bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma phase transition
Authors: Norman G E , Saitov I M 
Published: July 2021

Abstract
Recently developed experimental methods for the generation and diagnostics of nonideal plasma and warm dense matter are reviewed. Modern theoretical methods applied to solve the problem of fluid–fluid phase transitions, including the plasma phase transition, are considered. Quantum simulation methods and the results obtained in the chemical model of plasma are analyzed. Particular attention is paid to the phase transition in warm dense hydrogen/deuterium at high pressures. Results for helium, aluminum, cesium, cerium, ionic, and exciton plasmas and some other substances are also considered.
Differentially Expressed Circular Non-coding RNAs in Atherosclerotic Aortic Vessels and Their Potential Functions in Endothelial Injury
Authors: Li Houwei , Liu Xue , Sun Na , Wang Tianshuo , Zhu Jia , Yang Shuang , Song Xia , Wang Ruishuai , Wang Xinhui , Zhao Yixiu , Zhang Yan 
Published: July 2021

Background: Circular non-coding RNA (circRNA) has a variety of biological functions. However, the expression profile and potential effects of circRNA on atherosclerosis (AS) and vascular endothelial injury have not been fully elucidated. This study aims to identify the differentially expressed circRNAs in atherosclerotic aortic vessels and predict their potential functions in endothelial injury.Method: ApoE-/- mice were fed with high-fat diet for 12 weeks to induce AS. Atherosclerotic plaques were evaluated by H&amp;E and Masson staining and immunohistochemistry; differentially expressed circRNAs were detected by Arraystar Circular RNA Microarray and verified by RT-PCR; the potential target mircoRNAs of circRNAs were predicted by miRanda, Tarbase, Targetscan and their expression changes were verified by RT-PCR; the potential target genes of mircoRNAs were predicted by Targetscan and verified by Western blot; the signaling pathways that they might annotate or regulate and their potential functions in vascular endothelial injury were predicted by gene enrichment analysis.Results: Fifty two circRNAs were up-regulated more than twice and 47 circRNAs were down-regulated more than 1.5 times in AS aortic vessels. Mmmu_circRNA_36781 and 37699 were up-regulated both in AS aortic vessels and H2O2-treated mouse aortic endothelial cells (MAECs). The expression of miR-30d-3p and miR-140-3p, the target microRNA of circRNA_37699 and circRNA_36781, were downregulated both in AS vessels and H2O2-treated MAECs. On the contrary, MKK6 and TP53RK, the potential target gene of miR-140-3p and miR-30d-3p, were upregulated both in AS aortic roots and H2O2-treated MAECs. Besides, gene enrichment analysis showed that MAPK and PI3K-AKT signaling pathway were the most potential signaling pathways regulated by the differentially expressed circRNAs in atherosclerosis.Conclusions: Mmu_circRNA_36781 (circRNA ABCA1) and 37699 (circRNA KHDRBS1) were significantly up-regulated in AS aortic vessels and H2O2-treated MAECs. They have potential regulatory effects on atherosclerosis and vascular endothelial injury by targeting miR-30d-3p-TP53RK and miR-140-3p-MKK6 axis and their downstream signaling pathways.
Automated Quality-Controlled Cardiovascular Magnetic Resonance Pericardial Fat Quantification Using a Convolutional Neural Network in the UK Biobank
Authors: Bard Andrew , Raisi-Estabragh Zahra , Ardissino Maddalena , Lee Aaron Mark , Pugliese Francesca , Dey Damini , Sarkar Sandip , Munroe Patricia B. , Neubauer Stefan , Harvey Nicholas C. , Petersen Steffen E. 
Published: July 2021

Background: Pericardial adipose tissue (PAT) may represent a novel risk marker for cardiovascular disease. However, absence of rapid radiation-free PAT quantification methods has precluded its examination in large cohorts.Objectives: We developed a fully automated quality-controlled tool for cardiovascular magnetic resonance (CMR) PAT quantification in the UK Biobank (UKB).Methods: Image analysis comprised contouring an en-bloc PAT area on four-chamber cine images. We created a ground truth manual analysis dataset randomly split into training and test sets. We built a neural network for automated segmentation using a Multi-residual U-net architecture with incorporation of permanently active dropout layers to facilitate quality control of the model's output using Monte Carlo sampling. We developed an in-built quality control feature, which presents predicted Dice scores. We evaluated model performance against the test set (n = 87), the whole UKB Imaging cohort (n = 45,519), and an external dataset (n = 103). In an independent dataset, we compared automated CMR and cardiac computed tomography (CCT) PAT quantification. Finally, we tested association of CMR PAT with diabetes in the UKB (n = 42,928).Results: Agreement between automated and manual segmentations in the test set was almost identical to inter-observer variability (mean Dice score = 0.8). The quality control method predicted individual Dice scores with Pearson r = 0.75. Model performance remained high in the whole UKB Imaging cohort and in the external dataset, with medium–good quality segmentation in 94.3% (mean Dice score = 0.77) and 94.4% (mean Dice score = 0.78), respectively. There was high correlation between CMR and CCT PAT measures (Pearson r = 0.72, p-value 5.3 ×10−18). Larger CMR PAT area was associated with significantly greater odds of diabetes independent of age, sex, and body mass index.Conclusions: We present a novel fully automated method for CMR PAT quantification with good model performance on independent and external datasets, high correlation with reference standard CCT PAT measurement, and expected clinical associations with diabetes.
Investigation of a Novel LRP6 Variant Causing Autosomal-Dominant Tooth Agenesis
Authors: Huang Yan-xia , Gao Chun-yan , Zheng Chun-yan , Chen Xu , Yan You-sheng , Sun Yong-qing , Dong Xing-yue , Yang Kai , Zhang Dong-liang 
Published: July 2021

BackgroundThe low-density lipoprotein receptor-related protein 6 (LRP6) gene is a recently defined gene that is associated with the autosomal-dominant inherited tooth agenesis (TA). In the present study, a family of four generations having TA was recruited and subjected to a series of clinical, genetic, in silico, and in vitro investigations.MethodsAfter routine clinical evaluation, the proband was subjected to whole-exome sequencing (WES) to detect the diagnostic variant. Next, in silico structural and molecular dynamics (MD) analysis was conducted on the identified novel missense variant for predicting its intramolecular impact. Subsequently, an in vitro study was performed to further explore the effect of this variant on protein maturation and phosphorylation.ResultsWES identified a novel variant, designated as LRP6: c.2570G &gt; A (p.R857H), harbored by six members of the concerned family, four of whom exhibited varied TA symptoms. The in silico analysis suggested that this novel variant could probably damage the Wnt bonding function of the LRP6 protein. The experimental study demonstrated that although this novel variant did not affect the LRP6 gene transcription, it caused a impairment in the maturation and phosphorylation of LRP6 protein, suggesting the possibility of the disruption of the Wnt signaling.ConclusionThe present study expanded the mutation spectrum of human TA in the LRP6 gene. The findings of the present study are insightful and conducive to understanding the functional significance of specific LRP6 variants.
Evaluation of the Clinical, Biochemical, Neurological, and Genetic Presentations of Glutaric Aciduria Type 1 in Patients From China
Authors: E. Huishu , Liang Lili , Zhang Huiwen , Qiu Wenjuan , Ye Jun , Xu Feng , Gong Zhuwen , Gu Xuefan , Han Lianshu 
Published: July 2021

PurposeTo characterize the phenotypic and genotypic variations associated with Glutaric aciduria type 1 (GA1) in Chinese patients.MethodsWe analyzed the clinical, neuroradiological, biochemical, and genetic information from 101 GA1 patients in mainland China.Results20 patients were diagnosed by newborn screening and the remaining 81 cases were identified following clinical intervention. Macrocephaly was the most common presentation, followed by movement disorders and seizures. A total of 59 patients were evaluated by brain MRI and 58 patients presented with abnormalities, with widening of the sylvian fissures being the most common symptom. The concentration of glutarylcarnitine in the blood, glutarylcarnitine/capryloylcarnitine ratio, and urine levels of glutaric acid were increased in GA1 patients and were shown to decrease following intervention. A total of 88 patient samples were available for genotyping and 74 variants within the GCDH gene, including 23 novel variants, were identified. The most common variant was c.1244-2A &gt; C (18.4%) and there were no significant differences in the biochemical or clinical phenotypes described for patients with the four most common variants: c.1244-2A &gt; C, c.1064G &gt; A, c.533G &gt; A, and c.1147C &gt; T. Patients identified by newborn screening had better outcomes than clinical patients.ConclusionOur findings expand the spectrum of phenotypes and genotypes for GA1 in Chinese populations and suggest that an expanded newborn screening program using tandem mass spectrometry may facilitate the early diagnosis and treatment of this disease, improving clinical outcomes for patients in China.
Mucosal Vaccination Primes NK Cell-Dependent Development of CD8+ T Cells Against Pulmonary Brucella Infection
Authors: Bhagyaraj Ella , Wang Hongbin , Yang Xinghong , Hoffman Carol , Akgul Ali , Goodwin Zakia I. , Pascual David W. 
Published: July 2021

Past studies with the live, double-mutant B. abortus (znBAZ) strain resulted in nearly complete protection of mice against pulmonary challenge with wild-type (wt) Brucella via a dominant CD8+ T cell response. To understand the contribution innate immune cells in priming CD8+ T cell responses, mice were nasally dosed with wt B. abortus, smooth vaccine strain 19 (S19), or znBAZ, and examined for innate immune cell activation. Flow cytometric analysis revealed that znBAZ, but not wt B. abortus nor S19 infection, induces up to a 5-fold increase in the frequency of IFN-γ-producing NK cells in mouse lungs. These NK cells express increased CXCR3 and Ki67, indicating their recruitment and proliferation subsequent to znBAZ infection. Their activation status was augmented noted by the increased NKp46 and granzyme B, but decreased NKG2A expression. Further analysis demonstrated that both lung caspase-1+ inflammatory monocytes and monocyte-derived macrophages secrete chemokines and cytokines responsible for NK cell recruitment and activation. Moreover, neutralizing IL-18, an NK cell-activating cytokine, reduced the znBAZ-induced early NK cell response. NK cell depletion also significantly impaired lung dendritic cell (DC) activation and migration to the lower respiratory lymph nodes (LRLNs). Both lung DC activation and migration to LRLNs were significantly impaired in NK cell-depleted or IFN-γ-/- mice, particularly the CD11b+ and monocytic DC subsets. Furthermore, znBAZ vaccination significantly induced CD8+ T cells, and upon in vivo NK cell depletion, CD8+ T cells were reduced 3-fold compared to isotype-treated mice. In summary, these data show that znBAZ induces lung IFN-γ+ NK cells, which plays a critical role in influencing lung DC activation, migration, and promoting protective CD8+ T cell development.
Dynamic Decrease in Eosinophil After Intravenous Thrombolysis Predicts Poor Prognosis of Acute Ischemic Stroke: A Longitudinal Study
Authors: Yang Dehao , Huang Honghao , Weng Yiyun , Ren Junli , Yang Chenguang , Wang Jianing , Gao Beibei , Zeng Tian , Hu Jingyu , Pan Wenjing , Sun Fangyue , Zhou Xinbo , Chen Guangyong 
Published: July 2021

Background and PurposeBlood eosinophil counts are thought to be associated with atherosclerosis in acute ischemic stroke (AIS) and AIS severity. We aimed to investigate 1): the temporal profile of eosinophil in AIS patients treated with recombinant tissue plasminogen activator (r-tPA); 2): The association between dynamic eosinophil and 3-month outcomes in different AIS etiologies; 3): incremental predictive ability of dynamic eosinophil adding to conventional model; and 4): the longitudinal change of neutrophil-to-lymphocyte ratio (NLR) and compared its prognostic value with eosinophils.MethodsA total of 623 AIS patients with intravenous thrombolysis in two hospitals were included. Blood samples were obtained on admission, within 24 h after an intravenous thrombolysis and on the seventh day. A multivariate logistic regression model with restricted cubic spline was performed to explore the association between dynamic eosinophil and a 3-month poor outcome. C-statistic, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were adopted to explore the incremental predictive ability.ResultsPercent change in eosinophil counts after intravenous thrombolysis was median −25.00% (IQR −68.25%–+14.29%). Decrease in eosinophil &gt;75% after intravenous thrombolysis was associated with 2.585 times risk for poor outcome and 13.836 times risk for death. However, the association were weak for patients outside of cardioembolic stroke. Adding eosinophil changes to a conventional model improved the discriminatory ability of poor outcome (NRI = 53.3%; IDI = 2.2%) and death (NRI = 101.0%; IDI = 6.9%).ConclusionsDynamic decrease in eosinophil after intravenous thrombolysis predicts a 3-month poor outcome and death in AIS patients with r-tPA treatment and improved the predictive ability of conventional model. However, this result needs to be interpreted carefully in non-cardioembolic AIS patients.
Syphilis Testing as a Proxy Marker for a Subgroup of Men Who Have Sex With Men With a Central Role in HIV-1 Transmission in Guangzhou, China
Authors: Huang Liping , Wu Hao , Yan Huanchang , Liang Yuanhao , Li Qingmei , Shui Jingwei , Han Zhigang , Tang Shixing 
Published: July 2021

Objectives: The objectives of this study were to distinguish the role of men who have sex with men (MSM) with or without syphilis testing in HIV-1 transmission and to provide molecular evidence of syphilis testing as a proxy marker for identifying the subgroup of MSM.Methods: HIV-1 transmission clusters were constructed by HIV-TRACE and Cluster Picker using HIV-1 pol sequences from 729 newly diagnosed HIV-infected MSM from 2008 to 2012 in Guangzhou, China. The role of MSM in HIV-1 transmission networks was determined by a node influence measurement and centrality analysis. The association between syphilis testing and factors related to HIV-1 transmission and antiretroviral treatment (ART) were analyzed by the Cox regression model.Results: Among HIV-infected MSM, 56.7% did not test for syphilis at the time of HIV-1 diagnosis. MSM without syphilis testing was a specific subgroup of MSM with a larger closeness centrality and clustering coefficient than the recipients of syphilis testing (P &lt; 0.001), indicating their central position in the HIV-1 transmission networks. The median degree and radiality within HIV-1 transmission networks as well as the median K-shell scores were also greater for MSM without syphilis testing (P &lt; 0.001), suggesting their relatively greater contribution in transmitting HIV-1 than the receipts of syphilis testing. MSM with syphilis testing usually did not disclose their occupation or were more likely to be unemployed or to take non-skilled jobs, to have a history of sexually transmitted infections (STIs), and to be AIDS patients when diagnosed with HIV-1 infection (P &lt; 0.05). Multivariable Cox regression analysis indicated that syphilis testing per se did not promote the engagement of ART (P = 0.233) or affect the speed of CD4+ T cell count recovery after treatment (P = 0.256).Conclusions: Our study identifies syphilis testing as a proxy marker of a specific subgroup of HIV-infected MSM who refuse syphilis testing during HIV-1 diagnosis with an important role in HIV-1 transmission. Specific prevention and intervention targeting MSM without syphilis testing during HIV-1 care are urgently needed.
Validation and Extrapolation of a Multimodal Infection Prevention and Control Intervention on Carbapenem-Resistant Klebsiella pneumoniae in an Epidemic Region: A Historical Control Quasi-Experimental Study
Authors: Dai Yunqi , Meng Tianjiao , Wang Xiaoli , Tang Bin , Wang Feng , Du Ying , Qiu Yuzhen , Liu Jialin , Tan Ruoming , Qu Hongping 
Published: July 2021

Objective: To verify the effects of comprehensive infection prevention and control (IPC) interventions for the prevention of the cross-transmission of carbapenem-resistant Klebsiella pneumoniae (CRKP) within intensive care units (ICUs) in an epidemic region.Methods: A historical control, quasi-experimental design was performed. The study was conducted between January 2017 and December 2019, following the implementation of a multimodal IPC bundle. The baseline period was established from January 2013 to June 2013, when only basic IPC measures were applied.Results: A total of 748 patients were enrolled during the entire study. The incidence of ICU-acquired CRKP colonization/infection was 1.16 per 1,000 patient-days during the intervention period, compared with 10.19 per 1,000 patient-days during the baseline period (p = 0.002). The slope of the monthly incidence of CRKP at admission showed an increasing trend (p = 0.03). The incidence of ICU-acquired catheter-related bloodstream infections caused by CRKP decreased from 2.54 to 0.96 per 1,000 central-line-days (p = 0.08). Compliance with contact precautions and terminal room disinfection improved during the intervention period. All environmental surface culture samples acquired after terminal room disinfection were negative for CRKP.Conclusion: Our findings suggest that in epidemic settings, multimodal IPC intervention strategies and consistent monitoring of compliance, may limit the spread of CRKP in ICUs.
Comprehensive Molecular Analyses of a Novel Mutational Signature Classification System with Regard to Prognosis, Genomic Alterations, and Immune Landscape in Glioma
Authors: Liu Zaoqu , Lu Taoyuan , Wang Libo , Liu Long , Li Lifeng , Han Xinwei 
Published: July 2021

Background: Glioma is the most common malignant brain tumor with complex carcinogenic process and poor prognosis. The current molecular classification cannot fully elucidate the molecular diversity of glioma.Methods: Using broad public datasets, we performed cluster analysis based on the mutational signatures and further investigated the multidimensional heterogeneity of the novel glioma molecular subtypes. The clinical significance and immune landscape of four clusters also investigated. The nomogram was developed using the mutational clusters and clinical characteristics.Results: Four heterogenous clusters were identified, termed C1, C2, C3, and C4, respectively. These clusters presented distinct molecular features: C1 was characterized by signature 1, PTEN mutation, chromosome seven amplification and chromosome 10 deletion; C2 was characterized by signature 8 and FLG mutation; C3 was characterized by signature 3 and 13, ATRX and TP53 mutations, and 11p15.1, 11p15.5, and 13q14.2 deletions; and C4 was characterized by signature 16, IDH1 mutation and chromosome 1p and 19q deletions. These clusters also varied in biological functions and immune status. We underlined the potential immune escape mechanisms: abundant stromal and immunosuppressive cells infiltration and immune checkpoints (ICPs) blockade in C1; lack of immune cells, low immunogenicity and antigen presentation defect in C2 and C4; and ICPs blockade in C3. Moreover, C4 possessed a better prognosis, and C1 and C3 were more likely to benefit from immunotherapy. A nomogram with excellent performance was also developed for assessing the prognosis of patients with glioma.Conclusion: Our results can enhance the mastery of molecular features and facilitate the precise treatment and clinical management of glioma.
Association Between Amygdala Volume and Trajectories of Neuropsychiatric Symptoms in Alzheimer's Disease and Dementia With Lewy Bodies
Authors: Jaramillo-Jimenez Alberto , Giil Lasse M. , Tovar-Rios Diego A. , Borda Miguel Germán , Ferreira Daniel , Brønnick Kolbjørn , Oppedal Ketil , Aarsland Dag 
Published: July 2021

Introduction: The amygdala is implicated in psychiatric illness. Even as the amygdala undergoes significant atrophy in mild dementia, amygdala volume is underexplored as a risk factor for neuropsychiatric symptoms (NPS).Objective: To analyze the association between baseline amygdala volume and the longitudinal trajectories of NPS and cognitive decline in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) over 5 years.Methods: Eighty-nine patients with mild dementia were included (AD = 55; DLB = 34). Amygdala volume was segmented from structural magnetic resonance images (sMRI) using a semi-automatic method (Freesurfer 6.0) and normalized by intracranial volumes. The intracranial volume-normalized amygdala was used as a predictor of the Neuropsychiatric Inventory (NPI) total score, ordinal NPI item scores (0 = absence of symptoms, 1–3 = mild symptoms, ≥4 = clinically relevant symptoms), and Mini-Mental State Examination (MMSE) as measured annually over 5 years using gamma, ordinal, and linear mixed-effects models, respectively. The models were adjusted for demographic variables, diagnosis, center of sMRI acquisition, and cognitive performance. Multiple testing-corrected p-values (q-values) are reported.Results: Larger intracranial volume-normalized amygdala was associated with less agitation/aggression (odds ratio (OR) = 0.62 [0.43, 0.90], p = 0.011, q = 0.038) and less MMSE decline per year (fixed effect = 0.70, [0.29, 1.03], p = 0.001, q = 0.010) but more depression (OR = 1.49 [1.09, 2.04], p = 0.013, q = 0.040).Conclusions: Greater amygdala volume in mild dementia is associated with lower odds of developing agitation/aggression, but higher odds of developing depression symptoms during the 5-year study period.