bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between altered tryptophan metabolism, plasma aryl hydrocarbon receptor agonists, and inflammatory Chagas disease
Authors: Ambrosio Laura Fernanda , Volpini Ximena , Quiroz Juan Nahuel , Brugo María Belén , Knubel Carolina Paola , Herrera Melisa Rocío , Fozzatti Laura , Avila Pacheco Julián , Clish Clary B. , Takenaka Maisa C. , Beloscar Juan , Theumer Martín Gustavo , Quintana Francisco Javier , Perez Ana Rosa , Motrán Claudia Cristina 
Published: January 2024

IntroductionChagas disease causes a cardiac illness characterized by immunoinflammatory reactions leading to myocardial fibrosis and remodeling. The development of Chronic Chagas Cardiomyopathy (CCC) in some patients while others remain asymptomatic is not fully understood, but dysregulated inflammatory responses are implicated. The Aryl hydrocarbon receptor (AhR) plays a crucial role in regulating inflammation. Certain tryptophan (Trp) metabolites have been identified as AhR ligands with regulatory functions.Methods, results, and discussionWe investigated AhR expression, agonist response, ligand production, and AhR-dependent responses, such as IDO activation and regulatory T (Treg) cells induction, in two T. cruzi-infected mouse strains (B6 and Balb/c) showing different polymorphisms in AhR. Furthermore, we assessed the metabolic profile of Trp catabolites and AhR agonistic activity levels in plasma samples from patients with chronic Chagas disease (CCD) and healthy donors (HD) using a luciferase reporter assay and liquid chromatography-mass spectrophotometry (LC-MS) analysis. T. cruzi-infected B6 mice showed impaired AhR-dependent responses compared to Balb/c mice, including reduced IDO activity, kynurenine levels, Treg cell induction, CYP1A1 up-regulation, and AhR expression following agonist activation. Additionally, B6 mice exhibited no detectable AhR agonist activity in plasma and displayed lower CYP1A1 up-regulation and AhR expression upon agonist activation. Similarly, CCC patients had decreased AhR agonistic activity in plasma compared to HD patients and exhibited dysregulation in Trp metabolic pathways, resulting in altered plasma metabolite profiles. Notably, patients with severe CCC specifically showed increased N-acetylserotonin levels in their plasma. The methods and findings presented here contribute to a better understanding of CCC development mechanisms and may identify potential specific biomarkers for T. cruzi infection and the severity of associated heart disease. These insights could be valuable in designing new therapeutic strategies. Ultimately, this research aims to establish the AhR agonistic activity and Trp metabolic profile in plasma as an innovative, non-invasive predictor of prognosis for chronic Chagas disease.
Modified live vaccine strains of porcine reproductive and respiratory syndrome virus cause immune system dysregulation similar to wild strains
Authors: Stepanova Katerina , Toman Miroslav , Sinkorova Jana , Sinkora Simon , Pfeiferova Sarka , Kupcova Skalnikova Helena , Abuhajiar Salim , Moutelikova Romana , Salat Jiri , Stepanova Hana , Nechvatalova Katerina , Leva Lenka , Hermanova Petra , Kratochvilova Mirka , Dusankova Blanka , Sinkora Marek , Horak Vratislav , Hudcovic Tomas , Butler John E. , Sinkora Marek 
Published: January 2024

IntroductionPorcine reproductive and respiratory syndrome virus (PRRSV) emerged about 30 years ago and continues to cause major economic losses in the pork industry. The lack of effective modified live vaccines (MLV) allows the pandemic to continue.Background and objectiveWe have previously shown that wild strains of PRRSV affect the nascent T cell repertoire in the thymus, deplete T cell clones recognizing viral epitopes essential for neutralization, while triggering a chronic, robust, but ineffective antibody response. Therefore, we hypothesized that the current MLV are inappropriate because they cause similar damage and fail to prevent viral-induced dysregulation of adaptive immunity. MethodsWe tested three MLV strains to demonstrate that all have a comparable negative effect on thymocytes in vitro. Further in vivo studies compared the development of T cells in the thymus, peripheral lymphocytes, and antibody production in young piglets. These three MLV strains were used in a mixture to determine whether at least some of them behave similarly to the wild virus type 1 or type 2. ResultsBoth the wild and MLV strains cause the same immune dysregulations. These include depletion of T-cell precursors, alteration of the TCR repertoire, necrobiosis at corticomedullary junctions, low body weight gain, decreased thymic cellularity, lack of virus-neutralizing antibodies, and production of non-neutralizing anti-PRRSV antibodies of different isotypes. Discussion and conclusionThe results may explain why the use of current MLV in young animals may be ineffective and why their use may be potentially dangerous. Therefore, alternative vaccines, such as subunit or mRNA vaccines or improved MLV, are needed to control the PRRSV pandemic.
Macrophage subpopulation identity in Drosophila is modulated by apoptotic cell clearance and related signalling pathways
Authors: Brooks Elliot C. , Zeidler Martin P. , Ong Albert C. M. , Evans Iwan R. 
Published: January 2024

In Drosophila blood, plasmatocytes of the haemocyte lineage represent the functional equivalent of vertebrate macrophages and have become an established in vivo model with which to study macrophage function and behaviour. However, the use of plasmatocytes as a macrophage model has been limited by a historical perspective that plasmatocytes represent a homogenous population of cells, in contrast to the high levels of heterogeneity of vertebrate macrophages. Recently, a number of groups have reported transcriptomic approaches which suggest the existence of plasmatocyte heterogeneity, while we identified enhancer elements that identify subpopulations of plasmatocytes which exhibit potentially pro-inflammatory behaviours, suggesting conservation of plasmatocyte heterogeneity in Drosophila. These plasmatocyte subpopulations exhibit enhanced responses to wounds and decreased rates of efferocytosis when compared to the overall plasmatocyte population. Interestingly, increasing the phagocytic requirement placed upon plasmatocytes is sufficient to decrease the size of these plasmatocyte subpopulations in the embryo. However, the mechanistic basis for this response was unclear. Here, we examine how plasmatocyte subpopulations are modulated by apoptotic cell clearance (efferocytosis) demands and associated signalling pathways. We show that loss of the phosphatidylserine receptor Simu prevents an increased phagocytic burden from modulating specific subpopulation cells, while blocking other apoptotic cell receptors revealed no such rescue. This suggests that Simu-dependent efferocytosis is specifically involved in determining fate of particular subpopulations. Supportive of our original finding, mutations in amo (the Drosophila homolog of PKD2), a calcium-permeable channel which operates downstream of Simu, phenocopy simu mutants. Furthermore, we show that Amo is involved in the acidification of the apoptotic cell-containing phagosomes, suggesting that this reduction in pH may be associated with macrophage reprogramming. Additionally, our results also identify Ecdysone receptor signalling, a pathway related to control of cell death during developmental transitions, as a controller of plasmatocyte subpopulation identity. Overall, these results identify fundamental pathways involved in the specification of plasmatocyte subpopulations and so further validate Drosophila plasmatocytes as a heterogeneous population of macrophage-like cells within this important developmental and immune model.
Enhanced CT-based radiomics model to predict natural killer cell infiltration and clinical prognosis in non-small cell lung cancer
Authors: Meng Xiangzhi , Xu Haijun , Liang Yicheng , Liang Mei , Song Weijian , Zhou Boxuan , Shi Jianwei , Du Minjun , Gao Yushun 
Published: January 2024

BackgroundNatural killer (NK) cells are crucial for tumor prognosis; however, their role in non-small-cell lung cancer (NSCLC) remains unclear. The current detection methods for NSCLC are inefficient and costly. Therefore, radiomics represent a promising alternative.MethodsWe analyzed the radiogenomics datasets to extract clinical, radiological, and transcriptome data. The effect of NK cells on the prognosis of NSCLC was assessed. Tumors were delineated using a 3D Slicer, and features were extracted using pyradiomics. A radiomics model was developed and validated using five-fold cross-validation. A nomogram model was constructed using the selected clinical variables and a radiomic score (RS). The CIBERSORTx database and gene set enrichment analysis were used to explore the correlations of NK cell infiltration and molecular mechanisms.ResultsHigher infiltration of NK cells was correlated with better overall survival (OS) (P = 0.002). The radiomic model showed an area under the curve of 0.731, with 0.726 post-validation. The RS differed significantly between high and low infiltration of NK cells (P &lt; 0.01). The nomogram, using RS and clinical variables, effectively predicted 3-year OS. NK cell infiltration was correlated with the ICOS and BTLA genes (P &lt; 0.001) and macrophage M0/M2 levels. The key pathways included TNF-α signaling via NF-κB and Wnt/β-catenin signaling.ConclusionsOur radiomic model accurately predicted NK cell infiltration in NSCLC. Combined with clinical characteristics, it can predict the prognosis of patients with NSCLC. Bioinformatic analysis revealed the gene expression and pathways underlying NK cell infiltration in NSCLC.
Influence of cultivation duration on microbial taxa aggregation in Panax ginseng soils across ecological niches
Authors: Shi Zhenting , Yang Meling , Li Kexin , Yang Li , Yang Limin 
Published: January 2024

IntroductionMicrobial communities are crucial for plant health and productivity. However, the influence of cultivation age on the ecological processes in assembling plant microbiomes at various ecological niches remains unclear.MethodsWe selected 12 samples from ginseng farmlands with different cultivation years (N4: 4 years old, N6: 6 years old). We used soil physicochemical properties, enzyme activities, and high-throughput sequencing (16S rDNA and ITS) to examine the rhizoplane (RP), rhizosphere (RS), and bulk soil (BS).ResultsOur results indicated that cultivation years significantly affect the soil microbiome’s diversity and community composition across different ecological niches. The BS microbiome experienced the largest effect, while the RS experienced the smallest. N6 showed a greater impact than N4. This effect was more pronounced on the fungal communities than the bacterial communities of various ecological niches and can be closely related to the soil’s physicochemical properties. In N4 soils, we observed an upward trend in both the number of ASVs (amplicon sequence variations) and the diversity of soil microbial taxa across various ecological niches. In N4RP, the bacteria Sphingomonas, known for degrading toxic soil compounds, was present. All ecological niches in N4 showed significant enrichment of Tetracladium fungi, positively associated with crop yield (N4RP at 6.41%, N4RS at 11.31%, and N4BS at 3.45%). In N6 soils, we noted a stark decline in fungal diversity within the BS, with a 57.5% reduction in ASVs. Moreover, Sphingomonas was abundantly present in N6RS and N6BS soils. The relative abundance of the pathogen-inhibiting fungus Exophiala in N6RP and N6RS reached 34.18% and 13.71%, respectively, marking increases of 4.9-fold and 7.7-fold. Additionally, another pathogeninhibiting fungus, Humicola, showed significant enrichment in N6BS, with a 7.5-fold increase. The phenolic acid-producing fungus Pseudogymnoascus in N6RP, N6RS, and N6BS showed increases of 2.41-fold, 2.55-fold, and 4.32-fold, respectively. We hypothesize that functional genes related to the metabolism of terpenoids and polyketides, as well as signaling molecules and interactions, regulate soil microbial taxa in ginseng from different cultivation years.DiscussionIn conclusion, our study enhances understanding of plant-microbe interactions and aids the sustainable development of medicinal plants, particularly by addressing ginseng succession disorder.
Risk factors for intraoperative in-stent thrombosis during stent-assisted coiling of paraclinoid aneurysms
Authors: Zeng Chun , Wang Jing 
Published: January 2024

ObjectivesTo identify independent risk factors for intraoperative in-stent thrombosis (IST) in paraclinoid aneurysms (PAs).Methods172 PA patents undergoing stent-assisted coiling (SAC) were divided into an IST group (n = 12) and a non-IST group (n = 160). Clinical characteristics, aneurysm morphologies, and laboratory parameters were measured. We performed independent t tests (for normally distributed data) or non-parametric tests (for non-normally distributed data) to compare continuous parameters. Multivariate logistic regression analysis with a stepwise forward method was conducted to determine independent risk factors. Receiver operating characteristic curves were generated, and the Delong test was employed for comparisons.ResultsIndependent risk factors for IST included size ratio (SR) (p &lt; 0.001, odds ratio [OR] = 3.909, confidence interval [CI] = 1.925–7.939), adenosine diphosphate (ADP) inhibition (p = 0.028, OR = 0.967, CI = 0.938–0.996), and reaction time (R) (p = 0.006, OR = 0.326, CI = 0.147–0.725). The combined factors (SR, ADP inhibition, and R) exhibited area under the curves of 0.870, 0.720, 0.716, and 0.697, with cutoff values of 2.46, 69.90%, and 4.65, respectively.ConclusionThe SR, ADP inhibition, and R values were independent risk factors for the IST in the PAs undergoing SAC. For PAs with a large SR, surgeons could prepare for long-term dual antiplatelet therapy before SAC.
Data-driven analysis and prediction of dynamic postprandial metabolic response to multiple dietary challenges using dynamic mode decomposition
Authors: Skantze Viktor , Jirstrand Mats , Brunius Carl , Sandberg Ann-Sofie , Landberg Rikard , Wallman Mikael 
Published: January 2024

MotivationIn the field of precision nutrition, predicting metabolic response to diet and identifying groups of differential responders are two highly desirable steps toward developing tailored dietary strategies. However, data analysis tools are currently lacking, especially for complex settings such as crossover studies with repeated measures.Current methods of analysis often rely on matrix or tensor decompositions, which are well suited for identifying differential responders but lacking in predictive power, or on dynamical systems modeling, which may be used for prediction but typically requires detailed mechanistic knowledge of the system under study. To remedy these shortcomings, we explored dynamic mode decomposition (DMD), which is a recent, data-driven method for deriving low-rank linear dynamical systems from high dimensional data.Combining the two recent developments “parametric DMD” (pDMD) and “DMD with control” (DMDc) enabled us to (i) integrate multiple dietary challenges, (ii) predict the dynamic response in all measured metabolites to new diets from only the metabolite baseline and dietary input, and (iii) identify inter-individual metabolic differences, i.e., metabotypes. To our knowledge, this is the first time DMD has been applied to analyze time-resolved metabolomics data.ResultsWe demonstrate the potential of pDMDc in a crossover study setting. We could predict the metabolite response to unseen dietary exposures on both measured (R2 = 0.40) and simulated data of increasing size (Rmax2= 0.65), as well as recover clusters of dynamic metabolite responses. We conclude that this method has potential for applications in personalized nutrition and could be useful in guiding metabolite response to target levels.Availability and implementationThe measured data analyzed in this study can be provided upon reasonable request. The simulated data along with a MATLAB implementation of pDMDc is available at https://github.com/FraunhoferChalmersCentre/pDMDc.
Emerging trends and thematic evolution of immunotherapy for glioma based on the top 100 cited articles
Authors: Zhou Yan , Liu Min , Huang Xing , Liu Zhen , Sun Yun , Wang Minjie , Huang Tao , Wang Xianke , Chen Long , Jiang Xiaobing 
Published: January 2024

PurposeThis study aims to depict the scientific advancements in immunotherapy for glioma by analyzing the top 100 most frequently cited articles over the past 20 years.MethodsThe top 100 most influential papers in immunotherapy for glioma were identified from the Web of Science Core Collection. Citations, countries/regions, institutions, journals, authorships, keywords, and references were extracted and analyzed by CiteSpace, VOSviewer, R software, and an online bibliometric platform.ResultsThe United States possessed a robust global presence, leading in terms of publications and maintaining strong collaborative ties with numerous countries. The institution that made the greatest contributions was Duke University, with 16 papers. Heimberger AB, Sampson JH, and Reardon DA secured the top three positions with 15, 12, and 11 papers, respectively. “Macrophage ontogeny,” “microglia,” “polarization,” “mass cytometry,” “tumor mutation burden,” “sensitivity,” “msh6,” “pd-1 blockade,” and “dna repair” were the recent hot keywords. “Microglia” and “polarization” as the emerging research directions should be given more consideration.ConclusionsThis is the first bibliometric analysis to identify the top 100 papers on immunotherapy for glioma. “Microglia” and “polarization” will be hot spots for future research. The clinical efficacy of glioma immunotherapy is not yet satisfactory, and there is an urgent need to search for more tumor specific antigens and targets that can assist in early diagnosis, precise treatment, prognosis, and recurrence prediction of glioma.
Loss of TROP2 and epithelial cell adhesion molecule expression is linked to grade progression in pTa but unrelated to disease outcome in pT2-4 urothelial bladder carcinomas
Authors: Müller Jan H. , Plage Henning , Elezkurtaj Sefer , Mandelkow Tim , Huang Zhihao , Lurati Magalie C. J. , Raedler Jonas B. , Debatin Nicolaus F. , Vettorazzi Eik , Samtleben Henrik , Hofbauer Sebastian , Furlano Kira , Neymeyer Jörg , Goranova Irena , Ralla Bernhard , Weinberger Sarah , Horst David , Roßner Florian , Schallenberg Simon , Marx Andreas H. , Fisch Margit , Rink Michael , Slojewski Marcin , Kaczmarek Krystian , Ecke Thorsten , Hallmann Steffen , Koch Stefan , Adamini Nico , Lennartz Maximilian , Minner Sarah , Simon Ronald , Sauter Guido , Zecha Henrik , Schlomm Thorsten , Bady Elena 
Published: January 2024

IntroductionTrophoblast cell surface antigen 2 (TROP2; EpCAM2) is a transmembrane glycoprotein which is closely related to EpCAM (EpCAM; EpCAM1). Both proteins share partial overlapping functions in epithelial development and EpCAM expression but have not been comparatively analyzed together in bladder carcinomas. TROP2 constitutes the target for the antibody-drug conjugate Sacituzumab govitecan (SG; TrodelvyTM) which has been approved for treatment of metastatic urothelial carcinoma by the United States Food and Drug administration (FDA) irrespective of its TROP2 expression status. MethodsTo evaluate the potential clinical significance of subtle differences in TROP2 and EpCAM expression in urothelial bladder cancer, both proteins were analyzed by multiplex fluorescence immunohistochemistry in combination with a deep-learning based algorithm for automated cell detection on more than 2,700 urothelial bladder carcinomas in a tissue microarray (TMA) format. ResultsThe staining pattern of TROP2 and EpCAM were highly similar. For both proteins, the staining intensity gradually decreased from pTa G2 low grade (TROP2: 68.8±36.1; EpCAM: 21.5±11.7) to pTa G2 high grade (64.6±38.0; 19.3±12.2) and pTa G3 (52.1±38.7; 16.0±13.0, p&lt;0.001 each). In pT2-4 carcinomas, the average TROP2 and EpCAM staining intensity was intermediate (61.8±40.9; 18.3±12.3). For both proteins, this was significantly lower than in pTa G2 low grade (p&lt;0.001 each) but also higher than in pTa G3 tumors (p=0.022 for TROP2, p=0.071 for EpCAM). Within pT2-4 carcinomas, the TROP2 and EpCAM staining level was unrelated to pT, grade, UICC-category, and overall or tumor-specific patient survival. The ratio TROP2/EpCAM was unrelated to malignant phenotype and patient prognosis. ConclusionOur data show that TROP2 and EpCAM expression is common and highly interrelated in urothelial neoplasms. Despite of a progressive loss of TROP2/EpCAM during tumor cell dedifferentiation in pTa tumors, the lack of associations with clinicopathological parameters in pT2-4 cancer argues against a major cancer driving role of both proteins for the progression of urothelial neoplasms.
Danggui Shaoyao San: comprehensive modulation of the microbiota-gut-brain axis for attenuating Alzheimer’s disease-related pathology
Authors: He Jiawei , Jin Yijie , He Chunxiang , Li Ze , Yu Wenjing , Zhou Jinyong , Luo Rongsiqing , Chen Qi , Wu Yixiao , Wang Shiwei , Song Zhenyan , Cheng Shaowu 
Published: January 2024

Background: Alzheimer’s disease (AD), an age-associated neurodegenerative disorder, currently lacks effective clinical therapeutics. Traditional Chinese Medicine (TCM) holds promising potential in AD treatment, exemplified by Danggui Shaoyao San (DSS), a TCM formulation. The precise therapeutic mechanisms of DSS in AD remain to be fully elucidated. This study aims to uncover the therapeutic efficacy and underlying mechanisms of DSS in AD, employing an integrative approach encompassing gut microbiota and metabolomic analyses.Methods: Thirty Sprague-Dawley (SD) rats were allocated into three groups: Blank Control (Con), AD Model (M), and Danggui Shaoyao San (DSS). AD models were established via bilateral intracerebroventricular injections of streptozotocin (STZ). DSS was orally administered at 24 g·kg−1·d−1 (weight of raw herbal materials) for 14 days. Cognitive functions were evaluated using the Morris Water Maze (MWM) test. Pathological alterations were assessed through hematoxylin and eosin (HE) staining. Bloodstream metabolites were characterized, gut microbiota profiled through 16S rDNA sequencing, and cortical metabolomics analyzed. Hippocampal proinflammatory cytokines (IL-1β, IL-6, TNF-α) were quantified using RT-qPCR, and oxidative stress markers (SOD, CAT, GSH-PX, MDA) in brain tissues were measured with biochemical assays.Results: DSS identified a total of 1,625 bloodstream metabolites, predominantly Benzene derivatives, Carboxylic acids, and Fatty Acyls. DSS significantly improved learning and spatial memory in AD rats and ameliorated cerebral tissue pathology. The formulation enriched the probiotic Ligilactobacillus, modulating metabolites like Ophthalmic acid (OA), Phosphocreatine (PCr), Azacridone A, Inosine, and NAD. DSS regulated Purine and Nicotinate-nicotinamide metabolism, restoring balance in the Candidatus Saccharibacteria-OA interplay and stabilizing gut microbiota-metabolite homeostasis. Additionally, DSS reduced hippocampal IL-1β, IL-6, TNF-α expression, attenuating the inflammatory state. It elevated antioxidative enzymes (SOD, CAT, GSH-PX) while reducing MDA levels, indicating diminished oxidative stress in AD rat brains.Conclusion: DSS addresses AD pathology through multifaceted mechanisms, encompassing gut microbiome regulation, specific metabolite modulation, and the mitigation of inflammation and oxidative stress within the brain. This holistic intervention through the Microbial-Gut-Brain Axis (MGBA) underscores DSS’s potential as an integrative therapeutic agent in combatting AD.