bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multilayer brain network modeling and dynamic analysis of juvenile myoclonic epilepsy
Authors: Ke Ming , Wang Changliang , Liu Guangyao 
Published: March 2023

Objective: It is indisputable that the functional connectivity of the brain network in juvenile myoclonic epilepsy (JME) patients is abnormal. As a mathematical extension of the traditional network model, the multilayer network can fully capture the fluctuations of brain imaging data with time, and capture subtle abnormal dynamic changes. This study assumed that the dynamic structure of JME patients is abnormal and used the multilayer network framework to analyze the change brain community structure in JME patients from the perspective of dynamic analysis.Methods: First, functional magnetic resonance imaging (fMRI) data were obtained from 35 JME patients and 34 healthy control subjects. In addition, the communities of the two groups were explored with the help of a multilayer network model and a multilayer community detection algorithm. Finally, differences were described by metrics that are specific to the multilayer network.Results: Compared with healthy controls, JME patients had a significantly lower modularity degree of the brain network. Furthermore, from the level of the functional network, the integration of the default mode network (DMN) and visual network (VN) in JME patients showed a significantly higher trend, and the flexibility of the attention network (AN) also increased significantly. At the node level, the integration of seven nodes of the DMN was significantly increased, the integration of five nodes of the VN was significantly increased, and the flexibility of three nodes of the AN was significantly increased. Moreover, through division of the core-peripheral system, we found that the left insula and left cuneus were core regions specific to the JME group, while most of the peripheral systems specific to the JME group were distributed in the prefrontal cortex and hippocampus. Finally, we found that the flexibility of the opercular part of the inferior frontal gyrus was significantly correlated with the severity of JME symptoms.Conclusion: Our findings indicate that the dynamic community structure of JME patients is indeed abnormal. These results provide a new perspective for the study of dynamic changes in communities in JME patients.
Glutamine metabolism-related genes predict prognosis and reshape tumor microenvironment immune characteristics in diffuse gliomas
Authors: Fan Huanhuan , Zhang Shuxin , Yuan Yunbo , Chen Siliang , Li Wenhao , Wang Zhihao , Xiang Yufan , Li Junhong , Ma Xiaohong , Liu Yanhui 
Published: March 2023

BackgroundDiffuse gliomas possess a kind of malignant brain tumor with high mortality. Glutamine represents the most abundant and versatile amino acid in the body. Glutamine not only plays an important role in cell metabolism but also involves in cell survival and malignancies progression. Recent studies indicate that glutamine could also affect the metabolism of immune cells in the tumor microenvironment (TME).Materials and methodsThe transcriptome data and clinicopathological information of patients with glioma were acquired from TCGA, CGGA, and West China Hospital (WCH). The glutamine metabolism-related genes (GMRGs) were retrieved from the Molecular Signature Database. Consensus clustering analysis was used to discover expression patterns of GMRGs, and glutamine metabolism risk scores (GMRSs) were established to model tumor aggressiveness-related GMRG expression signature. ESTIMATE and CIBERSORTx were applied to depict the TME immune landscape. The tumor immunological phenotype analysis and TIDE were utilized for predicting the therapeutic response of immunotherapy.ResultsA total of 106 GMRGs were retrieved. Two distinct clusters were established by consensus clustering analysis, which showed a close association with the IDH mutational status of gliomas. In both IDH-mutant and IDH-wildtype gliomas, cluster 2 had significantly shorter overall survival compared with cluster 1, and the differentially expressed genes between the two clusters enriched in pathways related to malignant transformation as well as immunity. In silico TME analysis of the two IDH subtypes revealed not only significantly different immune cell infiltrations and immune phenotypes between the GMRG expression clusters but also different predicted responses to immunotherapy. After the screening, a total of 10 GMRGs were selected to build the GMRS. Survival analysis demonstrated the independent prognostic role of GMRS. Prognostic nomograms were established to predict 1-, 2-, and 3-year survival rates in the four cohorts.ConclusionDifferent subtypes of glutamine metabolism could affect the aggressiveness and TME immune features of diffuse glioma, despite their IDH mutational status. The expression signature of GMRGs could not only predict the outcome of patients with glioma but also be combined into an accurate prognostic nomogram.
Urbanization, air pollution, and water pollution: Identification of potential environmental risk factors associated with amyotrophic lateral sclerosis using systematic reviews
Authors: Saucier Daniel , Registe Pierre Philippe Wilson , Bélanger Mathieu , O'Connell Colleen 
Published: March 2023

IntroductionDespite decades of research, causes of ALS remain unclear. To evaluate recent hypotheses of plausible environmental factors, the aim of this study was to synthesize and appraise literature on the potential associations between the surrounding environment, including urbanization, air pollution and water pollution, and ALS.MethodsWe conducted a series (n = 3) of systematic reviews in PubMed and Scopus to identify epidemiological studies assessing relationships between urbanization, air pollution and water pollution with the development of ALS.ResultsThe combined search strategy led to the inclusion of 44 articles pertaining to at least one exposure of interest. Of the 25 included urbanization studies, four of nine studies on living in rural areas and three of seven studies on living in more highly urbanized/dense areas found positive associations to ALS. There were also three of five studies for exposure to electromagnetic fields and/or proximity to powerlines that found positive associations to ALS. Three case-control studies for each of diesel exhaust and nitrogen dioxide found positive associations with the development of ALS, with the latter showing a dose-response in one study. Three studies for each of high selenium content in drinking water and proximity to lakes prone to cyanobacterial blooms also found positive associations to ALS.ConclusionWhereas markers of air and water pollution appear as potential risk factors for ALS, results are mixed for the role of urbanization.
Clustering and prediction of long-term functional recovery patterns in first-time stroke patients
Authors: Shin Seyoung , Chang Won Hyuk , Kim Deog Young , Lee Jongmin , Sohn Min Kyun , Song Min-Keun , Shin Yong-Il , Lee Yang-Soo , Joo Min Cheol , Lee So Young , Han Junhee , Ahn Jeonghoon , Oh Gyung-Jae , Kim Young-Taek , Kim Kwangsu , Kim Yun-Hee 
Published: March 2023

ObjectivesThe purpose of this study was to cluster long-term multifaceted functional recovery patterns and to establish prediction models for functional outcome in first-time stroke patients using unsupervised machine learning.MethodsThis study is an interim analysis of the dataset from the Korean Stroke Cohort for Functioning and Rehabilitation (KOSCO), a long-term, prospective, multicenter cohort study of first-time stroke patients. The KOSCO screened 10,636 first-time stroke patients admitted to nine representative hospitals in Korea during a three-year recruitment period, and 7,858 patients agreed to enroll. Early clinical and demographic features of stroke patients and six multifaceted functional assessment scores measured from 7 days to 24 months after stroke onset were used as input variables. K-means clustering analysis was performed, and prediction models were generated and validated using machine learning.ResultsA total of 5,534 stroke patients (4,388 ischemic and 1,146 hemorrhagic; mean age 63·31 ± 12·86; 3,253 [58.78%] male) completed functional assessments 24 months after stroke onset. Through K-means clustering, ischemic stroke (IS) patients were clustered into five groups and hemorrhagic stroke (HS) patients into four groups. Each cluster had distinct clinical characteristics and functional recovery patterns. The final prediction models for IS and HS patients achieved relatively high prediction accuracies of 0.926 and 0.887, respectively.ConclusionsThe longitudinal, multi-dimensional, functional assessment data of first-time stroke patients were successfully clustered, and the prediction models showed relatively good accuracies. Early identification and prediction of long-term functional outcomes will help clinicians develop customized treatment strategies.
Intrinsic brain abnormalities in chronic rhinosinusitis associated with mood and cognitive function
Authors: Lin Simin , Nie Miaomiao , Wang Bingshan , Duan Shaoyin , Huang Qianwen , Wu Naiming , Chen Zhishang , Zhao Hengyu , Han Yi 
Published: March 2023

BackgroundChronic rhinosinusitis (CRS) poses a risk for developing emotional and cognitive disorders. However, the neural evidence for this association is largely unclear. Resting-state functional magnetic resonance imaging (rs-fMRI) analysis can demonstrate abnormal brain activity and functional connectivity and contribute to explaining the potential pathophysiology of CRS-related mood and cognitive alterations.MethodsChronic rhinosinusitis patients (CRS, n = 26) and gender- and age-matched healthy control subjects (HCs, n = 38) underwent resting-state functional MRI scanning. The amplitude of low-frequency fluctuations (ALFF) was calculated to observe the intrinsic brain activity. The brain region with altered ALFF was further selected as the seed for functional connectivity (FC) analysis. Correlation analysis was performed between the ALFF/FC and clinical parameters in CRS patients.ResultsCompared with HCs, CRS patients exhibited significantly increased ALFF in the left orbital superior frontal cortex and reduced connectivity in the right precuneus using the orbital superior frontal cortex as the seed region. The magnitude of the orbital superior frontal cortex increased with inflammation severity. In addition, ALFF values in the orbital superior frontal cortex were positively correlated with the hospital anxiety and depression scale (HADS) scores. The ROC curves of altered brain regions indicated great accuracy in distinguishing between CRS patients and HCs.ConclusionIn this study, patients with CRS showed increased neural activity in the orbital superior frontal cortex, a critical region in emotional regulation, and this region also indicated hypoconnectivity to the precuneus with a central role in modulating cognition. This study provided preliminary insights into the potential neural mechanism related to mood and cognitive dysfunctions in CRS patients.
Moderately hypo-fractionated radiotherapy combined with S-1 in inoperable locally advanced esophageal squamous cell carcinoma: A prospective, single-arm phase II study (GASTO-1045)
Authors: Zhou Rui , Luo Guangyu , Guo Suping , Wu Yingjia , Luo Qiaoting , Wang Daquan , Chen Naibin , Liu Fangjie , Guo Jinyu , Ye Wenfeng , Qiu Bo , Liu Hui 
Published: March 2023

PurposeWe launched this prospective phase II single-arm trial on the combination of moderately hypo-fractionated radiotherapy and S-1, to explore the safety and efficacy of the new potent regimen in inoperable locally advanced esophageal squamous carcinoma (LA-ESCC) patients.MethodsPatients with unresectable stage II-IVB LA-ESCC (UICC 2002, IVB only with metastatic celiac or supraclavicular lymph nodes) were included. Moderately hypofractionated radiotherapy (60Gy in 24 fractions) concurrent with S-1 was delivered. Meanwhile, gastrostomy tube placement by percutaneous endoscopic gastrostomy (PEG) was performed to provide nutritional support. Nutritional supplements were prescribed to meet requirements. The study outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), failure pattern, toxicities, nutritional status and treatment compliance. Endoscopy was routinely performed during post-treatment follow-up.ResultsFifty-eight patients were included with a median follow-up of 24.4 months. The median age was 63 years (range 49-83 years) and 42 patients (72.4%) had stage III or IV diseases. The ORR was 91.3% and the CR rate was 60.3%. The estimated 2-year PFS rate and 2-year OS rate was 44.2% (95% confidence interval (CI), 31.3-57.1%) and 71.4% (95% CI, 59.4-83.4%), respectively. Radiation-induced esophagitis was the most common non-hematologic toxicity and 5 patients (8.6%) developed grade≥3 esophagitis. While, with PEG nutrition support, the nutrition-related indicators presented a clear trend toward a gradual improvement. Treatment-related death was not observed.ConclusionsThe moderately hypo-fractionated radiotherapy combined with S-1 showed promising loco-regional disease control and survival benefit in inoperable LA-ESCC patients. Meanwhile, favorable nutritional status and low incidence of severe radiation-induced esophagitis were observed with PEG nutritional support. Moreover, endoscopy examination contributed to the early detection of recurrent esophageal lesions and timely salvage treatment. The efficacy and toxicity of the combined regimen deserved further evaluation.Trial registrationClinicaltrials.gov, identifier NCT03660449.
Adenosine and P1 receptors: Key targets in the regulation of sleep, torpor, and hibernation
Authors: Ma Wei-Xiang , Yuan Ping-Chuan , Zhang Hui , Kong Ling-Xi , Lazarus Michael , Qu Wei-Min , Wang Yi-Qun , Huang Zhi-Li 
Published: March 2023

Graphical AbstractAdenosine mediates sleep, torpor and hibernation through P1 receptors. Recent reasearch has shown that P1 receptors play a vital role in the regulation of sleep-wake, torpor and hibernation-like states. In this review, we focus on the roles and neurobiological mechanisms of the CNS adenosine and P1 receptors in these three states. Among them, A1 and A2A receptors are key targets for sleep-wake regulation, A1Rs and A3Rs are very important for torpor induction, and activation of A1Rs is sufficient for hibernation-like state.
Integrating RNA-seq and scRNA-seq to explore the mechanism of macrophage ferroptosis associated with COPD
Authors: Fan Pengbei , Zhang Yige , Ding Shenao , Du Zhixin , Zhou Chunyu , Du Xiaodan 
Published: March 2023

Aims: Our study focused on whether macrophages ferroptosis is associated with the pathogenesis of chronic obstructive pulmonary disease (COPD) or not.Main methods: We first identified macrophage module genes by weighted gene co-expression network analysis (WGCNA) in RNA sequencing (RNA-seq) date from COPD, and then identified macrophage marker genes by comprehensive analysis of single-cell RNA sequencing (scRNA-seq) data from COPD macrophages. There were 126 macrophage marker genes identified, and functional enrichment analyses indicated that ferroptosis pathway genes were significantly enriched. Secondly, we identified eight macrophage ferroptosis related genes and based on these eight genes, we performed co-expression analysis and drug prediction. Thirdly, two biomarkers (SOCS1 and HSPB1) were screened by the least absolute shrinkage and selection operator (LASSO), random forest (RF), and support vector machine-recursive feature elimination (SVM-RFE) and established an artificial neural network (ANN) for diagnosis. Subsequently, the biomarkers were validated in the dataset and validation set. These two biomarkers were then subjected to single gene-gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) analysis, and the ceRNA network was constructed. Finally, we carried out molecular validation with COPD models in vitro for cell counting kit-8 (CCK8) experiments, Western blot and quantitative real-time PCR (qRT-PCR) analysis and transmission electron microscopy (TEM).Key findings: This study revealed the vital role of macrophage ferroptosis in COPD, and novel biomarkers (SOCS1 and HSPB1) may be involved in the pathogenesis of COPD by regulating macrophage ferroptosis.Significance: Taken together, our results suggest that targeting SOCS1 and HSPB1 could treat COPD by inhibiting macrophage ferroptosis.
Quantitative assessment of biceps brachii muscle stiffness by using Young’s modulus–Angle curve during passive stretching in stroke patients
Authors: Zhang Xinpei , Zhang Li , Sun Yang , Li Tao , Zhou Mouwang 
Published: March 2023

Purpose: This study aims to use shear wave elastography (SWE) to dynamically describe the characteristics of biceps brachii muscle stiffness during passive stretching in healthy participants, investigate changes in the Young’s modulus–angle curve under various states of muscle tone in stroke patients, and develop a new method for measuring muscle tone quantitatively.Methods: In total, 30 healthy volunteers and 54 stroke patients were evaluated for elbow flexor muscle tone on both sides using passive motion examination and were divided into groups based on their muscle tone status. The real-time SWE video of the biceps brachii and the Young’s modulus data were recorded during the passive straightening of the elbow. The Young’s modulus–elbow angle curves were created and fitted using an exponential model. The parameters yielded from the model were subjected to further intergroup analysis.Results: The repeatability of the Young’s modulus measurement was generally good. During passive elbow extension, the Young’s modulus of the biceps brachii steadily increased as muscle tone increased, and it increased faster when the modified Ashworth scale (MAS) score got higher. The exponential model’s fitness was generally good. The curvature coefficient was significantly different between the MAS 0 group and the hypertonia groups (MAS 1, 1+, and 2 groups).Conclusion: The passive elastic characteristics of the biceps brachii are consistent with the exponential model. The Young’s modulus–elbow angle curve of the biceps brachii changes in distinct ways depending on the muscle tone status. SWE can be used to quantify muscular stiffness during passive stretching as a new way of muscle tone evaluation, allowing for quantitative muscle tone evaluation and mathematical assessment of muscle mechanical properties in stroke patients.
Aggressiveness and mycotoxin profile of Fusarium avenaceum isolates causing Fusarium seedling blight and Fusarium head blight in UK malting barley
Authors: Inbaia Safieddin , Farooqi Arifa , Ray Rumiana V. 
Published: March 2023

IntroductionFusarium avenaceum causing Fusarium seedling blight (FSB) and Fusarium head blight (FHB) on barley is associated with economic losses of crop yield and quality, and the accumulation of mycotoxins including the enniatins (ENNs) A, A1, B and B1. Although F. avenaceum is the main producer of ENNs, studies on the ability of isolates to cause severe Fusarium diseases or produce mycotoxins in barley are limited.MethodsIn this work, we investigated the aggressiveness of nine isolates of F. avenaceum to two cultivars of malting barley, Moonshine and Quench, and defined their ENN mycotoxin profiles in in vitro and in planta experiments. We assessed and compared the severity of FSB and FHB caused by these isolates to disease severity by F. graminearum, F. tricinctum and F. poae. Quantitative real-time polymerase chain reaction and Liquid Chromatography Tandem Mass Spectrometry assays were used to quantify pathogen DNA and mycotoxin accumulation, respectively, in barley heads.ResultsIsolates of F. avenaceum were equally aggressive to barley stems and heads and caused the most severe FSB symptoms resulting in up to 55% reductions of stem and root length. Fusarium graminearum caused the most severe FHB disease, followed by the isolates of F. avenaceum with the most aggressive F. avenaceum isolates capable of causing similar bleaching of barley heads as F. avenaceum. Fusarium avenaceum isolates produced ENN B as the predominant mycotoxin, followed by ENN B1 and A1 in vitro. However, only the most aggressive isolates produced ENN A1 in planta and none produced ENN A or beauvericin (BEA) either in planta or in vitro.DiscussionThe capacity of F. avenaceum isolates to produce ENNs was related to the accumulation of pathogen DNA in barley heads, whilst FHB severity was related to the synthesis and accumulation of ENN A1 in planta. Cv. Moonshine was significantly more resistant than Quench to FSB or FHB, caused by any Fusarium isolate, and to the accumulation of pathogen DNA, ENNs or BEA. In conclusion, aggressive F. avenaceum isolates are potent ENN producers causing severe FSB and FHB with ENN A1 requiring further investigation as potential virulence factor for F. avenaceum in cereals.
The Mental Models Training App: Enhancing verbal reasoning through a cognitive training mobile application
Authors: Cortes Robert A. , Weinberger Adam B. , Green Adam E. 
Published: March 2023

IntroductionReasoning is a complex form of human cognition whose nature has long been debated. While a number of neurocognitive mechanisms for deductive reasoning have been offered, one of the most prominent accounts is Mental Model Theory (MMT). According to MMT, humans are able to manipulate and represent information for reasoning and problem solving by leveraging the brain’s evolved visuospatial resources. Thus, when solving deductive reasoning problems, reasoners build “mental models” of the essential pieces of information conveyed in the premises, with their relations to each other represented spatially—even when the information contained within a reasoning problem is not intrinsically spatial. Crucially, taking a spatially-based approach, such as building mental models, supports higher accuracy on deductive reasoning problems. However, no study has empirically tested whether explicitly training this mental modeling ability leads to improved deductive reasoning performance.MethodTherefore, we designed the Mental Models Training App, a cognitive training mobile application which requires participants to complete increasingly difficult reasoning problems while using an external mental modeling tool. In this preregistered study (https://osf.io/4b7kn), we conducted a between-subjects experiment (N = 301) which compared the Mental Models Training App to 3 distinct control conditions in order to examine which specific components (if any) of the training were causally responsible for improved reasoning performance.ResultsResults demonstrate that, when compared to a passive control condition, the Mental Models Training App led to improvements in adults’ verbal deductive reasoning performance both during and after the training intervention. However, contrary to our preregistered hypotheses, the training-induced improvements were not significantly larger than the effects of the active control conditions—one which included adaptive practice of the reasoning problems, and one which included adaptive practice as well as a spatial alphabetization control task.DiscussionTherefore, while the present results demonstrate the ability of the Mental Models Training App to enhance verbal deductive reasoning, they do not support the hypothesis that directly training participants mental modeling ability yields improved performance beyond the effects of adaptive practice of reasoning. Future research should examine the long-term effects of repeated usage of the Mental Models Training App, as well as transfer effects to other forms of reasoning. Finally, we present the Mental Models Training App as a free mobile application available on the Apple App store (https://apps.apple.com/us/app/mental-models-training/id1664939931), in the hope that this translational research may be utilized by the general public to improve their reasoning ability.