bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of fatty acid-derived lipids in critically ill patients after cardiac surgery yields novel pathophysiologically relevant mediators with possible relevance for systemic inflammatory reactions
Authors: Neb Holger , Roth Verena , Roos Jessica , Bauer Tom , Urbschat Anja , Heinicke Ulrike , Angioni Carlo , Steinhilber Dieter , Piesche Matthias , Ferreirós Nerea , Gurke Robert , Geisslinger Gerd , Utech Edith , Zacharowski Kai , Meybohm Patrick , Paulus Patrick , Schmitt Elke , Maier Thorsten Jürgen 
Published: January 2025

IntroductionCritically ill patients suffer from a wide variety of clinical events, most of them leading to pro-inflammatory states such as sepsis or simply as consequence of major surgery. Many of these patients develop forms of acute kidney injury, heart or acute liver failure during intensive care. Lipid signaling is critically involved in triggering systemic inflammation processes, pain and vascular tone. We therefore hypothesized that fatty-acid-derived lipid mediators might be regulated during inflammatory stages and other clinical events in critically ill patients and might serve as potential biomarker candidates.Methods and study designUsing liquid chromatography-tandem mass spectrometry (LC-MS/MS), we determined the levels of 53 lipid mediators in plasma from nine patients. These patients were hospitalized at Frankfurt University Hospital’s intensive care unit (ICU) after cardiac surgery. Inflammatory stages were illustrated over time using clinically established biomarkers such as interleukin-6 (IL-6) and leukocyte count. Normal range values of the lipids were obtained from healthy volunteers.ResultsPlasma levels clearly outside the normal range were observed for 22 of 53 lipid mediators, of which 13 were increased (including ceramides Cer (d18:0/18:0), Cer (d18:1/16:0), Cer (d18:1/18:1), glucosyl-ceramide GluCer (d18:1/24:1), lactosylceramide LacCer (d18:1/18:0), and LacCer (d18:1/24:1), 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha), 11,12- and 14,15-DHET and 1- and 2-arachidonoyl glycerol (1-AG and 2-AG), Sphingosine SPH (d18:1) and 20-HETE. Furthermore, nine lipids were decreased (Cer (d18:1/24:0), LacCer (d18:1/16:0), LacCer (d18:1/24:0), sphingosine-1-phosphate S1P (d18:1), S1P (d18:0), the lysophosphatidic acids LPA (16:0), LPA (18:0), LPA (18:1) and 9-HODE. Among increased lipids, the remarkable changes in 1-AG, 2-AG, and to a lower extent of 6-keto-PGF1-alpha plasma levels showed a certain agreement with inflammatory phases. Furthermore, 6-keto-PGF1alpha had its peak shortly before initiation of continuous veno-venous hemodialysis (at least in 5 of the observed patients), 2-AG was elevated in all our nine patients during (right) heart failure in the context of either re-opening patient’s chest, implementation of veno-arterial ECMO or at least while significantly increasing the amount of catecholamines.DiscussionIn this pilot trial we identified several evaluated lipids in critically ill patients representing either potentially (patho-) physiologically relevant mediators of the pro-inflammatory processes and during heart failure or possible markers preceding veno-venous hemodialysis.
Exploring the shared mechanism of fatigue between systemic lupus erythematosus and myalgic encephalomyelitis/chronic fatigue syndrome: monocytic dysregulation and drug repurposing
Authors: Zheng Daisi , Li Xiaolong , Wang Peicheng , Zhu Qingmiao , Huang Zhiyan , Zhao Ting 
Published: January 2025

BackgroundSLE and ME/CFS both present significant fatigue and share immune dysregulation. The mechanisms underlying fatigue in these disorders remain unclear, and there are no standardized treatments. This study aims to explore shared mechanisms and predict potential therapeutic drugs for fatigue in SLE and ME/CFS.MethodsGenes associated with SLE and ME/CFS were collected from disease target and clinical sample databases to identify overlapping genes. Bioinformatics analyses, including GO, KEGG, PPI network construction, and key target identification, were performed. ROC curve and correlation analysis of key targets, along with single-cell clustering, were conducted to validate their expression in different cell types. Additionally, an inflammation model was established using THP-1 cells to simulate monocyte activation in both diseases in vitro, and RT-qPCR was used to validate the expression of the key targets. A TF-mRNA-miRNA co-regulatory network was constructed, followed by drug prediction and molecular docking.ResultsFifty-eight overlapping genes were identified, mainly involved in innate immunity and inflammation. Five key targets were identified (IL1β, CCL2, TLR2, STAT1, IFIH1). Single-cell sequencing revealed that monocytes are enriched with these targets. RT-qPCR confirmed significant upregulation of these targets in the model group. A co-regulatory network was constructed, and ten potential drugs, including suloctidil, N-Acetyl-L-cysteine, simvastatin, ACMC-20mvek, and camptothecin, were predicted. Simvastatin and camptothecin showed high affinity for the key targets.ConclusionSLE and ME/CFS share immune and inflammatory pathways. The identified key targets are predominantly enriched in monocytes at the single-cell level, suggesting that classical monocytes may be crucial in linking inflammation and fatigue. RT-qPCR confirmed upregulation in activated monocytes. The TF-mRNA-miRNA network provides a foundation for future research, and drug prediction suggests N-Acetyl-L-cysteine and camptothecin as potential therapies.
Case report of neurobrucellosis: a rare complication and neuroimaging findings of a common disease
Authors: Zhang Yu , Zou Xiao-Yi , Liu Ling 
Published: January 2025

Background and objectiveNeurobrucellosis is a rare neurological disorder characterized by diverse clinical manifestations. Although several relevant cases were reported, our understanding of this disorder is limited. In this study, we presented the clinical and imaging characteristics of four cases of neurobrucellosis.MethodsFour patients with neurobrucellosis were diagnosed and treated in the West China Hospital of Sichuan University and Chengdu Shangjin Nanfu Hospital, from January 2020 to September 2023. Data on demographics, clinical phenotypes and symptoms, cerebrospinal fluid investigations, radiological investigations, and therapies were collected and reviewed. This study was approved by and conducted in accordance with the recommendations of West China Hospital’s ethics -.1clinical manifestations of neurobrucellosis in these patients included meningitis, meningoencephalitis, encephalitis, cranial neuropathy, intracranial hypertension, radiculitis, peripheral neuropathy, myelitis, and other psychiatric symptoms. Brucella species were isolated from blood or cerebrospinal fluid (CSF) in four patients; three patients had elevated CSF protein levels, and two had elevated CSF leukocyte counts. All four patients had abnormal imaging findings, including meningeal signs, abnormal cortex and subcortical white matter signals, and signal abnormalities in the vertebral body and spinal cord. All patients were treated with rifampicin (450 mg once daily) and minocycline (100 mg twice daily) for at least 12 weeks, and their clinical symptoms showed significant improvements.ConclusionThis report reviews four cases of neurobrucellosis. All four patients had headache, fever, seizure, cranial nerve damage, low back pain, along with imaging abnormalities, and were successfully treated with antibiotics. The symptoms of neurobrucellosis can be insidious, mild, and non-specific, characterized by various clinical manifestations and atypical imaging findings. This complexity increases the risk of misdiagnosis and missed diagnosis; thus, careful identification, extended treatment, and close follow-up are required.
Gαi1/3 signaling mediates IL-5-induced eosinophil activation and type 2 inflammation in eosinophilic chronic rhinosinusitis
Authors: Xie Huanxia , Ji Jiang , Liu Zhichen , Lu Ning , Wei Yuqian , Zhou Aina , Liu Jisheng , Jiao Qingqing 
Published: January 2025

BackgroundUncontrolled severe eosinophilic chronic rhinosinusitis (eCRS) is associated with elevated levels of Th2 cells and raised immunoglobulin concentrations in nasal polyp tissue. eCRS is characterized by high eosinophilic infiltration and type 2 inflammation. Gαi1/3 proteins participate in allergic inflammation by regulating immune cells. Whether Gαi1/3 proteins have a role in the development of eCRS remains unknown.ObjectivesTo investigate the association between Gαi1/3 expression levels and CRS and the underlying mechanismsMethodsWestern blotting and immunohistology were used to detect Gαi1/3 expression. Correlations between Gαi1/3 and immune cells and clinical parameters were analyzed. Signaling pathway activation in IL-5-induced Gαi1/3-knockout or knockdown mouse embryonic fibroblasts (MEFs) and eosinophils (EoL-1 cells) was detected by western blotting. EdU/DAPI was used to evaluate the proliferation of EoL-1 cells. A CRS model was established using Gαi1/3-knockout mice, and histological analysis and inflammatory cytokine measurements were performed.ResultsCompared with the non-eCRS subset, the eCRS subset showed significantly increased Gαi1/3 expression levels. High nasal tissue Gαi1/3 levels were linked to high tissue eosinophil infiltration, and high disease severity and allergic conditions in CRS patients. Gαi1/3 were required for IL-5-induced Akt-mTOR and Erk activation in MEFs. In EoL-1 cells, Gαi1/3 was associated with IL-5-activated IL-5Rα, promoting IL-5Rα endocytosis and transducing downstream signaling. IL-5-induced EoL-1 cell proliferation and degranulation were suppressed after Gαi1/3 silencing. In a CRS murine model, immune cell infiltration and type 2 inflammation were largely impaired in Gαi1/3-double-knockout mice.ConclusionIncreased Gαi1/3 expression levels in nasal tissue are linked to eosinophil infiltration and increased disease severity in CRS patients. Gαi1/3 contributes to eosinophil activation and participates in regulating allergic inflammation in CRS patients.
Mycophenolate mofetil: an update on its mechanism of action and effect on lymphoid tissue
Authors: Krawczyk Anna , Kravčenia Bernard , Maślanka Tomasz 
Published: January 2025

IntroductionMycophenolate mofetil (MMF) is an immunosuppressive drug administered in the management of both autoimmune diseases and organ transplantation. The main aims of the study were: (a) to obtain information regarding the safety of using MMF in respect of its effect on normal T and B cells in lymphoid tissues; (b) to investigate whether the generation of inducible Foxp3-expressing regulatory T cells (Treg) might constitute additional mechanisms underlying the immunosuppressive properties of MMF.MethodsThe effect of MMF (in vivo studies) and its active metabolite, mycophenolic acid, (in vitro studies) on murine CD4+ and CD8+ T cells as well as B cells was determined, regarding: (a) absolute count, proliferation and apoptosis of these cells (in vitro studies); (b) absolute count of these cells in the head and neck lymph nodes, mesenteric lymph nodes and the spleen (in vivo studies).ResultsThe study found that the treatment of mice with MMF induced depletion of CD4+ and CD8+ T cells and B cells in lymph nodes and the spleen, and the magnitude of these effects should be considered as clinically relevant. The study demonstrated the following actions of the drug: (a) proapoptotic action on effector CD4+ and CD8+ T (Teff) cells, and B cells; (b) the down-regulation or prevention of activation-induced expression of CD25 on CD4+ and CD8+ Teff cells; (c) the generation of Foxp3+CD25+CD4+ and Foxp3+CD25+CD8+ T cells resulting in the shift of the Treg cell/activated Teff cell balance toward an increased proportion of Treg cells.ConclusionThe depletive effect of MMF on CD4+ and CD8+ T cells and B cells in lymphoid tissues should be taken into account when assessing the benefit-risk ratio of using MMF in patients with microbial infections and undergoing vaccination. The study contributed new insight into this mechanism, indicating that MMF effectively prevents the proliferation of T and B cells, but may be less effective against already proliferating cells. Moreover, the findings of the study strongly suggest the existence of additional mechanisms that may be responsible for the clinical efficacy of the drug, including the induction of Foxp3-expressing CD4+ and CD8+ Treg cells.
Restoring natural killer cell activity in lung injury with 1,25-hydroxy vitamin D3: a promising therapeutic approach
Authors: Amer Johnny , Salhab Ahmad , Abuawad Mohammad 
Published: January 2025

Background and aimNK cells and NK-cell-derived cytokines were shown to regulate neutrophil activation in acute lung injury (ALI). However, the extent to which ALI regulates lung tissue-resident NK (trNK) activity and their molecular phenotypic alterations are not well defined. We aimed to assess the impact of 1,25-hydroxy-vitamin-D3 [1,125(OH)2D] on ALI clinical outcome in a mouse model and effects on lung trNK cell activations.MethodsOleic acid (OA)-induced ALI in C57BL/6J mice and 1,25(OH)2D treatment 2×/2 weeks were performed. Lung tissue was harvested to assess alveolar I/II cell apoptosis and lung injury marker of Surfactant-Protein-D (SP-D). Pulmonary edema markers of epithelial sodium channel, cystic fibrosis transmembrane conductance regulator, and aquaporin 5 were assessed by RT-PCR. Lung trNK cells were assessed for activation markers of CD107a and NKp46, vitamin D receptor (VDR), and programmed cell death protein-1 (PD-1) via flow cytometry. The bronchoalveolar lavage fluid (BALF) obtained was investigated for soluble receptor for advanced glycation end products (sRAGE), inflammatory cytokines, soluble 1,25(OH)2D, and PDL-1. Naïve mice treated with DMSO (vehicle) were used as a control.ResultsFlow cytometry analysis displayed a high apoptotic rate in alveolar I/II cells of threefold in ALI mice as compared to naïve mice. These findings were accompanied by elevated markers of pulmonary edema as well as lung injury markers of SP-D. Isolated lung trNK cells of the ALI mice exhibited reduced CD107a and NKp46 markers and cytotoxicity potentials and were correlated through significantly 2.1-fold higher levels of PD-1 and diminished VDR expressions as compared to naïve mice. BALF samples of ALI mice displayed high soluble PDL-1 and reduced soluble 1,25(OH)2D levels compared to naïve mice. 1,25(OH)2D treatment alongside OA led to a significant fourfold increase in the CD107a and NKp46 expressions to levels higher than the mice treated with the vehicle. Furthermore, 1,25(OH)2D ameliorates free radical scavengers of GSH, GPX, CAT, and GPx-1; decreased pro-inflammatory cytokines and soluble PDL-1; and increased soluble 1,25(OH)2D with amelioration in pulmonary edema markers and alveolar I/II apoptosis.ConclusionOur results indicate 1,25(OH)2D’s potential therapeutic effect in preventing clinical outcomes associated with ALI via regulating NK cells through inhibiting inflammatory cytokines and alleviating levels of PDL-1 and 1,25(OH)2D released by lung tissue.
Apigenin inhibits NLRP3 inflammasome activation in monocytes and macrophages independently of CD38
Authors: Lauritzen Knut Husø , Yang Kuan , Frisk Michael , Louwe Mieke C. , Olsen Maria Belland , Ziegler Mathias , Louch William E. , Halvorsen Bente , Aukrust Pål , Yndestad Arne , Sandanger Øystein 
Published: January 2025

IntroductionCD38, a regulator of intracellular calcium signalling, is highly expressed in immune cells. Mice lacking CD38 are very susceptible to acute bacterial infections, implicating CD38 in innate immune responses. The effects of CD38 inhibition on NLRP3 inflammasome activation in human primary monocytes and monocyte-derived macrophages have not been investigated. Apigenin is a naturally occurring flavonoid known to inhibit CD38. However, apigenin has also been proposed to inhibit the extracellular ATP receptor P2XR7, an upstream activator of NLRP3. In this study we aimed to investigate whether apigenin attenuates NLRP3 inflammasome activation in human monocytes and monocyte-derived macrophages through CD38 inhibition. MethodsLPS-primed human monocytes and monocyte-derived macrophages were treated with apigenin, the CD38 inhibitor 78c, antagonists of CD38 second messengers (8-br-ADPR and 8-br-cADPR) or the ATP hydrolase, apyrase, prior to NLRP3 activation with ATP, monosodium urate crystals (MSU) or nigericin. IL-1β and TNF secretion and mRNA expression, as well as N-terminal gasdermin-D formation were quantified. Ca2+ mobilization was determined by live confocal microscopy. NLRP3 activity was also compared in WT and CD38-/- mouse bone marrow-derived macrophages (BMDMs) with and without CD38 inhibitors.ResultsApigenin significantly inhibited IL-1β release from LPS-primed monocytes and macrophages activated with ATP, MSU, or nigericin. CD38 inhibition with 78c also attenuated NLRP3-dependent IL-1β release. Apigenin was a potent inhibitor of Ca2+ flux from the endoplasmic reticulum to the cytosol in human monocyte-derived macrophages. Apyrase attenuated IL-1β release induced by ATP or MSU, but not by nigericin. However, the NLRP3 inflammasome is not compromised in CD38-/- bone marrow-derived macrophages compared to corresponding WT cells, and apigenin moderated IL-1β release in both genotypes. DiscussionOur data support that apigenin attenuates NLRP3 activation independently of CD38. Our results also suggest that MSU crystals activate NLRP3 through autocrine or paracrine ATP signalling.
Impact of glioma metabolism-related gene ALPK1 on tumor immune heterogeneity and the regulation of the TGF-β pathway
Authors: Hu YaoFeng , Qin Sen , Deng RuCui 
Published: January 2025

BackgroundRecent years have seen persistently poor prognoses for glioma patients. Therefore, exploring the molecular subtyping of gliomas, identifying novel prognostic biomarkers, and understanding the characteristics of their immune microenvironments are crucial for improving treatment strategies and patient outcomes.MethodsWe integrated glioma datasets from multiple sources, employing Non-negative Matrix Factorization (NMF) to cluster samples and filter for differentially expressed metabolic genes. Additionally, we utilized Weighted Gene Co-expression Network Analysis (WGCNA) to identify key genes. A predictive model was developed utilizing the optimal consistency index derived from a combination of 101 machine learning techniques, and its effectiveness was confirmed through multiple datasets employing different methodologies. In-depth analyses were conducted on immune cell infiltration and tumor microenvironmental aspects. Single-cell sequencing data were employed for clustering and differential expression analysis of genes associated with glioma. Finally, the immune relevance of the model gene ALPK1 in the context of pan-cancer was explored, including its relationship with immune checkpoints.ResultsThe application of NMF, coupled with differential analysis of metabolic-related genes, led to the identification of two clusters exhibiting significant differences in survival, age, and metabolic gene expression among patients. Core genes were identified through WGCNA, and a total of 101 machine learning models were constructed, with LASSO+GBM selected as the optimal model, demonstrating robust validation performance. Comprehensive analyses revealed that high-risk groups exhibited greater expression of specific genes, with ALPK1 showing significant correlations with immune regulation.ConclusionThis research employed a multi-dataset strategy and various methods to clarify the differences in metabolic traits and immune conditions in glioma patients, while creating an innovative prognostic risk evaluation framework. These results offer fresh perspectives on the intricate biological processes that define gliomas.
An intelligent manufacturing system based on a recursive control structure
Authors: Teng Bingyan 
Published: January 2025

IntroductionThe excessive uncertainty of in modern manufacturing systems is caused by machine failures, changes in material information, and other factors. In addition, the organizational production mode conflicts brought about by economic and technological development further exacerbate the perception of workshop interference in manufacturing systems.MethodIn order to further improve the adaptability of manufacturing systems, a control technique based on recursive control structure is proposed, which introduces an immune working mechanism to design the framework network of multi-agent manufacturing systems. Meanwhile, a negative selection algorithm is used to construct an antibody training system that considers perturbation problems.ResultThe results indicate that immune sensing nodes can effectively monitor manufacturing systems, reducing false alarm rates by over 4%. In the scheduling experiment, the completion time and equipment load improvement rate demonstrated by the research model were 3.29% and 12.38%, respectively. The production balance optimization rate exceeded 90%, far exceeding the results of traditional scheduling schemes, greatly improving the adaptive control capability of manufacturing system production.DiscussionThe regulatory approach proposed in this study can provide reference and assistance for improving the level of industrial production intelligence and establishing a sustainable economic system. However, the research results have not been applied to actual production processes, and the autonomy and coordination of intelligent manufacturing units in actual production processes still need to be further improved. In the future, research models and algorithms will be further explored in this area.
Psychological wellbeing and treatment adherence among cardio-renal syndrome patients in Yemen: a cross section study
Authors: Laradhi Adel Omar , Shan Yan , Allawy Mohamed Elsayed 
Published: January 2025

BackgroundAnxiety and depression are associated with adverse outcomes in cardiorenal syndrome patients undergoing hemodialysis, including decreased quality of life, poorer clinical parameters, and lower treatment adherence.ObjectiveThis study aimed to examine the level of psychological wellbeing and its relationship with treatment adherence among dialysis patients with cardiorenal syndrome.MethodsThis cross-sectional descriptive study was conducted between February and May 2021 on convenience sampling of 100 patients in two dialysis centers in Hadhramout, Yemen. Patients’ depression and anxiety levels were assessed using the Hospital Anxiety and Depression Scale (HADS)—Arabic version, and patient treatment adherence was assessed using the Treatment Adherence Questionnaire (TAQ). Descriptive statistics, Pearson’s correlation analysis, and multiple linear regression analyzes were performed to analyze data with a significance level set at p &lt; 0.05.ResultsThe mean age ± standard deviation of participants was 53.46 ± 14.24 years. Most (90%) of patients had moderate to high levels of anxiety and depression. Most of the patients (87%) had a low level of treatment adherence. The findings revealed that psychological wellbeing is significantly association with treatment adherence t = 2.577 (95% CI 0.029, 0.225), p = 0.011.ConclusionAnxiety and depression symptoms occurred more frequently among dialysis patients with cardiorenal syndrome, and there was a significant association between psychological wellbeing and treatment adherence. Our findings suggest that nurse managers should take into account that adding psychotherapies into the present cardiorenal syndrome treatment programs would improve patients’ clinical and psychological parameters and, consequently, their clinical outcomes while taking patient heterogeneity and resource limitations into consideration.