bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blast‐Overpressure Induced Modulation of PARP‐SIRT‐NRF2 Axis in Stress Signaling of Astrocytes and Microglia
Authors: Krishnan Muthaiah Vijaya Prakash , Kaliyappan Kathiravan , Thiayagarajan Ramkumar , Mahajan Supriya , Gunasekaran Krishnamoorthy 
Published: January 2025

ABSTRACTBackgroundThe pathomechanism of blast traumatic brain injury (TBI) and blunt TBI is different. In blast injury, evidence indicates that a single blast exposure can often manifest long‐term neurological impairments. However, its pathomechanism is still elusive, and treatments have been symptomatic. Poly adenosine diphosphate (ADP) ribose polymerase‐1 (PARP1) is implicated in the parthanatos and secondary neuroinflammation. Animal studies indicate the over‐activation of PARP1 as a significant downstream event underlying the neurological sequelae of several traumatic and neurodegenerative disorders, irrespective of the mode of cell death. PARP over‐activation forms ADP polymers on several nuclear proteins, known as trans‐PARylation, by consuming nicotinamide adenine dinucleotide (NAD+) and ATP. As NAD+ is a substrate for sirtuins, ithas also been implicated in the oxidative stress underlying TBI pathology.HypothesisWe recently established the implication of PARP1 following blast overpressure (BOP) and its differential response on astrocytes and microglial cells. We found that the inhibition of PARP is proven beneficial by attenuating oxidative stress. In this study, we hypothesized the involvement of the PARP1‐SIRT‐NRF2 axis following induced blast‐induced PARP over‐activation in glial cells for the manifestation of oxidative stress in BOP insults.ObjectiveThe objective is to determine the downstream modulation of the PARP‐SIRT‐NRF2 axis and changes in ATP levels following blast exposure in astrocytes and microglia cell lines.ResultsAs a result of NAD+ being a common substrate for PARP1 and Sirtuins, we found the decreased expression of SIRT1, SIRT3, and NRF2, a central transcriptional regulator for the expression of antioxidant genes. We found that ATP levels were elevated post‐BOP from both glycolysis and oxidative phosphorylation (OXPHOS), an increase of ATP by glycolysis more significant than OXPHOS source, indicating the proinflammation post‐BOP.ConclusionThis result shows that blast‐induced PARP1 over‐activation impacts the deacetylation activity of sirtuins and consequently impacts the regulation of antioxidant levels in astrocytes and microglia.
CDKN3 as a key regulator of G2M phase in triple‐negative breast cancer: Insights from multi‐transcriptomic analysis
Authors: Ma Haodi , Dong Yirui , Zheng Jiayu , Zhang Shunshun , Tang Siya , Wang Junxiang , Qu Zhifeng , Li Xiucheng , Zeng Li , Song Kena , Liu Chunyan , Shi Linlin , Yin Qinan , Zheng Xuewei 
Published: January 2025

AbstractTriple‐negative breast cancer (TNBC) remains a significant global health challenge, emphasizing the need for precise identification of patients with specific therapeutic targets and those at high risk of metastasis. This study aimed to identify novel therapeutic targets for personalized treatment of TNBC patients by elucidating their roles in cell cycle regulation. Using weighted gene co‐expression network analysis (WGCNA), we identified 83 hub genes by integrating gene expression profiles with clinical pathological grades. A machine learning‐based integrative approach further pinpointed 12 prognostic genes, among which CDKN3 exhibited the highest hazard ratio and the most adverse impact on overall survival (OS) in BC patients. Additionally, CDKN3 was identified as an independent prognostic factor for OS prediction. CDKN3 overexpression was confirmed in BC patients and validated at both mRNA and protein levels in BC cells. Knockdown of CDKN3 significantly inhibited the migration and proliferation of BC cells. Cell cycle pathway analysis revealed significant enrichment in G2M‐associated pathways in BC patients, with multi‐transcriptomic data indicating a close association between enhanced G2M cell cycle activity and CDKN3 upregulation in basal cancer subtypes. Pseudotime analysis further suggested CDKN3 upregulation during the G2M phase at the terminal trajectory of basal cancer subtypes, implying that CDKN3 may drive BC cell progression by promoting G2M cell cycle activity. Mechanistically, CDKN3 knockdown induced G2M cell cycle arrest in TNBC cells by downregulating CCNB2. In conclusion, CDKN3 knockdown effectively inhibits TNBC by arresting the G2M cell cycle, underscoring CDKN3 as a promising therapeutic target in TNBC treatment.
Zinc finger protein 169 promotes tumor progress of hepatocellular cancer via up‐regulating cyclin‐dependent kinase 19
Authors: Hu Chaoquan , Ainiwaer Aizier , Lu Ying , Li Jiaxing , Fu Yongmei , Luo Jun , Wu Baijun , Yin Peng , Hu Xiao , Sun Yao , Li Hong , Lu He , Dong Zheng 
Published: January 2025

AbstractHepatocellular carcinoma (HCC) ranks among the most prevalent types of cancer globally. Zinc finger protein 169 (ZNF169) holds significant importance as a transcription factor, yet its precise function in HCC remains to be elucidated. This study aims to examine the clinical importance, biological functions, and molecular pathways associated with ZNF169 in the development of HCC. The study employed lentiviral transduction for ZNF169 overexpression and the use of small interfering RNAs (siRNAs) to suppress its expression. ZNF169 was upregulated in HCC tissues and cell lines. Additionally, HCC patients exhibiting elevated ZNF169 levels experienced reduced overall survival, shorter disease‐free survival, and diminished progression‐free survival. Silencing of ZNF169 inhibited cell proliferation, migration, and cell cycle progression. Whereas ectopic expression of ZNF169 promoted HCC progression in vivo and ex vivo. Subsequently, Pearson analysis results showed that cyclin‐dependent kinase 19 (CDK19) was positively correlated with ZNF169 levels in HCC using TCGA dataset. Luciferase assay findings indicated a potential interaction between ZNF169 and CDK19 promoter. Additionally, our data showed that CDK19 expression levels were elevated in HCC tissues, and patients with higher CDK19 expression faced a poorer prognosis. Furthermore, recovery experiments demonstrated that CDK19 could reverse the impact of ZNF169 on HCC cell amplification. Our findings indicate that ZNF169 promotes HCC progression by upregulating CDK19, highlighting its role as a therapeutic target or prognostic biomarker for HCC.
Sirtuin 1 Suppresses Hydrogen Peroxide‐Induced Senescence and Promotes Viability and Migration in Lens Epithelial Cells by Inhibiting Forkhead Box Protein O1/Toll‐Like Receptor 4 Pathway
Authors: Jiang Hongda , Liu Yuting , Yu Yinggui , Yan Yu 
Published: January 2025

ABSTRACTAge‐related cataracts (ARCs) are associated with increased oxidative stress and cellular senescence. Our objective is to investigate the function of Sirtuin 1 (SIRT1) within ARCs. In ARCs tissues and H2O2‐treated lens epithelial cells (LECs), the expression levels of SIRT1 were examined. Senescence‐associated β‐galactosidase (SA‐β‐gal) staining was employed to evaluate cellular senescence. The Cell Counting Kit‐8 assay was employed to measure viability. A wound healing assay was performed to assess migratory capacity in LECs. Oxidative stress‐related indicators were determined by enzyme‐linked immunosorbent assay kits. Additionally, the Coxpresdb and GeneCards databases were utilized to identify downstream pathways of SIRT1 in ARCs. The expression levels of protein and mRNA were detected using western blot and real‐time quantitative polymerase chain reaction, respectively. The expression of SIRT1 was downregulated in ARCs tissues with an increase in reactive oxygen species. In H2O2‐induced LECs, SIRT1 was downregulated and its overexpression inhibited oxidative stress and cellular senescence while promoting viability and migration. Furthermore, FoxO1/TLR4 pathway was screened out as the key pathway of SIRT1, which was activated in H2O2‐induced LECs senescence. Overexpression of SIRT1 suppressed FoxO1/TLR4 pathway. Further research demonstrated that the activation of FoxO1/TLR4 pathway reversed the inhibitory role of SIRT1 in oxidative stress‐induced cellular senescence and the promotion effect of SIRT1 on viability and migration in H2O2‐induced LECs. SIRT1 inhibits oxidative stress‐induced cellular senescence and promotes the viability and migration in H2O2‐induced LECs via suppressing FoxO1/TLR4 pathway.
Hybrid Unsupervised/Supervised Machine Learning for Identifying Molecular Structural Fingerprints From Ensemble Property
Authors: Choudhury Arpan , Ghosh Debashree 
Published: January 2025

ABSTRACTThe ensemble properties of a system are obtained by averaging over the properties calculated for the various configurations it can have at a finite temperature and thus cannot be captured by a single molecular structure. Such ensemble properties are often important in material discovery. In designing new materials, the goal is to predict those ensemble structures that display a tailored property. However, mapping this average property to multiple structures introduces ambiguities and unreliable convergence in supervised machine learning. This presents a major obstacle in designing new materials. Here, we introduce a hybrid unsupervised/supervised learning method and demonstrate how to predict the structural parameters defining the conformers of a heterogeneous system, melanin, from its ensemble‐averaged spectra. This also shows a new way to identify different structural fingerprints responsible for an ensemble‐averaged superposition spectrum.
NK Count and Natural Cytotoxicity in Immune Nonresponders Versus Responders Living With HIV
Authors: Silvestre Charlotte , Tuaillon Edouard , Duroyon Maël‐Morvan , Abrantes Magali , Thibout Jenny‐Constanza , Villalba Martin , Picot Marie‐Christine , Gross Antoine , Makinson Alain 
Published: January 2025

AbstractDespite viral suppression with antiretroviral therapy, immune nonresponders (INR) among people living with HIV (PLWH) still have a higher risk of developing AIDS‐related and non‐AIDS‐related complications. Our study aimed to investigate the phenotype and functions of Natural Killer (NK) cells in INR, to better understand underlying mechanisms of immune nonresponse. Our cross‐sectional study included PLWH aged over 45 with an undetectable HIV viral load sustained for at least 2 years. Participant CD4+ T‐cell counts exceeded 500 cells/mm3 for IR or below 350 cells/mm3 for INR. We characterized NK cell subsets, performed natural cytotoxicity and ADCC assays, and phenotyped NK cells before and after functional assays. Median CD4 levels were 247.5 (IQR, 208.8–286.3) cells/mm3 and 768.5 (IQR, 673.3–957.8) cells/mm3 in the INR (n = 20) and IR (n = 40), respectively. NK cell counts were lower in INR (p = 0.00066), but the percentages were similar between IR and INR. NKG2A was the only differentially expressed marker between groups, showing higher expression in INR. Additionally, NK cell natural cytotoxicity was elevated in the INR group. Multivariate analyses associated CD4 nadir and low NK cell count with immune nonresponse. Our results do not indicate a clear role for NK‐mediated ADCC in immune nonresponse. We did not objectify an association between CD8 hyperactivation and INR.
A Novel HTNV Budding Inhibitor Interferes the Interaction Between Viral Glycoprotein and Host ESCRT Accessory Protein ALIX
Authors: Ying Qikang , Zhang Xiaoxiao , Wang Shengzheng , Gu Tianle , Zhang Junmei , Feng Wenjie , Li Dongjing , Dong Yuhang , Wu Xingan , Wang Fang 
Published: January 2025

ABSTRACTVirus budding is a critical step in the replication cycle of enveloped viruses, closely linked to viral spread, disease progression, and clinical outcomes. The budding of many enveloped RNA viruses is facilitated by the hijacking of the host endosomal sorting complex required for transport (ESCRT) proteins through viral late domains. These late domains are essential for progeny virus production and are highly conserved, making the interaction between late domains and host ESCRT proteins a potential target for the development of antiviral therapeutics. In this study, we elucidated the functional role of the conserved YRTL motif within the glycoprotein Gn cytoplasmic tail of Orthohantavirus hantanense (Hantaan virus, HTNV), demonstrating that HTNV production is regulated by the interaction between YRTL and the ESCRT accessory protein ALIX (ALG‐2 interacting protein X). Through virtual molecule docking screening, followed by in vitro and in vivo assays, we discovered a novel compound, AN‐329, which disrupts the YRTL−ALIX interaction and effectively inhibits infectious HTNV production, as well as Crimean−Congo hemorrhagic fever virus (CCHFV) and Rift Valley fever virus (RVFV) VLP release. This makes AN‐329 a promising therapeutic candidate for reducing viral dissemination. Given that YRTL is conserved across many hantaviruses, our findings may serve as a prototype for the development of broad‐spectrum antiviral drugs.
Building a Bridge Between the Mechanism of EBV Reactivation and the Treatment of EBV‐Associated Cancers
Authors: Jiang Jialin , Zhu Xinlei , Li Shukun , Yan Qun , Ma Jian 
Published: January 2025

ABSTRACTEpstein‐Barr virus (EBV) infection is closely associated with the development of various tumors such as lymphomas and epithelial cancers. EBV has a discrete life cycle with latency and lytic phases. In recent years, significant progress has been made in the understanding of the mechanism underlying the transition of EBV from latency to lytic replication. Multiple new lytic activation factors have been emerged and promoted our understanding of this field. In addition, we have comprehensively presented the existing therapeutic strategies and their relationship to the mechanism underlying the transition of EBV from latency to lytic replication in this review, such as lytic induction therapy and drugs to prevent EBV from entering the lytic phase fully utilize the EBV reactivation mechanisms. This year marks the 60th anniversary of the discovery of EBV, and building a bridge between the mechanism of EBV reactivation and the treatment may help us to design new approaches for treating EBV‐associated diseases.
Separation and quantification of mycotoxins in floral tissue of hemp (Cannabis sativa) infected with Fusarium graminearum
Authors: Kagan Isabelle A. , Smith Henry S. , Schendel Rachel R. , Gauthier Nicole 
Published: January 2025

AbstractBackgroundThe fungal pathogen Fusarium graminearum produces mycotoxins when it infects grains. This pathogen also infects hemp (Cannabis sativa L. containing less than 0.3% tetrahydrocannabinol or THC). The presence of trichothecene mycotoxins like deoxynivalenol (DON) has not been reported in floral tissue of hemp infected with F. graminearum. The object of this study was to develop a method to extract three trichothecene mycotoxins—DON, 3‐acetyldeoxynivalenol (3‐ADON), and 15‐acetyldeoxynivalenol (15‐ADON)—from hemp floral tissue, and to quantify the mycotoxins by high‐performance liquid chromatography (HPLC) with ultraviolet detection.ResultsStandards of nivalenol (NIV), DON‐3‐glucoside (D3G), DON, 3‐ADON, and 15‐ADON were separated from each other and from standards of several cannabinoids. Standard curves were linear (R‐squared values >0.99). Recoveries from hemp spiked with 36 μg/g mycotoxins were 86%–90% for DON, 75%–77% for 15‐ADON, and 86%–101% for 3‐ADON. In extracts of hemp inflorescences infected with different strains of F. graminearum (15‐ADON chemotypes), DON was detected in one sample. Other samples contained 15‐ADON but no detectable DON, or neither mycotoxin in detectable amounts.ConclusionMycotoxins were separated from cannabinoids. DON was also separated from matrix components, and 15‐ADON and 3‐ADON were partially separated from matrix components. The presence of DON in hemp may depend on fungal strain or stage of disease development, as well as the sensitivity of the method. The current method could quantify DON and 15‐ADON at about 3 μg/g in hemp floral tissue, and 3‐ADON at about 6 μg/g.
Shear Wave Elastography as an Supplement Tool in Differentiating Benign and Malignant Axillary Lymph Nodes
Authors: Sharma Aishwarya , Kaur Ravinder , Kaur Narinder , Handa Uma , Dalal Usha , Gupta Anurag 
Published: January 2025

ObjectivesTo determine the efficacy of quantitative shear wave elastography in differentiating benign and malignant axillary lymph nodes (ALN).MethodsExactly 127 lymph nodes from 127 patients with clinically palpable axillary swelling were examined by both B‐mode sonography and elastography from November 2022 to March 2024. Gray‐scale sonograms were evaluated based on: the short‐axis diameter, shape, hilum, maximum cortical thickness, and border of the ALN. Shear wave elastography determined the mean elasticity modulus (E‐mean) and elasticity ratio (E‐ratio). Fine needle aspiration cytology or histopathological examination was kept as the gold standard and diagnostic performance shear wave elastography was compared.ResultsThe data showed that out of 127 lymph nodes, 77 (60.6%) were benign and 50 (39.4%) were malignant based on pathological results. The E‐mean for malignant lymph nodes (mean, 73.15 kPa) was higher than that for benign lymph nodes (mean, 21.47 kPa; P < .001). The area under the receiver operating characteristic curve for E‐ratio in predicting malignant and benign lymph nodes was 0.897 (95% CI: 0.839–0.955). The E‐ratio for malignant lymph nodes was also higher (mean, 10.2) than for benign nodes (mean, 2.95; P < .001). The area under the receiver operating characteristic curve for E‐ratio in predicting malignant and benign lymph nodes was 0.816 (95% CI: 0.733–0.899).ConclusionOur results showed a significant association between tissue elasticity and pathological correlation.
Airway stenosis: classification, pathogenesis, and clinical management
Authors: Zhao Pengwei , Jiang Zheng , Li Xuexin , Ainiwaer Mailudan , Li Leyu , Wang Dejuan , Fan Lixiao , Chen Fei , Liu Jun 
Published: January 2025

AbstractAirway stenosis (AS) is a fibroinflammatory disease characterized by abnormal activation of fibroblasts and excessive synthesis of extracellular matrix, which has puzzled many doctors despite its relatively low prevalence. Traditional treatment such as endoscopic surgery, open surgery, and adjuvant therapy have many disadvantages and are limited in the treatment of patients with recurrent AS. Therefore, it is urgent to reveal the pathogenesis of AS and accelerate its clinical transformation. Based on the discovered pathogenesis, including fibrosis, inflammation, epithelial–mesenchymal transition, metabolic reprogramming, microbiome, genetic susceptibility, and other mechanisms, researchers have developed a series of treatments, such as drug therapy, gene therapy, stem cell therapy, growth factor therapy, protein therapy, and photodynamic therapy. This review introduces the classification of AS, explores the existing pathogenesis and preclinical treatments developed based on the pathogenesis, and finally summarizes the current clinical management. In addition, the prospect of exploring the interaction between different types of cells and between microorganisms and cells to identify the intersection of multiple mechanisms based on single‐cell RNA sequencing, 16S rRNA gene sequencing and shotgun metagenomic sequencing is worth looking forward to.
A Short Cognitive and Neuropsychiatric Assessment Scale for Progressive Supranuclear Palsy
Authors: Porsche Sonja , Klietz Martin , Greten Stephan , Piot Ines A. , Jensen Ida , Wegner Florian , Ye Lan , Krey Lea , Höllerhage Matthias , Pötter‐Nerger Monika , Zeitzschel Molly , Hagena Keno , Kassubek Jan , Süß Patrick , Winkler Jürgen , Berg Daniela , Paschen Steffen , Tönges Lars , Gruber Doreen , Gandor Florin , Jost Wolfgang H. , Kühn Andrea A. , Claus Inga , Warnecke Tobias , Pedrosa David J. , Eggers Carsten , Trenkwalder Claudia , Classen Joseph , Schwarz Johannes , Schnitzler Alfons , Krause Patricia , Schneider Anja , Brandt Moritz , Falkenburger Björn , Zerr Inga , Bähr Mathias , Weidinger Endy , Levin Johannes , Katzdobler Sabrina , Düzel Emrah , Glanz Wenzel , Teipel Stefan , Kilimann Ingo , Prudlo Johannes , Gasser Thomas , Brockmann Kathrin , Spottke Annika , Esser Anna , Petzold Gabor C. , Respondek Gesine , Höglinger Günter U. 
Published: January 2025

AbstractBackgroundPatients with Progressive Supranuclear Palsy (PSP) suffer from several neuropsychological impairments. These mainly affect the frontal lobe and subcortical brain structures. However, a scale for the assessment of cognitive and neuropsychiatric disability in PSP is still missing.ObjectivesTo create and validate a new scale for cognitive and neuropsychiatric impairment in PSP.MethodsThe Short Cognitive and Neuropsychiatric (ShoCo) scale was developed containing five items (bradyphrenia, apathy, aphasia, dysexecution and disinhibition). Each item can be categorized into 0 = no deficit, 1 = mild deficit, 2 = moderate deficit and 3 = severe deficit. The total score includes 15 points, 0 meaning no deficit and 15 severe deficits. Cross‐sectional and longitudinal data from 201 baseline and 71 follow up patients were analyzed.ResultsBaseline ShoCo scale results were 5.9 ± 2.9. No significant differences between patients with Richardson syndrome (PSP‐RS) and variants (vPSP) could be detected in the PSP‐ShoCo scale scores (PSP‐RS 6.1 ± 3.0, n = 160, vPSP 5.1 ± 2.6, n = 41, P = 0.057). The scale showed good correlation with established scores (eg, Montreal cognitive assessment r = −0.535, P = 0.001). The ShoCo scale showed significant annualized change within the PSP‐RS patients (baseline 6.2 ± 2.9, follow up 6.9 ± 3.1, annualized diff. 1.0 ± 3.1, n = 57, P = 0.022).ConclusionsThe ShoCo scale seems a promising and valid tool to measure specific neuropsychological disabilities of PSP patients in clinical routine and research.
Systematic Review of the Presentation, Treatment, and Outcome of Chronic Disseminated Candidiasis in Children with Cancer or Following Hematopoietic Cell Transplant
Authors: Eagling‐Every Emelia , Tsoi Shu Ki , Walker Hannah , Haeusler Gabrielle M. 
Published: January 2025

ABSTRACTChronic disseminated candidiasis (CDC) is a rare complication of immunosuppression. This review describes the presentation, management, and outcomes of CDC in pediatric patients with cancer or following hematopoietic cell transplant (HCT). PubMed, Embase, and Medline were searched identifying 32 studies, describing 95 cases of CDC. CDC occurred almost exclusively in patients with leukemia (91%), with only 5% occurring in lymphoma, 1% post HCT, and 3% in solid tumor. The most frequent presenting symptoms were fever (97%) and abdominal pain (45%), with lesions in liver in 63% and spleen in 54% (less common in kidney, lungs and skin/soft tissue). Of the 67 (71%) episodes with microbiological confirmation, Candida tropicalis (28%) was the most common causative species. Antifungal treatment durations varied from 14 days to 28 months. Additionally, 31 (33%) patients received an adjuvant therapy, the most common being corticosteroids. Mortality, directly attributable to CDC, occurred in nine (9%). There remains insufficient data to guide a unified approach to management.