bluuebunny/crossref_metadata_2025 huggingface dataset:
Resistance and Vulnerability of Honeybee (Apis mellifera) Gut Bacteria to Commonly Used Pesticides
Authors: Cuesta-Maté Ana , Renelies-Hamilton Justinn , Kryger Per , Jensen Annette Bruun , Sinotte Veronica M. , Poulsen Michael
Published: September 2021

Agricultural and apicultural practices expose honeybees to a range of pesticides that have the potential to negatively affect their physiology, neurobiology, and behavior. Accumulating evidence suggests that these effects extend to the honeybee gut microbiome, which serves important functions for honeybee health. Here we test the potential effects of the pesticides thiacloprid, acetamiprid, and oxalic acid on the gut microbiota of honeybees, first in direct in vitro inhibition assays and secondly in an in vivo caged bee experiment to test if exposure leads to gut microbiota community changes. We found that thiacloprid did not inhibit the honeybee core gut bacteria in vitro, nor did it affect overall community composition or richness in vivo. Acetamiprid did also not inhibit bacterial growth in vitro, but it did affect community structure within bees. The eight bacterial genera tested showed variable levels of susceptibility to oxalic acid in vitro. In vivo, treatment with this pesticide reduced amplicon sequence variant (ASV) richness and affected gut microbiome composition, with most marked impact on the common crop bacteria Lactobacillus kunkeei and the genus Bombella. We conducted network analyses which captured known associations between bacterial members and illustrated the sensitivity of the microbiome to environmental stressors. Our findings point to risks of honeybee exposure to oxalic acid, which has been deemed safe for use in treatment against Varroa mites in honeybee colonies, and we advocate for more extensive assessment of the long-term effects that it may have on honeybee health.
Compositional Shift of Bacterial, Archaeal, and Fungal Communities Is Dependent on Trophic Lifestyles in Rice Paddy Soil
Authors: Kim Hyun , Jeon Jongbum , Lee Kiseok Keith , Lee Yong-Hwan
Published: September 2021

The soil environment determines plants’ health and performance during their life cycle. Therefore, ecological understanding on variations in soil environments, including physical, chemical, and biological properties, is crucial for managing agricultural fields. Here, we present a comprehensive and extensive blueprint of the bacterial, archaeal, and fungal communities in rice paddy soils with differing soil types and chemical properties. We discovered that natural variations of soil nutrients are important factors shaping microbial diversity. The responses of microbial diversity to soil nutrients were related to the distribution of microbial trophic lifestyles (oligotrophy and copiotrophy) in each community. The compositional changes of bacterial and archaeal communities in response to soil nutrients were mainly governed by oligotrophs, whereas copiotrophs were mainly involved in fungal compositional changes. Compositional shift of microbial communities by fertilization is linked to switching of microbial trophic lifestyles. Random forest models demonstrated that depletion of prokaryotic oligotrophs and enrichment of fungal copiotrophs are the dominant responses to fertilization in low-nutrient conditions, whereas enrichment of putative copiotrophs was important in high-nutrient conditions. Network inference also revealed that trophic lifestyle switching appertains to decreases in intra- and inter-kingdom microbial associations, diminished network connectivity, and switching of hub nodes from oligotrophs to copiotrophs. Our work provides ecological insight into how soil nutrient-driven variations in microbial communities affect soil health in modern agricultural systems.
Understanding Metabolic Remodeling in Mycobacterium smegmatis to Overcome Energy Exigency and Reductive Stress Under Energy-Compromised State
Authors: Patil Varsha , Jain Vikas
Published: September 2021

Mycobacteria such as Mycobacterium tuberculosis, the causative agent of tuberculosis that annually kills several million people worldwide, and Mycobacterium smegmatis, the non-pathogenic fast-growing mycobacteria, require oxidative phosphorylation to meet their energy requirements. We have previously shown that deletion of one of the two copies of atpD gene that codes for the ATP synthase β-subunit establishes an energy-compromised state in M. smegmatis. Here we report that upon such deletion, a major routing of electron flux occurs through the less energy-efficient complexes of its respiratory chain. ΔatpD bacterium also shows an increased reduced state which is further confirmed by the overexpression of WhiB3, a major redox sensor. We show a substantial modulation of the biosynthesis of cell wall associated lipids and triacylglycerol (TAG). An accumulation of TAG-containing lipid bodies is further confirmed by using 14C oleate incorporation. Interestingly, the mutant also shows an overexpression of TAG-degrading lipase genes, and the intracellular lipolytic enzymes mediate TAG hydrolysis for their utilization as energy source. We believe that our in vitro energy-depleted model will allow us to explore the critical link between energy metabolism, redox homeostasis, and lipid biosynthesis during ATP-depleted state, which will enhance our understanding of the bacterial adaptation, and will allow us to identify novel drug targets to counter mycobacterial infections.
Improvement of the Catalytic Ability of a Thermostable and Acidophilic β-Mannanase Using a Consensus Sequence Design Strategy
Authors: Liang Qingping , Zhan Yuming , Yuan Mingxue , Cao Linyuan , Zhu Changliang , Mou Haijin , Liu Zhemin
Published: September 2021

In order to improve the catalytic efficiency of a thermostable and acidophilic β-mannanase (ManAK; derived from marine Aspergillus kawachii IFO 4308), three mutants were designed by amino acid sequence consensus analysis with a second β-mannanase (ManCbs), which also belongs to the glycoside hydrolase family 5 (GH5) and has excellent catalytic efficiency. Three mutants were constructed and their biochemical characteristics were measured after heterologous expression in Pichia pastoris. The results revealed that the kcat/Km values of the three recombinant mannanases ManAKC292V, ManAKL293V, and ManAKL294H were enhanced by 303.0, 280.4, and 210.1%, respectively. Furthermore, ManAKL293V showed greater thermostability than ManAK, retaining 36.5% of the initial enzyme activity after incubation at 80°C for 5min. This study therefore provides a rational design strategy based on consensus sequence analysis to develop industrially valuable β-mannanase for future applications in marine aquafeed.
Schistosome AMPK Is Required for Larval Viability and Regulates Glycogen Metabolism in Adult Parasites
Authors: Hunter Kasandra S. , Miller André , Mentink-Kane Margaret , Davies Stephen J.
Published: September 2021

On entering the mammalian host, schistosomes transition from a freshwater environment where resources are scarce, to an environment where there is an unlimited supply of glucose, their preferred energy substrate. Adult schistosome glycolytic activity consumes almost five times the parasite’s dry weight in glucose per day to meet the parasite’s energy demands, and the schistosome glycolytic enzymes and mechanisms for glucose uptake that sustain this metabolic activity have previously been identified. However, little is known of the parasite processes that regulate schistosome glucose metabolism. We previously described the Schistosoma mansoni ortholog of 5′ AMP-Activated Protein Kinase (AMPK), which is a central regulator of energy metabolism in eukaryotes, and characterized the developmental regulation of its expression and activity in S. mansoni. Here we sought to explore the function of AMPK in schistosomes and test whether it regulates parasite glycolysis. Adult schistosomes mounted a compensatory response to chemical inhibition of AMPK α, resulting in increased AMPK α protein abundance and activity. RNAi inhibition of AMPK α expression, however, suggests that AMPK α is not required for adult schistosome viability in vitro. Larval schistosomula, on the other hand, are sensitive to chemical AMPK α inhibition, and this correlates with inactivity of the AMPK α gene in this life cycle stage that precludes a compensatory response to AMPK inhibition. While our data indicate that AMPK is not essential in adult schistosomes, our results suggest that AMPK regulates adult worm glycogen stores, influencing both glycogen utilization and synthesis. AMPK may therefore play a role in the ability of adult schistosomes to survive in vivo stressors such as transient glucose deprivation and oxidative stress. These findings suggest that AMPK warrants further investigation as a potential drug target, especially for interventions aimed at preventing establishment of a schistosome infection.
Effects of Total Dietary Fiber on Cecal Microbial Community and Intestinal Morphology of Growing White Pekin Duck
Authors: Hao Yongsheng , Ji Zhanqing , Shen Zhongjian , Wu Yongbao , Zhang Bo , Tang Jing , Hou Shuisheng , Xie Ming
Published: September 2021

The current study was to investigate the effects of total dietary fiber (TDF) on growth performance, cecal structure, cecal microbial community, and short-chain fatty acids (SCFAs) profiles in the cecum of growing White Pekin ducks. A total of 108 male Pekin ducks of 14-days-old were randomly allocated and fed diets containing 12.4, 14.7, and 16.2% TDF for 35 days. Each dietary treatment consisted of six replicates with six birds each. The results showed that 14.7 and 16.2% TDF treatments promoted growth performance relative to 12.4% TDF treatments (P < 0.05). A total of 14.7 and 16.2% TDF treatments significantly elevated villus height, the ratio of villus height to crypt depth and muscle layer thickness of cecum, and lowered crypt depth compared with 12.4% TDF treatment (P < 0.05). Simultaneously, 14.7 and 16.2% TDF treatments up-regulated Claudin-1 mRNA expression of barrier genes in the cecum compared with 12.4% TDF (P < 0.05). Butyrate-producing bacteria like Oscillopiraceae affiliating to the phyla Firmicutes were observed as a biomarker in the 16.2% TDF. Higher concentration of butyrate in the cecum was obtained in the 14.7% TDF compared with 12.4 and 16.2% TDF (P < 0.05). The concentrations of isobutyrate, valerate, and isovalerate in the cecum were significantly increased in the 16.2% TDF compared with 12.4 and 14.7% TDF (P < 0.05). Meanwhile, the abundance of genus UCG-005 and Enterococcus was positive correlations with isobutyrate and valerate (P < 0.05). However, the concentration of propionate in the cecum significantly decreased in 14.7 and 16.2% TDF treatments relative to 12.4% TDF treatments (P < 0.05). In summary, increasing TDF levels improved growth performance, cecal histomorphology, and barrier function of meat ducks and it might be mediated by the changes of microbiota communities, especially bloom of SCFAs-producing bacteria, which facilitated the interaction between intestinal mucosa and microbiota.
NMR Metabolite Profiles of the Bivalve Mollusc Mytilus galloprovincialis Before and After Immune Stimulation With Vibrio splendidus
Authors: Frizzo Riccardo , Bortoletto Enrico , Riello Tobia , Leanza Luigi , Schievano Elisabetta , Venier Paola , Mammi Stefano
Published: September 2021

The hemolymph metabolome of Mytilus galloprovincialis injected with live Vibrio splendidus bacteria was analyzed by 1H-NMR spectrometry. Changes in spectral hemolymph profiles were already detected after mussel acclimation (3 days at 18 or 25 °C). A significant decrease of succinic acid was accompanied by an increase of most free amino acids, mytilitol, and, to a smaller degree, osmolytes. These metabolic changes are consistent with effective osmoregulation, and the restart of aerobic respiration after the functional anaerobiosis occurred during transport. The injection of Vibrio splendidus in mussels acclimated at 18°C caused a significant decrease of several amino acids, sugars, and unassigned chemical species, more pronounced at 24 than at 12 h postinjection. Correlation heatmaps indicated dynamic metabolic adjustments and the relevance of protein turnover in maintaining the homeostasis during the response to stressful stimuli. This study confirms NMR-based metabolomics as a feasible analytical approach complementary to other omics techniques in the investigation of the functional mussel responses to environmental challenges.
CD74 Correlated With Malignancies and Immune Microenvironment in Gliomas
Authors: Xu Shengchao , Li Xizhe , Tang Lu , Liu Zhixiong , Yang Kui , Cheng Quan
Published: September 2021

Background: Cluster of differentiation 74 (CD74) is found to be highly involved in the development of various types of cancers and could affect the activities of infiltrated cells in the tumor microenvironment. However, these studies only focus on a few types of immune cells. Our study aims to comprehensively explore the role of CD74 in glioma prognosis and immune microenvironment.

Methods: A total of 40 glioma specimens were collected in this study. We extracted data from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene-Expression Omnibus (GEO) databases to explore the expression pattern of CD74 in gliomas. gene sets enrichment analysis and gene set variation analysis analyses were conducted to characterize the immune features of CD74. ESTIMATE, ssGSEA, Tumor IMmune Estimation Resource, and CIBERSORT algorithms were applied to assess the immune infiltration. Kaplan-Meier analysis was used for survival analysis. Receiver operating characteristic analysis was used to evaluate the predictive accuracy of CD74 in glioma diagnosis and prognosis.

Results: A total of 2,399 glioma patients were included in our study. CD74 was highly expressed in glioma tissue compared to normal brain tissue and its expression was significantly higher in the high-grade glioma compared to the lower grade glioma at transcriptional and translational levels. Besides, CD74 was positively associated with immune checkpoints and inflammatory cytokines as well as immune processes including cytokine secretion and leukocyte activation. The high expression of CD74 indicated a high infiltration of immune cells such as macrophages, dendritic cells, and neutrophils. Moreover, patients with high expression of CD74 had poor prognoses. CD74 had moderate predictive accuracy in the diagnosis of glioblastoma and prediction of survival.

Conclusions: In conclusion, our study revealed that the high expression of CD74 was associated with poor prognosis and high immune infiltration. CD74 could be used as a potential target for glioma treatment and as a biomarker to predict the prognosis of glioma patients.
Recent Developments Toward Integrated Metabolomics Technologies (UHPLC-MS-SPE-NMR and MicroED) for Higher-Throughput Confident Metabolite Identifications
Authors: Ghosh Rajarshi , Bu Guanhong , Nannenga Brent L. , Sumner Lloyd W.
Published: September 2021

Metabolomics has emerged as a powerful discipline to study complex biological systems from a small molecule perspective. The success of metabolomics hinges upon reliable annotations of spectral features obtained from MS and/or NMR. In spite of tremendous progress with regards to analytical instrumentation and computational tools, < 20% of spectral features are confidently identified in most untargeted metabolomics experiments. This article explores the integration of multiple analytical instruments such as UHPLC-MS/MS-SPE-NMR and the cryo-EM method MicroED to achieve large-scale and confident metabolite identifications in a higher-throughput manner. UHPLC-MS/MS-SPE allows for the simultaneous automated purification of metabolites followed by offline structure elucidation and structure validation by NMR and MicroED. Large-scale study of complex metabolomes such as that of the model plant legume Medicago truncatula can be achieved using an integrated UHPLC-MS/MS-SPE-NMR metabolomics platform. Additionally, recent developments in MicroED to study structures of small organic molecules have enabled faster, easier and precise structure determinations of metabolites. A MicroED small molecule structure elucidation workflow (e.g., crystal screening, sample preparation, data collection and data processing/structure determination) has been described. Ongoing MicroED methods development and its future scope related to structure elucidation of specialized metabolites and metabolomics are highlighted. The incorporation of MicroED with a UHPLC-MS/MS-SPE-NMR instrumental ensemble offers the potential to accelerate and achieve higher rates of metabolite identification.
Dissecting Monomer-Dimer Equilibrium of an RNase P Protein Provides Insight Into the Synergistic Flexibility of 5’ Leader Pre-tRNA Recognition
Authors: Zeng Danyun , Abzhanova Ainur , Brown Benjamin P. , Reiter Nicholas J.
Published: September 2021

Ribonuclease P (RNase P) is a universal RNA-protein endonuclease that catalyzes 5’ precursor-tRNA (ptRNA) processing. The RNase P RNA plays the catalytic role in ptRNA processing; however, the RNase P protein is required for catalysis in vivo and interacts with the 5’ leader sequence. A single P RNA and a P protein form the functional RNase P holoenzyme yet dimeric forms of bacterial RNase P can interact with non-tRNA substrates and influence bacterial cell growth. Oligomeric forms of the P protein can also occur in vitro and occlude the 5’ leader ptRNA binding interface, presenting a challenge in accurately defining the substrate recognition properties. To overcome this, concentration and temperature dependent NMR studies were performed on a thermostable RNase P protein from Thermatoga maritima. NMR relaxation (R1, R2), heteronuclear NOE, and diffusion ordered spectroscopy (DOSY) experiments were analyzed, identifying a monomeric species through the determination of the diffusion coefficients (D) and rotational correlation times (τc). Experimental diffusion coefficients and τc values for the predominant monomer (2.17 ± 0.36 * 10−10 m2/s, τc = 5.3 ns) or dimer (1.87 ± 0.40* 10−10 m2/s, τc = 9.7 ns) protein assemblies at 45°C correlate well with calculated diffusion coefficients derived from the crystallographic P protein structure (PDB 1NZ0). The identification of a monomeric P protein conformer from relaxation data and chemical shift information enabled us to gain novel insight into the structure of the P protein, highlighting a lack of structural convergence of the N-terminus (residues 1–14) in solution. We propose that the N-terminus of the bacterial P protein is partially disordered and adopts a stable conformation in the presence of RNA. In addition, we have determined the location of the 5’ leader RNA in solution and measured the affinity of the 5’ leader RNA–P protein interaction. We show that the monomer P protein interacts with RNA at the 5’ leader binding cleft that was previously identified using X-ray crystallography. Data support a model where N-terminal protein flexibility is stabilized by holoenzyme formation and helps to accommodate the 5’ leader region of ptRNA. Taken together, local structural changes of the P protein and the 5’ leader RNA provide a means to obtain optimal substrate alignment and activation of the RNase P holoenzyme.
Rebleeding of Ruptured Intracranial Aneurysm After Admission: A Multidimensional Nomogram Model to Risk Assessment
Authors: Liu Qingyuan , Yang Yi , Yang Junhua , Li Maogui , Yang Shuzhe , Wang Nuochuan , Wu Jun , Jiang Pengjun , Wang Shuo
Published: September 2021

Objective

Rebleeding is recognized as the main cause of mortality after intracranial aneurysm rupture. Though timely intervention can prevent poor prognosis, there is no agreement on the surgical priority and choosing medical treatment for a short period after rupture. The aim of this study was to investigate the risk factors related to the rebleeding after admission and establish predicting models for better clinical decision-making.

Methods

The patients with ruptured intracranial aneurysms (RIAs) between January 2018 and September 2020 were reviewed. All patients fell to the primary and the validation cohort by January 2020. The hemodynamic parameters were determined through the computational fluid dynamics simulation. Cox regression analysis was conducted to identify the risk factors of rebleeding. Based on the independent risk factors, nomogram models were built, and their predicting accuracy was assessed by using the area under the curves (AUCs).

Result

A total of 577 patients with RIAs were enrolled in this present study, 86 patients of them were identified as undergoing rebleeding after admission. Thirteen parameters were identified as significantly different between stable and rebleeding aneurysms in the primary cohort. Cox regression analysis demonstrated that six parameters, including hypertension [hazard ratio (HR), 2.54; P = 0.044], bifurcation site (HR, 1.95; P = 0.013), irregular shape (HR, 4.22; P = 0.002), aspect ratio (HR, 12.91; P < 0.001), normalized wall shear stress average (HR, 0.16; P = 0.002), and oscillatory stress index (HR, 1.14; P < 0.001) were independent risk factors related to the rebleeding after admission. Two nomograms were established, the nomogram including clinical, morphological, and hemodynamic features (CMH nomogram) had the highest predicting accuracy (AUC, 0.92), followed by the nomogram including clinical and morphological features (CM nomogram; AUC, 0.83), ELAPSS score (AUC, 0.61), and PHASES score (AUC, 0.54). The calibration curve for the probability of rebleeding showed good agreement between prediction by nomograms and actual observation. In the validation cohort, the discrimination of the CMH nomogram was superior to the other models (AUC, 0.93 vs. 0.86, 0.71 and 0.48).

Conclusion

We presented two nomogram models, named CMH nomogram and CM nomogram, which could assist in identifying the RIAs with high risk of rebleeding.
Reduced Risk of Atrial Fibrillation Following Cholecystectomy: A Nationwide Population-Based Study
Authors: Ho Tung Ching , Chen Yu-Ching , Lin Che-Chen , Tai Hsu-Chih , Wei Cheng-Yu , Yeh Yung-Hsiang , Hsu Chung Y.
Published: September 2021

Background: Gallstone disease (GD) is associated with a high risk of cardiovascular disease. However, it is unknown whether GD contributes to atrial fibrillation (AF). We aimed to investigate the association between GD and AF.

Methods: We performed a population-based cohort study using data from the Taiwan National Health Insurance Research Database between 2001 and 2011. A GD cohort of 230,076 patients was compared with a control cohort consisting of an equal number of patients matched for age, sex, cardiovascular and gastrointestinal comorbidities.

Results: In total, 5,992 (49.8/10,000 person-years) patients with GD and 5,804 (44.5/10,000 person-years) controls developed AF. GD increased AF risk with a hazard ratio (HR) of 1.20 [95% confidence interval (CI), 1.16–1.25]. In patients with GD but without cholecystectomy, the HR of AF reached 1.57 (95% CI = 1.50–1.63). After cholecystectomy, the HR of AF significantly decreased to 0.85 (95% CI = 0.81–0.90). Among the three age groups with GD (<45, 45–64, and ≥65 years), the adjusted HRs of AF were 1.59 (95% CI = 1.08–2.33), 1.31 (95% CI = 1.18–1.45), and 1.18 (95% CI = 1.13–1.22), respectively. Compared with patients with a CHA2DS2-VASc score equal to 0, the HRs of AF risk among total cohort patients and a score equal to 1, 2, 3, and ≥ 4 were 1.28 (95% CI = 1.15–1.43), 2.26 (95% CI = 2.00–2.56), 3.81 (95% CI = 3.35–4.34), and 5.09 (95% CI = 4.42–5.87), respectively.

Conclusion: This population-based longitudinal follow-up study showed that patients with GD had an increased AF risk. Moreover, cholecystectomy was related to reduced AF risk. Cardiovascular checkups may be necessary for patients with GD, especially those who are young and have other typical risk factors.
Secular Trends in the Incidence of and Mortality Due to Alzheimer’s Disease and Other Forms of Dementia in China From 1990 to 2019: An Age-Period-Cohort Study and Joinpoint Analysis
Authors: Gao Yongliang , Liu Xiaonan
Published: September 2021

Background

The number of individuals with dementia is increasing, which negatively affects families, communities, and health care systems worldwide. The changes in the incidence of and mortality due to Alzheimer’s disease and other forms of dementia at the national level in China have remained unknown over the past three decades.

Methods

Following the general analytical strategy used in the Global Burden of Disease Study (GBD) 2019, the age- and sex-specific incidence and mortality rates for dementia in China were analyzed. Trends in the incidence of and mortality due to dementia from 1990 to 2019 were assessed by joinpoint regression analysis. The effects of age, period and cohort on the incidence of and mortality due to dementia were estimated by an age-period-cohort model.

Results

The age-standardized incidence and mortality rates per 100,000 population were 103.83 (95% UI, 87.93–118.87) and 23.32 (95% UI, 5.66–61.31), respectively, for dementia in 2019. From 1990 to 2019, a significant average annual percentage change (AAPC) in the age-standardized incidence rate was observed in both males [0.49% (95% CI, 0.43–0.55%)] and females [0.31% (95% CI, 0.24–0.38%)], and the age-standardized mortality rate significantly increased in males [0.42% (95% CI, 0.31–0.53%)]. The population aged 55–59 years had the highest AAPC in the incidence of dementia [0.87% (95% CI, 0.81–0.93%)]. The age effect showed that the relative risks (RRs) of incident dementia and dementia-associated mortality increased with age among males and females, and individuals aged 60 years and older had significantly higher RRs. The RR of incident dementia increased with time, and the RR started to substantially increase in 2009. The cohort effect showed that the incidence decreased in successive birth cohorts.

Conclusion

Alzheimer’s disease and other forms of dementia continue to become more common among males and females in China, and the associated mortality rate in males significantly increased from 1990 to 2019. Early interventions should be implemented to reduce the burden of dementia on individuals at high risk in China.
Investigating Associations Between Inflammatory Biomarkers, Gray Matter, Neurofilament Light and Cognitive Performance in Healthy Older Adults
Authors: Karoly Hollis C. , Skrzynski Carillon J. , Moe Erin , Bryan Angela D. , Hutchison Kent E.
Published: September 2021

Background: Exploring biological variables that may serve as indicators of the development and progression of cognitive decline is currently a high-priority research area. Recent studies have demonstrated that during normal aging, individuals experience increased inflammation throughout the brain and body, which may be linked to cognitive impairment and reduced gray matter volume in the brain. Neurofilament light polypeptide (NfL), which is released into the circulation following neuronal damage, has been proposed as a biomarker for neurodegenerative diseases, and may also have utility in the context of normal aging. The present study tested associations between age, peripheral levels of the pro-inflammatory cytokine IL-6, peripheral NfL, brain volume, and cognitive performance in a sample of healthy adults over 60 years old.

Methods: Of the 273 individuals who participated in this study, 173 had useable neuroimaging data, a subset of whom had useable blood data (used for quantifying IL-6 and NfL) and completed a cognitive task. Gray matter (GM) thickness values were extracted from brain areas of interest using Freesurfer. Regression models were used to test relationships between IL-6, NfL, GM, and cognitive performance. To test putative functional relationships between these variables, exploratory path analytic models were estimated, in which the relationship between age, IL-6, and working memory performance were linked via four different operationalizations of brain health: (1) a latent GM variable composed of several regions linked to cognitive impairment, (2) NfL alone, (3) NfL combined with the GM latent variable, and (4) the hippocampus alone.

Results: Regression models showed that IL-6 and NfL were significantly negatively associated with GM volume and that GM was positively associated with cognitive performance. The path analytic models indicated that age and cognitive performance are linked by GM in the hippocampus as well as several other regions previously associated with cognitive impairment, but not by NfL alone. Peripheral IL-6 was not associated with age in any of the path models.

Conclusions: Results suggest that among healthy older adults, there are several GM regions that link age and cognitive performance. Notably, NfL alone is not a sufficient marker of brain changes associated with aging, inflammation, and cognitive performance.
Polygenic Hazard Score Associated Multimodal Brain Networks Along the Alzheimer’s Disease Continuum
Authors: Li Kaicheng , Fu Zening , Qi Shile , Luo Xiao , Zeng Qingze , Xu Xiaopei , Huang Peiyu , Zhang Minming , Calhoun Vince D.
Published: September 2021

Background

Late-onset Alzheimer’s disease (AD) is a polygenic neurodegenerative disease. Identifying the neuroimaging phenotypes behind the genetic predisposition of AD is critical to the understanding of AD pathogenesis. Two major questions which previous studies have led to are: (1) should the general “polygenic hazard score” (PHS) be a good choice to identify the individual genetic risk for AD; and (2) should researchers also include inter-modality relationships in the analyses considering these may provide complementary information about the AD etiology.

Methods

We collected 88 healthy controls, 77 patients with mild cognitive impairment (MCI), and 22 AD patients to simulate the AD continuum included from the ADNI database. PHS-guided multimodal fusion was used to investigate the impact of PHS on multimodal brain networks in AD-continuum by maximizing both inter-modality association and reference-modality correlation. Fractional amplitude of low frequency fluctuations, gray matter (GM) volume, and amyloid standard uptake value ratios were included as neuroimaging features. Eventually, the changes in neuroimaging features along AD continuum were investigated, and relationships between cognitive performance and identified PHS associated multimodal components were established.

Results

We found that PHS was associated with multimodal brain networks, which showed different functional and structural impairments under increased amyloid deposits. Notably, along with AD progression, functional impairment occurred before GM atrophy, amyloid deposition started from the MCI stage and progressively increased throughout the disease continuum.

Conclusion

PHS is associated with multi-facets of brain impairments along the AD continuum, including cognitive dysfunction, pathological deposition, which might underpin the AD pathogenesis.
Risk Factors for Atorvastatin as a Monotherapy for Chronic Subdural Hematoma: A Retrospective Multifactor Analysis
Authors: Zhang Xinjie , Wang Dong , Tian Ye , Wei Huijie , Liu Xuanhui , Xiang Tangtang , Fan Yibing , Gao Chuang , Huang Jinhao , Sha Zhuang , Quan Wei , Zhang Jianning , Jiang Rongcai
Published: September 2021

Chronic subdural hematoma (CSDH) is a common form of intracranial hemorrhage in the aging population. We aimed to investigate the predictive factors for atorvastatin efficacy as a monotherapy for moderate CSDH. We retrospectively reviewed the medical records of patients who were diagnosed with moderate CSDH and received atorvastatin monotherapy between February 5, 2014, and November 7, 2015, in multiple neurosurgical departments. Univariate, multivariate and receiver operating characteristic curve analyses were performed to identify the potential significant factors indicative of the good therapeutic efficacy or poor therapeutic efficacy of atorvastatin for mild CSDH, such as age, sex, history of injury, Markwalder grading scale–Glasgow Coma Scale (MGS-GCS), Activities of Daily Life-the Barthel Index scale (ADL-BI), American Society of Anesthesiologists Physical Status classification system (ASA-PS), blood cell counts, serum levels and computed tomography findings. A total of 89 patients (75 men and 14 women) aged 24–88 years (mean age 61.95 ± 15.30 years) were followed-up for 24 weeks. Computed tomography findings at admission showed mixed-density hematoma in 22 patients, isodense hematoma in 13 patients, high-density hematoma in 26 patients, and low-density hematoma in 28 patients. In total, 3, 80, and 6 patients had MGS-GCS grades of 0, 1, and 2, respectively. The efficacy rate at 6 months was 87.6% (78/89). Eleven patients were switched to surgery due to a worsened neurological condition, of whom 8, 1, 1, and 1 had high-density, low-density, isodense and mixed-density hematomas, respectively. These patients were switched to surgery over a range of 2–27 days, with a median interval of 12 days after the medication treatment. Univariate and multivariate analyses, confirmed by ROC curves, revealed that high-density hematoma, basal cistern compression, and hematoma volume to be independent risk factors for the efficacy of atorvastatin monotherapy in patients with moderate CSDH. Atorvastatin is an effective monotherapy for the treatment of mild CSDH. High-density hematoma, basal cistern compression, and hematoma volume are independent predictors of the efficacy of atorvastatin as a non-surgical treatment. The results suggested that ADL-BI was more sensitive than the MGS-GCS and ASA-PS for determining patient outcomes in our moderate CSDH cohort.
Effects of an Oroxylum indicum Extract (Sabroxy®) on Cognitive Function in Adults With Self-reported Mild Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled Study
Authors: Lopresti Adrian L. , Smith Stephen J. , Majeed Muhammed , Drummond Peter D.
Published: September 2021

Background: Oroxylum indicum has been used in traditional Ayurvedic medicine for the prevention and treatment of several diseases and may have neuroprotective effects.

Purpose: Examine the effects of Oroxylum indicum on cognitive function in older adults with self-reported cognitive complaints.

Study Design: Two-arm, parallel-group, 12-week, randomized, double-blind, placebo-controlled trial.

Methods: Eighty-two volunteers received either 500 mg, twice daily of a standardized Oroxylum indicum extract or placebo. Outcome measures included several computer-based cognitive tasks, the Control, Autonomy, Self-Realization, and Pleasure scale (CASP-19), Cognitive Failures Questionnaire (CFQ), and the Montreal Cognitive Assessment (MoCA). Changes in the concentration of brain-derived neurotrophic factor (BDNF) were also examined.

Results: Compared to the placebo, Oroxylum indicum was associated with greater improvements in episodic memory, and on several computer-based cognitive tasks such as immediate word recall and numeric working memory, and a faster rate of learning on the location learning task. However, there were no other significant differences in performance on the other assessed cognitive tests, the MoCA total score, or other self-report questionnaires. BDNF concentrations increased significantly in both groups, with no statistically-significant between-group differences. Oroxylum indicum was well tolerated except for an increased tendency for mild digestive complaints and headaches.

Conclusion: The results of this first human trial on the cognitive-enhancing effects of Oroxylum indicum suggest that it is a promising herbal candidate for the improvement of cognitive function in older adults with self-reported cognitive complaints.
The Rhesus Macaque as a Translational Model for Neurodegeneration and Alzheimer’s Disease
Authors: Stonebarger Gail A. , Bimonte-Nelson Heather A. , Urbanski Henryk F.
Published: September 2021

A major obstacle to progress in understanding the etiology of normative and pathological human brain aging is the availability of suitable animal models for experimentation. The present article will highlight our current knowledge regarding human brain aging and neurodegeneration, specifically in the context of Alzheimer’s disease (AD). Additionally, it will examine the use of the rhesus macaque monkey as a pragmatic translational animal model in which to study underlying causal mechanisms. Specifically, the discussion will focus on behavioral and protein-level brain changes that occur within the central nervous system (CNS) of aged monkeys, and compare them to the changes observed in humans during clinically normative aging and in AD.
Spatial Recognition Memory: Differential Brain Strategic Activation According to Sex
Authors: Castillo Joaquín , Carmona Isabel , Commins Sean , Fernández Sergio , Ortells Juan José , Cimadevilla José Manuel
Published: September 2021

Human spatial memory research has significantly progressed since the development of computerized tasks, with many studies examining sex-related performances. However, few studies explore the underlying electrophysiological correlates according to sex. In this study event-related potentials were compared between male and female participants during the performance of an allocentric spatial recognition task. Twenty-nine university students took part in the research. Results showed that while general performance was similar in both sexes, the brain of males and females displayed a differential activation. Males showed increased N200 modulation than females in the three phases of memory process (encoding, maintenance, and retrieval). Meanwhile females showed increased activation of P300 in the three phases of memory process compared to males. In addition, females exhibited more negative slow wave (NSW) activity during the encoding phase. These differences are discussed in terms of attentional control and the allocation of attentional resources during spatial processing. Our findings demonstrate that sex modulates the resources recruited to performed this spatial task.
Utilization of Robotic Exoskeleton for Overground Walking in Acute and Chronic Stroke
Authors: Nolan Karen J. , Karunakaran Kiran K. , Roberts Pamela , Tefertiller Candy , Walter Amber M. , Zhang Jun , Leslie Donald , Jayaraman Arun , Francisco Gerard E.
Published: September 2021

Stroke commonly results in gait deficits which impacts functional ambulation and quality of life. Robotic exoskeletons (RE) for overground walking are devices that are programmable to provide high dose and movement-impairment specific assistance thus offering new rehabilitation possibilities for recovery progression in individuals post stroke. The purpose of this investigation is to present preliminary utilization data in individuals with acute and chronic stroke after walking overground with an RE. Secondary analysis on a subset of individuals is presented to understand the mechanistic changes due to RE overground walking. Thirty-eight participants with hemiplegia secondary to stroke were enrolled in a clinical trial conducted at eight rehabilitation centers. Data is presented for four sessions of overground walking in the RE over the course of 2 weeks. Participants continued their standard of care if they had any ongoing therapy at the time of study enrollment. Gait speed during the 10 Meter Walk Test, Gait deviations and the Functional Ambulation Category (FAC) data were collected before (baseline) and after (follow-up) the RE walking sessions. Walking speed significantly increased between baseline and follow-up for participants in the chronic (p <0.01) and acute (p < 0.05) stage of stroke recovery. FAC level significantly improved (p < 0.05) and there were significantly fewer (p < 0.05) gait deviations observed for participants in the acute stages of stroke recovery between baseline and follow-up. Secondary analysis on a subset of eight participants indicated that after four sessions of overground walking with the RE, the participants significantly improved their spatial symmetry. The walk time, step count and ratio of walk time to up time increased from first session to the last session for participants in the chronic and acute stages of stroke. The RE was effectively utilized for overground walking for individuals with acute and chronic stroke with varying severity levels. The results demonstrated an increase in walking speed, improvement in FAC and a decrease in gait deviations (from baseline to follow-up) after four sessions of overground walking in the RE for participants. In addition, preliminary data indicated that spatial symmetry and step length also improved after utilization of an RE for overground walking.
Introducing Depth Information Into Generative Target Tracking
Authors: Sun Dongyue , Wang Xian , Lin Yonghong , Yang Tianlong , Wu Shixu
Published: September 2021

Common visual features used in target tracking, including colour and grayscale, are prone to failure in a confusingly similar-looking background. As the technology of three-dimensional visual information acquisition has gradually gained ground in recent years, the conditions for the wide use of depth information in target tracking has been made available. This study focuses on discussing the possible ways to introduce depth information into the generative target tracking methods based on a kernel density estimation as well as the performance of different methods of introduction, thereby providing a reference for the use of depth information in actual target tracking systems. First, an analysis of the mean-shift technical framework, a typical algorithm used for generative target tracking, is described, and four methods of introducing the depth information are proposed, i.e., the thresholding of the data source, thresholding of the density distribution of the dataset applied, weighting of the data source, and weighting of the density distribution of the dataset. Details of an experimental study conducted to evaluate the validity, characteristics, and advantages of each method are then described. The experimental results showed that the four methods can improve the validity of the basic method to a certain extent and meet the requirements of real-time target tracking in a confusingly similar background. The method of weighting the density distribution of the dataset, into which depth information is introduced, is the prime choice in engineering practise because it delivers an excellent comprehensive performance and the highest level of accuracy, whereas methods such as the thresholding of both the data sources and the density distribution of the dataset are less time-consuming. The performance in comparison with that of a state-of-the-art tracker further verifies the practicality of the proposed approach. Finally, the research results also provide a reference for improvements in other target tracking methods in which depth information can be introduced.
Review and Hypothesis: A Potential Common Link Between Glial Cells, Calcium Changes, Modulation of Synaptic Transmission, Spreading Depression, Migraine, and Epilepsy—H+
Authors: Malchow Robert Paul , Tchernookova Boriana K. , Choi Ji-in Vivien , Smith Peter J. S. , Kramer Richard H. , Kreitzer Matthew A.
Published: September 2021

There is significant evidence to support the notion that glial cells can modulate the strength of synaptic connections between nerve cells, and it has further been suggested that alterations in intracellular calcium are likely to play a key role in this process. However, the molecular mechanism(s) by which glial cells modulate neuronal signaling remains contentiously debated. Recent experiments have suggested that alterations in extracellular H+ efflux initiated by extracellular ATP may play a key role in the modulation of synaptic strength by radial glial cells in the retina and astrocytes throughout the brain. ATP-elicited alterations in H+ flux from radial glial cells were first detected from Müller cells enzymatically dissociated from the retina of tiger salamander using self-referencing H+-selective microelectrodes. The ATP-elicited alteration in H+ efflux was further found to be highly evolutionarily conserved, extending to Müller cells isolated from species as diverse as lamprey, skate, rat, mouse, monkey and human. More recently, self-referencing H+-selective electrodes have been used to detect ATP-elicited alterations in H+ efflux around individual mammalian astrocytes from the cortex and hippocampus. Tied to increases in intracellular calcium, these ATP-induced extracellular acidifications are well-positioned to be key mediators of synaptic modulation. In this article, we examine the evidence supporting H+ as a key modulator of neurotransmission, review data showing that extracellular ATP elicits an increase in H+ efflux from glial cells, and describe the potential signal transduction pathways involved in glial cell—mediated H+ efflux. We then examine the potential role that extracellular H+ released by glia might play in regulating synaptic transmission within the vertebrate retina, and then expand the focus to discuss potential roles in spreading depression, migraine, epilepsy, and alterations in brain rhythms, and suggest that alterations in extracellular H+ may be a unifying feature linking these disparate phenomena.
She Doesn’t Even Go Here: The Role of Inflammatory Astrocytes in CNS Disorders
Authors: Reid Jacqueline Kelsey , Kuipers Hedwich Fardau
Published: September 2021

Astrocyte heterogeneity is a rapidly evolving field driven by innovative techniques. Inflammatory astrocytes, one of the first described subtypes of reactive astrocytes, are present in a variety of neurodegenerative diseases and may play a role in their pathogenesis. Moreover, genetic and therapeutic targeting of these astrocytes ameliorates disease in several models, providing support for advancing the development of astrocyte-specific disease modifying therapies. This review aims to explore the methods and challenges of identifying inflammatory astrocytes, the role these astrocytes play in neurological disorders, and future directions in the field of astrocyte heterogeneity.
Hyoid Elongation May Be a Rare Cause of Recurrent Ischemic Stroke in Youth-A Case Report and Literature Review
Authors: Liu Gang , Wang Yuan , Chu Changbiao , Ren Yi , Hua Yang , Ji Xunming , Song Haiqing
Published: September 2021

The investigation for etiology of ischemic stroke in young adults remains a diagnostic challenge. Hyoid bone–related carotid injury is a rare and under-recognized cause of ischemic stroke, without established guidelines. We describe a case of recurrent ischemic stroke in a young patient presumably attributed to an impingement of the carotid artery by an elongated hyoid bone, and present other cases reported in the literature. Based on the imaging study as well as the lack of other findings, we attributed recurrent neurovascular events to the repetitive mechanical stimulation by the elongated hyoid bone that caused a vessel wall injury with subsequent thrombus and embolus. Given repeated recurrence under antiplatelet treatment, anticoagulation was added. The following 2-year follow-up showed no new neurologic events or any other complaints. Among the young, a broad spectrum of possibilities should be considered and we call attention to this infrequent etiology of ischemic stroke.