate earlier detection, enable timely intervention, and help slow the rate of cognitive and functional decline in AD. This case-control study was performed to compare the prevalence of comorbidities between AD cases and controls during the 5 years prior to diagnosis (or index date for controls); and to identify comorbidities with a differential time-dependent prevalence trajectory during the 5 years prior to AD diagnosis.

Methods: Incident AD cases and individually matched controls were identified in a United States claims database between January 1, 2000 and December 31, 2016. AD status and comorbidities were defined based on the presence of diagnosis codes in administrative claims records. Generalized estimating equations were used to assess evidence of changes over time and between AD and controls. A principal component analysis and hierarchical clustering was performed to identify groups of AD-related comorbidities with respect to prevalence changes over time (or trajectory), and differences between AD and controls.

Results: Data from 186,064 individuals in the IBM MarketScan Commercial Claims and Medicare Supplementary databases were analyzed (93,032 AD cases and 93,032 non-AD controls). In total, there were 177 comorbidities with a ≥ 5% prevalence. Five main clusters of comorbidities were identified. Clusters differed between AD cases and controls in the overall magnitude of association with AD, in their diverging time trajectories, and in comorbidity prevalence. Three clusters contained comorbidities that notably increased in frequency over time in AD cases but not in controls during the 5-year period before AD diagnosis. Comorbidities in these clusters were related to the early signs and/or symptoms of AD, psychiatric and mood disorders, cerebrovascular disease, history of hazard and injuries, and metabolic, cardiovascular, and respiratory complaints.

Conclusion: We demonstrated a greater comorbidity burden among those who later developed AD vs. controls, and identified comorbidity clusters that could distinguish these two groups. Further investigation of comorbidity burden is warranted to facilitate early detection of individuals at risk of developing AD.
Opposing Changes in Synaptic and Extrasynaptic N-Methyl-D-Aspartate Receptor Function in Response to Acute and Chronic Restraint Stress
Authors: Tse Yiu Chung , Nath Moushumi , Larosa Amanda , Wong Tak Pan
Published: October 2021

A pertinent mechanism by which stress impacts learning and memory is through stress-induced plastic changes in glutamatergic transmission in the hippocampus. For instance, acute stress has been shown to alter the expression, binding, and function of the ionotropic glutamate N-methyl-D-aspartate receptor (NMDAR). However, the consequences of chronic stress, which could lead to various stress-related brain disorders, on NMDAR function remain unclear. While most studies on NMDARs focused on these receptors in synapses (synaptic NMDARs or sNMDARs), emerging findings have revealed functional roles of NMDARs outside synapses (extrasynaptic NMDARs or exNMDARs) that are distinct from those of sNMDARs. Using a restraint stress paradigm in adult rats, the objective of the current study is to examine whether sNMDARs and exNMDARs in the hippocampus are differentially regulated by acute and chronic stress. We examined sNMDAR and exNMDAR function in dorsal CA1 hippocampal neurons from brain slices of adult rats that were acutely (1 episode) or chronically (21 daily episodes) stressed by restraint (30 min). We found that acute stress increases sNMDAR but suppresses exNMDAR function. Surprisingly, we only observed a reduction in exNMDAR function after chronic stress. Taken together, our findings suggest that sNMDARs and exNMDARs may be differentially regulated by acute and chronic stress. Most importantly, the observed suppression in exNMDAR function by both acute and chronic stress implies crucial but overlooked roles of hippocampal exNMDARs in stress-related disorders.