bluuebunny/crossref_metadata_2025 huggingface dataset:
Innovative Tele-Instruction Approach Impacts Basic Life Support Performance: A Non-inferiority Trial
Authors: Schauwinhold Michael Tobias , Schmidt Michelle , Rudolph Jenny W. , Klasen Martin , Lambert Sophie Isabelle , Krusch Alexander , Vogt Lina , Sopka Saša
Published: May 2022

Background

Sustaining Basic Life Support (BLS) training during the COVID-19 pandemic bears substantial challenges. The limited availability of highly qualified instructors and tight economic conditions complicates the delivery of these life-saving trainings. Consequently, innovative and resource-efficient approaches are needed to minimize or eliminate contagion while maintaining high training standards and managing learner anxiety related to infection risk.

Methods

In a non-inferiority trial 346 first-year medical, dentistry, and physiotherapy students underwent BLS training at AIXTRA—Competence Center for Training and Patient Safety at the University Hospital RWTH Aachen. Our objectives were (1) to examine whether peer feedback BLS training supported by tele-instructors matches the learning performance of standard instructor-guided BLS training for laypersons; and (2) to minimize infection risk during BLS training. Therefore, in a parallel group design, we compared arm (1) Standard Instructor Feedback (SIF) BLS training (Historical control group of 2019) with arm (2) a Tele-Instructor Supported Peer-Feedback (TPF) BLS training (Intervention group of 2020). Both study arms were based on Peyton's 4-step approach. Before and after each training session, objective data for BLS performance (compression depth and rate) were recorded using a resuscitation manikin. We also assessed overall BLS performance via standardized instructor evaluation and student self-reports of confidence via questionnaire. Non-inferiority margins for the outcome parameters and sample size calculation were based on previous studies with SIF. Two-sided 95% confidence intervals were employed to determine significance of non-inferiority.

Results

The results confirmed non-inferiority of TPF to SIF for all tested outcome parameters. A follow-up after 2 weeks found no confirmed COVID-19 infections among the participants.

Conclusion

Tele-instructor supported peer feedback is a powerful alternative to in-person instructor feedback on BLS skills during a pandemic, where infection risk needs to be minimized while maximizing the quality of BLS skill learning.

Trial registration

https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00025199, Trial ID: DRKS00025199.
Harnessing PM2.5 Exposure Data to Predict Progression of Fibrotic Interstitial Lung Diseases Based on Telomere Length
Authors: Shull Jessica Germaine , Planas-Cerezales Lurdes , Lara Compte Carla , Perona Rosario , Molina-Molina Maria
Published: May 2022

Cross-analysis of clinical and pollution factors could help calculate the risk of fibrotic interstitial lung disease (ILD) development and progression. The intent of this study is to build a body of knowledge around early detection and diagnosis of lung disease, harnessing new data sets generated for other purposes. We cross-referenced exposure levels to particulate matter 2.5 (PM2.5) with telomere length of a cohort of 280 patients with fibrotic ILD to weigh impact and associations. There was no linear correlation between PM2.5 and telomere length in our data sets, as the value of the correlation coefficient was 0.08. This exploratory study offers additional insights into methodologies for investigating the development and prognosis of pulmonary fibrosis.
Association Between Hair Diseases and COVID-19 Pandemic-Related Stress: A Cross-Sectional Study Analysis
Authors: Mahadi Ashrafur Rahaman , Rafi Md. Abdur , Shahriar Tasnim , Seemanta Senjuti , Rabbani Md. Golam , Akter Munjarin , Majumder Mahabubul Islam , Hasan M. Tasdik
Published: May 2022

Introduction:

Psychological stress from the ongoing coronavirus disease 2019 (COVID-19) pandemic can potentially aggravate the course of several stress-sensitive skin and hair diseases. This study aimed to determine the potential association of COVID-19 stress with hair diseases, such as telogen effluvium (TE), alopecia areata (AA), and seborrheic dermatitis (SD), among medical students in Bangladesh.

Methods

This online-based cross-sectional study was conducted among 404 medical students of Bangladesh using a self-administered questionnaire, including sociodemographic information, status of hair diseases (i.e., TE, AA, and SD), COVID-19 fear scale, impact of event scale specific for COVID-19 (IES-COVID-19), and COVID-19 student stress questionnaire (CSSQ) scale, to determine pandemic-related stress. The logistic regression model was used to analyze the association.

Results

Overall prevalence of TE, AA, and SD was 61.1, 24.7, and 57.7%, respectively, with female predominance in case of TE and male predominance in case of AA and SD. More than half of the participants had COVID-19-related fear and traumatic stress symptoms. In the multiple logistic regression model, smoking [adjusted odds ratio (aOR) 2.93, 95% CI 1.29–6.65 for AA and aOR 4.19, 95% CI 1.83–9.56 for TE], COVID-19-related fear (aOR 1.70, 95% CI 1.01–2.89 for AA and aOR 2.620, 95% CI 1.25–5.48 for TE), and COVID-19-related traumatic stress symptoms (aOR 1.84, 95% CI 1.08–3.13 for AA, aOR 2.61, 95% CI 1.19–5.68 for TE, and aOR 1.92, 95% CI 1.14–3.25 for SD) were the risk factors of hair fall disorders.

Conclusion

Our study showed that a large number of medical students experienced TE, AA, and SD during the pandemic era. COVID-19-related stress and fear potentially have an association with these diseases.
Religiosity/Spirituality and Mental Health in Older Adults: A Systematic Review and Meta-Analysis of Observational Studies
Authors: Coelho-Júnior Hélio José , Calvani Riccardo , Panza Francesco , Allegri Riccardo F. , Picca Anna , Marzetti Emanuele , Alves Vicente Paulo
Published: May 2022

Objectives

The present study investigated the association between religious and spiritual (RS) practices with the prevalence, severity, and incidence of mental health problems in older adults.

Methods

We conducted a systematic review and meta-analysis of cross-sectional and longitudinal studies that investigated older adults aged 60+ years and assessed RS using valid scales and questions from valid scales, and mental health according to validated multidimensional or specific instruments. Studies were retrieved from MEDLINE, LILACS, SCOPUS, CINAHL, and AgeLine databases until July 31, 2021. The risk of bias was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS). A pooled effect size was calculated based on the log odds ratio (OR) and Z-scores. This study is registered on PROSPERO.

Results

One hundred and two studies that investigated 79.918 community-dwellers, hospitalized, and institutionalized older adults were included. Results indicated that high RS was negatively associated with anxiety and depressive symptoms, while a positive association was observed with life satisfaction, meaning in life, social relations, and psychological well-being. Specifically, people with high spirituality, intrinsic religiosity, and religious affiliation had a lower prevalence of depressive symptoms. In relation to longitudinal analysis, most studies supported that high RS levels were associated with a lower incidence of depressive symptoms and fear of death, as well as better mental health status.

Conclusion

Findings of the present study suggest that RS are significantly associated with mental health in older adults. People with high RS levels had a lower prevalence of anxiety and depressive symptoms, as well as reported greater life satisfaction and psychological well-being, better social relations, and more definite meaning in life. Data provided by an increasing number of longitudinal studies have supported most of these findings.
Prevalence of Tobacco Smoking and Its Association With Disease Severity Among Patients With Psoriasis in China: A Cross-Sectional Study
Authors: Wei Lei , Chen Siting , Zhang Zhan , Kuai Le , Zhang Rui , Yu Ning , Shi Yuling , Li Bin , Wang Ruiping
Published: May 2022

Introduction

Tobacco smoking is associated with the onset and severity of psoriasis, and understanding the prevalence of tobacco smoking among patients with psoriasis is critical due to its high physical and mental influence and heavy disease burden. However, evidence on the association between tobacco smoking and psoriasis severity is still limited in China.

Objectives

The objective of this study was to examine the prevalence of tobacco smoking and explore the association between tobacco smoking and diseases severity among patients with psoriasis.

Methods

A total of 4,529 patients with psoriasis in 200 selected hospitals were recruited in China between January 2020 and September 2021. Detailed information covering demographic feature, tobacco smoking, and psoriasis history were collected through an electronic questionnaire, and clinical data were extracted from the health information system (HIS). SAS 9.4 was used for data analysis, and a p-value of <0.05 was considered statistically significant.

Results

The prevalence of tobacco smoking was 30.8%, with 24.6% for current smoking. The average Psoriasis Area and Severity Index (PASI) score for patients with psoriasis was 9.4, with male patients having a higher PASI score than female patients. The odds ratio (OR) of former tobacco smoking prevalence was 1.5 [95% confidence interval (CI): (1.0–2.3)] for PASI score (3.0–7.0), 2.2 for PASI score (7.1–13.0), and 4.2 for PASI score >13, when compared with patients with PASI score < 3.0. Similarly, the OR of current tobacco smoking prevalence was 1.8 [95% CI: (1.5–2.2)] for PASI score (3.0–7.0), 1.9 for PASI score (7.1–13.0), and 3.1 for PASI score >13, when compared with patients with PASI score <3.0. The Spearman correlation analysis indicated that both tobacco smoking intensity and smoking duration were positively correlated with psoriasis severity (p < 0.05).

Conclusion

The prevalence of tobacco smoking was high, especially among male patients with psoriasis and those with senior high education. Tobacco smoking was positively associated with psoriasis severity; moreover, both smoking intensity and smoking duration were positively correlated with the severity of psoriasis in a dose-dependent fashion.
Indigenous Non-Saccharomyces Yeasts With β-Glucosidase Activity in Sequential Fermentation With Saccharomyces cerevisiae: A Strategy to Improve the Volatile Composition and Sensory Characteristics of Wines
Authors: Gao Pingping , Peng Shuai , Sam Faisal Eudes , Zhu Yatong , Liang Lihong , Li Min , Wang Jing
Published: May 2022

Non-Saccharomyces (NS) yeasts with high β-glucosidase activity play a vital role in improving the aroma complexity of wines by releasing aroma compounds from glycosidic precursors during fermentation. In this study, the effect of sequential inoculation fermentation of Meyerozyma guilliermondii NM218 and Hanseniaspora uvarum BF345 with two Saccharomyces cerevisiae strains [Vintage Red™ (VR) and Aroma White™ (AW)] on volatile compounds and sensory characteristics of wines was investigated. Prior to winemaking trials, the sequential inoculation times of the two NS yeasts were evaluated in synthetic must, based on changes in strain population and enzyme activity. The intervals for inoculation of NM218 and BF345 with the S. cerevisiae strains were 48 and 24 h, respectively. In the main experiment, sequential inoculation fermentations of the two strains with S. cerevisiae were carried out in Cabernet Sauvignon (CS) and Chardonnay (CH) grape must. The oenological parameters, volatile composition, and sensory characteristics of the final wines were assessed. No clear differences were observed in the oenological parameters of the sequentially fermented CH wines compared with the control, except for residual sugar and alcohol. However, in CS wines, the total acid contents were significantly lower in the wines fermented by sequential inoculation compared to the control. Both NM218 and BF345 improved the aroma complexity of wines by increasing esters and terpenes when inoculated with S. cerevisiae strains compared to inoculation with S. cerevisiae strains alone. NM218 resulted in a more positive effect on CS wine aroma, with higher levels of citronellol and trans-nerolidol. BF345 significantly enhanced the floral and fruity aromas of CH wine by producing higher concentrations of geranyl acetone, β-damascenone, trans-nerolidol, and nerol. Both NM218 and BF345 yeasts could potentially be used to improve wine aroma and overall quality, especially wine floral and fruity aromas, when used in sequential inoculation with S. cerevisiae.
Regulating Root Fungal Community Using Mortierella alpina for Fusarium oxysporum Resistance in Panax ginseng
Authors: Wang Yan , Wang Liwei , Suo Meng , Qiu Zhijie , Wu Hao , Zhao Min , Yang Hongyan
Published: May 2022

Plant-associated microbes play important roles in plant health and disease. Mortierella is often found in the plant rhizosphere, and its possible functions are not well known, especially in medical plants. Mortierella alpina isolated from ginseng soil was used to investigate its effects on plant disease. The promoting properties and interactions with rhizospheric microorganisms were investigated in a medium. Further, a pot experiment was conducted to explore its effects on ginseng root rot disease. Physicochemical properties, high-throughput sequencing, network co-occurrence, distance-based redundancy analysis (db-RDA), and correlation analysis were used to evaluate their effects on the root rot pathogen. The results showed that Mortierella alpina YW25 had a high indoleacetic acid production capacity, and the maximum yield was 141.37 mg/L at 4 days. The growth of M. alpina YW25 was inhibited by some probiotics (Bacillus, Streptomyces, Brevibacterium, Trichoderma, etc.) and potential pathogens (Cladosporium, Aspergillus, etc.), but it did not show sensitivity to the soil-borne pathogen Fusarium oxysporum. Pot experiments showed that M. alpina could significantly alleviate the diseases caused by F. oxysporum, and increased the available nitrogen and phosphorus content in rhizosphere soil. In addition, it enhanced the activities of soil sucrase and acid phosphatase. High-throughput results showed that the inoculation of M. alpina with F. oxysporum changed the microbial community structure of ginseng, stimulated the plant to recruit more plant growth-promoting bacteria, and constructed a more stable microbial network of ginseng root. In this study, we found and proved the potential of M. alpina as a biocontrol agent against F. oxysporum, providing a new idea for controlling soil-borne diseases of ginseng by regulating rhizosphere microorganisms.
Endophytism: A Multidimensional Approach to Plant–Prokaryotic Microbe Interaction
Authors: Rani Simran , Kumar Pradeep , Dahiya Priyanka , Maheshwari Rajat , Dang Amita Suneja , Suneja Pooja
Published: May 2022

Plant growth and development are positively regulated by the endophytic microbiome via both direct and indirect perspectives. Endophytes use phytohormone production to promote plant health along with other added benefits such as nutrient acquisition, nitrogen fixation, and survival under abiotic and biotic stress conditions. The ability of endophytes to penetrate the plant tissues, reside and interact with the host in multiple ways makes them unique. The common assumption that these endophytes interact with plants in a similar manner as the rhizospheric bacteria is a deterring factor to go deeper into their study, and more focus was on symbiotic associations and plant–pathogen reactions. The current focus has shifted on the complexity of relationships between host plants and their endophytic counterparts. It would be gripping to inspect how endophytes influence host gene expression and can be utilized to climb the ladder of “Sustainable agriculture.” Advancements in various molecular techniques have provided an impetus to elucidate the complexity of endophytic microbiome. The present review is focused on canvassing different aspects concerned with the multidimensional interaction of endophytes with plants along with their application.
Intercropping Pinto Peanut in Litchi Orchard Effectively Improved Soil Available Potassium Content, Optimized Soil Bacterial Community Structure, and Advanced Bacterial Community Diversity
Authors: Zhao Ya , Yan Caibin , Hu Fuchu , Luo Zhiwen , Zhang Shiqing , Xiao Min , Chen Zhe , Fan Hongyan
Published: May 2022

Intercropping is widely used in agricultural production due to its capability of raising land productivity and providing an opportunity to achieve sustainable intensification of agriculture. In this study, soil samples from 10 to 20 cm depth of intercropping Pinto peanut in litchi orchard and litchi monoculture mode were established to determine soil attributes, enzyme activities, as well as the effect on soil bacterial diversity. On this basis, 16S rRNA V4-V5 region of soil bacterial communities in litchi/Pinto peanut intercropping (LP) mode and litchi monoculture mode (CK) was detected by the Illumina MiSeq sequencing platform. The results showed that the content of available potassium (AK) in LP was significantly higher than that in CK by 138.9%, and the content of available nitrogen (AN) in LP was significantly lower than that in CK by 19.6%. The soil enzyme activities were higher in LP as a whole, especially sucrase (SC) and acid protease (PT) were significantly higher by 154.4 and 76.5%, respectively. The absolute abundance and alpha diversity of soil microbiota were significantly higher in the intercropping group. Most importantly, endemic species with a significant difference in LP was higher by ~60 times compared to CK treatment. In the aspect of soil bacterial community structure, the dominant phyla of the two groups were Acidobacteria, Proteobacteria, Chloroflexi, and Actinobacteria. At the genus level, the absolute abundance of Flavobacterium and Nitrososphaera was significantly higher by 79.20 and 72.93%, respectively, while that of Candidatus_Koribacter was significantly lower with an amplitude of 62.24% in LP than in CK. Furthermore, the redundancy analysis (RDA) suggested that AK, which was highly associated with the dominant genera and phyla, is the vitally dominating environmental factors in LP groups, while in CK groups, it is AN and pH. In addition, PICRUSt2 analysis indicated that intercropping improved the metabolic activity of bacteria which can be correlated to the resistance of litchi root systems to soil-borne diseases. Overall, this study is expected to provide a theoretical basis and technical support for the healthy intercropping cultivation of litchi.
Evolutionary Dynamics of Begomoviruses and Its Satellites Infecting Papaya in India
Authors: Srivastava Aarshi , Pandey Vineeta , Sahu Anurag Kumar , Yadav Dinesh , Al-Sadi Abdullah M. , Shahid Muhammad Shafiq , Gaur R. K.
Published: May 2022

The genus Begomovirus represents a group of multipartite viruses that significantly damage many agricultural crops, including papaya, and influence overall production. Papaya leaf curl disease (PaLCD) caused by the complex begomovirus species has several important implications and substantial losses in papaya production in many developing countries, including India. The increase in the number of begomovirus species poses a continuous threat to the overall production of papaya. Here, we attempted to map the genomic variation, mutation, evolution rate, and recombination to know the disease complexity and successful adaptation of PaLCD in India. For this, we retrieved 44 DNA-A and 26 betasatellite sequences from GenBank reported from India. An uneven distribution of evolutionary divergence has been observed using the maximum-likelihood algorithm across the branch length. Although there were phylogenetic differences, we found high rates of nucleotide substitution mutation in both viral and sub-viral genome datasets. We demonstrated frequent recombination of begomovirus species, with a maximum in intra-species recombinants. Furthermore, our results showed a high degree of genetic variability, demographic selection, and mean substitution rate acting on the population, supporting the emergence of a diverse and purifying selection of viruses and associated betasatellites. Moreover, variation in the genetic composition of all begomovirus datasets revealed a predominance of nucleotide diversity principally driven by mutation, which might further accelerate the advent of new strains and species and their adaption to various hosts with unique pathogenicity. Therefore, the finding of genetic variation and selection emphases on factors that contribute to the universal spread and evolution of Begomovirus and this unanticipated diversity may also provide guidelines toward future evolutionary trend analyses and the development of wide-ranging disease control strategies for begomoviruses associated with PaLCD.
Subchronic Toxicity of Microcystin-LR on Young Frogs (Xenopus laevis) and Their Gut Microbiota
Authors: Li Jinjin , Sun Hongzhao , Wang Chun , Li Shangchun , Cai Yunfei
Published: May 2022

Although toxic effects of microcystins (MCs) in mammals and fish have been extensively studied, the effects of MCs on the immune system and gut microbiota of amphibians have not received sufficient attention. As MCs cause general damage to the vertebrate liver and immune system and trigger an inflammatory response, and the gut microbiota is closely related to host metabolism and immunity, we speculated that MCs can cause changes in the immune system and gut microbiota of amphibians. To verify this, we examined the intestinal and liver injury of Xenopus laevis exposed to different microcystin-leucine-arginine (MC-LR) concentrations and the effects on the gut microbiota through high-throughput sequencing of 16S rDNA of the gut microbiota combined with histopathological analysis, enzyme activity determination, and qRT-PCR. Our results showed that MC-LR caused focal infiltration of inflammatory cells and increased the number of T cells and local congestion and vacuolization in X. laevis liver, but reduced the number, density, height, and regularity of villi. These liver and intestinal injuries became more obvious with an increase in MC-LR concentration. MC-LR significantly decreased the activities of malondialdehyde and alkaline phosphatase and the expression of TGF-β in the liver. Moreover, MC-LR significantly altered the gut microbiota of X. laevis. The relative abundance of Firmicutes and Bacteroidetes in high-concentration MC-LR groups was significantly reduced compared to that in low-concentration MC-LR groups, whereas Fusobacteria was significantly enriched. The metabolic gene composition of the gut microbiota in low-concentration MC-LR (≤5 μg/L) groups was significantly different from that in high-concentration MC-LR (≥20 μg/L) groups. These results deepen our understanding of the toxicity of MCs to aquatic organisms and assessment of the ecological risk of MCs in amphibians.
Characterization of Deltacoronavirus in Black-Headed Gulls (Chroicocephalus ridibundus) in South China Indicating Frequent Interspecies Transmission of the Virus in Birds
Authors: Chu Kan-Kan , Zhou Zhi-Jian , Wang Qiong , Ye Sheng-Bao , Guo Ling , Qiu Ye , Zhang Yun-Zhi , Ge Xing-Yi
Published: May 2022

Deltacoronavirus (DCoV) is a genus of coronavirus (CoV) commonly found in avian and swine, but some DCoVs are capable of infecting humans, which causes the concern about interspecies transmission of DCoVs. Thus, monitoring the existence of DCoVs in animals near communities is of great importance for epidemic prevention. Black-headed gulls (Chroicocephalus ridibundus) are common migratory birds inhabiting in most urban and rural wetlands of Yunnan Province, China, which is a typical habitat for black-headed gulls to overwinter. Whether Yunnan black-headed gulls carry CoV has never been determined. In this study, we identified three strains of DCoVs in fecal samples of Yunnan black-headed gulls by reverse-transcriptional PCR and sequenced their whole genomes. Genomic analysis revealed that these three strains shared genomic identity of more than 99%, thus named DCoV HNU4-1, HNU4-2, and HNU4-3; their NSP12 showed high similarity of amino acid sequence to the homologs of falcon coronavirus UAE-HKU27 (HKU27), houbara coronavirus UAE-HKU28 (HKU28), and pigeon coronavirus UAE-HKU29 (HKU29). Since both HKU28 and HKU29 were found in Dubai, there might be cross-border transmission of these avian DCoVs through specific routes. Further coevolutionary analysis supported this speculation that HNU4 (or its ancestors) in black-headed gulls originated from HKU28 (or its homologous strain) in houbara, which was interspecies transmission between two different avian orders. In addition, interspecies transmission of DCoV, from houbara to falcon, pigeon and white-eye, from sparrow to common-magpie, and quail and mammal including porcine and Asian leopard cat, from munia to magpie-robin, was predicted. This is the first report of black-headed gull DCoV in Asia which was highly homolog to other avian DCoVs, and the very “active” host-switching events in DCoV were predicted, which provides important reference for the study of spread and transmission of DCoVs.
Minimal Yet Powerful: The Role of Archaeal Small Heat Shock Proteins in Maintaining Protein Homeostasis
Authors: Roy Mousam , Bhakta Koustav , Ghosh Abhrajyoti
Published: May 2022

Small heat shock proteins (sHsp) are a ubiquitous group of ATP-independent chaperones found in all three domains of life. Although sHsps in bacteria and eukaryotes have been studied extensively, little information was available on their archaeal homologs until recently. Interestingly, archaeal heat shock machinery is strikingly simplified, offering a minimal repertoire of heat shock proteins to mitigate heat stress. sHsps play a crucial role in preventing protein aggregation and holding unfolded protein substrates in a folding-competent form. Besides protein aggregation protection, archaeal sHsps have been shown recently to stabilize membranes and contribute to transferring captured substrate proteins to chaperonin for refolding. Furthermore, recent studies on archaeal sHsps have shown that environment-induced oligomeric plasticity plays a crucial role in maintaining their functional form. Despite being prokaryotes, the archaeal heat shock protein repository shares several features with its highly sophisticated eukaryotic counterpart. The minimal nature of the archaeal heat shock protein repository offers ample scope to explore the function and regulation of heat shock protein(s) to shed light on their evolution. Moreover, similar structural dynamics of archaeal and human sHsps have made the former an excellent system to study different chaperonopathies since archaeal sHsps are more stable under in vitro experiments.
Circulating Tumor DNA in Pediatric Cancer
Authors: Doculara Louise , Trahair Toby N. , Bayat Narges , Lock Richard B.
Published: May 2022

The measurement of circulating tumor DNA (ctDNA) has gained increasing prominence as a minimally invasive tool for the detection of cancer-specific markers in plasma. In adult cancers, ctDNA detection has shown value for disease-monitoring applications including tumor mutation profiling, risk stratification, relapse prediction, and treatment response evaluation. To date, there are ctDNA tests used as companion diagnostics for adult cancers and it is not understood why the same cannot be said about childhood cancer, despite the marked differences between adult and pediatric oncology. In this review, we discuss the current understanding of ctDNA as a disease monitoring biomarker in the context of pediatric malignancies, including the challenges associated with ctDNA detection in liquid biopsies. The data and conclusions from pediatric cancer studies of ctDNA are summarized, highlighting treatment response, disease monitoring and the detection of subclonal disease as applications of ctDNA. While the data from retrospective studies highlight the potential of ctDNA, large clinical trials are required for ctDNA analysis for routine clinical use in pediatric cancers. We outline the requirements for the standardization of ctDNA detection in pediatric cancers, including sample handling and reproducibility of results. With better understanding of the advantages and limitations of ctDNA and improved detection methods, ctDNA analysis may become the standard of care for patient monitoring in childhood cancers.
Lewy Body-Associated Proteins A-Synuclein (a-syn) as a Plasma-Based Biomarker for Parkinson’s Disease
Authors: Zhao Xuemiao , He Haijun , Xiong Xi , Ye Qianqian , Feng Feifei , Zhou Shuoting , Chen Weian , Xia Kai , Qian Shuangjie , Yang Yunjun , Xie Chenglong
Published: May 2022

Introduction

To explore the combined diagnostic value of plasma Lewy body-associated proteins (p-Asyn at ser129, total α-syn, and oligomeric α-syn) for the diagnosis of PD versus healthy controls (HCs) and other PD syndromes (PDs), as well as clinical characteristics prediction.

Methods

This study included 145 participants: 79 patients with PD, 24 patients with PDs, and 42 HCs. A panel of plasma levels of p-Asyn, total α-syn, and oligomeric α-syn was measured by enzyme-linked immunosorbent assay (ELISA). The primary outcome was the discriminative accuracy of the combined three plasma biomarkers for PD.

Results

The mean age was 65.43 (SD, 7.467) in the control group, 64.49 (SD, 8.224) in participants with PD, and 69.25 (SD, 7.952) in PDs. The plasma Lewy body-associated protein levels were significantly higher in patients with PD than in age-matched HCs, However, there was no difference in patients with PD and PDs. Of note, a combination of plasma p-Asyn, total α-syn, and oligomeric α-syn was a better biomarker for discriminating PD from HCs, with an AUC of 0.8552 (p < 0.0001, 95%CI, 0.7635–0.9409), which was significantly higher than plasma p-Asyn (ΔAUC, 0.1797), total α-syn (ΔAUC, 0.0891) and oligomeric α-syn (ΔAUC, 0.1592) alone. Meanwhile, Lewy body-associated proteins had no connections between different motor stages and dementia performances.

Conclusion

Our results suggested that plasma Lewy body-associated proteins, may serve as a non-invasive biomarker to aid the diagnosis of PD from HCs. In addition, increased plasma Lewy body-associated proteins were not associated with the progression of motor and non-motor symptoms.
A Diagnostic Model for Alzheimer’s Disease Based on Blood Levels of Autophagy-Related Genes
Authors: Qin Qiangqiang , Gu Zhanfeng , Li Fei , Pan Yanbing , Zhang TianXiang , Fang Yang , Zhang Lesha
Published: May 2022

Alzheimer’s disease (AD) is a common neurodegenerative disease. The major problems that exist in the diagnosis of AD include the costly examinations and the high-invasive sampling tissue. Therefore, it would be advantageous to develop blood biomarkers. Because AD’s pathological process is considered tightly related to autophagy; thus, a diagnostic model for AD based on ATGs may have more predictive accuracy than other models. We obtained GSE63060 dataset from the GEO database, ATGs from the HADb and screened 64 differentially expressed autophagy-related genes (DE-ATGs). We then applied them to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses as well as DisGeNET and PaGenBase enrichment analyses. By using the univariate analysis, least absolute shrinkage and selection operator (LASSO) regression method and the multivariable logistic regression, nine DE-ATGs were identified as biomarkers, which are ATG16L2, BAK1, CAPN10, CASP1, RAB24, RGS19, RPS6KB1, ULK2, and WDFY3. We combined them with sex and age to establish a nomogram model. To evaluate the model’s distinguishability, consistency, and clinical applicability, we applied the receiver operating characteristic (ROC) curve, C-index, calibration curve, and on the validation datasets GSE63061, GSE54536, GSE22255, and GSE151371 from GEO database. The results show that our model demonstrates good prediction performance. This AD diagnosis model may benefit both clinical work and mechanistic research.
Effects of Sport Stacking on Neuropsychological, Neurobiological, and Brain Function Performances in Patients With Mild Alzheimer's Disease and Mild Cognitive Impairment: A Randomized Controlled Trial
Authors: Yang Ziying , Zhang Wenbo , Liu Dunxiu , Zhang Shan-shan , Tang Yong , Song Jiaqi , Long Jinfeng , Yang Jun , Jiang Hong , Li Yaling , Liu Xintong , Lü Yang , Ding Fu
Published: May 2022

Objective

To investigate the effects of sport stacking on the overall cognition and brain function in patients with mild Alzheimer's disease (AD) and mild cognitive impairment (MCI).

Methods

A single-blind randomized controlled design was performed using sport stacking for 30 min, 5 days/week for 12 weeks. Forty-eight subjects with mild AD or MCI were randomly divided into the sport stacking group (T-mAD = 12, T-MCI = 12) and the active control group (C-mAD = 11, C-MCI = 13). Auditory Verbal Learning Test (AVLT), Alzheimer's Disease Cooperative Study–Activities of Daily Living scale (ADCS-ADL), Geriatric Depression Scale (GDS-30), and Pittsburgh Sleep Quality Index (PSQI) were performed, the level of amyloid β-protein-40 (Aβ-40), Aβ-42, brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1(IGF-1), tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), and soluble trigger receptor expressed on myeloid cells 2 (sTREM2) in plasma were tested, and brain functional connectivity in resting state and activation under finger movement task were analyzed by functional near-infrared spectroscopy (fNIRS).

Results

Thirty-nine patients completed the trial. After 4 weeks, we found a significant increase in AVLT score in T-MCI (6.36 ± 5.08 vs. −1.11 ± 4.23, p = 0.004), and T-mAD group (4.60 ± 4.77 vs. −0.11 ± 2.89, p = 0.039). After 12 weeks, there was a significantly improved in AVLT (9.64 ± 4.90 vs. −0.33 ± 6.10, p = 0.002) and ADCS-ADL (3.36 ± 3.59 vs. −1.89 ± 2.71, p = 0.003) in T-MCI. There was a significant improvement in AVLT (5.30 ± 5.42 vs. 0.44 ± 2.40) in T-mAD (p < 0.05). Plasma levels of BDNF were upregulated in both T-MCI and T-mAD, and IGF-1 increased in T-MCI (P < 0.05) compared to the control groups. The functional connectivity in MCI patients between DLPFC.R and SCA.R, SMA.L, and SCA.R was decreased. In contrast, in mAD patients, the brain regional function connection was increased between DLPFC.R and Broca's.L. The activation of channel 36 located in the left primary somatosensory cortex was significantly increased after 12-week training, which was correlated with the improved AVLT and the increase of BDNF.

Conclusion

Our findings suggested that sport stacking is effective for patients with MCI and mild AD, possibly through increasing the expression of neuroprotective growth factors and enhancing neural plasticity to improve neurocognitive performance.

Clinical Trial Registration

https://www.ClinicalTrials.gov, ChiCTR.org.cn, identifier: ChiCTR-2100045980.
Low-Intensity Focused Ultrasound Alleviates Spasticity and Increases Expression of the Neuronal K-Cl Cotransporter in the L4–L5 Sections of Rats Following Spinal Cord Injury
Authors: Liao Ye-Hui , Chen Mo-Xian , Chen Shao-Chun , Luo Kai-Xuan , Wang Bing , Ao Li-Juan , Liu Yao
Published: May 2022

Low-intensity focused ultrasound (LIFU) has been shown to provide effective activation of the spinal cord neurocircuits. The aim of this study was to investigate the effects of LIFU in order to alleviate spasticity following spinal cord injury (SCI) by activating the spinal neurocircuits and increasing the expression of the neuronal K-Cl cotransporter KCC2. Adult male Sprague Dawley (SD) rats (220–300 g) were randomly divided into a sham control group, a LIFU− group, and a LIFU+ group. The mechanical threshold hold (g) was used to evaluate the behavioral characteristics of spasm. Electromyography (EMG) was used to assess activation of the spinal cord neurocircuits and muscle spontaneous contraction. Spasticity was assessed by frequency-dependent depression (FDD). The expression of KCC2 of the lumbar spinal cord was determined via western blot (WB) and immunofluorescence (IF) staining. The spinal cord neurocircuits were activated by LIFU simulation, which significantly reduced the mechanical threshold (g), FDD, and EMG recordings (s) after 4 weeks of treatment. WB and IF staining both demonstrated that the expression of KCC2 was reduced in the LIFU− group (P < 0.05). After 4 weeks of LIFU stimulation, expression of KCC2 had significantly increased (P < 0.05) in the LIFU+ group compared with the LIFU− group. Thus, we hypothesized that LIFU treatment can alleviate spasticity effectively and upregulate the expression of KCC2 in the L4–L5 section of SCI rats.
Downregulation of Fat Mass and Obesity-Related Protein in the Anterior Cingulate Cortex Participates in Anxiety- and Depression-Like Behaviors Induced by Neuropathic Pain
Authors: Wang Xiao-Ling , Wei Xin , Yuan Jing-Jing , Mao Yuan-Yuan , Wang Zhong-Yu , Xing Na , Gu Han-Wen , Lin Cai-Hong , Wang Wen-Ting , Zhang Wei , Xing Fei
Published: May 2022

N6-methyladenosine (m6A) is the most abundant methylation modification on mRNA in mammals. Fat mass and obesity-related protein (FTO) is the main RNA m6A demethylase. FTO is involved in the occurrence and maintenance of neuropathic pain (NP). NP often induces mental disorders. We found that NP downregulated the expression of FTO in the anterior cingulate cortex (ACC), inhibited the expression of matrix metalloproteinase-9 (MMP-9) in the ACC, maladjusted the brain-derived neurotrophic factor precursor (proBDNF) and mature brain-derived neurotrophic factor (mBDNF) levels in the ACC, and induced anxiety- and depression-like behaviors in mice. Blocking the downregulation of FTO in the ACC induced by peripheral nerve injury could reverse the anxiety- and depression-like behaviors of mice. Contrarily, downregulation of simulated FTO induced anxiety- and depression-like behaviors in mice. After peripheral nerve injury, the binding of FTO to MMP-9 mRNA decreased and the enrichment of m6A on MMP-9 mRNA increased. In conclusion, downregulation of FTO in ACC by regulating MMP-9 mRNA methylation level contributes to the occurrence of anxiety- and depression-like behaviors in NP mice.
An Integrated Model Combining Machine Learning and Deep Learning Algorithms for Classification of Rupture Status of IAs
Authors: Chen Rong , Mo Xiao , Chen Zhenpeng , Feng Pujie , Li Haiyun
Published: May 2022

Background

The rupture risk assessment of intracranial aneurysms (IAs) is clinically relevant. How to accurately assess the rupture risk of IAs remains a challenge in clinical decision-making.

Purpose

We aim to build an integrated model to improve the assessment of the rupture risk of IAs.

Materials and Methods

A total of 148 (39 ruptured and 109 unruptured) IA subjects were retrospectively computed with computational fluid dynamics (CFDs), and the integrated models were proposed by combining machine learning (ML) and deep learning (DL) algorithms. ML algorithms that include random forest (RF), k-nearest neighbor (KNN), XGBoost (XGB), support vector machine (SVM), and LightGBM were, respectively, adopted to classify ruptured and unruptured IAs. A Pointnet DL algorithm was applied to extract hemodynamic cloud features from the hemodynamic clouds obtained from CFD. Morphological variables and hemodynamic parameters along with the extracted hemodynamic cloud features were acted as the inputs to the classification models. The classification results with and without hemodynamic cloud features are computed and compared.

Results

Without consideration of hemodynamic cloud features, the classification accuracy of RF, KNN, XGB, SVM, and LightGBM was 0.824, 0.759, 0.839, 0.860, and 0.829, respectively, and the AUCs of them were 0.897, 0.584, 0.892, 0.925, and 0.890, respectively. With the consideration of hemodynamic cloud features, the accuracy successively increased to 0.908, 0.873, 0.900, 0.926, and 0.917. Meanwhile, the AUCs reached 0.952, 0.881, 0.950, 0.969, and 0.965 eventually. Adding consideration of hemodynamic cloud features, the SVM could perform best with the highest accuracy of 0.926 and AUC of 0.969, respectively.

Conclusion

The integrated model combining ML and DL algorithms could improve the classification of IAs. Adding consideration of hemodynamic cloud features could bring more accurate classification, and hemodynamic cloud features were important for the discrimination of ruptured IAs.
Mitigating Computer Limitations in Replicating Numerical Simulations of a Neural Network Model With Hodgkin-Huxley-Type Neurons
Authors: Lopes Paulo H. , Oliveira Bruno Cruz , Souza Anderson Abner de S. , Blanco Wilfredo
Published: May 2022

Computational experiments have been very important to numerically simulate real phenomena in several areas. Many studies in computational biology discuss the necessity to obtain numerical replicability to accomplish new investigations. However, even following well-established rules in the literature, numerical replicability is unsuccessful when it takes the computer's limitations for representing real numbers into consideration. In this study, we used a previous published recurrent network model composed by Hodgkin-Huxley-type neurons to simulate the neural activity during development. The original source code in C/C++ was carefully refactored to mitigate the lack of replicability; moreover, it was re-implemented to other programming languages/software (XPP/XPPAUT, Python and Matlab) and executed under two operating systems (Windows and Linux). The commutation and association of the input current values during the summation of the pre-synaptic activity were also analyzed. A total of 72 simulations which must obtain the same result were executed to cover these scenarios. The results were replicated when the high floating-point precision (supplied by third-party libraries) was used. However, using the default floating-point precision type, none of the results were replicated when compared with previous results. Several new procedures were proposed during the source code refactorization; they allowed replicating only a few scenarios, regardless of the language and operating system. Thus, the generated computational “errors” were the same. Even using a simple computational model, the numerical replicability was very difficult to be achieved, requiring people with computational expertise to be performed. After all, the research community must be aware that conducting analyses with numerical simulations that use real number operations can lead to different conclusions.
EZH2-Mediated H3K27me3 Targets Transcriptional Circuits of Neuronal Differentiation
Authors: Buontempo Serena , Laise Pasquale , Hughes James M. , Trattaro Sebastiano , Das Vivek , Rencurel Chantal , Testa Giuseppe
Published: May 2022

The Polycomb Repressive Complex 2 (PRC2) plays important roles in the epigenetic regulation of cellular development and differentiation through H3K27me3-dependent transcriptional repression. Aberrant PRC2 activity has been associated with cancer and neurodevelopmental disorders, particularly with respect to the malfunction of sits catalytic subunit EZH2. Here, we investigated the role of the EZH2-mediated H3K27me3 apposition in neuronal differentiation. We made use of a transgenic mouse model harboring Ezh2 conditional KO alleles to derive embryonic stem cells and differentiate them into glutamatergic neurons. Time course transcriptomics and epigenomic analyses of H3K27me3 in absence of EZH2 revealed a significant dysregulation of molecular networks affecting the glutamatergic differentiation trajectory that resulted in: (i) the deregulation of transcriptional circuitries related to neuronal differentiation and synaptic plasticity, in particular LTD, as a direct effect of EZH2 loss and (ii) the appearance of a GABAergic gene expression signature during glutamatergic neuron differentiation. These results expand the knowledge about the molecular pathways targeted by Polycomb during glutamatergic neuron differentiation.
Performance of Single-Shot Echo-Planar Imaging in Diffusion Tensor Imaging in Rat Sciatic Nerve Compared With Readout-Segmented Echo-Planar Imaging
Authors: Chen Yueyao , Pan Zhongxian , Meng Fanqi , Li Zhujing , Hu Yuanming , Yu Xuewen , Gao Jinyun , Guo Yihao , Lyu Hanqing , Lin Xiaofeng
Published: May 2022

Objectives

To compare the performances of single-shot echo-planar imaging (SS–EPI) and readout-segmented echo-planar imaging (RS–EPI) for diffusion tensor imaging (DTI) of the rat sciatic nerve.

Methods

Eight healthy adult male Sprague-Dawley rats were anesthetized and scanned with a 3T MRI scanner using SS–EPI and RS–EPI DTI sequences. The image quality in terms of the morphology of the nerve, distortions of the nearby femur, muscles, and homogeneity of neuromuscular were evaluated and scored. The correlations between the DTI parameters including fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), apparent diffusion coefficient (ADC), and histopathological parameters were calculated by using the Pearson correlation coefficient and compared by the modified Fisher Z-transform, respectively.

Results

The quality scores were higher for the images from the SS–EPI sequence compared with the RS–EPI sequence for characteristics such as sharpness of the sciatic nerve margin (P = 0.008), artifacts of the sciatic nerve (P = 0.008), and homogeneity of the neuromuscular region (P = 0.007), as well as the contrast-to-noise ratio (CNR) of DW images (P < 0.001). The correlation coefficients were higher for the FA and RD values from the SS–EPI sequence compared with those from the RS–EPI sequence. Furthermore, the correlation coefficients between FA and myelin thickness (P = 0.027), FA and diameter of the myelinated fiber (P = 0.036), as well as RD and myelin thickness (P = 0.05) were statistically higher for the SS–EPI sequence compared with those for the RS–EPI sequence.

Conclusion

Diffusion tensor imaging analysis of the rat sciatic nerve showed that the image quality from the SS–EPI sequence was significantly higher compared with that from the RS–EPI sequence. Furthermore, the FA and RD derived from the SS–EPI sequence are promising and sensitive biomarkers to detect the histopathological changes in the rat sciatic nerve.
Own Race Eye-Gaze Bias for All Emotional Faces but Accuracy Bias Only for Sad Expressions
Authors: Ma Xiaole , Fu Meina , Zhang Xiaolu , Song Xinwei , Becker Benjamin , Wu Renjing , Xu Xiaolei , Gao Zhao , Kendrick Keith , Zhao Weihua
Published: May 2022

Own race faces tend to be recognized more accurately than those of other less familiar races, however, findings to date have been inconclusive. The present study aimed to determine whether Chinese exhibit different recognition accuracy and eye gaze patterns for Asian (own-race) and White (other-race) facial expressions (neutral, happiness, sadness, anger, disgust, fear). A total of 89 healthy Chinese adults viewed Asian and White facial expressions while undergoing eye-tracking and were subsequently required to identify expressions and rate their intensity and effect on arousal. Results revealed that subjects recognized sad expressions in Asian faces better than in White ones. On the other hand, recognition accuracy was higher for White neutral, happy, fearful, and disgusted expressions although this may have been due to subjects more often misclassifying these Asian expressions as sadness. Moreover, subjects viewed the eyes of emotional expressions longer in Asian compared to White faces and the nose of sad ones, especially during the late phase of presentation, whereas pupil sizes, indicative of cognitive load and arousal, were smaller. Eye-gaze patterns were not, however, associated with recognition accuracy. Overall, findings demonstrate an own-race bias in Chinese for identifying sad expressions and more generally across emotional expressions in terms of viewing the eye region of emotional faces for longer and with reduced pupil size. Interestingly, subjects were significantly more likely to miss-identify Asian faces as sad resulting in an apparent other-race bias for recognizing neutral, happy, fearful, and disgusted expressions.