bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shallow Depth, Substantial Change: Fluid-Metasomatism Causes Major Compositional Modifications of Subducted Volcanics (Mariana Forearc)
Authors: Albers Elmar , Shervais John W. , Hansen Christian T. , Ichiyama Yuji , Fryer Patricia 
Published: April 2022

Mass transfer at shallow subduction levels and its ramifications for deeper processes remain incompletely constrained. New insights are provided by ocean island basalt (OIB) clasts from the Mariana forearc that experienced subduction to up to ∼25–30 km depth and up to blueschist-facies metamorphism; thereafter, the clasts were recycled to the forearc seafloor via serpentinite mud volcanism. We demonstrate that the rocks were, in addition, strongly metasomatized: they exhibit K2O contents (median = 4.6 wt%) and loss on ignition (median = 5.3 wt%, as a proxy for H2O) much higher than OIB situated on the Pacific Plate, implying that these were added during subduction. This interpretation is consistent with abundant phengite in the samples. Mass balance calculations further reveal variable gains in SiO2 for all samples, and increased MgO and Na2O at one but losses of MgO and Fe2O3* at the other study site. Elevated Cs and Rb concentrations suggest an uptake whereas low Ba and Sr contents indicate the removal of trace elements throughout all clasts. The metasomatism was likely induced by the OIBs’ interaction with K-rich fluids in the subduction channel. Our thermodynamic models imply that such fluids are released from subducted sediments and altered igneous crust at 5 kbar and even below 200°C. Equilibrium assemblage diagrams show that the stability field of phengite significantly increases with the metasomatism and that, relative to not-metasomatized OIB, up to four times as much phengite may form in the metasomatized rocks. Phengite in turn is considered as an important carrier for K2O, H2O, and fluid-mobile elements to sub-arc depths. These findings demonstrate that mass transfer from the subducting lithosphere starts at low P/T conditions. The liberation of solute-rich fluids can evoke far-reaching compositional and mineralogical changes in rocks that interact with these fluids. Processes at shallow depths (&lt;30 km) thereby contribute to controlling which components as well as in which state (i.e., bound in which minerals) these components ultimately reach greater depths where they may or may not contribute to arc magmatism. For a holistic understanding of deep geochemical cycling, metasomatism and rock transformation need to be acknowledged from shallow depths on.
Hepatic IGF2/H19 Epigenetic Alteration Induced Glucose Intolerance in Gestational Diabetes Mellitus Offspring via FoxO1 Mediation
Authors: Jiang Ying , Zhu Hong , Chen Zi , Yu Yi-Chen , Guo Xiao-Han , Chen Yuan , Yang Meng-Meng , Chen Bang-Wu , Sagnelli Matthew , Xu Dong , Zhao Bai-Hui , Luo Qiong 
Published: April 2022

ObjectiveThe offspring of women with gestational diabetes mellitus (GDM) have a high predisposition to developing type 2 diabetes during childhood and adulthood. The aim of the study was to evaluate how GDM exposure in the second half of pregnancy contributes to hepatic glucose intolerance through a mouse model.MethodsBy creating a GDM mouse model, we tested glucose and insulin tolerance of offspring by intraperitoneal glucose tolerance test (IPGTT), insulin tolerance test (ITT), and pyruvate tolerance test (PTT). In addition, we checked the expression of genes IGF2/H19, FoxO1, and DNMTs in the mouse liver by RT-qPCR. Pyrosequencing was used to detect the methylation status on IGF2/H19 differentially methylated regions (DMRs). In vitro insulin stimulation experiments were performed to evaluate the effect of different insulin concentrations on HepG2 cells. Moreover, we detect the interaction between FoxO1 and DNMT3A by chromatin immunoprecipitation–quantitative PCR (Chip-qPCR) and knock-down experiments on HepG2 cells.ResultsWe found that the first generation of GDM offspring (GDM-F1) exhibited impaired glucose tolerance (IGT) and insulin resistance, with males being disproportionately affected. In addition, the expression of imprinted genes IGF2 and H19 was downregulated in the livers of male mice via hypermethylation of IGF2-DMR0 and IGF2-DMR1. Furthermore, increased expression of transcriptional factor FoxO1 was confirmed to regulate DNMT3A expression, which contributed to abnormal methylation of IGF2/H19 DMRs. Notably, different insulin treatments on HepG2 demonstrated those genetic alterations, suggesting that they might be induced by intrauterine hyperinsulinemia.ConclusionOur results demonstrated that the intrauterine hyperinsulinemia environment has increased hepatic FoxO1 levels and subsequently increased expression of DNMT3A and epigenetic alterations on IGF2/H19 DMRs. These findings provide potential molecular mechanisms responsible for glucose intolerance and insulin resistance in the first male generation of GDM mice.
An Interpretable Double-Scale Attention Model for Enzyme Protein Class Prediction Based on Transformer Encoders and Multi-Scale Convolutions
Authors: Lin Ken , Quan Xiongwen , Jin Chen , Shi Zhuangwei , Yang Jinglong 
Published: April 2022

Background Classification and annotation of enzyme proteins are fundamental for enzyme research on biological metabolism. Enzyme Commission (EC) numbers provide a standard for hierarchical enzyme class prediction, on which several computational methods have been proposed. However, most of these methods are dependent on prior distribution information and none explicitly quantifies amino-acid-level relations and possible contribution of sub-sequences.Methods In this study, we propose a double-scale attention enzyme class prediction model named DAttProt with high reusability and interpretability. DAttProt encodes sequence by self-supervised Transformer encoders in pre-training and gathers local features by multi-scale convolutions in fine-tuning. Specially, a probabilistic double-scale attention weight matrix is designed to aggregate multi-scale features and positional prediction scores. Finally, a full connection linear classifier conducts a final inference through the aggregated features and prediction scores.Results On DEEPre and ECPred datasets, DAttProt performs as competitive with the compared methods on level 0 and outperforms them on deeper task levels, reaching 0.788 accuracy on level 2 of DEEPre and 0.967 macro-F1 on level 1 of ECPred. Moreover, through case study, we demonstrate that the double-scale attention matrix learns to discover and focus on the positions and scales of bio-functional sub-sequences in the protein.Conclusion Our DAttProt provides an effective and interpretable method for enzyme class prediction. It can predict enzyme protein classes accurately and furthermore discover enzymatic functional sub-sequences such as protein motifs from both positional and spatial scales.
Designing a Novel Functional Peptide With Dual Antimicrobial and Anti-inflammatory Activities via in Silico Methods
Authors: Shin Min Kyoung , Lee Byungjo , Kim Seung Tae , Yoo Jung Sun , Sung Jung-Suk 
Published: April 2022

As spider venom is composed of various bioactive substances, it can be utilized as a platform for discovering future therapeutics. Host defense peptides are great candidates for developing novel antimicrobial agents due to their multifunctional properties. In this study, novel functional peptides were rationally designed to have dual antibacterial and anti-inflammatory activities with high cytocompatibility. Based on a template sequence from the transcriptome of spider Agelena koreana, a series of via in silico analysis were conducted, incorporating web-based machine learning tools along with the alteration of amino acid residues. Two peptides, Ak-N’ and Ak-N’m, were designed and were subjected to functional validation. The peptides inhibited gram-negative and gram-positive bacteria by disrupting the outer and bacterial cytoplasmic membrane. Moreover, the peptides down-regulated the expression of pro-inflammatory mediators, tumor necrosis factor-α, interleukin (IL)-1β, and IL6. Along with low cytotoxicity, Ak-N’m was shown to interact with macrophage surface receptors, inhibiting both Myeloid differentiation primary response 88-dependent and TIR-domain-containing adapter-inducing interferon-β-dependent pathways of Toll-like receptor 4 signaling on lipopolysaccharide-stimulated THP-1-derived macrophages. Here, we rationally designed functional peptides based on the suggested in silico strategy, demonstrating new insights for utilizing biological resources as well as developing therapeutic agents with enhanced properties.
Comprehensive Analysis on Prognosis and Immune Infiltration of Lysyl Oxidase Family Members in Pancreatic Adenocarcinoma With Experimental Verification
Authors: Jiang Chao , Wang Meng , Yao Weikai , Lv Guoyue , Liu Xueyan , Wang Guangyi 
Published: April 2022

Background: Pancreatic adenocarcinoma (PDAC) is the most aggressive among all solid malignancies with delayed disease detection and limited effective treatment. However, due to the intricate heterogeneity and exclusive tumor microenvironment (TME), the development of effective therapy has been facing enormous challenges. The lysyl oxidases (LOXs) underpin the shaping of the TME to promote cancer growth, metastasis and modulate response to treatment.Materials and Methods: The mRNA expression, prognostic, and clinicopathological data for LOXs in PDAC from multiple open-access databases were summarized and analyzed. The protein expression was verified by immunohistochemistry (IHC). Co-expressed genes of LOXs were predicted and elaborated by LinkedOmics. Functional enrichment analysis of LOXs co-expressed genes was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). TIMER and TISIDB were applied to analyze the relationship between LOXs expression and immune infiltration.Results: The mRNA expression levels of LOX, LOXL1 and LOXL2 were significantly higher in PDAC, the expression levels of LOXL3 and LOXL4 were contrary in different databases. High mRNA levels of LOX and LOXL2 were associated with advanced PDAC stage, while elevated LOX and LOXL3 expression correlated with high tumor grade. The IHC staining showed higher expression levels of LOX, LOXL1 and LOXL2, lower expression level of LOXL3 in PDAC tissues, while the protein expression of LOXL4 made no difference. Functional enrichment analysis showed a close relationship with extracellular matrix (ECM) regulation, except that LOXL3 and its ligands were highly associated with immune-related functions. Further analysis suggested that LOX and LOXL3 strongly correlated with tumor-infiltrating lymphocytes (TILs), various immune signatures, and immune checkpoints. Finally, survival analysis revealed high LOX and LOXL2 expression predicted worse overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS).Conclusion: These findings indicated that the LOX family, especially LOX and LOXL2, might have a prospective value in PDAC oncogenesis, and they may become prognostic biomarkers, revealing a promising field in targeted therapy.
Prism Adaptation Treatment of Spatial Neglect: Feasibility During Inpatient Rehabilitation and Identification of Patients Most Likely to Benefit
Authors: Gillen Robert W. , Harmon Erin Y. , Weil Brittany , Fusco-Gessick Benjamin , Novak Paul P. , Barrett A. M. 
Published: April 2022

ObjectiveSpatial Neglect is prevalent among stroke survivors, yet few treatments have evidence supporting efficacy. This study examines the feasibility of Prism Adaptation Treatment (PAT) within an inpatient rehabilitation facility and the degree by which PAT improves symptoms of spatial neglect and functional independence among sub-acute survivors of right hemispheric stroke.DesignIn this retrospective cohort study, 37 right hemispheric stroke patients were identified as having received at least 4 PAT sessions during their inpatient stay. Spatial neglect and functional independence levels of patients in the PAT cohort were compared to a matched active control group comprised of rehabilitation patients receiving alternative therapies to address neglect admitted during the same time period.ResultsMost patients received the full recommended 10 sessions of PAT (average sessions completed = 8.6). A higher percentage of severe neglect patients receiving PAT (69%) displayed clinically significant gains on FIM (≥22 points) compared to those receiving alternative treatments (6%). Patients with mild or moderate neglect in the PAT cohort did not exhibit greater benefit than controls.ConclusionProvision of PAT for treatment of spatial neglect in right hemispheric stroke patients was feasible during the inpatient rehabilitation admission. Patients with severe neglect showed the most benefit from PAT.Clinical Trial RegistrationThis study was registered as a retrospective observational study on Itab Clinical Trials.gov. NCT04977219.
Multi-Dimensional and Objective Assessment of Motion Sickness Susceptibility Based on Machine Learning
Authors: Li Cong-cong , Zhang Zhuo-ru , Liu Yu-hui , Zhang Tao , Zhang Xu-tao , Wang Han , Wang Xiao-cheng 
Published: April 2022

BackgroundAs human transportation, recreation, and production methods change, the impact of motion sickness (MS) on humans is becoming more prominent. The susceptibility of people to MS can be accurately assessed, which will allow ordinary people to choose comfortable transportation and entertainment and prevent people susceptible to MS from entering provocative environments. This is valuable for maintaining public health and the safety of tasks.ObjectiveTo develop an objective multi-dimensional MS susceptibility assessment model based on physiological indicators that objectively reflect the severity of MS and provide a reference for improving the existing MS susceptibility assessment methods.MethodsMS was induced in 51 participants using the Coriolis acceleration stimulation. Some portable equipment were used to digitize the typical clinical manifestations of MS and explore the correlations between them and Graybiel's diagnostic criteria. Based on significant objective parameters and selected machine learning (ML) algorithms, several MS susceptibility assessment models were developed, and their performances were compared.ResultsGastric electrical activity, facial skin color, skin temperature, and nystagmus are related to the severity of MS. Among the ML assessment models based on these variables, the support vector machine classifier had the best performance with an accuracy of 88.24%, sensitivity of 91.43%, and specificity of 81.25%.ConclusionThe severity of symptoms and signs of MS can be objectively quantified using some indicators. Multi-dimensional and objective assessment models for MS susceptibility based on ML can be successfully established.
Establishment and Optimization of Radiomics Algorithms for Prediction of KRAS Gene Mutation by Integration of NSCLC Gene Mutation Mutual Exclusion Information
Authors: Wang Jingyi , Lv Xing , Huang Weicheng , Quan Zhiyong , Li Guiyu , Wu Shuo , Wang Yirong , Xie Zhaojuan , Yan Yuhao , Li Xiang , Ma Wenhui , Yang Weidong , Cao Xin , Kang Fei , Wang Jing 
Published: April 2022

Purpose: To assess the significance of mutation mutual exclusion information in the optimization of radiomics algorithms for predicting gene mutation.Methods: We retrospectively analyzed 258 non-small cell lung cancer (NSCLC) patients. Patients were randomly divided into training (n = 180) and validation (n = 78) cohorts. Based on radiomics features, radiomics score (RS) models were developed for predicting KRAS proto-oncogene mutations. Furthermore, a composite model combining mixedRS and epidermal growth factor receptor (EGFR) mutation status was developed.Results: Compared with CT model, the PET/CT radiomics score model exhibited higher AUC for predicting KRAS mutations (0.834 vs. 0.770). By integrating EGFR mutation information into the PET/CT RS model, the AUC, sensitivity, specificity, and accuracy for predicting KRAS mutations were all elevated in the validation cohort (0.921, 0.949, 0.872, 0.910 vs. 0.834, 0.923, 0.641, 0.782). By adding EGFR exclusive mutation information, the composite model corrected 64.3% false positive cases produced by the PET/CT RS model in the validation cohort.Conclusion: Integrating EGFR mutation status has potential utility for the optimization of radiomics models for prediction of KRAS gene mutations. This method may be used when repeated biopsies would carry unacceptable risks for the patient.
Beware of the Potential Risks for Polygoni Multiflori Caulis-Induced Liver Injury
Authors: Kong Wei-Song , Zhou Gui , Xu Li-Wei , Wang Kun , Feng Yi-Ming , Tao Li-Yu , Xie Rui-Fang , Yang Ming , Zhou Xin 
Published: April 2022

Background:Reynoutria multiflora (Thunb.) Moldenke (PM) is a widely-used medicinal plant in China, whose root and stem are included in the Chinese Pharmacopoeia as Polygoni Multiflori Radix (RPM), Polygoni Multiflori Radix Preparata (PMP), and Polygoni Multiflori Caulis (PMC). The hepatotoxicity of RPM and PMP is concerned by the public, while the risk of PMC is ignored.Purpose: Here, we investigate the potential risks for PMC-induced liver injury from clinical, chemical, and animal features.Study design: First, we analyzed the 12-month usage of RPM, PMP, and PMC in Longhua Hospital. Second, we determined the contents of gallic acid, cis-2,3,5,4′-tetrahydroxy-stilbene-2-O-β-D-glucoside (cis-SG), trans-2,3,5,4′-tetrahydroxy-stilbene-2-O-β-D-glucoside (trans-SG), emodin-8-O-β-D-glucoside (EG), physcion-8-O-β-D-glucoside (PG), emodin, and physcion in the water extracts from 15 batches of RPM, PMP, and PMC. Third, we probed the hepatotoxic effect of RPM, PMP, and PMC in mice and explored the mechanism of cis-SG and trans-SG causing the liver injury at the dosages based on our results from the first and second parts.Results: PMC had nearly five times the amount of usage in both outpatient prescriptions and inpatient orders than RPM and PMP. Overall, 68% dosage of PMC was 30 g. The contents of cis-SG, trans-SG, and emodin in PMC water extracts were significantly lower than those in RPM and PMP water extracts. PMC induced milder idiosyncratic liver injury for its lower content of cis-SG and trans-SG than its root counterparts.Conclusion: The potential risks for PMC-induced liver injury should be fully aware of.
Depression, Anxiety, Insomnia, and Quality of Life in a Representative Community Sample of Older Adults Living at Home
Authors: Kennair Leif Edward Ottesen , Hagen Roger , Hjemdal Odin , Havnen Audun , Ryum Truls , Solem Stian 
Published: April 2022

BackgroundThe aim of the study was to explore symptoms of anxiety and depression, insomnia, and quality of life in a Norwegian community sample of older adults.MethodsA representative sample (N = 1069) was drawn from home-dwelling people of 60 years and above, living in a large municipality in Norway (Trondheim).ResultsBased on established cut-off scores, 83.7% of the participants showed no symptoms of anxiety/depression, 12% had mild symptoms, 2.7% moderate symptoms, 1.5% showed severe symptoms of anxiety/depression. A total of 18.4% reported insomnia symptoms. Regarding health-related quality of life, few participants reported problems with self-care, but pain and discomfort were common (59%). Depression/anxiety, insomnia, and health-related quality of life showed moderate to strong associations.DiscussionThe results suggest a close interplay between anxiety/depression, insomnia, and health-related quality of life in older adults.
Aberrant Neural Response to Social Exclusion Without Significantly Greater Distress in Youth With Bipolar Disorder: Preliminary Findings
Authors: Roybal Donna J. , Cosgrove Victoria E. , Kelley Ryan , Smallwood Shoukry Rachel , Larios Rose Marie , Novy Blake , Chang Kiki D. , Garrett Amy S. 
Published: April 2022

BackgroundLittle is known about the effects of social exclusion on youth with bipolar disorder (BD). Understanding these effects and the functional neural correlates of social exclusion in youth with BD may establish differences from healthy youth and help identify areas of intervention.MethodsWe investigated brain function in 19 youth with BD and 14 age and gender matched healthy control (HC) participants while performing Cyberball, an fMRI social exclusion task. Whole brain activation, region-of-interest, and functional connectivity were compared between groups and examined with behavioral measures.ResultsCompared with the HC group, youth with BD exhibited greater activation in the left fusiform gyrus (FFG) during social exclusion. Functional connectivity between the left FFG and the posterior cingulate/precuneus was significantly greater in the HC compared with the BD group. For the HC group only, age and subjective distress during Cyberball significantly predicted mean FFG activation. No significant differences in distress during social exclusion were found between groups.ConclusionAlthough preliminary due to small sample size, these data suggest that youth with BD process social exclusion in a manner that focuses on basic visual information while healthy youth make use of past experiences to interpret current social encounters. This difference may account for the social cognitive issues experienced by youth with BD, which can lead to more severe anxiety and mood symptoms.
Network Analysis of Time Use and Depressive Symptoms Among Emerging Adults: Findings From the Guizhou Population Health Cohort Study
Authors: Ma Zhihao , Zhao Fouxi , Wang Yiying , Liu Tao , Chao Naipeng 
Published: April 2022

BackgroundTo date, the relationship between diverse time use behaviors and depression status among emerging adults have not been disentangled in the literature. Therefore, if and how the time displacement mechanism activates depressive symptoms among emerging adults remains unclear.MethodsTo fill this gap in the literature, we employed a network analysis to make estimations. The emerging adult sample (N = 1,811) was collected by the Guizhou Population Health Cohort Study. Time use behaviors were measured by an adaption of the self-administered International Physical Activity Questionnaire, and depressive symptoms were assessed using the 9-item Patient Health Questionnaire (PHQ-9).ResultsThe results revealed that the time displacement mechanism of emerging adults differed from that of adolescents. Sleep duration was not crowded out by other activities, while the time spent on computer use was found to be negatively related to time spent on heavy work activities. Moreover, computer use behavior triggered three depressive symptoms (“Anhedonia,” “Guilt,” and “Motor”), but inhibited “Suicide.” The results of the directed acyclic graph revealed that females and heavy drinkers were at risk of depression.LimitationsThe study sample was confined to only one province, which may limit its generalizability. The cross-sectional design impeded the ability to draw causal inferences.ConclusionOur results enhance the current understanding of the internal mechanism of how time use behaviors influence depressive symptoms among emerging adults.