bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cross-Linking Cellular Prion Protein Induces Neuronal Type 2-Like Hypersensitivity
Authors: Adhikari Utpal Kumar , Sakiz Elif , Zhou Xian , Habiba Umma , Kumar Sachin , Mikhael Meena , Senesi Matteo , Guang Li Chun , Guillemin Gilles J. , Ooi Lezanne , David Monique Antoinette , Collins Steven , Karl Tim , Tayebi Mourad 
Published: July 2021

BackgroundPrevious reports identified proteins associated with ‘apoptosis’ following cross-linking PrPCwith motif-specific anti-PrP antibodiesin vivoandin vitro. The molecular mechanisms underlying this IgG-mediated neurotoxicity and the role of the activated proteins in the apoptotic pathways leading to neuronal death has not been properly defined. Previous reports implicated a number of proteins, including apolipoprotein E, cytoplasmic phospholipase A2, prostaglandin and calpain with anti-PrP antibody-mediated ‘apoptosis’, however, these proteins are also known to play an important role in allergy. In this study, we investigated whether cross-linking PrPCwith anti-PrP antibodies stimulates a neuronal allergenic response.MethodsInitially, we predicted the allergenicity of the epitope sequences associated with ‘neurotoxic’ anti-PrP antibodies using allergenicity prediction servers. We then investigated whether anti-PrP antibody treatment of mouse primary neurons (MPN), neuroblastoma cells (N2a) and microglia (N11) cell lines lead to a neuronal allergenic response.ResultsIn-Silicostudies showed that both tail- and globular-epitopes were allergenic. Specifically, binding regions that contain epitopes for previously reported ‘neurotoxic’ antibodies such as ICSM18 (146-159), ICSM35 (91-110), POM 1 (138-147) and POM 3 (95-100) lead to activation of allergenic related proteins. Following direct application of anti-PrPCantibodies on N2a cells, we identified 4 neuronal allergenic-related proteins when compared with untreated cells. Furthermore, we identified 8 neuronal allergenic-related proteins following treatment of N11 cells with anti-PrPCantibodies prior to co-culture with N2a cells when compared with untreated cells. Antibody treatment of MPN or MPN co-cultured with antibody-treated N11 led to identifying 10 and 7 allergenic-related proteins when compared with untreated cells. However, comparison with 3F4 antibody treatment revealed 5 and 4 allergenic-related proteins respectively. Of importance, we showed that the allergenic effects triggered by the anti-PrP antibodies were more potent when antibody-treated microglia were co-cultured with the neuroblastoma cell line. Finally, co-culture of N2a or MPN with N11-treated with anti-PrP antibodies resulted in significant accumulation of NO and IL6 but not TNF-α in the cell culture media supernatant.ConclusionsThis study showed for the first time that anti-PrP antibody binding to PrPCtriggers a neuronal hypersensitivity response and highlights the important role of microglia in triggering an IgG-mediated neuronal hypersensitivity response. Moreover, this study provides an important impetus for including allergenic assessment of therapeutic antibodies for neurodegenerative disorders to derive safe and targeted biotherapeutics.
A Complete Two-Dimensional Avalanche Photodiode Based on MoTe2−WS2−MoTe2 Heterojunctions With Ultralow Dark Current
Authors: Ouyang Tenghui , Wang Ximiao , Liu Shaojing , Chen Huanjun , Deng Shaozhi 
Published: July 2021

Two-dimensional (2D)-material-based photodetectors have recently received great attention due to their potentials in developing ultrathin and highly compact devices. Avalanche photodiodes (APDs) are widely used in a variety of fields such as optical communications and bioimaging due to their fast responses and high sensitivities. However, conventional APDs based on bulk materials are limited by their relatively high dark current. One solution to tackle this issue is by employing nanomaterials and nanostructures as the active layers for APDs. In this study, we proposed and fabricated an atomically-thick APD based on heterojunctions formed by 2D transition metal dichalcogenides (TMDs). A typical device structure was formed by stacking a semiconducting monolayer WS2 onto two metallic few-layer MoTe2 flakes. Due to the Schottky barrier formed between the TMD layers and their atomic thicknesses, the dark current of the APD is greatly reduced down to 93 pA. In addition, the APD can operate through a broad spectral range from visible to near-infrared region, with a responsivity of 6.02 A/W, an external quantum eﬃciency of 1,406%, and an avalanche gain of 587. We believe that the 2D APD demonstrated here provides a feasible approach for developing all-2D optoelectronic devices with simultaneous high-sensitivity and low noise.
Therapeutic Hypothermia Reduces Peritoneal Dialysis Induced Myocardial Blood Flow Heterogeneity and Arrhythmia
Authors: Kharche Sanjay R. , Lemoine Sandrine , Tamasi Tanya , Hur Lisa , So Aaron , McIntyre Christopher W. 
Published: July 2021

Background: Moderate therapeutic hypothermia (TH) is a well-recognized cardio-protective strategy. The instillation of fluid into the peritoneum provides an opportunity to deliver moderate hypothermia as primary prevention against cardiovascular events. We aimed to to investigate both cardiac perfusion consequences (overall blood flow and detailed assessment of perfusion heterogeneity) and subsequently simulate the associated arrhythmic risk for patients undergoing peritoneal dialysis (PD) induced TH.Methods: Patients underwent high resolution myocardial perfusion scanning using high resolution 256 slice CT scanning, at rest and with adenosine stress. The first visit using the patient's usual PD regimen, on the second visit the same regime was utilized but with cooled peritoneal dialysate at 32°C. Myocardial blood flow (MBF) was quantified from generated perfusion maps, reconstructed in 3D. MBF heterogeneity was assessed by fractal dimension (FD) measurement on the 3D left ventricular reconstruction. Arrhythmogenicity was quantified from a sophisticated computational simulation using a multi-scale human 3D ventricle wedge electrophysiological computational model.Results: We studied 7 PD patients, mean age of 60 ± 7 and mean vintage dialysis of 23.6 ± 17.6 months. There were no significant different in overall segmental MBF between normothermic condition (NT) and TH. MBF heterogeneity was significantly decreased (−14%, p = 0.03) at rest and after stress (−14%, p = 0.03) when cooling was applied. Computational simulation showed that TH allowed a normalization of action potential, QT duration and T wave.Conclusion: TH-PD results in moderate hypothermia leading to a reduction in perfusion heterogeneity and simulated risk of non-terminating malignant ventricular arrhythmias.
Production, Storage Stability, and Susceptibility Testing of Reuterin and Its Impact on the Murine Fecal Microbiome and Volatile Organic Compound Profile
Authors: Castellani Christoph , Obermüller Beate , Kienesberger Bernhard , Singer Georg , Peterbauer Clemens , Grabherr Reingard , Mayrhofer Sigrid , Klymiuk Ingeborg , Horvath Angela , Stadlbauer Vanessa , Russmayer Hannes , Miekisch Wolfram , Fuchs Patricia , Till Holger , Heinl Stefan 
Published: July 2021

Background: Probiotics are generally considered as safe, but infections may rarely occur in vulnerable patients. Alternatives to live microorganisms to manage dysbiosis may be of interest in these patients. Reuterin is a complex component system exhibiting broad spectrum antimicrobial activity and a possible candidate substance in these cases.Methods: Reuterin supernatant was cultured from Lentilactobacillus diolivorans in a bioreactor in a two-step process. Storage stability at −20°C and effect of repeated freeze-thaw cycles were assessed by high performance liquid chromatography (HPLC). Antimicrobial activity was tested against Clostridium difficile, Listeria monocytogenes, Escherichia coli, Enterococcus faecium, Staphylococcus (S.) aureus, Staphylococcus epidermidis, Streptococcus (S.) agalactiae, Propionibacterium acnes, and Pseudomonas aeruginosae. Male BALBc mice were gavage fed with reuterin supernatant (n = 10) or culture medium (n = 10). Fecal volatile organic compounds (VOC) were assessed by gas chromatography mass spectroscopy; the microbiome was examined by 16S rRNA gene sequencing.Results: The supernatant contained 13.4 g/L reuterin (3-hydroxypropionaldehyde; 3-HPA). 3-HPA content remained stable at −20°C for 35 days followed by a slow decrease of its concentration. Repeated freezing/thawing caused a slow 3-HPA decrease. Antimicrobial activity was encountered against S. aureus, S. epidermidis, and S. agalactiae. Microbiome analysis showed no differences in alpha and beta diversity markers. Linear discriminant effect size (LEfSe) analysis identified Lachnospiraceae_bacterium_COE1 and Ruminoclostridium_5_uncultured_Clostridiales_ bacterium (in the reuterin medium group) and Desulfovibrio_uncultured_ bacterium, Candidatus Arthromitus, Ruminococcae_NK4A214_group, and Eubacterium_xylanophilum_group (in the reuterin group) as markers for group differentiation. VOC analysis showed a significant decrease of heptane and increase of 3-methylbutanal in the reuterin group.Conclusion: The supernatant produced in this study contained acceptable amounts of 3-HPA remaining stable for 35 days at −20°C and exhibiting an antimicrobial effect against S. aureus, S. agalactiae, and S. epidermidis. Under in vivo conditions, the reuterin supernatant caused alterations of the fecal microbiome. In the fecal, VOC analysis decreased heptane and increased 3-methylbutanal were encountered. These findings suggest the high potential of the reuterin system to influence the intestinal microbiome in health and disease, which needs to be examined in detail in future projects.
Temporal, Spatial, and Genomic Analyses of Enterobacteriaceae Clinical Antimicrobial Resistance in Companion Animals Reveals Phenotypes and Genotypes of One Health Concern
Authors: Singleton David A. , Pongchaikul Pisut , Smith Shirley , Bengtsson Rebecca J. , Baker Kate , Timofte Dorina , Steen Stephen , Jones Matthew , Roberts Larry , Sánchez-Vizcaíno Fernando , Dawson Susan , Noble P.-J. M. , Radford Alan D. , Pinchbeck Gina L. , Williams Nicola J. 
Published: July 2021

BackgroundAntimicrobial resistance (AMR) is a globally important one health threat. The impact of resistant infections on companion animals, and the potential public health implications of such infections, has not been widely explored, largely due to an absence of structured population-level data.ObjectivesWe aimed to efficiently capture and repurpose antimicrobial susceptibility test (AST) results data from several veterinary diagnostic laboratories (VDLs) across the United Kingdom to facilitate national companion animal clinical AMR surveillance. We also sought to harness and genotypically characterize isolates of potential AMR importance from these laboratories.MethodsWe summarized AST results for 29,330 canine and 8,279 feline Enterobacteriaceae isolates originating from companion animal clinical practice, performed between April 2016 and July 2018 from four VDLs, with submissions from 2,237 United Kingdom veterinary practice sites.ResultsEscherichia coli (E. coli) was the most commonly isolated Enterobacteriaceae in dogs (69.4% of AST results, 95% confidence interval, CI, 68.7–70.0) and cats (90.5%, CI 89.8–91.3). Multi-drug resistance was reported in 14.1% (CI 13.5–14.8) of canine and 12.0% (CI 11.1–12.9) of feline E. coli isolates. Referral practices were associated with increased E. coli 3rd generation ≤ cephalosporin resistance odds (dogs: odds ratio 2.0, CI 1.2–3.4). We selected 95 E. coli isolates for whole genome analyses, of which seven belonged to sequence type 131, also carrying the plasmid-associated extended spectrum β-lactamase gene blaCTX–M–15. The plasmid-mediated colistin resistance gene mcr-9 was also identified for the first time in companion animals.ConclusionsLinking clinical AMR data with genotypic characterization represents an efficient means of identifying important resistance trends in companion animals on a national scale.
Prognostic Prediction, Immune Microenvironment, and Drug Resistance Value of Collagen Type I Alpha 1 Chain: From Gastrointestinal Cancers to Pan-Cancer Analysis
Authors: Liu Yi , Xue Jinmin , Zhong Maoxi , Wang Zhi , Li Jie , Zhu Yuxi 
Published: July 2021

Background: Gastrointestinal cancers patients might experience multiple primary tumors in the digestive tract. Therefore, identifying potential biomarkers can help us better understand the underlying mechanism. From the GEO database, four profiles of gastrointestinal cancers were gathered for the screening process, and six hub genes were found by bioinformatics analysis. Collagen type I alpha 1 chain (COL1A1), one of the hub genes, is a component of the extracellular matrix and is critical for tumor microenvironment. However, the expression level, signaling pathway, prognostic prediction, and immunological value of COL1A1 in different cancers remain unclear.Methods: We comprehensively analyzed gene expression and genetic alteration patterns of COL1A1 among 33 types of malignancies from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression projects. Besides, we explored the correlation of COL1A1 with cancer prognosis, immune infiltrates, PD-L1, tumor mutational burden (TMB)/microsatellite instability status (MSI), and the pathway and drug sensitivity of co-expressed genes.Results: The results showed that COL1A1 was highly expressed and associated with poor prognosis in the majority of cancers. The most common alteration type of COL1A1 was missense mutation, and COL1A1 was associated with poor prognosis in KIRP, LGG, MESO, SKCM, and STAD. For the immunologic significance, COL1A1 expression was closely related to high TMB in THYM, LAML, ACC, KICH, PRAD, and LGG, and high MSI in TGCT, MESO, PRAD, COAD, SARC, and CESC. In addition, COL1A1 was positively correlated with the abundance of CAFs, macrophages, and tumor-infiltrating lymphocytes. However, it was negatively correlated with CD8+ T cells mainly in CESC, HNSC-HPV+, and SKCM. Besides, as a component of the extracellular matrix, COL1A1 was involved in the activation of epithelial-mesenchymal transition (EMT), and high expression of HTRA1 was resistant to multiple drugs.Conclusion:COL1A1 can serve as a prognostic and immunological biomarker in different cancers.
Ferroptosis-Related Gene Signature and Patterns of Immune Infiltration Predict the Overall Survival in Patients With Lung Adenocarcinoma
Authors: Wang Yuxuan , Chen Weikang , Zhu Minqi , Xian Lei 
Published: July 2021

Background:Lung adenocarcinoma (LUAD) is a malignant tumor with high heterogeneity and poor prognosis. Ferroptosis, a form of regulated cell-death–related iron, has been proven to trigger inflammation-associated immunosuppression in the tumor microenvironment, which promotes tumor growth. Therefore, the clinical prognostic value of ferroptosis-related genes in LUAD needs to be further explored.Method:In this study, we downloaded the mRNA expression profiles and corresponding clinical data of LUAD patients from the Cancer Genome Atlas database. The least absolute shrinkage and selection operator (LASSO) Cox regression model was utilized to construct ferroptosis-related gene signature. Based on these, we established the nomograms for prognosis prediction and validated the model in the GSE72094 dataset. The cell type was identified using the CIBERSORT algorithm for estimating relative subsets of RNA transcripts, which was then used to screen significant tumor immune-infiltrating cells associated with the LUAD prognosis prediction model. Subsequently, we applied co-expression analysis to reveal the relationship between ferroptosis-related genes and significant immune cells.Results:The univariate COX regression analysis showed that 20 genes were associated with the overall survival (OS) as prognostic differentially expressed genes (DEGs) (FDR &lt;0.05). Patients were divided into two risk groups using a 13-gene signature, with the high-risk group having a significantly worse OS than their low-risk counterparts (p&lt; 0.001). We used receiver operating characteristic (ROC) curve analysis to confirm the predictive capacity of the signature. Besides, we identified seven pairs of ferroptosis-related genes and tumor-infiltrating immune cells associated with the prognosis of LUAD patients.Conclusion:In this study, we construct a ferroptosis-related gene signature that can be used for prognostic prediction in LUAD. In addition, we reveal a potential connection between ferroptosis and tumor-infiltrating immune cells.
Combined Support Vector Machine Classifier and Brain Structural Network Features for the Individual Classification of Amnestic Mild Cognitive Impairment and Subjective Cognitive Decline Patients
Authors: Huang Weijie , Li Xuanyu , Li Xin , Kang Guixia , Han Ying , Shu Ni 
Published: July 2021

ObjectiveIndividuals with subjective cognitive decline (SCD) or amnestic mild cognitive impairment (aMCI) represent important targets for the early detection and intervention of Alzheimer’s disease (AD). In this study, we employed a multi-kernel support vector machine (SVM) to examine whether white matter (WM) structural networks can be used for screening SCD and aMCI.MethodsA total of 138 right-handed participants [51 normal controls (NC), 36 SCD, 51 aMCI] underwent MRI brain scans. For each participant, three types of WM networks with different edge weights were constructed with diffusion MRI data: fiber number-weighted networks, mean fractional anisotropy-weighted networks, and mean diffusivity (MD)-weighted networks. By employing a multiple-kernel SVM, we seek to integrate information from three weighted networks to improve classification performance. The accuracy of classification between each pair of groups was evaluated via leave-one-out cross-validation.ResultsFor the discrimination between SCD and NC, an area under the curve (AUC) value of 0.89 was obtained, with an accuracy of 83.9%. Further analysis revealed that the methods using three types of WM networks outperformed other methods using single WM network. Moreover, we found that most of discriminative features were from MD-weighted networks, which distributed among frontal lobes. Similar classification performance was also reported in the differentiation between subjects with aMCI and NCs (accuracy = 83.3%). Between SCD and aMCI, an AUC value of 0.72 was obtained, with an accuracy of 72.4%, sensitivity of 74.5% and specificity of 69.4%. The highest accuracy was achieved with features only selected from MD-weighted networks.ConclusionWhite matter structural network features help machine learning algorithms accurately identify individuals with SCD and aMCI from NCs. Our findings have significant implications for the development of potential brain imaging markers for the early detection of AD.
Omega-3 Fatty Acids Supplementation Improve Nutritional Status and Inflammatory Response in Patients With Lung Cancer: A Randomized Clinical Trial
Authors: Cheng Mingjin , Zhang Shengqiang , Ning Chengdong , Huo Qianlun 
Published: July 2021

Background and Aims: Clinical studies have reported positive results with omega-3 supplements in patients with cancer. This study aimed to evaluate the efficacy of omega-3 fatty acid supplementation in improving the nutritional status and inflammatory markers of patients with lung cancer.Methods: In a randomized, double-blind, parallel design trial, 60 patients with lung cancer at nutritional status/risk based on the Nutrition Risk Screening 2002 were randomized to be allocated to two study groups, receiving omega-3 fatty acid supplements [eicosapentaenoic acid (EPA) 1.6 g and docosahexaenoic acid (DHA) 0.8 g] or placebo for 12 weeks. Anthropometric measurements [weight, body mass index (BMI), the circumference of the upper arm, and skinfold thickness of triceps], nutrition-based laboratory indices (hemoglobin, albumin, triglyceride, and cholesterol), and inflammatory markers [C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6)] were measured before and after the intervention as study outcomes.Results: No significant difference between the two study groups was observed regarding basic characteristics and study outcomes. Compared with placebo group, omega-3 fatty acid supplementation group showed significant higher weight (66.71 ± 9.17 vs. 61.33 ± 8.03, p = 0.021), albumin (4.74 ± 0.80 vs. 4.21 ± 0.77, p = 0.013), and triglyceride (130.90 ± 25.17 vs. 119.07 ± 14.44, p = 0.032). Inflammatory markers were significantly reduced in omega-3 group compared to placebo (CRP 1.42 ± 0.63 vs. 3.00 ± 1.05, p = 0.001 and TNF-α 1.92 ± 0.65 vs. 4.24 ± 1.19, p = 0.001). No significant difference was observed between the two study groups regarding changes in BMI, the circumference of the upper arm, skinfold thickness of triceps, triglyceride, cholesterol, and IL-6 (p &gt; 0.05).Conclusions: Omega-3 fatty acid supplementation can improve nutritional status and suppress the systemic inflammatory response in patients with lung cancer.Clinical Trial Registration:www.socialscienceregistry.org, identifier: AEARCTR-0007165.
A Novel Prognostic Model for Oral Squamous Cell Carcinoma: The Functions and Prognostic Values of RNA-Binding Proteins
Authors: Lu Yingjuan , Yan Yongcong , Li Bowen , Liu Mo , Liang Yancan , Ye Yushan , Cheng Weiqi , Li Jinsong , Jiao Jiuyang , Chang Shaohai 
Published: July 2021

PurposeThe biological roles and clinical significance of RNA-binding proteins (RBPs) in oral squamous cell carcinoma (OSCC) are not fully understood. We investigated the prognostic value of RBPs in OSCC using several bioinformatic strategies.Materials and MethodsOSCC data were obtained from a public online database, the Limma R package was used to identify differentially expressed RBPs, and functional enrichment analysis was performed to elucidate the biological functions of the above RBPs in OSCC. We performed protein-protein interaction (PPI) network and Cox regression analyses to extract prognosis-related hub RBPs. Next, we established and validated a prognostic model based on the hub RBPs using Cox regression and risk score analyses.ResultsWe found that the differentially expressed RBPs were closely related to the defense response to viruses and multiple RNA processes. We identified 10 prognosis-related hub RBPs (ZC3H12D, OAS2, INTS10, ACO1, PCBP4, RNASE3, PTGES3L-AARSD1, RNASE13, DDX4, and PCF11) and effectively predicted the overall survival of OSCC patients. The area under the receiver operating characteristic (ROC) curve (AUC) of the risk score model was 0.781, suggesting that our model exhibited excellent prognostic performance. Finally, we built a nomogram integrating the 10 RBPs. The internal validation cohort results showed a reliable predictive capability of the nomogram for OSCC.ConclusionWe established a novel 10-RBP-based model for OSCC that could enable precise individual treatment and follow-up management strategies in the future.