bluuebunny/crossref_metadata_2025 huggingface dataset:
Cryptococcal chest wall mass and rib osteomyelitis associated with the use of fingolimod: A case report and literature review
Authors: Carpenter Kent , Etemady-Deylamy Ali , Costello Victoria , Khasawneh Mohammad , Chamberland Robin , Tian Katherine , Donlin Maureen , Moreira-Walsh Brenda , Reisenbichler Emily , Abate Getahun
Published: September 2022

Being introduced in 2010, fingolimod was among the first oral therapies for relapsing multiple sclerosis (MS). Since that time, postmarketing surveillance has noted several case reports of various cryptococcal infections associated with fingolimod use. To date, approximately 15 such case reports have been published. We present the first and unique case of cryptococcal chest wall mass and rib osteomyelitis associated with fingolimod use. The patient presented with left-side chest pain and was found to have a lower left chest wall mass. Computerized tomography (CT) showed chest wall mass with the destruction of left 7th rib. Aspirate from the mass grew Cryptococcus neoformans. The isolate was serotype A. Fingolimod was stopped. The patient received liposomal amphotericin B for 2 weeks and started on fluconazole with a plan to continue for 6–12 months. The follow-up CT in 6 weeks showed a marked decrease in the size of the chest wall mass. In conclusion, our case highlights the atypical and aggressive form of cryptococcal infection possibly related to immunosuppression from fingolimod use.
COVID-19 and related social distancing measures induce significant metabolic complications without prominent weight gain in Korean adults
Authors: Ko Hae-Jin , Cho Yoon Jeong , Kim Kyoung-Kon , Kang Jee-Hyun , Kim Young-Sang , Haam Ji-Hee , Hur Yang-Im , Choi Hye-In , Lee Kyu Rae , Park Jung Ha , Cho Soo Hyun , Kim Jong-Koo , Lee Taesic , Seo Myung-Jae , Yoon Yeong Sook , Seo Yoobin , Nam Ga Eun , Kim Sun Hyun
Published: September 2022

Background

This study using multi-center health examination data from Korean adults was conducted to confirm changes in weight, and their related cardiometabolic parameters, before and after strengthening of social distancing regulations.

Methods

A retrospective cohort study was conducted using health check-up data from 13 university hospitals. The study period was from January 2018 to July 2020. To examine the effect of systematic social distancing measures, participants who underwent a health check-up (Visit 3) between July 2020 and July 2021 (during full scale social distancing), and had undergone two previous health check-ups (Visits 1 and 2) between January 2018 and June 2020 (before social distancing), were selected. In total, data from 7,875 participants were analyzed. Linear mixed-effect models were used to calculate estimates of anthropometric indices and metabolic markers measured on Visits 2 and 3, compared with measurements from Visit 1.

Results

There were no significant differences in body weight, body mass index, waist circumference, and body composition on Visit 3 than on Visits 1 and 2. However, the odds of metabolic syndrome and its components, including hypertension, high glucose, diabetes, hypercholesterolemia, hypertriglyceridemia, hyper-non-high-density lipoprotein cholesterolemia, and dyslipidemia were significantly higher on Visit 3 than on Visits 1 and 2. The increase in metabolic complications was marked, particularly in relatively young adults who visited health check-up centers located in the capital area.

Conclusion

Metabolic syndrome and its components were significantly worse after high level social distancing, although there were no significant increases in anthropometric indices and body fat levels. Healthcare providers need to prevent and manage worsening of metabolic parameters in subpopulations prone to be more sedentary and eat unhealthy food during the COVID-19 pandemic and associated social distancing measures.
In vitro models as tools for screening treatment options of head and neck cancer
Authors: Seliger Barbara , Al-Samadi Ahmed , Yang Bo , Salo Tuula , Wickenhauser Claudia
Published: September 2022

Various in vitro models using primary and established 2- and 3-dimensional cultures, multicellular tumor spheroids, standardized tumor slice cultures, tumor organoids, and microfluidic systems obtained from tumor lesions/biopsies of head and neck cancer (HNC) have been employed for exploring and monitoring treatment options. All of these in vitro models are to a different degree able to capture the diversity of tumors, recapitulate the disease genetically, histologically, and functionally and retain their tumorigenic potential upon xenotransplantation. The models were used for the characterization of the malignant features of the tumors and for in vitro screens of drugs approved for the treatment of HNC, including chemotherapy and radiotherapy as well as recently developed targeted therapies and immunotherapies, or for novel treatments not yet licensed for these tumor entities. The implementation of the best suitable model will enlarge our knowledge of the oncogenic properties of HNC, expand the drug repertoire and help to develop individually tailored treatment strategies resulting in the translation of these findings into the clinic. This review summarizes the different approaches using preclinical in vitro systems with their advantages and disadvantages and their implementation as preclinical platforms to predict disease course, evaluate biomarkers and test therapy efficacy.
Computational tumor stroma reaction evaluation led to novel prognosis-associated fibrosis and molecular signature discoveries in high-grade serous ovarian carcinoma
Authors: Jiang Jun , Tekin Burak , Yuan Lin , Armasu Sebastian , Winham Stacey J. , Goode Ellen L. , Liu Hongfang , Huang Yajue , Guo Ruifeng , Wang Chen
Published: September 2022

Background

As one of the key criteria to differentiate benign vs. malignant tumors in ovarian and other solid cancers, tumor-stroma reaction (TSR) is long observed by pathologists and has been found correlated with patient prognosis. However, paucity of study aims to overcome subjective bias or automate TSR evaluation for enabling association analysis to a large cohort.

Materials and methods

Serving as positive and negative sets of TSR studies, H&E slides of primary tumors of high-grade serous ovarian carcinoma (HGSOC) (n = 291) and serous borderline ovarian tumor (SBOT) (n = 15) were digitally scanned. Three pathologist-defined quantification criteria were used to characterize the extents of TSR. Scores for each criterion were annotated (0/1/2 as none-low/intermediate/high) in the training set consisting of 18,265 H&E patches. Serial of deep learning (DL) models were trained to identify tumor vs. stroma regions and predict TSR scores. After cross-validation and independent validations, the trained models were generalized to the entire HGSOC cohort and correlated with clinical characteristics. In a subset of cases tumor transcriptomes were available, gene- and pathway-level association studies were conducted with TSR scores.

Results

The trained models accurately identified the tumor stroma tissue regions and predicted TSR scores. Within tumor stroma interface region, TSR fibrosis scores were strongly associated with patient prognosis. Cancer signaling aberrations associated 14 KEGG pathways were also found positively correlated with TSR-fibrosis score.

Conclusion

With the aid of DL, TSR evaluation could be generalized to large cohort to enable prognostic association analysis and facilitate discovering novel gene and pathways associated with disease progress.
Metaphenotypes associated with recurrent genomic lineages of Campylobacter jejuni responsible for human infections in Luxembourg
Authors: Nennig Morgane , Clément Arnaud , Longueval Emmanuelle , Bernardi Thierry , Ragimbeau Catherine , Tresse Odile
Published: September 2022

Campylobacter jejuni is a leading cause of foodborne illnesses worldwide. Although considered fragile, this microaerophilic bacterium is able to survive in various challenging environments, which subsequently constitutes multiple sources of transmission for human infection. To test the assumption of acquiring specific features for adaptation and survival, we established a workflow of phenotypic tests related to the survival and the persistence of recurrent and sporadic strains. A representative collection of 83 strains isolated over 13 years from human, mammal, poultry, and environmental sources in Luxembourg, representing different spreading patterns (endemic, epidemic, and sporadic), was screened for survival to oxidative stresses, for acclimating to aerobic conditions (AC), and for persistence on abiotic surfaces. Using the cgMLST Oxford typing scheme for WGS data, the collection was classified into genomic lineages corresponding to host-generalist strains (lineages A and D, CC ST-21), host-specific strains (lineage B, CC ST-257 and lineage C, CC ST-464) and sporadic strains. We established that when a strain survives concentrations beyond 0.25 mM superoxide stress, it is six times more likely to survive hyperoxide stress and that a highly adherent strain is 14 times more likely to develop a biofilm. Surprisingly, more than half of the strains could acclimate to AC but this capacity does not explain the difference between recurrent genomic lineages and sporadic strains and the survival to oxidative stresses, while recurrent strains have a significantly higher adhesion/biofilm formation capacity than sporadic ones. From this work, the genomic lineages with more stable genomes could be characterized by a specific combination of phenotypes, called metaphenotypes. From the functional genomic analyses, the presence of a potentially functional T6SS in the strains of lineage D might explain the propensity of these strains to be strong biofilm producers. Our findings support the hypothesis that phenotypical abilities contribute to the spatio-temporal adaptation and survival of stable genomic lineages. It suggests a selection of better-adapted and persistent strains in challenging stress environments, which could explain the prevalence of these lineages in human infections.
House feeding system improves the estrus rate in yaks (Bos grunniens) by increasing specific fecal microbiota and myo-inositol content in serum
Authors: Zhu Yanbin , Li Xin , zhaxi Lousang , zhaxi Suolang , Suolang  , Ciyang  , Sun Guangming , yangji Cidan , wangdui Basang
Published: September 2022

Grazing (G) yaks (Bos grunniens) are generally of low fertility, which severely limits the income of local pastoralists. However, we recently found that yaks had a 52% higher estrus rate in house feeding (HF) than in G. Gas chromatography-mass spectrometry (GC-MS) and 16S rRNA gene sequencing were used to analyze serum metabolites and fecal microbiota of 20 rutting yaks in the G and HF systems, respectively, to explain this phenomenon. The results showed that 73 total metabolites differed significantly (p < 0.05 and VIP > 1) between the G and HF systems. In the HF system, 53 were upregulated and 20 were downregulated compared with the G system. Organic oxygen compounds, organic acids and their derivatives, and lipids and lipid-like molecules were the most common differential metabolites. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway mapper revealed that 25 metabolic signaling pathways differed significantly between the two systems. The top three enriched pathways included central carbon metabolism in cancer, aminoacyl–tRNA biosynthesis, and ABC transporters. The 16S rRNA gene sequencing data showed no significant differences in Chao 1 index between the two systems. According to principal component analysis (PCA), the HF and G systems were distinctly and separately clustered in terms of fecal microbiota distribution. The G system showed significantly higher abundances of Firmicutes. The HF system showed significantly higher abundances of Alistipes, Treponema, and Rikenellaceae_ RC9_ gut_ group. Pearson's correlation analysis and core network analysis revealed that Rikenellaceae_RC9_ gut_ group, Alistipes, and Treponema were positively correlated with myo-inositol and formed the core bacteria. In summary, the HF system promoted the estrus rate and changed the composition of yak fecal microbiota and serum metabolites. Increased estrus rate might be obtained due to enhanced myo-inositol content in yak serum via the HF system. Correlation analysis suggested that myo-inositol content might also be partly increased via yak-specific fecal microbiota, contributing to the estrus rate. These findings could lead to a novel therapeutic strategy for G yaks due to their low estrus rate.
PMA-qPCR method for the selective quantitation of viable lactic acid bacteria in fermented milk
Authors: Shi Zihang , Li Xiefei , Fan Xiankang , Xu Jue , Liu Qing , Wu Zhen , Pan Daodong
Published: September 2022

The number of viable lactic acid bacteria (LAB) is a key indicator of the quality of fermented milk. Currently, the combination of propidium monoazide (PMA) and qPCR has been applied in the quantification of viable bacteria in various matrices. In this research, the PMA-qPCR method was used to detect the number of viable bacteria of each LAB species in fermented milk. By analyzing pheS gene and 16S rRNA gene sequence similarities in five species of LAB, namely Lactobacillus delbrueckii subsp. bulgaricus, Lactiplantibacillus plantarum, Streptococcus thermophilus, Lactobacillus helveticus, and Lactococcus lactis subsp. lactis, the pheS gene resolved species identities better and was thus selected to design specific primers and probes. The pheS gene was cloned into the pUC19 vector and used to construct a standard curve for absolute quantification. Standard curves for quantification were constructed for each LAB species for serial dilutions between 1011 and 106 CFU/mL, with R2 > 0.99. The number of viable bacteria in the fermented milk detected by PMA-qPCR was significantly lower than that of qPCR (P < 0.05), indicating that PMA inhibited the amplification of DNA from dead cells. This was corroborated by the results from bacterial staining and plate count experiments. The proposed PMA-qPCR method provided rapid qualitative and quantitative determination of the number of viable bacteria for each LAB species in fermented milk within 3 h.
Impact of preservation method and storage period on ribosomal metabarcoding of marine microbes: Implications for remote automated samplings
Authors: Wietz Matthias , Metfies Katja , Bienhold Christina , Wolf Christian , Janssen Felix , Salter Ian , Boetius Antje
Published: September 2022

Automated sampling technologies can enhance the temporal and spatial resolution of marine microbial observations, particularly in remote and inaccessible areas. A critical aspect of automated microbiome sampling is the preservation of nucleic acids over long-term autosampler deployments. Understanding the impact of preservation method on microbial metabarcoding is essential for implementing genomic observatories into existing infrastructure, and for establishing best practices for the regional and global synthesis of data. The present study evaluates the effect of two preservatives commonly used in autosampler deployments (mercuric chloride and formalin) and two extraction kits (PowerWater and NucleoSpin) on amplicon sequencing of 16S and 18S rRNA gene over 50 weeks of sample storage. Our results suggest the combination of mercuric chloride preservation and PowerWater extraction as most adequate for 16S and 18S rRNA gene amplicon-sequencing from the same seawater sample. This approach provides consistent information on species richness, diversity and community composition in comparison to control samples (nonfixed, filtered and frozen) when stored up to 50 weeks atin situtemperature. Preservation affects the recovery of certain taxa, with specific OTUs becoming overrepresented (SAR11 and diatoms) or underrepresented (Colwelliaand pico-eukaryotes) after preservation. In case eukaryotic sequence information is the sole target, formalin preservation and NucleoSpin extraction performed best. Our study contributes to the design of long-term autonomous microbial observations in remote ocean areas, allowing cross-comparison of microbiome dynamics across sampling devices (e.g., water and particle samplers) and marine realms.
RNA interference (RNAi) applications to the management of fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae): Its current trends and future prospects
Authors: Kebede Megersa , Fite Tarekegn
Published: September 2022

The fall armyworm Spodoptera frugiperda (Lepidoptera: Noctuidae) is among the invasive insect pests that damages maize and sorghum, the high-priority crops in newly colonized agro-ecologies, including African contexts. Owing to the increasing infestation of the pest and the limitations of current conventional methods for its management, there is a call for discovering advanced pest management approaches. RNA interference (RNAi) is an emerging molecular tool showing flexible potential for the management of S. frugiperda. We conducted a search of the recent application of RNAi literature using Google Scholar and Mendeley to find advanced papers on S. frugiperda management using RNAi molecular tools that led to growth inhibition, developmental aberrations, reduced fecundity, and mortality, mainly by disruption of normal biological processes of the pest. Although efforts have been made to accelerate the utility of RNAi, many factors limit the efficiency of RNAi to achieve successful control over S. frugiperda. Owing to RNAi’s potential bioactivity and economic and ecological acceptability, continued research efforts should focus on improving its broad applicability, including field conditions. Screening and identification of key target genes should be a priority task to achieve effective and sustainable management of this insect via RNAi. In addition, a clear understanding of the present status of RNAi utilization in S. frugiperda management is of paramount importance to improve its efficiency. Therefore, in this review, we highlight the biology of S. frugiperda and the RNAi mechanism as a foundation for the molecular management of the pest. Then, we discuss the current knowledge of the RNAi approach in S. frugiperda management and the factors affecting the efficiency of RNAi application. Finally, the prospects for RNAi-based insect pest management are highlighted for future research to achieve effective management of S. frugiperda.
Integrative bioinformatics analysis to identify the effects of circadian rhythm on Crohn’s disease
Authors: Liu Dan , Chen Yin-Yun , Li Qing-qing , Xu Ming , Liao Jiang-Tao , Wang Ben
Published: September 2022

Background: Crohn’s disease (CD) is a multifactorial inflammatory bowel disease characterized by complex aberrant autoimmune disorders. Currently, the involvement of the circadian rhythm in the pathogenesis of CD is unknown.

Methods: Bulk and single-cell RNA-seq data and associated clinical data from patients with CD were downloaded from the Gene Expression Omnibus (GEO). Single-sample gene set enrichment analysis was performed to calculate the enrichment score (ES) of circadian rhythm-related genes. Differential expression analysis was used to identify differentially expressed genes. Functional enrichment analysis was used to explore potential disease mechanisms. CIBERSORT was used to estimate immune cell abundance. Single-cell RNA-seq data were analyzed using the R package “Seurat.”

Results: The ES of circadian rhythm-related genes was lower in the CD tissue than in the normal tissue. Ubiquitin-specific protease 2 (USP2), a circadian rhythm-related gene, was identified as a potential modulator of CD pathogenesis. USP2 expression was reduced in CD and was associated with disease severity. Moreover, the analysis of bulk RNA-seq and single-cell RNA-seq data showed that monocyte and neutrophil abundance was elevated in CD and was negatively correlated with USP2 expression. It should be noted that USP2 expression in acinar cells was negatively correlated with monocyte and neutrophil abundance. Functional enrichment analysis revealed several canonical pathways to be enriched in CD, including the interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, cytokine–cytokine receptor interaction, toll-like receptor signaling pathway, and nod-like receptor signaling pathway.

Conclusion: Aberrant expression of circadian rhythm-related genes is correlated with CD pathogenesis. USP2 might be related to crosstalk among the different cell types in CD. These findings provide insights into future chronotherapy for CD.
Use of electroencephalogram, gait, and their combined signals for classifying cognitive impairment and normal cognition
Authors: Min Jin-Young , Ha Sang-Won , Lee Kiwon , Min Kyoung-Bok
Published: September 2022

Background

Early identification of people at risk for cognitive decline is an important step in delaying the occurrence of cognitive impairment. This study investigated whether multimodal signals assessed using electroencephalogram (EEG) and gait kinematic parameters could be used to identify individuals at risk of cognitive impairment.

Methods

The survey was conducted at the Veterans Medical Research Institute in the Veterans Health Service Medical Center. A total of 220 individuals volunteered for this study and provided informed consent at enrollment. A cap-type wireless EEG device was used for EEG recording, with a linked-ear references based on a standard international 10/20 system. Three-dimensional motion capture equipment was used to collect kinematic gait parameters. Mild cognitive impairment (MCI) was evaluated by Seoul Neuropsychological Screening Battery-Core (SNSB-C).

Results

The mean age of the study participants was 73.5 years, and 54.7% were male. We found that specific EEG and gait parameters were significantly associated with cognitive status. Individuals with decreases in high-frequency EEG activity in high beta (25–30 Hz) and gamma (30–40 Hz) bands increased the odds ratio of MCI. There was an association between the pelvic obliquity angle and cognitive status, assessed by MCI or SNSB-C scores. Results from the ROC analysis revealed that multimodal signals combining high beta or gamma and pelvic obliquity improved the ability to discriminate MCI individuals from normal controls.

Conclusion

These findings support prior work on the association between cognitive status and EEG or gait, and offer new insights into the applicability of multimodal signals to distinguish cognitive impairment.
Frailty and hearing loss: From association to causation
Authors: Liu Yun , Qian Peiyi , Guo Shuli , Liu Shuangyan , Wang Dahui , Yang Lei
Published: September 2022

Background

Observational studies suggest that frailty is associated with hearing loss (HL) but with inconsistent results. This study aims to examine such association and to assess its causality.

Materials and methods

The cross-sectional data from the National Health and Nutrition Examination Survey (NHANES). Multivariate logistic regression models were used to assess the association between HL and frailty index (FI). Genetic variants associated with the FI and HL were obtained from a large genome-wide association study (GWAS) meta-analysis and UK Biobank GWAS. The inverse variance weighting (IVW) method was used to estimate causal effects. Sensitivity analyses were performed to further validate the robustness of results.

Results

In this cross-sectional analysis, results support the possibility that frailty may be associated with a higher risk of developing HL, with self-reported [odds ratio (OR) = 2.813; 95% CI, 2.386, 3.317; p < 0.001], speech frequency HL (OR = 1.975; 95% CI, 1.679–2.323; p < 0.001), and high frequency HL (OR = 1.748; 95% CI, 1.459–2.094; p < 0.001). In the adjusted model, frail participants remained at high risk of HL. Mendelian randomization (MR) studies showed a bidirectional causal association between genetically predicted FI and risk of HL (FI for exposure: OR = 1.051; 95% CI, 1.020–1.083; p = 0.001; HL for exposure: OR = 1.527; 95% CI, 1.227–1.901; p < 0.001).

Conclusion

Our observational study found that inter-individual differences in frailty were associated with the risk of developing HL. Genetic evidence suggests a potential bidirectional causal association between FI and HL. Furthermore, the potential mechanisms of this association require investigation.
Tumor necrosis factor-α mediated inflammation versus apoptosis in age-related hearing loss
Authors: Wu Ting , Zhou Jiamin , Qiu Jingjing , Song Yuwan , Guo Wentao , Cui Limei , Song Xicheng , Sun Yan
Published: September 2022

An almost universal phenomenon occurring during aging is a state of chronic, low-grade, sterile inflammation. Inflammation is a crucial contributor to various age-related pathologies and natural processes in aging tissues. Tumor necrosis factor-α (TNF-α), a master regulator of the immune system, plays an important role in the propagation of inflammation. Recent research has found correlations between hearing loss and markers such as TNF-α. However, the intrinsic molecular mechanism by which TNF-α influences aging individuals’ increased risk of hearing loss remains unclear. In this study, we found that TNF-α expression gradually increased with age in DBA/2J mice. We then used recombinant TNF-α to upregulate TNF-α levels in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and found that low concentrations of TNF-α could activate the nuclear factor kappa B (NF-κB) transcriptional response to mediate hair cell survival, while high concentrations of TNF-α could activate the Caspase-3 cascade to mediate hair cell apoptosis, which preliminarily confirmed that a TNF-α mediated signaling pathway plays an important role in the pathogenesis of age-related hearing loss.
Effects of Wu Qin Xi exercise on reactive inhibition in Parkinson’s disease: A randomized controlled clinical trial
Authors: Wang Zhen , Pi Yanling , Tan Xiaoyin , Wang Zhen , Chen Robert , Liu Yu , Guo Wei , Zhang Jian
Published: September 2022

Objective

Motor symptom in patients with Parkinson’s disease (PD) are related to reduced motor inhibitory ability (proactive and reactive inhibition). Although exercise has been shown to improve this ability, its effects on different levels of motor inhibition have not been determined.

Materials and methods

Sixty patients with PD aged 55–75 years were allocated randomly to 24-week exercise interventions [Wu Qin Xi exercise (WQX) and stretching exercise (SE)]. The stop signal task and questionnaires were administered pre and post interventions. Twenty-five age-matched healthy controls were recruited to obtain reference values for inhibition.

Results

Compared to healthy controls, patients with PD showed motor inhibition deficits in reactive inhibition, but not in proactive inhibition. Post-intervention, the WQX group showed significant improvement in reactive inhibition compared to the SE group. In both the WQX and SE groups, movement speed was improved post-intervention, accompanied by reduction in negative emotions, stable improvement of sleep quality, and high self-reported satisfaction levels.

Conclusion

This study demonstrated that Wu Qin Xi exercise can improve the reactive inhibition of patients with PD. Our results provide theoretical support for the formulation of reasonable and effective exercise prescriptions for PD rehabilitation.

Clinical trial registration

[http://www.chictr.org.cn], identifier [ChiCTR2000038517].
A quantitative meta-analysis of vitamin C in the pathophysiology of Alzheimer’s disease
Authors: Hamid Maryam , Mansoor Sumaiya , Amber Sanila , Zahid Saadia
Published: September 2022

Purpose

Alzheimer’s disease (AD) is a multifaceted neurodegenerative disorder with many complex pathways feeding into its pathogenesis and progression. Vitamin C, an essential dietary antioxidant, is vital for proper neurological development and maintenance. This meta-analysis and systematic review attempted to define the relationship between vitamin C plasma levels and AD while highlighting the importance and involvement of vitamin C in the pathogenesis of AD.

Materials and methods

PRISMA guidelines were used to obtain studies quantifying the plasma levels of vitamin C in AD and control subjects. The literature was searched in the online databases PubMed, Google Scholar, and Web of Science. A total of 12 studies were included (n = 1,100) and analyzed using Comprehensive Meta-Analysis 3.0.

Results

The results show that there is a significant decrease in the plasma vitamin C levels of AD patients as compared to healthy controls (pooled SMD with random-effect model: −1.164, with 95%CI: −1.720 to −0.608, Z = −4.102, p = 0.00) with significant heterogeneity (I2 = 93.218). The sensitivity analysis showed directionally similar results. Egger’s regression test (p = 0.11) and visual inspection of the funnel plot showed no publication bias.

Conclusion

Based on these studies, it can be deduced that the deficiency of vitamin C is involved in disease progression and supplementation is a plausible preventive and treatment strategy. However, clinical studies are warranted to elucidate its exact mechanistic role in AD pathophysiology and prevention.
Alterations of structure and functional connectivity of visual brain network in patients with freezing of gait in Parkinson’s disease
Authors: Gan Lu , Yan Rui , Su Dongning , Liu Zhu , Miao Guozhen , Wang Zhan , Wang Xuemei , Ma Huizi , Bai Yutong , Zhou Junhong , Feng Tao
Published: September 2022

Freezing of gait (FOG) is a disabling gait disorder common in advanced stage of Parkinson’s disease (PD). The gait performance of PD-FOG patients is closely linked with visual processing. Here, we aimed to investigate the structural and functional change of visual network in PD-FOG patients. Seventy-eight PD patients (25 with FOG, 53 without FOG) and 29 healthy controls (HCs) were included. All the participants underwent structural 3D T1-weighted magnetic resonance imaging (MRI) and resting state functional MRI scan. Our results demonstrated a significant decrease of right superior occipital gyrus gray matter density in PD-FOG relative to non-FOG (NFOG) patients and healthy controls (PD-FOG vs. PD-NFOG: 0.33 ± 0.04 vs. 0.37 ± 0.05, p = 0.005; PD-FOG vs. HC: 0.37 ± 0.05 vs. 0.39 ± 0.06, p = 0.002). Functional MRI revealed a significant decrease of connectivity between right superior occipital gyrus and right paracentral lobule in PD-FOG compared to PD-NFOG (p = 0.045). In addition, the connectivity strength was positively correlated with gray matter density of right superior occipital gyrus (r = 0.471, p = 0.027) and negatively associated with freezing of gait questionnaire (FOGQ) score (r = -0.562, p = 0.004). Our study suggests that the structural and functional impairment of visual-motor network might underlie the neural mechanism of FOG in PD.
Research trends and hotspots of exercise for Alzheimer’s disease: A bibliometric analysis
Authors: Chen Binglin , Fu Yujie , Song Ge , Zhong Weiquan , Guo Jiabao
Published: September 2022

Objective

Alzheimer’s disease (AD) is a socially significant neurodegenerative disorder among the elderly worldwide. An increasing number of studies have revealed that as a non-pharmacological intervention, exercise can prevent and treat AD. However, information regarding the research status of this field remains minimal. Therefore, this study aimed to analyze trends and topics in exercise and AD research by using a bibliometric method.

Methods

We systematically searched the Web of Science Core Collection for published papers on exercise and AD. The retrieved data regarding institutions, journals, countries, authors, journal distribution, and keywords were analyzed using CiteSpace software. Meanwhile, the co-occurrence of keywords was constructed.

Results

A total of 1,104 papers were ultimately included in accordance with our specified inclusion criteria. The data showed that the number of published papers on exercise and AD is increasing each year, with papers published in 64 countries/regions and 396 academic journals. The Journal of Alzheimer’s Disease published the most papers (73 publications). Journals are concentrated in the fields of neuroscience and geriatrics gerontology. The University of Kansas and the United States are the major institution and country, respectively. The cited keywords show that oxidative stress, amyloid beta, and physical exercise are the research hotspots in recent years. After analysis, the neuroprotective effect of exercise was identified as the development trend in this field.

Conclusions

Based on a bibliometric analysis, the number of publications on exercise and AD has been increasing rapidly, especially in the past 10 years. “Amyloid beta,” “oxidative stress,” and “exercise program” trigger the most interest among researchers in this field. The study of exercise program and mechanism of exercise in AD is still the focus of future research.
A diagnosis model of dementia via machine learning
Authors: Zhao Ming , Li Jie , Xiang Liuqing , Zhang Zu-hai , Peng Sheng-Lung
Published: September 2022

As the aging population poses serious challenges to families and societies, the issue of dementia has also received increasing attention. Dementia detection often requires a series of complex tests and lengthy questionnaires, which are time-consuming. In order to solve this problem, this article aims at the diagnosis method of questionnaire survey, hoping to establish a diagnosis model to help doctors make a diagnosis through machine learning method, and use feature selection method to select important questions to reduce the number of questions in the questionnaire, so as to reduce medical and time costs. In this article, Clinical Dementia Rating (CDR) is used as the data source, and various methods are used for modeling and feature selection, so as to combine similar attributes in the data set, reduce the categories, and finally use the confusion matrix to judge the effect. The experimental results show that the model established by the bagging method has the best effect, and the accuracy rate can reach 80% of the true diagnosis rate; in terms of feature selection, the principal component analysis (PCA) has the best effect compared with other methods.
Aminoacyl transfer ribonucleic acid synthetase complex-interacting multifunctional protein 1 induces microglial activation and M1 polarization via the mitogen-activated protein kinase/nuclear factor-kappa B signaling pathway
Authors: Oh Yebin , Jung Hak-Jun , Hong Seungwon , Cho Yerim , Park Jiyeong , Cho Daeho , Kim Tae Sung
Published: September 2022

Activation of microglia, which is the primary immune cell of the central nervous system, plays an important role in neuroinflammation associated with several neuronal diseases. Aminoacyl tRNA synthetase (ARS) complex-interacting multifunctional protein 1 (AIMP1), a structural component of the multienzyme ARS complex, is secreted to trigger a pro-inflammatory function and has been associated with several inflammatory diseases. However, the effect of AIMP1 on microglial activation remains unknown. AIMP1 elevated the expression levels of activation-related cell surface markers and pro-inflammatory cytokines in primary and BV-2 microglial cells. In addition to the AIMP1-mediated increase in the expression levels of M1 markers [interleukin (IL)-6, tumor necrosis factor-α, and IL-1β], the expression levels of CD68, an M1 cell surface molecule, were also increased in AIMP-1-treated microglial cells, while those of CD206, an M2 cell surface molecule, were not, indicating that AIMP1 triggers the polarization of microglial cells into the M1 state but not the M2 state. AIMP1 treatment induced the phosphorylation of mitogen-activated protein kinases (MAPKs), while MAPK inhibitors suppressed the AIMP1-induced microglial cell activation. AIMP1 also induced the phosphorylation of the nuclear factor-kappa B (NF-κB) components and nuclear translocation of the NF-κB p65 subunit in microglial cells. Furthermore, c-Jun N-terminal kinase (JNK) and p38 inhibitors markedly suppressed the AIMP1-induced phosphorylation of NF-κB components as well as the nuclear translocation of NF-κB p65 subunit, suggesting the involvement of JNK and p38 as upstream regulators of NF-κB in AIMP1-induced microglial cell activation. The NF-κB inhibitor suppressed the AIMP1-induced M1 polarization of the microglial cells. Taken together, AIMP1 effectively induces M1 microglial activationviathe JNK and p38/NF-κB-dependent pathways. These results suggest that AIMP1 released under stress conditions may be a pathological factor that induces neuroinflammation.
Fighting for recovery on multiple fronts: The past, present, and future of clinical trials for spinal cord injury
Authors: Dietz Valerie A. , Roberts Nolan , Knox Katelyn , Moore Sherilynne , Pitonak Michael , Barr Chris , Centeno Jesus , Leininger Scott , New Kent C. , Nowell Peter , Rodreick Matthew , Geoffroy Cedric G. , Stampas Argyrios , Dulin Jennifer N.
Published: September 2022

Through many decades of preclinical research, great progress has been achieved in understanding the complex nature of spinal cord injury (SCI). Preclinical research efforts have guided and shaped clinical trials, which are growing in number by the year. Currently, 1,149 clinical trials focused on improving outcomes after SCI are registered in the U.S. National Library of Medicine at ClinicalTrials.gov. We conducted a systematic analysis of these SCI clinical trials, using publicly accessible data downloaded from ClinicalTrials.gov. After extracting all available data for these trials, we categorized each trial according to the types of interventions being tested and the types of outcomes assessed. We then evaluated clinical trial characteristics, both globally and by year, in order to understand the areas of growth and change over time. With regard to clinical trial attributes, we found that most trials have low enrollment, only test single interventions, and have limited numbers of primary outcomes. Some gaps in reporting are apparent; for instance, over 75% of clinical trials with “Completed” status do not have results posted, and the Phase of some trials is incorrectly classified as “Not applicable” despite testing a drug or biological compound. When analyzing trials based on types of interventions assessed, we identified the largest representation in trials testing rehab/training/exercise, neuromodulation, and behavioral modifications. Most highly represented primary outcomes include motor function of the upper and lower extremities, safety, and pain. The most highly represented secondary outcomes include quality of life and pain. Over the past 15 years, we identified increased representation of neuromodulation and rehabilitation trials, and decreased representation of drug trials. Overall, the number of new clinical trials initiated each year continues to grow, signifying a hopeful future for the clinical treatment of SCI. Together, our work provides a comprehensive glimpse into the past, present, and future of SCI clinical trials, and suggests areas for improvement in clinical trial reporting.
Forebrain epileptiform activity is not required for seizure-induced apnea in a mouse model of Scn8a epilepsy
Authors: Wenker Ian C. , Boscia Alexis R. , Lewis Christine , Tariq Anas , Miralles Raquel , Hanflink Jessica C. , Saraf Priyanka , Patel Manoj K.
Published: September 2022

Sudden unexpected death in epilepsy (SUDEP) accounts for the deaths of 8–17% of patients with epilepsy. Although the mechanisms of SUDEP are essentially unknown, one proposed mechanism is respiratory arrest initiated by a convulsive seizure. In mice, we have previously observed that extended apnea occurs during the tonic phase of seizures. Although often survived, tonic seizures became fatal when breathing did not immediately recover postictally. We also found that respiratory muscles were tonically contracted during the apnea, suggesting that muscle contraction could be the cause of apnea. In the present study, we tested the hypothesis that pyramidal neurons of the motor cortex drive motor units during the tonic phase, which produces apnea. Mice harboring the patient-derived N1768D point mutation of an Scn8a allele were crossed with transgenic mice such that inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADD) receptors were selectively expressed in excitatory forebrain neurons. We then triggered audiogenic and hippocampal (HC) stimulated seizures under control conditions and when excitatory forebrain neurons were inhibited with the synthetic ligand Clozapine-N-Oxide (CNO). We found that inhibition with CNO was sufficient to increase seizure threshold of HC stimulated, but not audiogenic, seizures. In addition, regardless of seizure type, CNO nearly eliminated epileptiform activity that occurred proximal to the tonic phase; however, the seizure behaviors, notably the tonic phase and concomitant apnea, were unchanged. We interpret these results to indicate that while cortical neurons are likely critical for epileptogenesis and seizure initiation, the behavioral manifestations of tonic seizures are generated by neural circuitry in the mid- and/or hindbrain.
Compensatory mechanism of attention-deficit/hyperactivity disorder recovery in resting state alpha rhythms
Authors: Han Chuanliang , Wang Tian , Wu Yujie , Li Hui , Wang Encong , Zhao Xixi , Cao Qingjiu , Qian Qiujin , Wang Yufeng , Dou Fei , Liu Jian K. , Sun Li , Xing Dajun
Published: September 2022

Alpha rhythms in the human electroencephalogram (EEG), oscillating at 8-13 Hz, are located in parieto-occipital cortex and are strongest when awake people close their eyes. It has been suggested that alpha rhythms were related to attention-related functions and mental disorders (e.g., Attention-deficit/hyperactivity disorder (ADHD)). However, many studies have shown inconsistent results on the difference in alpha oscillation between ADHD and control groups. Hence it is essential to verify this difference. In this study, a dataset of EEG recording (128 channel EGI) from 87 healthy controls (HC) and 162 ADHD (141 persisters and 21 remitters) adults in a resting state with their eyes closed was used to address this question and a three-gauss model (summation of baseline and alpha components) was conducted to fit the data. To our surprise, the power of alpha components was not a significant difference among the three groups. Instead, the baseline power of remission and HC group in the alpha band is significantly stronger than that of persister groups. Our results suggest that ADHD recovery may have compensatory mechanisms and many abnormalities in EEG may be due to the influence of behavior rather than the difference in brain signals.
Physical exercise and mitochondrial function: New therapeutic interventions for psychiatric and neurodegenerative disorders
Authors: Sun Lina , Liu Tianbiao , Liu Jingqi , Gao Chong , Zhang Xiaohui
Published: September 2022

Psychiatric and neurodegenerative diseases, including major depression disorder (MDD), bipolar disorder, and Alzheimer's disease, are a burden to society. Deficits of adult hippocampal neurogenesis (AHN) have been widely considered the main hallmark of psychiatric diseases as well as neurodegeneration. Herein, exploring applicable targets for improving hippocampal neural plasticity could provide a breakthrough for the development of new treatments. Emerging evidence indicates the broad functions of mitochondria in regulating cellular behaviors of neural stem cells, neural progenitors, and mature neurons in adulthood could offer multiple neural plasticities for behavioral modulation. Normalizing mitochondrial functions could be a new direction for neural plasticity enhancement. Exercise, a highly encouraged integrative method for preventing disease, has been indicated to be an effective pathway to improving both mitochondrial functions and AHN. Herein, the relative mechanisms of mitochondria in regulating neurogenesis and its effects in linking the effects of exercise to neurological diseases requires a systematic summary. In this review, we have assessed the relationship between mitochondrial functions and AHN to see whether mitochondria can be potential targets for treating neurological diseases. Moreover, as for one of well-established alternative therapeutic approaches, we summarized the evidence to show the underlying mechanisms of exercise to improve mitochondrial functions and AHN.
Transcranial direct current stimulation for gait recovery following stroke: A systematic review of current literature and beyond
Authors: Corominas-Teruel Xavier , Mozo Rosa María San Segundo , Simó Montserrat Fibla , Colomina Fosch Maria Teresa , Valero-Cabré Antoni
Published: September 2022

Background

Over the last decade, transcranial direct current stimulation (tDCS) has set promise contributing to post-stroke gait rehabilitation. Even so, results are still inconsistent due to low sample size, heterogeneity of samples, and tDCS design differences preventing comparability. Nonetheless, updated knowledge in post-stroke neurophysiology and stimulation technologies opens up opportunities to massively improve treatments.

Objective

The current systematic review aims to summarize the current state-of-the-art on the effects of tDCS applied to stroke subjects for gait rehabilitation, discuss tDCS strategies factoring individual subject profiles, and highlight new promising strategies.

Methods

MEDLINE, SCOPUS, CENTRAL, and CINAHL were searched for stroke randomized clinical trials using tDCS for the recovery of gait before 7 February 2022. In order to provide statistical support to the current review, we analyzed the achieved effect sizes and performed statistical comparisons.

Results

A total of 24 records were finally included in our review, totaling n = 651 subjects. Detailed analyses revealed n = 4 (17%) studies with large effect sizes (≥0.8), n = 6 (25%) studies with medium ones (≥0.5), and n = 6 (25%) studies yielding low effects sizes (≤ 0.2). Statistically significant negative correlations (rho = −0.65, p = 0.04) and differences (p = 0.03) argued in favor of tDCS interventions in the sub-acute phase. Finally, significant differences (p = 0.03) were argued in favor of a bifocal stimulation montage (anodal M1 ipsilesional and cathodal M1 contralesional) with respect to anodal ipsilesional M1.

Conclusion

Our systematic review highlights the potential of tDCS to contribute to gait recovery following stroke, although also the urgent need to improve current stimulation strategies and subject-customized interventions considering stroke severity, type or time-course, and the use of network-based multifocal stimulation approaches guided by computational biophysical modeling.

Systematic review registration

PROSPERO: CRD42021256347.
Contrast reversal of the iris and sclera increases the face sensitive N170
Authors: Jantzen Kelly J. , McNamara Nicole , Harris Adam , Schubert Anna , Brooks Michael , Seifert Matthew , Symons Lawrence A.
Published: September 2022

Previous research has demonstrated that reversing the contrast of the eye region, which includes the eyebrows, affects the N170 ERP. To selectively assess the impact of just the eyes, the present study evaluated the N170 in response to reversing contrast polarity of just the iris and sclera in upright and inverted face stimuli. Contrast reversal of the eyes increased the amplitude of the N170 for upright faces, but not for inverted faces, suggesting that the contrast of eyes is an important contributor to the N170 ERP.