bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of liver fibrosis in hepatolenticular degeneration with traditional Chinese medicine: systematic review of meta-analysis, network pharmacology and molecular dynamics simulation
Authors: Yang Xulong , Wang Tiancheng , Tang Yiping , Shao Yawen , Gao Yaqin , Wu Peng
Published: May 2023

Background

Traditional Chinese medicine (TCM) is widely used in the clinical treatment of hepatolenticular degeneration (HLD) and liver fibrosis (LF). In the present study, the curative effect was assessed using meta-analysis. The possible mechanism of TCM against LF in HLD was investigated using network pharmacology and molecular dynamics simulation.

Methods

For literature collection, we searched several databases, including PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals (VIP) and Wan Fang database until February 2023, and the Review Manager 5.3 was used to analyze the data. Network pharmacology and molecular dynamics simulation were used to explore the mechanism of TCM in treating LF in HLD.

Results

The results of the meta-analysis revealed that the addition of Chinese herbal medicine (CHM) in treating HLD resulted in a higher total clinical effective rate than western medicine alone [RR 1.25, 95% CI (1.09, 1.44), p = 0.002]. It not only has a better effect on liver protection [Alanine aminotransferase: SMD = −1.20, 95% CI (−1.70, −0.70), p < 0.00001; Aspartate aminotransferase: SMD = −1.41, 95% CI (−2.34, −0.49), p = 0.003; Total bilirubin: SMD = −1.70, 95% CI (−3.36, −0.03), p = 0.05] but also had an excellent therapeutic effect on LF through four indexes [Hyaluronic acid: SMD = −1.15, 95% CI (−1.76, −0.53), p = 0.0003; Procollagen peptide III: SMD = −0.72, 95% CI (−1.29, −0.15), p = 0.01; Collagen IV: SMD = −0.69, 95% CI (−1.21, −0.18), p = 0.008; Laminin: SMD = −0.47, 95% CI (−0.95, 0.01), p = 0.06]. Concurrently, the liver stiffness measurement decreased significantly [SMD = −1.06, 95% CI (−1.77, −0.36), p = 0.003]. The results of network pharmacological experiments and molecular dynamics simulation indicate that the three high-frequency TCMs (Rhei Radix Et Rhizoma-Coptidis Rhizoma-Curcumae Longae Rhizoma, DH-HL-JH) primarily act on the core targets (AKT1, SRC, and JUN) via the core components (rhein, quercetin, stigmasterol, and curcumin), regulate the signal pathway (PI3K-Akt, MAPK, EGFR, and VEGF signaling pathways), and play a role of anti-LF.

Conclusion

Meta-analysis indicates that TCM is beneficial in treating HLD patients and improving LF. The present study successfully predicts the effective components and potential targets and pathways involved in treating LF for the three high-frequency CHMs of DH-HL-JH. The findings of the present study are hoped to provide some evidence support for clinical treatment.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42022302374.
Using a multi-omic approach to investigate the mechanism of 12-bis-THA activity against Burkholderia thailandensis
Authors: Pattinson Adam , Bahia Sandeep , Le Gall Gwénaëlle , Morris Christopher J. , Harding Sarah V. , McArthur Michael
Published: May 2023

Burkholderia pseudomallei is the causative agent of the tropical disease, melioidosis. It is intrinsically resistant to many antimicrobials and treatment requires an onerous regimen of intravenous and orally administered drugs. Relapse of disease and high rates of mortality following treatment are common, demonstrating the need for new anti-Burkholderia agents. The cationic bola-amphiphile, 12,12′-(dodecane-1,12-diyl) bis (9-amino-1,2,3,4-tetrahydroacridinium), referred to as 12-bis-THA, is a molecule with the potential to treat Burkholderia infections. 12-bis-THA spontaneously forms cationic nanoparticles that bind anionic phospholipids in the prokaryotic membrane and are readily internalized. In this study, we examine the antimicrobial activity of 12-bis-THA against strains of Burkholderia thailandensis. As B. pseudomallei produces a polysaccharide capsule we first examined if this extra barrier influenced the activity of 12-bis-THA which is known to act on the bacterial envelope. Therefore two strains of B. thailandensis were selected for further testing, strain E264 which does not produce a capsule and strain E555 which does produce a capsule that is chemically similar to that found in B. pseudomallei. In this study no difference in the minimum inhibitory concentration (MIC) was observed when capsulated (E555) and unencapsulated (E264) strains of B. thailandensis were compared, however time-kill analysis showed that the unencapsulated strain was more susceptible to 12-bis-THA. The presence of the capsule did not affect the membrane permeation of 12-bis-THA at MIC concentrations. Proteomic and metabolomic analyses showed that 12-bis-THA causes a shift in central metabolism away from glycolysis and glyoxylate cycle, and suppressed the production of the F1 domain of ATP synthase. In summary, we provide insight into the molecular mechanisms underpinning the activity of 12-bis-THA against B. thailandensis and discuss its potential for further development.
House ammonia exposure causes alterations in microbiota, transcriptome, and metabolome of rabbits
Authors: Li Keyao , Pang Shuo , Li Zhechen , Ding Xiaoning , Gan Yating , Gan Qianfu , Fang Shaoming
Published: May 2023

Introduction

Pollutant gas emissions in the current production system of the livestock industry have negative influences on environment as well as the health of farm staffs and animals. Although ammonia (NH3) is considered as the primary and harmful gas pollutant in the rabbit farm, less investigation has performed to determine the toxic effects of house ammonia exposure on rabbit in the commercial confined barn.

Methods

In this study, we performed multi-omics analysis on rabbits exposed to high and low concentration of house ammonia under similar environmental conditions to unravel the alterations in nasal and colonic microbiota, pulmonary and colonic gene expression, and muscular metabolic profile.

Results and discussion

The results showed that house ammonia exposure notably affected microbial structure, composition, and functional capacity in both nasal and colon, which may impact on local immune responses and inflammatory processes. Transcriptome analysis indicated that genes related to cell death (MCL1, TMBIM6, HSPB1, and CD74) and immune response (CDC42, LAMTOR5, VAMP8, and CTSB) were differentially expressed in the lung, and colonic genes associated with redox state (CAT, SELENBP1, GLUD1, and ALDH1A1) were significantly up-regulated. Several key differentially abundant metabolites such as L-glutamic acid, L-glutamine, L-ornithine, oxoglutaric acid, and isocitric acid were identified in muscle metabolome, which could denote house ammonia exposure perturbed amino acids, nucleotides, and energy metabolism. In addition, the widespread and strong inter-system interplay were uncovered in the integrative correlation network, and central features were confirmed by in vitro experiments. Our findings disclose the comprehensive evidence for the deleterious effects of house ammonia exposure on rabbit and provide valuable information for understanding the underlying impairment mechanisms.
Association of residual feed intake with intestinal microbiome and metabolome in laying period of ducks
Authors: Sun Hanxue , Xu Wenwu , Gu Tiantian , Sun Jing , Li Chengfeng , Chen Li , Tian Yong , Li Guoqin , Lu Lizhi , Zeng Tao
Published: May 2023

Introduction

Residual feed intake (RFI) is a indicator to evaluate animal feed. This experiment was explored to study the relationship between intestinal microbiome and metabolome of ducks with different residual feed intake during laying period.

Methods

A total of 300 Shaoxing ducks aged 42 weeks were randomly selected and fed a diet of 60 d. At the end of the trial, 20 samples were selected according to the phenotype of RFI and divided into two groups (HRFI and LRFI). The cecal microbiota composition was explored by 16S ribosomal RNA gene sequencing and rectal metabolomics uses liquid chromatography-mass spectrometry (LC–MS) to identify the composition of metabolites in a non-targeted manner.

Results

Results show feed intake and feed conversion ratio in the group HRFI were significantly higher than those in the group LRFI (p < 0.05). Chao1 indices were higher in the group LRFI than in the HRFI (p < 0.05), Shannon and Simpson indices were higher in the group LRFI than in the HRFI (p < 0.01). After linear discriminant analysis effect size (p < 0.05, LDA score > 3), Rikenellaceae, Rikenellaceae_RC9_gut_group, Lactobacillales and Ruminococcus_2, etc. were significantly enriched in the group LRFI at the genus level, while Prevotellaceae_NK3B31_group and Bacteria were significantly enriched in the group HRFI. After LC–MS analysis we found 338 metabolic difference products and 10 metabolic pathways, including the ABC transporter system, cysteine and methionine metabolism, arginine and proline metabolism, and vitamin B6 metabolism, were identified to be associated with the significantly differentially expressed between the groups LRFI and HRFI (p < 0.05). We hypothesize that the difference between ducks with different RFIs is mainly due to the fact that ducks with LRFI have more SCFAs-producing bacteria in their gut microorganisms, which regulate the RFI of animals. This process we found that Phascolarctobaterium and Anaerobiospirillum may provide energy for ABC transporter system by producing SCFAs, and regulate RFI to improve feed utilization efficiency.

Discussion

These results revealed the relationship between microbiome and metabonomics in laying ducks with different RFI, and provided theoretical basis for further study on the relationship between them.
Interaction between nematodes and bacteria enhances soil carbon sequestration under organic material amendments
Authors: Shi Guangping , Luan Lu , Zhu Guofan , Zeng Zhaoyang , Zheng Jie , Shi Yue , Sun Bo , Jiang Yuji
Published: May 2023

The process of carbon (C) sequestration plays an important role in soil fertility and productivity, yet most studies have focused on the individual role of the bacterial community. However, an in-depth mechanistic understanding of how soil nematodes interact with the bacterial community to regulate soil C accumulation is still lacking. We conducted a 10-year field experiment to explore the nematode and bacterial communities and determine the influence of nematode-bacteria interactions on C mineralization, microbial metabolic quotient (qCO2), and carbon use efficiency (CUE) under the organic material amendments, including chemical fertilizers with straw (NS), chemical fertilizers with straw and pig manure (NSM), and chemical fertilizer with straw biochar (NB). Here, our results showed the abundance of bacterial and nematode communities was significantly higher under NS, NSM, and NB treatments than under chemical fertilizers (N) treatment, with the highest abundance under the NSM treatment. The enrichment index and functional dispersion index were significantly higher under NSM treatment than under N, NS, and NB treatments, while the channel index followed the opposite pattern. Structural equation modeling indicated that the potential predation pressure induced by nematodes may improve bacterial abundance, with positive cascading effects on C sequestration. Collectively, our study highlights the functional importance of nematode-microorganism interactions in mediating C dynamics under organic material amendments.
Genomic and phenotypic characterization of a red-pigmented strain of Massilia frigida isolated from an Antarctic microbial mat
Authors: Shaffer Jacob M. C. , Giddings Lesley-Ann , Samples Robert M. , Mikucki Jill A.
Published: May 2023

The McMurdo Dry Valleys of Antarctica experience a range of selective pressures, including extreme seasonal variation in temperature, water and nutrient availability, and UV radiation. Microbial mats in this ecosystem harbor dense concentrations of biomass in an otherwise desolate environment. Microbial inhabitants must mitigate these selective pressures via specialized enzymes, changes to the cellular envelope, and the production of secondary metabolites, such as pigments and osmoprotectants. Here, we describe the isolation and characterization of a Gram-negative, rod-shaped, motile, red-pigmented bacterium, strain DJPM01, from a microbial mat within the Don Juan Pond Basin of Wright Valley. Analysis of strain DJMP01’s genome indicates it can be classified as a member of the Massilia frigida species. The genome contains several genes associated with cold and salt tolerance, including multiple RNA helicases, protein chaperones, and cation/proton antiporters. In addition, we identified 17 putative secondary metabolite gene clusters, including a number of nonribosomal peptides and ribosomally synthesized and post-translationally modified peptides (RiPPs), among others, and the biosynthesis pathway for the antimicrobial pigment prodigiosin. When cultivated on complex agar, multiple prodiginines, including the antibiotic prodigiosin, 2-methyl-3-propyl-prodiginine, 2-methyl-3-butyl-prodiginine, 2-methyl-3-heptyl-prodiginine, and cycloprodigiosin, were detected by LC–MS. Genome analyses of sequenced members of the Massilia genus indicates prodigiosin production is unique to Antarctic strains. UV-A radiation, an ecological stressor in the Antarctic, was found to significantly decrease the abundance of prodiginines produced by strain DJPM01. Genomic and phenotypic evidence indicates strain DJPM01 can respond to the ecological conditions of the DJP microbial mat, with prodiginines produced under a range of conditions, including extreme UV radiation.
Predicting antimicrobial resistance of bacterial pathogens using time series analysis
Authors: Kim Jeonghoon , Rupasinghe Ruwini , Halev Avishai , Huang Chao , Rezaei Shahbaz , Clavijo Maria J. , Robbins Rebecca C. , Martínez-López Beatriz , Liu Xin
Published: May 2023

Antimicrobial resistance (AMR) is arguably one of the major health and economic challenges in our society. A key aspect of tackling AMR is rapid and accurate detection of the emergence and spread of AMR in food animal production, which requires routine AMR surveillance. However, AMR detection can be expensive and time-consuming considering the growth rate of the bacteria and the most commonly used analytical procedures, such as Minimum Inhibitory Concentration (MIC) testing. To mitigate this issue, we utilized machine learning to predict the future AMR burden of bacterial pathogens. We collected pathogen and antimicrobial data from >600 farms in the United States from 2010 to 2021 to generate AMR time series data. Our prediction focused on five bacterial pathogens (Escherichia coli, Streptococcus suis, Salmonella sp., Pasteurella multocida, and Bordetella bronchiseptica). We found that Seasonal Auto-Regressive Integrated Moving Average (SARIMA) outperformed five baselines, including Auto-Regressive Moving Average (ARMA) and Auto-Regressive Integrated Moving Average (ARIMA). We hope this study provides valuable tools to predict the AMR burden not only of the pathogens assessed in this study but also of other bacterial pathogens.
Transcriptomic analyses reveal the potential antibacterial mechanism of citral against Staphylococcus aureus
Authors: Liao Zedong , Lin Keshan , Liao Weijiang , Xie Ying , Yu Guoqing , Shao Yan , Dai Min , Sun Fenghui
Published: May 2023

Background

The emergence of multi-drug resistant Staphylococcus aureus (S. aureus) has posed a challenging clinical problem for treating its infection. The development of novel or new antibacterial agents becomes one of the useful methods to solve this problem, and has received more attention over the past decade. Citral is reported to have antibacterial activity against S. aureus, but its mechanism is yet entirely clear.

Methods

To reveal the antibacterial mechanism of citral against S. aureus, comparative transcriptomic analysis was carried out to analyze the gene expression differences between the citral-treated and untreated groups. The changes of protein, adenosine triphosphate (ATP) and reactive oxygen species (ROS) content in S. aureus caused by citral were also examined.

Results

Six hundred and fifty-nine differentially expressed genes were obtained according to the comparative transcriptomic analysis, including 287 up-regulated genes and 372 down-regulated genes. The oxidoreductase activity and fatty acid degradation pathway were enriched in up-regulated genes, and ribosome and S. aureus infection pathway were enriched in down-regulated genes. Meanwhile, physiological trials revealed a decline in ATP and protein levels, but an increase in ROS content within the citral-treated group. Thus, it can be inferred that the antibacterial effects of citral against S. aureus were likely due to its ability to decrease ATP content by down-regulating ATP synthase genes (atpD and atpG), reduce protein content, induce cell membrane and cell wall damages, accumulate ROS, and down-regulate virulence factor genes to reduce pathogenicity.

Conclusion

These findings revealed the antibacterial mechanism of citral was likely a type of multi-target mode that affected multiple molecular processes in S. aureus, which lays the groundwork for further exploitation of citral as a therapeutic candidate against S. aureus infections.
Obligate autotrophy at the thermodynamic limit of life in a new acetogenic bacterium
Authors: Frolov Evgenii N. , Elcheninov Alexander G. , Gololobova Alexandra V. , Toshchakov Stepan V. , Novikov Andrei A. , Lebedinsky Alexander V. , Kublanov Ilya V.
Published: May 2023

One of the important current issues of bioenergetics is the establishment of the thermodynamic limits of life. There is still no final understanding of what is the minimum value of the energy yield of a reaction that is sufficient to be used by an organism (the so-called “biological quantum of energy”). A reasonable model for determination of the minimal energy yield would be microorganisms capable of living on low-energy substrates, such as acetogenic prokaryotes. The most prominent metabolic feature of acetogens is autotrophic growth with molecular hydrogen and carbon dioxide as the substrates, which is hardly competitive in environments. Most probably, that is why only facultative autotrophic acetogens have been known so far. Here, we describe the first obligately autotrophic acetogenic bacterium Aceticella autotrophica gen. nov., sp. nov., strain 3443-3AcT. Phylogenetically, the new genus falls into a monophyletic group of heterotrophic bacteria of the genera Thermoanaerobacterium, Thermoanaerobacter, and Caldanaerobacter (hereinafter referred to as TTC group), where the sole acetogenic representative has so far been the facultatively autotrophic Thermoanaerobacter kivui. A. autotrophica and T. kivui both are acetogens employing energy-converting hydrogenase (Ech-acetogens) that are likely to have inherited the acetogenesis capacity vertically from common ancestor. However, their acetogenic machineries have undergone different adjustments by gene replacements due to horizontal gene transfers from different donors. Obligate autotrophy of A. autotrophica is associated with the lack of many sugar transport systems and carbohydrate catabolism enzymes that are present in other TTC group representatives, including T. kivui.
Serum cortisol is negatively related to hippocampal volume, brain structure, and memory performance in healthy aging and Alzheimer’s disease
Authors: Dronse Julian , Ohndorf Anna , Richter Nils , Bischof Gérard N. , Fassbender Ronja , Behfar Qumars , Gramespacher Hannes , Dillen Kim , Jacobs Heidi I. L. , Kukolja Juraj , Fink Gereon R. , Onur Oezguer A.
Published: May 2023

Objective

Elevated cortisol levels have been frequently reported in Alzheimer’s disease (AD) and linked to brain atrophy, especially of the hippocampus. Besides, high cortisol levels have been shown to impair memory performance and increase the risk of developing AD in healthy individuals. We investigated the associations between serum cortisol levels, hippocampal volume, gray matter volume and memory performance in healthy aging and AD.

Methods

In our cross-sectional study, we analyzed the relationships between morning serum cortisol levels, verbal memory performance, hippocampal volume, and whole-brain voxel-wise gray matter volume in an independent sample of 29 healthy seniors (HS) and 29 patients along the spectrum of biomarker-based AD.

Results

Cortisol levels were significantly elevated in patients with AD as compared to HS, and higher cortisol levels were correlated with worse memory performance in AD. Furthermore, higher cortisol levels were significantly associated with smaller left hippocampal volumes in HS and indirectly negatively correlated to memory function through hippocampal volume. Higher cortisol levels were further related to lower gray matter volume in the hippocampus and temporal and parietal areas in the left hemisphere in both groups. The strength of this association was similar in HS and AD.

Conclusion

In AD, cortisol levels are elevated and associated with worse memory performance. Furthermore, in healthy seniors, higher cortisol levels show a detrimental relationship with brain regions typically affected by AD. Thus, increased cortisol levels seem to be indirectly linked to worse memory function even in otherwise healthy individuals. Cortisol may therefore not only serve as a biomarker of increased risk for AD, but maybe even more importantly, as an early target for preventive and therapeutic interventions.
Quasi-passive lower limbs exosuit: an in-depth assessment of fatigue, kinematic and muscular patterns while comparing assistive strategies on an expert subject’s gait analysis
Authors: Di Natali Christian , Ortiz Jesus , Caldwell Darwin G.
Published: May 2023

Wearable robots are becoming a valuable solution that helps injured, and elderly people regain mobility and improve clinical outcomes by speeding up the rehabilitation process. The XoSoft exosuit identified several benefits, including improvement of assistance, usability, and acceptance with a soft, modular, bio-mimetic, and quasi-passive exoskeleton. This study compares two assistive configurations: (i) a bilateral hip flexion (HA, hips-assistance) and (ii) a bilateral hip flexion combined with ankle plantarflexion (HAA, hips-ankles-assistance) with the main goal of evaluating compensatory actions and synergetic effects generated by the human- exoskeleton interaction. A complete description of this complex interaction scenario with this actuated exosuit is evaluated during a treadmill walking task, using several indices to quantify the human-robot interaction in terms of muscular activation and fatigue, metabolic expenditure, and kinematic motion patterns. Evidence shows that the HAA biomimetic controller is synergetic with the musculature and performs better concerning the other control strategy. The experimentation demonstrated a metabolic expenditure reduction of 8% of Metabolic Equivalent of Task (MET), effective assistance of the muscular activation of 12.5%, a decrease of the muscular fatigue of 0.6% of the mean frequency, and a significant reduction of the compensatory actions, as discussed in this work. Compensatory effects are present in both assistive configurations, but the HAA modality provides a 47% reduction of compensatory effects when considering muscle activation.
Impact of redox-related genes on tumor microenvironment immune characteristics and prognosis of high-grade gliomas
Authors: Yuan Yunbo , Zuo Mingrong , Zhang Shuxin , Chen Siliang , Feng Wentao , Wang Zhihao , Chen Mina , Liu Yanhui
Published: May 2023

Introduction

High-grade glioma (HGG) defines a group of brain gliomas characterized by contrast enhancement, high tumor heterogeneity, and poor clinical outcome. Disturbed reduction–oxidation (redox) balance has been frequently associated with the development of tumor cells and their microenvironment (TME).

Methods

To study the influence of redox balance on HGGs and their microenvironment, we collected mRNA-sequencing and clinical data of HGG patients from TCGA and CGGA databases and our own cohort. Redox-related genes (ROGs) were defined as genes in the MSigDB pathways with keyword “redox” that were differentially expressed between HGGs and normal brain samples. Unsupervised clustering analysis was used to discover ROG expression clusters. Over-representation analysis (ORA), gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were also employed to understand the biological implication of differentially expressed genes between HGG clusters. CIBERSORTx and ESTIMATE were used to profile the immune TME landscapes of tumors, and TIDE was used to evaluated the potential response to immune checkpoint inhibitors. Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression was used to construct HGG-ROG expression risk signature (GRORS).

Results

Seventy-five ROGs were found and consensus clustering using the expression profile of ROGs divided the both IDH-mutant (IDHmut) and IDH-wildtype (IDHwt) HGGs into subclusters with different prognosis. Functional enrichment analysis revealed that the differential aggressiveness between redox subclusters in IDHmut HGGs were significantly associated with cell cycle regulation pathways, while IDHwt HGG redox subclusters showed differentially activated immune-related pathways. In silico TME analysis on immune landscapes in the TME showed that the more aggressive redox subclusters in both IDHmut and IDHwt HGGs may harbor a more diverse composition of tumor-infiltrating immune cells, expressed a higher level of immune checkpoints and were more likely to respond to immune checkpoint blockade. Next, we established a GRORS which showed AUCs of 0.787, 0.884, and 0.917 in predicting 1–3-year survival of HGG patients in the held-out validation datasets, and the C-index of a nomogram combining the GRORS and other prognostic information reached 0.835.

Conclusion

Briefly, our results suggest that the expression pattern of ROGs was closely associated with the prognosis as well as the TME immune profile of HGGs, and may serve as a potential indicator for their response to immunotherapies.
The multifaceted roles of embryonic microglia in the developing brain
Authors: Hattori Yuki
Published: May 2023

Microglia are the resident immune cells of the central nervous system (CNS). Microglia originate from erythromyeloid progenitors in the yolk sac at the early embryonic stage, and these progenitors then colonize the CNS through extensive migration and proliferation during development. Microglia account for 10% of all cells in the adult brain, whereas the proportion of these cells in the embryonic brain is only 0.5–1.0%. Nevertheless, microglia in the developing brain widely move their cell body within the structure by extending filopodia; thus, they can interact with surrounding cells, such as neural lineage cells and vascular-structure-composing cells. This active microglial motility suggests that embryonic microglia play a pivotal role in brain development. Indeed, recent increasing evidence has revealed diverse microglial functions at the embryonic stage. For example, microglia control differentiation of neural stem cells, regulate the population size of neural progenitors and modulate the positioning and function of neurons. Moreover, microglia exert functions not only on neural lineage cells but also on blood vessels, such as supporting vascular formation and integrity. This review summarizes recent advances in the understanding of microglial cellular dynamics and multifaceted functions in the developing brain, with particular focus on the embryonic stage, and discusses the fundamental molecular mechanisms underlying their behavior.
The mesoanatomy of the cortex, minimization of free energy, and generative cognition
Authors: Wright James Joseph , Bourke Paul David
Published: May 2023

Capacity for generativity and unlimited association is the defining characteristic of sentience, and this capacity somehow arises from neuronal self-organization in the cortex. We have previously argued that, consistent with the free energy principle, cortical development is driven by synaptic and cellular selection maximizing synchrony, with effects manifesting in a wide range of features of mesoscopic cortical anatomy. Here, we further argue that in the postnatal stage, as more structured inputs reach the cortex, the same principles of self-organization continue to operate at multitudes of local cortical sites. The unitary ultra-small world structures that emerged antenatally can represent sequences of spatiotemporal images. Local shifts of presynapses from excitatory to inhibitory cells result in the local coupling of spatial eigenmodes and the development of Markov blankets, minimizing prediction errors in each unit's interactions with surrounding neurons. In response to the superposition of inputs exchanged between cortical areas, more complicated, potentially cognitive structures are competitively selected by the merging of units and the elimination of redundant connections that result from the minimization of variational free energy and the elimination of redundant degrees of freedom. The trajectory along which free energy is minimized is shaped by interaction with sensorimotor, limbic, and brainstem mechanisms, providing a basis for creative and unlimited associative learning.
Role of PGC-1α mediated synaptic plasticity, mitochondrial function, and neuroinflammation in the antidepressant effect of Zi-Shui-Qing-Gan-Yin
Authors: Zhu Wen , Zhang Wen , Yang Feng , Cai Min , Li Xiangting , Xiang Yijin , Xiang Jun , Yang Yunke , Cai Dingfang
Published: May 2023

Depression is the most prevalent psychiatric disorder, which needs deeper mechanism research studies and effective therapy. Zi-Shui-Qing-Gan-Yin (ZSQGY) is a traditional Chinese medicine decoction that has been widely used in China in the treatment of depressive symptoms. The aim of the study was to examine the anti-depressive effects of ZSQGY and the possible mechanism of action in the monosodium glutamate (MSG)-induced depressive model and the corticosterone (CORT)-induced PC12 cell model. Liquid chromatography-mass spectrometry (LC–MS) was performed to determine the major compounds in the water extract of ZSQGY. The depressive behaviors were evaluated by the field swimming test (FST), the sucrose preference test (SPT), and the open field test (OFT). Golgi staining and transmission electron microscopy (TEM) were performed to display the alterations of synaptic ultrastructure. The mitochondrion function and inflammatory factors were also quantified. The changes in peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α) expression were evaluated. The results of this study demonstrated that ZSQGY significantly improved depressive behaviors. ZSQGY also reversed the changes in synaptic plasticity, improved mitochondrion function, and reduced the levels of inflammatory factors. The neuroprotective effects were accompanied by the increased expression of PGC-1α. However, the beneficial changes were reversed after the inhibition of PGC-1α. These results indicated that ZSQGY effectively could improve depressive behaviors via the mechanisms that regulate synaptic structural plasticity, improve mitochondrion function, and alleviate neuroinflammation, which could, or partly, attribute to the regulation of PGC-1α.
Morphological features predicting in-stent stenosis after pipeline implantation for unruptured intracranial aneurysm
Authors: Jin Hengwei , Lv Jian , Li Conghui , Wang Jiwei , Jiang Yuhua , Meng Xiangyu , Li Youxiang
Published: May 2023

Purpose

Elongation denotes the regularity of an aneurysm and parent artery. This retrospective research study was conducted to identify the morphological factors that could predict postoperative in-stent stenosis (ISS) after Pipeline Embolization Device (PED) implantation for unruptured intracranial aneurysms (UIAs).

Methods

Patients with UIA and treated with PED at our institute between 2015 and 2020 were selected. Preoperative morphological features including both manually measured shape features and radiomics shape features were extracted and compared between patients with and without ISS. Logistic regression analysis was performed for factors associated with postoperative ISS.

Results

A total of 52 patients (18 men and 34 women) were involved in this study. The mean angiographic follow-up time was 11.87 ± 8.26 months. Of the patients, 20 of them (38.46%) were identified with ISS. Multivariate logistic analysis showed that elongation (odds ratio = 0.008; 95% confidence interval, 0.001–0.255; p = 0.006) was an independent risk factor for ISS. The area under the curve (AUC) of the receiver operating characteristic curve(ROC) was 0.734 and the optimal cut-off value of elongation for ISS classification was 0.595. The sensitivity and specificity of prediction were 0.6 and 0.781, respectively. The ISS degree of elongation of less than 0.595 was larger than the ISS degree of elongation of more than 0.595.

Conclusion

Elongation is a potential risk factor associated with ISS after PED implantation for UIAs. The more regular an aneurysm and parent artery, the less likelihood of an ISS occurrence.
Texture analysis of apparent diffusion coefficient maps in predicting the clinical functional outcomes of acute ischemic stroke
Authors: Sun Yi , Zhuang Yuzhong , Zhu Jie , Song Bin , Wang Hao
Published: May 2023

Purpose

To investigate texture analysis (TA) based on apparent diffusion coefficient (ADC) map in predicting acute ischemic stroke (AIS) prognosis and discriminating TA features in stroke subtypes.

Methods

This retrospective study included patients with AIS between January 2018 and April 2021. The patients were assigned to the favorable [modified Rankin Scale (mRS) score ≤ 2] and unfavorable (mRS score > 2) outcome groups. All patients underwent stroke subtyping according to the Trial of Org 10,172 in Acute Stroke Treatment (TOAST) classification. The TA features were extracted from infarction lesions on the ADC map. The demographic characteristics, clinical characteristics, and texture features were used to construct prediction models with recurrent neural network (RNN). The receiver operating characteristic (ROC) curves were implemented to evaluate the performance of the predictive models.

Results

A total of 1,003 patients (682 male; mean age 65.90 ± 12.44) with AIS having documented the 90-day mRS score were identified, including 840 with favorable outcomes. In the validation set, the area under the curve (AUC) of the predictive model using only clinical characteristics achieved an AUC of 0.56, texture model 0.77, the model combining both clinical and texture features showed better with an AUC of 0.78. The texture feature profiles differed between large artery atherosclerosis (LAA) and small artery occlusion (SAO) subtypes (all p < 0.05). The AUC of combined prediction models for LAA and SAO subtypes was 0.80 and 0.81.

Conclusion

Texture analysis based on ADC map could be useful as an adjunctive tool for predicting ischemic stroke prognosis.
A practical approach to in-hospital management of new-onset refractory status epilepticus/febrile infection related epilepsy syndrome
Authors: Sheikh Zubeda , Hirsch Lawrence J.
Published: May 2023

New-onset refractory status epilepticus (NORSE) is “a clinical presentation, not a specific diagnosis, in a patient without active epilepsy or other preexisting relevant neurological disorder, with new onset of refractory status epilepticus without a clear acute or active structural, toxic, or metabolic cause.” Febrile infection related epilepsy syndrome (FIRES) is “a subcategory of NORSE that requires a prior febrile infection, with fever starting between 2 weeks and 24 h before the onset of refractory status epilepticus, with or without fever at the onset of status epilepticus.” These apply to all ages. Extensive testing of blood and CSF for infectious, rheumatologic, and metabolic conditions, neuroimaging, EEG, autoimmune/paraneoplastic antibody evaluations, malignancy screen, genetic testing, and CSF metagenomics may reveal the etiology in some patients, while a significant proportion of patients’ disease remains unexplained, known as NORSE of unknown etiology or cryptogenic NORSE. Seizures are refractory and usually super-refractory (i.e., persist despite 24 h of anesthesia), requiring a prolonged intensive care unit stay, often (but not always) with fair to poor outcomes. Management of seizures in the initial 24–48 h should be like any case of refractory status epilepticus. However, based on the published consensus recommendations, the first-line immunotherapy should begin within 72 h using steroids, intravenous immunoglobulins, or plasmapheresis. If there is no improvement, the ketogenic diet and second-line immunotherapy should start within seven days. Rituximab is recommended as the second-line treatment if there is a strong suggestion or proof of an antibody-mediated disease, while anakinra or tocilizumab are recommended for cryptogenic cases. Intensive motor and cognitive rehab are usually necessary after a prolonged hospital stay. Many patients will have pharmacoresistant epilepsy at discharge, and some may need continued immunologic treatments and an epilepsy surgery evaluation. Extensive research is in progress now via multinational consortia relating to the specific type(s) of inflammation involved, whether age and prior febrile illness affect this, and whether measuring and following serum and/or CSF cytokines can help determine the best treatment.
A comparison of altered white matter microstructure in youth born with congenital heart disease or born preterm
Authors: Easson Kaitlyn , Khairy May , Rohlicek Charles V. , Saint-Martin Christine , Gilbert Guillaume , Nguyen Kim-Anh , Luu Thuy Mai , Couture Élise , Nuyt Anne-Monique , Wintermark Pia , Deoni Sean C. L. , Descoteaux Maxime , Brossard-Racine Marie
Published: May 2023

Introduction

Alterations to white matter microstructure as detected by diffusion tensor imaging have been documented in both individuals born with congenital heart disease (CHD) and individuals born preterm. However, it remains unclear if these disturbances are the consequence of similar underlying microstructural disruptions. This study used multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) and neurite orientation dispersion and density imaging (NODDI) to characterize and compare alterations to three specific microstructural elements of white matter – myelination, axon density, and axon orientation – in youth born with CHD or born preterm.

Methods

Participants aged 16 to 26 years with operated CHD or born ≤33 weeks gestational age and a group of healthy peers of the same age underwent a brain MRI including mcDESPOT and high angular resolution diffusion imaging acquisitions. Using tractometry, average values of myelin water fraction (MWF), neurite density index (NDI), and orientation dispersion index (ODI) were first calculated and compared between groups for 30 white matter bundles. Afterwards, bundle profiling was performed to further characterize the topology of the detected microstructural alterations.

Results

The CHD and preterm groups both presented with widespread bundles and bundle segments with lower MWF, accompanied by some occurrences of lower NDI, relative to controls. While there were no differences in ODI between the CHD and control groups, the preterm group presented with both higher and lower ODI compared to the control group and lower ODI compared to the CHD group.

Discussion

While youth born with CHD or born preterm both presented with apparent deficits in white matter myelination and axon density, youth born preterm presented with a unique profile of altered axonal organization. Future longitudinal studies should aim to better understand the emergence of these common and distinct microstructural alterations, which could orient the development of novel therapeutic approaches.
Identification of mutations on the EMD and EYA4 genes associated with Emery–Dreifuss muscular dystrophy and deafness: a case report
Authors: Zambrano Ana Karina , Paz-Cruz Elius , Cadena-Ullauri Santiago , Guevara-Ramírez Patricia , Ruiz-Pozo Viviana A. , Tamayo-Trujillo Rafael , Ibarra-Castillo Rita , Laso-Bayas José Luis , Doménech Nieves , Ibarra-Rodríguez Adriana Alexandra , Hidalgo Ricardo
Published: May 2023

Introduction

Hearing loss is the most common sensory disability, and it is estimated that 50% of cases are caused by genetic factors. One of the genes associated with deafness is the eyes absent homolog 4 (EYA4) gene, a transcription factor related to the development and function of the inner ear. Emery–Dreifuss muscular dystrophy is a rare inherited disease characterized by atrophy and weakness of the humeroperoneal muscles, multi-joint contractures, and cardiac manifestations. It is inherited in an autosomal-dominant, X-linked, or less frequently autosomal recessive manner; one of the genes associated with EDMD is the emerin (EMD) gene.

Case description

A total of two Ecuadorian siblings aged 57 (Subject A) and 55 (Subject B) were diagnosed with deafness and an unspecified type of muscular dystrophy based on family history and clinical findings. Next-generation sequencing (NGS) using the TruSight Cardio and Inherited Disease kits at the Centro de Investigación Genética y Genómica CIGG, Universidad UTE, was performed. The genetic analyses showed two mutations: a stop mutation in exon 11/20 (NM_004100.4:c.940G>T) of the EYA4 gene and a missense mutation in exon 6 (NM_000117.2:c.548C>G) of the EMD gene.

Discussion and conclusion

The in silico predictions described the EYA4 variant as likely pathogenic and the EMD variant as a variant of uncertain significance (VUS). Moreover, an ancestry analysis was performed using 46 Ancestry Informative Insertion/Deletion Markers (AIM-InDels), and the ancestral composition of subject A was 46% African, 26.1% European, and 27.9% American Indian ancestry, whereas the ancestral composition of subject B was 41.3% African, 38.2% European, and 20.5% American Indian ancestry. The present case report describes two Ecuadorian siblings with a mainly African ancestral component, muscular dystrophy, and deafness phenotypes. Moreover, using next-generation sequencing (NGS), a mutation in the EMD and a novel mutation in EYA4 genes possibly associated with the subjects' phenotype were identified and discussed.
Neighborhood-level social vulnerability and individual-level cognitive and motor functioning over time in older non-Latino Black and Latino adults
Authors: Lamar Melissa , Kershaw Kiarri N. , Leurgans Sue E. , Mukherjee R. Reshmi , Lange-Maia Brittney S. , Marquez David X. , Barnes Lisa L.
Published: May 2023

Introduction

Despite known health disparities in cognitive aging, a comprehensive rationale for the increased burden in older minoritized populations including non-Latino Black and Latino adults has yet to be elucidated. While most work has focused on person-specific risk, studies are increasingly assessing neighborhood-level risk. We evaluated multiple aspects of the environmental milieu that may be critical when considering vulnerability to adverse health outcomes.

Methods

We investigated associations between a Census-tract derived Social Vulnerability Index (SVI) and level of and change in cognitive and motor functioning in 780 older adults (590 non-Latino Black adults, ∼73 years old at baseline; 190 Latinos, ∼70 years old baseline). Total SVI scores (higher = greater neighborhood-level vulnerability) were combined with annual evaluations of cognitive and motor functioning (follow-up ranged from 2 to 18 years). Demographically-adjusted mixed linear regression models tested for associations between SVI and cognitive and motor outcomes in analyses stratified by ethno-racial group.

Results

For non-Latino Black participants, higher SVI scores were associated with lower levels of global cognitive and motor functioning-specifically, episodic memory, motor dexterity and gait-as well as longitudinal change in visuospatial abilities and hand strength. For Latinos, higher SVI scores were associated with lower levels of global motor functioning only-specifically, motor dexterity; there were no significant associations between SVI and change in motor functioning.

Discussion

Neighborhood-level social vulnerability is associated with cognitive and motor functioning in non-Latino Black and Latino older adults, although associations appear to contribute to level more so than longitudinal change.
A mathematical model and experimental procedure to analyze the cognitive effects of audio frequency magnetic fields
Authors: Navarro Enrique A. , Navarro-Modesto Enrique
Published: May 2023

Audio frequency magnetic fields (20 Hz−20 kHz) are magnetic fields in extremely low frequency-very low frequency (ELF-VLF) bands that are present near audio equipment and acoustic transducers. These devices transform and operate the electrical signal from the recordings or other devices into acoustic and audio signals. The cognitive influence of sound and noise has been widely studied and recognized since the times of ancient Rome; however, the cognitive effects of the magnetic fields of these frequencies have not been studied. Due to the extensive use of audio devices that use this type of transducer near the temporal–parietal area, we believe that it is of interest to study their impact on short-term memory or working memory (WM) and to analyze their potential as they operate as a transcranial magnetic stimulation. In this study, a mathematical model and an experimental tool are introduced to analyze memory performance. The model dissociates the reaction time of a cognitive task. We analyze the model in data from a group of 65 young, healthy subjects. WM is assessed in our experimental setup by means of the Sternberg test (ST), whereby during the ST, one subgroup was exposed to an audio frequency magnetic stimulus, and the other subgroup received a sham stimulus. The magnetic stimulus was ~0.1 μT and was applied to both sides of the head at the frontal cortex near the temporal–parietal area, which is where WM is expected to be located. The ST records reaction times when determining whether an object displayed on the computer screen is one of the objects to be remembered. The results are analyzed within the mathematical model and changes are observed, including the deterioration of WM, which could affect 32% of its operability.