bluuebunny/crossref_metadata_2025_split huggingface dataset:
EMDL-ac4C: identifying N4-acetylcytidine based on ensemble two-branch residual connection DenseNet and attention
Authors: Jia Jianhua , Wei Zhangying , Cao Xiaojing 
Published: July 2023

Introduction: N4-acetylcytidine (ac4C) is a critical acetylation modification that has an essential function in protein translation and is associated with a number of human diseases.Methods: The process of identifying ac4C sites by biological experiments is too cumbersome and costly. And the performance of several existing computational models needs to be improved. Therefore, we propose a new deep learning tool EMDL-ac4C to predict ac4C sites, which uses a simple one-hot encoding for a unbalanced dataset using a downsampled ensemble deep learning network to extract important features to identify ac4C sites. The base learner of this ensemble model consists of a modified DenseNet and Squeeze-and-Excitation Networks. In addition, we innovatively add a convolutional residual structure in parallel with the dense block to achieve the effect of two-layer feature extraction.Results: The average accuracy (Acc), mathews correlation coefficient (MCC), and area under the curve Area under curve of EMDL-ac4C on ten independent testing sets are 80.84%, 61.77%, and 87.94%, respectively.Discussion: Multiple experimental comparisons indicate that EMDL-ac4C outperforms existing predictors and it greatly improved the predictive performance of the ac4C sites. At the same time, EMDL-ac4C could provide a valuable reference for the next part of the study. The source code and experimental data are available at: https://github.com/13133989982/EMDLac4C.
Noninvasive evaluation of neutrophil extracellular traps signature predicts clinical outcomes and immunotherapy response in hepatocellular carcinoma
Authors: Xin Hongjie , Lai Qianwei , Zhou Yuchen , He Jian , Song Yangda , Liao Minjun , Sun Jiarun , Li Meng , Zhang Mingxia , Liang Weifang , Bai Yang , Zhang Yongyuan , Zhou Yuanping 
Published: July 2023

BackgroundNeutrophil extracellular traps (NETs) have been shown to play a pivotal role in promoting metastasis and immune escape in hepatocellular carcinoma (HCC). Therefore, noninvasive tests to detect the formation of NETs in tumors can have significant implications for the treatment and prognoses of patients. Here, we sought to develop and validate a computed tomography (CT)-based radiomics model to predict the gene expression profiles that regulate the formation of NETs in HCC.MethodsThis study included 1133 HCC patients from five retrospective cohorts. Based on the mRNA expression levels of 69 biomarkers correlated with NET formation, a 6-gene score (NETs score, NETS) was constructed in cohort 1 from TCIA database (n=52) and validated in cohort 2 (n=232) from ICGC database and cohort 3 (n=365) from TCGA database. And then based on the radiomics features of CT images, a radiomics signature (RNETS) was developed in cohort 1 to predict NETS status (high- or low-NETS). We further employed two cohorts from Nanfang Hospital (Guangzhou, China) to evaluate the predictive power of RNETS in predicting prognosis in cohort 4 (n=347) and the responses to PD-1 inhibitor of HCC patients in cohort 5 (n=137).ResultsFor NETS, in cohort 1, the area under the curve (AUC) values predicting 1, 2, and 3-year overall survival (OS) were 0.836, 0.879, and 0.902, respectively. The low-NETS was associated with better survival and higher levels of immune cell infiltration. The RNETS yielded an AUC value of 0.853 in distinguishing between high-NETS or low-NETS and patients with low-RNETS were associated with significantly longer survival time in cohort 1 (P&lt;0.001). Notably, the RNETS was competent in predicting disease-free survival (DFS) and OS in cohort 4 (P&lt;0.001). In cohort 5, the RNETS was found to be an independent risk factor for progression-free survival (PFS) (P&lt;0.001). In addition, the objective response rate of HCC patients treated with PD-1 inhibitor was significantly higher in the low-RNETS group (27.8%) than in the high-RNETS group (10.8%).ConclusionsThis study revealed that RNETS as a radiomics biomarker could effectively predict prognosis and immunotherapy response in HCC patients.
Immune responses in COVID-19 patients during breakthrough infection with SARS-CoV-2 variants Delta, Omicron-BA.1 and Omicron-BA.5
Authors: Bormann Maren , Brochhagen Leonie , Alt Mira , Otte Mona , Thümmler Laura , van de Sand Lukas , Kraiselburd Ivana , Thomas Alexander , Gosch Jule , Braß Peer , Ciesek Sandra , Widera Marek , Dolff Sebastian , Dittmer Ulf , Witzke Oliver , Meyer Folker , Lindemann Monika , Schönfeld Andreas , Rohn Hana , Krawczyk Adalbert 
Published: July 2023

BackgroundBreakthrough infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are increasingly observed in vaccinated individuals. Immune responses towards SARS-CoV-2 variants, particularly Omicron-BA.5, are poorly understood. We investigated the humoral and cellular immune responses of hospitalized COVID-19 patients during Delta and Omicron infection waves.MethodsThe corresponding SARS-CoV-2 variant of the respective patients were identified by whole genome sequencing. Humoral immune responses were analyzed by ELISA and a cell culture-based neutralization assay against SARS-CoV-2 D614G isolate (wildtype), Alpha, Delta (AY.43) and Omicron (BA.1 and BA.5). Cellular immunity was evaluated with an IFN-γ ELISpot assay.ResultsOn a cellular level, patients showed a minor IFN-γ response after stimulating PBMCs with mutated regions of SARS-CoV-2 variants. Neutralizing antibody titers against Omicron-BA.1 and especially BA.5 were strongly reduced. Double-vaccinated patients with Delta breakthrough infection showed a significantly increased neutralizing antibody response against Delta compared to double-vaccinated uninfected controls (median complete neutralization titer (NT100) 640 versus 80, p&lt;0.05). Omicron-BA.1 infection increased neutralization titers against BA.1 in double-vaccinated patients (median NT100 of 160 in patients versus 20 in controls, p=0.07) and patients that received booster vaccination (median NT100 of 50 in patients versus 20 in controls, p=0.68). For boosted patients with BA.5 breakthrough infection, we found no enhancing effect on humoral immunity against SARS-CoV-2 variants.ConclusionNeutralizing antibody titers against Omicron-BA.1 and especially BA.5 were strongly reduced in SARS-CoV-2 breakthrough infections. Delta and Omicron-BA.1 but not Omicron-BA.5 infections boosted the humoral immunity in double-vaccinated patients and patients with booster vaccination. Despite BA.5 breakthrough infection, those patients may still be vulnerable for reinfections with BA.5 or other newly emerging variants of concern.
Cerebrospinal fluid inflammatory biomarkers for disease progression in Alzheimer’s disease and multiple sclerosis: a systematic review
Authors: Temmerman Joke , Engelborghs Sebastiaan , Bjerke Maria , D’haeseleer Miguel 
Published: July 2023

Inflammatory processes are involved in the pathophysiology of both Alzheimer’s disease (AD) and multiple sclerosis (MS) but their exact contribution to disease progression remains to be deciphered. Biomarkers are needed to define pathophysiological processes of these disorders, who may increasingly co-exist in the elderly generations of the future, due to the rising prevalence in both and ameliorated treatment options with improved life expectancy in MS. The purpose of this review was to provide a systematic overview of inflammatory biomarkers, as measured in the cerebrospinal fluid (CSF), that are associated with clinical disease progression. International peer-reviewed literature was screened using the PubMed and Web of Science databases. Disease progression had to be measured using clinically validated tests representing baseline functional and/or cognitive status, the evolution of such clinical scores over time and/or the transitioning from one disease stage to a more severe stage. The quality of included studies was systematically evaluated using a set of questions for clinical, neurochemical and statistical characteristics of the study. A total of 84 papers were included (twenty-five for AD and 59 for MS). Elevated CSF levels of chitinase-3-like protein 1 (YKL-40) were associated with disease progression in both AD and MS. Osteopontin and monocyte chemoattractant protein-1 were more specifically related to disease progression in AD, whereas the same was true for interleukin-1 beta, tumor necrosis factor alpha, C-X-C motif ligand 13, glial fibrillary acidic protein and IgG oligoclonal bands in MS. We observed a broad heterogeneity of studies with varying cohort characterization, non-disclosure of quality measures for neurochemical analyses and a lack of adequate longitudinal designs. Most of the retrieved biomarkers are related to innate immune system activity, which seems to be an important mediator of clinical disease progression in AD and MS. Overall study quality was limited and we have framed some recommendations for future biomarker research in this field.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021264741.
Splenic SUMO1 controls systemic inflammation in experimental sepsis
Authors: Youssef Ayman , Mohammed Bilal Khan , Prasad Abhishek , del Aguila Angela , Bassi Gabriel , Yang Wei , Ulloa Luis 
Published: July 2023

IntroductionThe recent discovery of TAK981(Subasumstat), the first-in-class selective inhibitor of SUMOylation, enables new immune treatments. TAK981 is already in clinical trials to potentiate immunotherapy in metastatic tumors and hematologic malignancies. Cancer patients have more than ten times higher risk of infections, but the effects of TAK981 in sepsis are unknown and previous studies on SUMO in infections are conflicting.MethodsWe used TAK981 in two sepsis models; polymicrobial peritonitis (CLP) and LPS endotoxemia. Splenectomy was done in both models to study the role of spleen. Western blotting of SUMO-conjugated proteins in spleen lysates was done. Global SUMO1 and SUMO3 knockout mice were used to study the specific SUMO regulation of inflammation in LPS endotoxemia. Splenocytes adoptive transfer was done from SUMO knockouts to wild type mice to study the role of spleen SUMOylation in experimental sepsis.Results and discussionHere, we report that inhibition of SUMOylation with TAK981 improved survival in mild polymicrobial peritonitis by enhancing innate immune responses and peritoneal bacterial clearance. Thus, we focused on the effects of TAK981 on the immune responses to bacterial endotoxin, showing that TAK981 enhanced early TNFα production but did not affect the resolution of inflammation. Splenectomy decreased serum TNFα levels by nearly 60% and TAK981-induced TNFα responses. In the spleen, endotoxemia induced a distinct temporal and substrate specificity for SUMO1 and SUMO2/3, and both were inhibited by TAK981. Global genetic depletion of SUMO1, but not SUMO3, enhanced TNFα production and metabolic acidosis. The transfer of SUMO1-null, but not wild-type, splenocytes into splenectomized wild-type mice exacerbated TNFα production and metabolic acidosis in endotoxemia.ConclusionThese results suggest that specific regulation of splenic SUMO1 can modulate immune and metabolic responses to bacterial infection.
Cancer-associated fibroblasts drive CXCL13 production in activated T cells via TGF-beta
Authors: O’Connor Richard A. , Martinez Begoña Roman , Koppensteiner Lilian , Mathieson Layla , Akram Ahsan R. 
Published: July 2023

IntroductionTumour-reactive T cells producing the B-cell attractant chemokine CXCL13, in solid tumours, promote development of tertiary lymphoid structures (TLS) and are associated with improved prognosis and responsiveness to checkpoint immunotherapy. Cancer associated fibroblasts are the dominant stromal cell type in non-small cell lung cancer (NSCLC) where they co-localise with T cells and can influence T cell activation and exhaustion. We questioned whether CAF directly promote CXCL13-production during T cell activation.MethodsWe characterised surface markers, cytokine production and transcription factor expression in CXCL13-producing T cells in NSCLC tumours and paired non-cancerous lung samples using flow cytometry. We then assessed the influence of human NSCLC-derived primary CAF lines on T cells from healthy donors and NSCLC patients during activation in vitro measuring CXCL13 production and expression of cell-surface markers and transcription factors by flow cytometry.ResultsCAFs significantly increased the production of CXCL13 by both CD4+ and CD8+ T cells. CAF-induced CXCL13-producing cells lacked expression of CXCR5 and BCL6 and displayed a T peripheral helper cell phenotype. Furthermore, we demonstrate CXCL13 production by T cells is induced by TGF-β and limited by IL-2. CAF provide TGF-β during T cell activation and reduce availability of IL-2 both directly (by reducing the capacity for IL-2 production) and indirectly, by expanding a population of activated Treg. Inhibition of TGF-β signalling prevented both CAF-driven upregulation of CXCL13 and Treg expansion.DiscussionPromoting CXCL13 production represents a newly described immune-regulatory function of CAF with the potential to shape the immune infiltrate of the tumour microenvironment both by altering the effector-function of tumour infiltrating T-cells and their capacity to attract B cells and promote TLS formation.
Culturing reef-building corals on a laboratory dish: a simple experimental platform for stony corals
Authors: Shikina Shinya , Lin Tzu-Chieh , Chu Yu-Ling , Cheng Yin-Chu , Chang Yu-En , Wada Naohisa , Tang Sen-Lin , Iizuka Yoshiyuki , Chiu Yi-Ling 
Published: July 2023

Development and maintenance of coral reef ecosystems rely on daily micro-biological activities of healthy corals. Although a comprehensive understanding of coral biological properties, as well as factors negatively affecting coral growth, are essential to conserve existing corals, the current lack of a tractable culture and experimental platform has delayed acquisition of such knowledge. Here we show a highly versatile culture system, “coral-on-a-laboratory dish” (CLD), allowing long-term culturing of various corals in plastic/glass Petri dishes with maintenance of their biological properties. Under optimized conditions, coral microcolonies (~5 mm x 5 mm fragments) of Pocillopora damicornis were cultured for several months in dishes with high survivorship and characteristic growth. These microcolonies maintained their biological properties, such as reproduction, skeleton formation, coral-algal symbiosis, ingestion, and digestion. Thus far, CLD has been used to maintain at least 4 other coral species from 4 other families, including the Acroporidae, the Pocilloporidae, the Poritidae, and the Merulinidae for more than 2 months with 100% survivorship. CLD is applicable to a variety of biophysiological studies, including coral-algal symbiosis and impact assessment of marine pollutants, e.g., a sunscreen substance, oxybenzone, and an organic biocide, Irgarol 1051, at cellular-level resolution. The CLD platform, which allows easy and inexpensive coral maintenance in a laboratory incubator, represents a technological breakthrough that will greatly advance coral studies.
Bioinformatics identification of ferroptosis-related genes and therapeutic drugs in rheumatoid arthritis
Authors: Li Xianbin , He Andong , Liu Yue , Huang Yuye , Zhang Xueli 
Published: July 2023

IntroductionRheumatoid arthritis (RA) is a chronic immune disease characterized by synovial inflammation and bone destruction, with a largely unclear etiology. Evidence has indicated that ferroptosis may play an increasingly important role in the onset and development of RA. However, ferroptosis-related genes are still largely unexplored in RA. Therefore, this work focused on identifying and validating the potential ferroptosis-related genes involved in RA through bioinformatics analysis.MethodsWe screened differentially expressed ferroptosis-related genes (DEFGs) between RA patients and healthy individuals based on GSE55235 dataset. Subsequently, correlation analysis, protein-protein interaction (PPI) network analysis, GO, and KEGG enrichment analyses were performed using these DEFGs. Finally, our results were validated by GSE12021 dataset.ResultsWe discovered 34 potential DEFGs in RA based on bioinformatics analysis. According to functional enrichment analysis, these genes were mainly enriched in HIF-1 signaling pathway, FoxO signaling pathway, and Ferroptosis pathway. Four genes (GABARPL1, DUSP1, JUN, and MAPK8) were validated to be downregulated by GSE12021 dataset and were diagnostic biomarkers and therapeutic targets for RA via the regulation of ferroptosis.DiscussionOur results help shed more light on the pathogenesis of RA. Ferroptosis-related genes in RA are valuable diagnostic biomarkers and they will be exploited clinically as therapeutic targets in the future.
Adverse pregnancy outcomes and associated risk factors among pregnant women with syphilis during 2013–2018 in Hunan, China
Authors: Gao Jie , Chen Xia , Yang Min , Wu Yinglan , Liang Ting , Li Huixia , Xie Wanqin 
Published: July 2023

ObjectiveTo investigate the adverse pregnancy outcomes and associated risk factors among pregnant women with syphilis.DesignPregnant women with syphilis in the registry for the prevention of mother-to-child transmission of AIDS, syphilis and hepatitis B in Hunan Province, China, from January 1, 2013 to December 31, 2018 were included in the study.ResultsAmong the 14,219 pregnant women with syphilis, 11,346 had definite pregnancy outcomes and were in singleton pregnancy. The risk factors related to adverse pregnancy outcomes include the age of pregnant women with syphilis &lt;20 years old (aOR = 1.274, 95% CI: 1.088–1.493) or ≥ 35 years old (aOR = 1.402, 95% CI: 1.167–1.686), not married (aOR = 1.855, 95% CI: 1.453–2.367), initial syphilis detection in the late pregnancy (aOR = 1.266, 95% CI: 1.032–1.555), diagnosis of syphilis in the late pregnancy (aOR = 5.806, 95% CI: 1.796–18.770), diagnosis of syphilis during labor (aOR = 4.102, 95% CI: 1.263–13.330), husband/sexual partner infected with syphilis (aOR = 1.222, 95% CI: 1.068–1.398), untreated (aOR = 6.756, 95% CI: 5.586–8.197), and nonstandard medication (aOR = 3.300, 95% CI: 2.841–3.846).ConclusionThe prevalence of adverse pregnancy outcomes among pregnant women with syphilis in Hunan Province, China from 2013 to 2018 was relatively high. The adverse pregnancy outcomes associated with syphilis could be reduced by early detection and standard treatment of syphilis for pregnant women and their husbands/sexual partners.
Comparison of MRCP and ERCP in the evaluation of common bile duct and pancreatic duct pathologies
Authors: Kumar Anand , Mohanty Nihar Ranjan , Mohanty Madhusmita , Dash Sashibhusan 
Published: July 2023

BackgroundMagnetic resonance cholangiopancreatography (MRCP) is a non-invasive imaging modality that has high diagnostic accuracy for a wide range of bile duct and pancreatic duct pathologies. Endoscopic retrograde cholangiopancreatography (ERCP) is still the gold standard for the exploration of the biliopancreatic region.AimThe aim of the study was to compare the diagnostic accuracy of MRCP with that of ERCP in the diagnosis of bile duct and pancreatic duct pathologies.Material and methodsA total of 60 patients with common bile duct (CBD) and pancreatic duct pathologies detected on MRCP were subsequently evaluated by ERCP in this observational study. A comparison of MRCP findings with ERCP was made.ResultsMRCP had a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 88.1%, 94.4%, 97.3%, 72.7%, and 90%, respectively, in diagnosing choledocholithiasis in comparison to ERCP. For CBD dilation, the sensitivity was 90.91%, specificity was 93.75% and the PPV, NPV, and accuracy were 97.56%, 78.95%, and 91.67%, respectively, for MRCP. In CBD stricture, MRCP showed a sensitivity, specificity, PPV, NPV, and accuracy of 83.33%, 97.92%, 90.91%, 95.92%, and 95%, respectively. In pancreatic duct dilatation, the sensitivity, specificity, PPV, NPV, and accuracy were all 100%. Pancreatic duct stricture showed a sensitivity, specificity, PPV, NPV, and accuracy of 80%, 98%, 88.89%, 96.08%, and 95%, respectively. For the diagnosis of periampullary carcinoma, the sensitivity, specificity, PPV, NPV, and accuracy rate of MRCP were 80%, 98%, 88.89%, 96.08%, and 95%, respectively.ConclusionNo significant difference was found between MRCP and ERCP in diagnosing those six pathologies.
Metabolomic analysis reveals a differential adaptation process of the larval stages of Anisakis simplex to the host environment
Authors: Polak Iwona , Stryiński Robert , Majewska Marta , Łopieńska-Biernat Elżbieta 
Published: July 2023

Introduction:Anisakis simplex are parasitic nematodes that cause anisakiasis. The possibility of infection with this parasite is through consumption of raw or undercooked fish products. A. simplex infections are often misdiagnosed, especially in subclinical cases that do not present with typical symptoms such as urticaria, angioedema, and gastrointestinal allergy. The resulting allergic reactions range from rapid-onset and potentially fatal anaphylactic reactions to chronic, debilitating conditions. While there have been numerous published studies on the genomes and proteomes of A. simplex, less attention has been paid to the metabolomes. Metabolomics is concerned with the composition of metabolites in biological systems. Dynamic responses to endogenous and exogenous stimuli are particularly well suited for the study of holistic metabolic responses. In addition, metabolomics can be used to determine metabolic activity at different stages of development or during growth.Materials and methods: In this study, we reveal for the first time the metabolomes of infectious stages (L3 and L4) of A. simplex using untargeted metabolomics by ultra-performance liquid chromatography-mass spectrometry.Results: In the negative ionization mode (ESI-), we identified 172 different compounds, whereas in the positive ionization mode (ESI+), 186 metabolites were found. Statistical analysis showed that 60 metabolites were found in the ESI- mode with different concentration in each group, of which 21 were more enriched in the L3 larvae and 39 in the L4 stage of A. simplex. Comparison of the individual developmental stages in the ESI + mode also revealed a total of 60 differential metabolites, but 32 metabolites were more enriched in the L3 stage larvae, and 28 metabolites were more concentrated in the L4 stage.Discussion: The metabolomics study revealed that the developmental stages of A. simplex differed in a number of metabolic pathways, including nicotinate and nicotinamide metabolism. In addition, molecules responsible for successful migration within their host, such as pyridoxine and prostaglandins (E1, E2, F1a) were present in the L4 stage. In contrast, metabolic pathways for amino acids, starch, and sucrose were mainly activated in the L3 stage. Our results provide new insights into the comparative metabolome profiles of two different developmental stages of A. simplex.