bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical Toxicological Assessment of 2‐(Benzoxazol‐2‐yl)[(2‐hydroxynaphthyl)diazenyl]phenol Derivatives for Blue Light and UV Radiation Photoprotection Applications
Authors: Sousa Karen , Corrêa Dione Silva , de Oliveira João Denis Medeiros , Rieth Gabriel Beilfuss , da Silva Juliana , Paczkowski Ingrid Maliszewski , Campo Leandra Franciscato , Grivicich Ivana , Picada Jaqueline Nascimento 
Published: January 2025

ABSTRACTThe widespread use of electronic devices has led to increased blue light exposure, highlighting the need for effective radiation blockers with blue light protection. Two synthetic 2‐(2′‐hydroxyphenyl)benzoxazole derivatives named azo‐4′‐benzoxazole and azo‐5′‐benzoxazole have shown an unprecedented blue light absorption capacity but had not been subjected to a safety evaluation. This study aimed to evaluate the cytotoxic, genotoxic, and mutagenic activities of these compounds. The cytotoxic and genotoxic activities were evaluated using MTT assay and comet assay in L929 fibroblast cells. Salmonella/microsome assay and micronucleus test were performed to detect gene and chromosomal mutations. The IC50 was 87.9 μg/mL for azo‐4′‐benzoxazole and 79.5 μg/mL for azo‐5′‐benzoxazole. In the Salmonella/microsome assay, the azo‐5′‐benzoxazole compound induced frameshift mutations in the TA97a strain in the presence of metabolic activation (S9 mix), while azo‐4′‐benzoxazole did not show mutagenic activities in all five strains tested. The azo‐5′‐benzoxazole showed genotoxic and mutagenic effects in L929 cells that were probably associated to the cleavage of azo‐5′ into its analogs 2‐(4′‐amino‐2′‐hydroxyphenyl)benzoxazole and 2‐amino‐1‐naphthol. In conclusion, the azo‐substituted group at the 5′ position of the phenyl ring appears to have greater toxicological risks than substituents at the 4′ position of 2‐(phenyl)benzoxazole. The findings warrant further preclinical studies to ensure the safety of these compounds for use as blue light filters.
The Pro‐Migratory and Pro‐Invasive Roles of Cancer‐Associated Fibroblasts Secreted IL‐17A in Prostate Cancer
Authors: Gao Feng , Chen Xuren , Li Xinyu , Deng Chunhua , Luo Peng 
Published: January 2025

ABSTRACTCancer‐associated fibroblasts (CAFs) are key stroma cells that play dominant roles in the migration and invasion of several types of cancer through the secretion of inflammatory cytokine IL‐17A. This study aims to identify the potential role and regulatory mechanism of CAFs‐secreted IL‐17A in the migration and invasion of prostate cancer (PC). CAFs and normal fibroblasts (NFs) were obtained from fresh PC and its adjacent normal tissues, respectively. PC cells LNCaP and DU145 were co‐cultured with the conditioned medium from the CAFs and NFs. IL‐17A level was determined by ELISA in the cell supernatant. CCK‐8, wound healing, Transwell assay, western blot analysis, staining, and primary PC lung metastasis assays were employed in vivo or in vitro to explore the effect of CAFs and IL‐17A secreted by them on proliferation, migration, invasion, epithelial−mesenchymal transition (EMT) and metastasis of PC. CAFs stimulated the migration and invasion of PC cells. Importantly, CAFs exerted their roles by directly secreting IL‐17A, leading to a significant increase in migration and invasion in PC cells. Mechanically, IL‐17A promoted Smad3/p38 MAPK pathway‐mediated EMT process, contributing to cell migration and invasion. Furthermore, CAFs secreting IL‐17A activated the Smad3/p38 MAPK pathway and thus facilitated tumor growth and metastasis in nude mice. This study identifies a novel signaling pathway by which CAFs mediate migration and invasion of PC via upregulation of Smad3/p38 MAPK‐mediated EMT in an IL‐17A‐dependent manner.
Estrogen Promotes the Proliferation and Migration of Endometrial Cancer Through the GPER‐Mediated NOTCH Pathway
Authors: Qi Meng , Jin Yuxi , Si Lulu , Fu Hanlin , Shi Xiaojing , Liu Yana , Wang Yifan , Guo Ruixia 
Published: January 2025

ABSTRACTThis study aims to investigate the expression of GPER in EC, assess the impact of estrogen on the proliferation and migration of EC via GPER, and examine the potential role of GPER in mediating the NOTCH pathway to influence EC proliferation and migration. The expression of GPER and its correlation with clinicopathological features were investigated using clinical data. Cell proliferation was assessed through MTT and EdU assays, while cell migration ability was evaluated using wound healing and transwell assays. Western blot analysis was conducted to detect proteins associated with the GPER and NOTCH signaling pathways. Additionally, xenograft tumor models were established to investigate the potential role of estrogen in mediating the NOTCH pathway via GPER. The results demonstrated a significant upregulation of GPER expression in EC, which was associated with clinical stage and metastasis. In vitro experiments provided evidence that estrogen promotes EC cell proliferation and metastasis by enhancing the expression levels of GPER, Notch1, and Hes‐1 proteins. Conversely, knocking down or suppressing GPER effectively reverses these effects. Furthermore, treatment with JAG‐1, an agonist for the NOTCH pathway, counteracts si‐GPER's inhibitory impact on both proliferation and migration abilities of EC cells while increasing Notch1 and Hes‐1 protein expression levels; however, it does not alter GPER expression. In vivo experiments have substantiated that estrogen facilitates EC proliferation via the GPER‐mediated NOTCH pathway.
Demography, Pleasure, State, and Market in Socialist Sexology: Medical‐Sexological and Sexual‐Psychological Public Discourse in Socialist Hungary Through Counseling Books From a Social‐Political Perspective
Authors: Csányi Gergely 
Published: January 2025

ABSTRACTThis paper analyzes medical‐sexological and sexual‐psychological public discourse in Hungary between the Second World War and the regime change, through counseling and science communication books. It engages with works on the history of Hungarian socialist sexual discourse. It differs from such works in two main respects. One is the method of selection of analyzed content: for this study, I systematically included in the database all of the books of two Budapest libraries. The second one is the framing: compared to previous work, I place more emphasis on the political embeddedness of the discourse and how the changing geopolitical situation of Hungary affected the discourse. I argue that discourse trends, initially responding to negative demographic trends the high number of divorces, evolved due to Hungary's “Westernization” and market logic, and the promotion of female sexual pleasure and socialist romanticism becoming increasingly pornified and technical between the 1970s and the regime change.
Surrogate Modeling for Drive Co‐Simulation Including Local Irreversible Demagnetization Knowledge
Authors: Henneron T. , Tomezyk J. , Semail E. 
Published: January 2025

ABSTRACTIn order to survey possible local demagnetization of permanent magnet drives during transient operations and/or faulty functioning in case of multi‐phase drives, co‐simulation including converter, vector control, and finite element model could be investigated. Nevertheless, expensive simulation time limits practically this solution. To solve this problem, the paper proposes a surrogate model of an electrical machine taking into account locally the irreversible demagnetization effect. In case of a multi‐phase machine working in transient operations and irreversible demagnetization, the proposed surrogate model gives large benefit in computational time in comparison with an finite element approach.
Interplay Among Recent Trends in Climate Extremes, Vegetation Phenology, and Crop Production in the Southern Mediterranean Region
Authors: Mirgol Behnam , Dieppois Bastien , Northey Jessica , Jarlan Lionel , Khabba Saïd , Le Page Michel , Eden Jonathan , Ekolu Job , El Hazdour Ikram , Mahe Gil 
Published: January 2025

ABSTRACTThe southern Mediterranean region is among the most vulnerable areas to climate change globally. However, in this region, there is a need to further understand the complex interactions between climate, vegetation, and crops to fully assess the combined impacts of extreme climate events on the agricultural sector. Using daily Normalised Difference Vegetation Index (NDVI) data, we evaluated trends across 15 vegetation phenology indicators between 1982 and 2019 and analysed their links to land‐use land‐cover changes. We found significant increases in the maximum value of NDVI (MaxV), length of growing seasons (LengthGS), and duration from crop emergence to anthesis (BMaxT), particularly within croplands. These changes positively correlated with regional crop production, especially in coastal and interior plains where croplands and forests are expanding. Conversely, southern areas bordering the Sahara showed declining MaxV and an expansion of sparsely vegetated areas. We then conducted a comprehensive seasonal trend analysis of climatic stresses and discussed how they align with recent trends in key phenological indicators. Coastal and interior plains experienced wetter conditions throughout the year, ensuring sufficient water during the growing season. Meanwhile, areas bordering the Sahara had wetter autumns and winters but drier springs and summers. Additionally, the region experienced warmer conditions from spring to autumn, with fewer cold wave events. Analysing the frequency and duration of compound extreme events, we observed a trend toward more light to moderate dry/hot days in spring and autumn and light to extreme wet/hot days from summer to autumn. These conditions are significantly correlated with increased MaxV, improved crop productivity, and extended LengthGS and BMaxT. These findings may serve as early indicators of how future climate changes could impact crop production, highlighting regional risks and opportunities to guide informed decision‐making and development of adaptive strategies in the southern Mediterranean region.
Association between enteral carboxymethyllysine intake and daily glycemic variability in critically ill adults: A retrospective cohort study
Authors: Doola Ra'eesa , Griffin Alison , Forbes Josephine M. , Kruger Peter S. , Deane Adam M. , Schalkwijk Casper G. , White Kyle C. 
Published: January 2025

AbstractBackgroundAdvanced glycation end‐products (AGEs) can enter patients' circulation through exogenous sources, such as enteral nutrition formulae. Circulating AGEs, specifically carboxymethyllysine, can promote insulin resistance and activation of pro‐inflammatory pathways leading to oxidative stress, cell death, and organ failure. Suboptimal kidney function increases the risk of elevated circulating AGEs because levels are controlled through urinary excretion. Our aim was to determine associations between carboxymethyllysine intake and glycemic control as well as clinical outcomes in critically ill patients and explore these in the subset of patients with an acute kidney injury (AKI).MethodsThis was a retrospective cohort study. Data were extracted from electronic medical records. Patients were eligible if they were ≥18 years and received enteral nutrition, with known carboxymethyllysine content, for ≥3 days. AKI was defined using the Kidney Disease: Improving Global Outcomes guidelines. Linear and logistic regression models were used to determine adjusted associations.ResultsBetween 2015 and 2021, 2636 patients met the eligibility criteria, with 848 (32%) patients having an AKI. Most were male (n = 1752, 67%) with a median (interquartile range) Acute Physiology And Chronic Health Evaluation III score of 59 (45–77). For every 10‐μmol increase in carboxymethyllysine provision, mean blood glucose increased by 0.05 mmol (95% CI, 0.03–0.07), and the odds of dying increased by 16% (odds ratio = 1.16; 95% CI, 1.06–1.27). A subgroup analysis indicated these associations persisted in patients with AKI but not in those without.ConclusionCarboxymethyllysine intake was associated with increased mean blood glucose and odds of dying in our study cohort.
CTCs Detection Methods In Vivo and In Vitro and Their Application in Tumor Immunotherapy
Authors: Sui Xiujie , Ji Jiahao , Zhang Hongyi 
Published: January 2025

ABSTRACTCirculating tumor cells (CTCs) are tumor cells that detach from the primary tumor site and enter the bloodstream. They hold significant value for the early detection, diagnosis, and treatment of tumors. CTC detection methods can be classified into in vivo and in vitro techniques. Compared to traditional tumor detection methods, CTC detection causes less harm to the body and allows for earlier identification of malignant tumors, thereby enabling timely treatment and improving patient survival rates. In recent years, CTC detection has been widely used to assess the effectiveness of tumor immunotherapy. Dynamic monitoring of CTCs can help optimize clinical treatment strategies. This review summarizes the latest in vivo and in vitro detection methods for CTCs and discusses their applications in immunotherapy for various common tumors, aiming to provide better guidance and support for clinical practice.
Explorative Study of Modulatory Effects of Notochordal Cell‐Derived Extracellular Vesicles on the IL‐1β‐Induced Catabolic Cascade in Nucleus Pulposus Cell Pellets and Explants
Authors: van Maanen J. C. , Bach F. C. , Snuggs J. W. , Ito K. , Wauben M. H. M. , Le Maitre C. L. , Tryfonidou M. A. 
Published: January 2025

ABSTRACTBackgroundCell‐free regenerative strategies, such as notochordal cell (NC)‐derived extracellular vesicles (EVs), are an attractive alternative in developing new therapies for intervertebral disc (IVD) degeneration. NC‐EVs have been reported to elicit matrix anabolic effects on nucleus pulposus cells from degenerated IVDs cultured under basal conditions. However, the degenerative process is exacerbated by pro‐inflammatory cytokines contributing to the vicious degenerative cycle. Therefore, this study explores whether NC‐EVs modulate interleukin (IL)‐1β‐mediated pro‐inflammatory responses in the degenerating disc.MethodsThis study utilized two IL‐1β induced pro‐catabolic culture models; a dog 3D nucleus pulposus (NP) cell pellet culture and a human patient‐derived, ex vivo NP tissue culture system. Porcine NC‐EVs were generated from NC‐conditioned medium by differential centrifugation followed by size exclusion chromatography. Donor matched EV‐depleted media were generated by overnight ultracentrifugation, whereafter the EV‐depleted NCCM supernatant was subjected to size exclusion chromatography. To investigate whether observed effects were EV‐associated, NC‐EVs conditions were compared to EV‐depleted controls in the absence and presence of IL‐1β.ResultsThe size and concentration of NC‐EVs were quantified by nanoparticle tracking analysis, which showed minimal donor variation and confirmed depletion of EVs in the EV‐depleted media. In the IL‐1β‐induced catabolic cascade, the NC‐EVs did not elicit anabolic effects at the matrix level nor did they rescue the pro‐catabolic phenotype within dog pellets. Modification of the CCL2 secretion seemed to be context dependent in the human explants: where EVs treatment stimulated CCL2 secretion but in the presence of IL‐1β this effect was counteracted. Secretion of IL‐6 and C‐X‐C motif chemokine ligand 1 was significantly decreased in NC‐EV + IL‐1β vs. control+IL‐1β but not compared to EV‐depleted human explant controls. Altogether, this data provides evidence for a protective modulatory role of NC‐EVs. Considering the homeostatic function EVs exert, inherently encompassing subtle biologic modifications, the current study may have lacked sufficient power to demonstrate statistical significance in a sample set with evident donor variation.ConclusionsNC‐EVs may modulate the production of specific cytokines and chemokines in human degenerate explants when the key pro‐inflammatory cytokine IL‐1β is present. Implementation of the technical EV‐depleted controls in further studies is essential to robustly demonstrate that these effects are EV‐mediated and not associated with other secreted factors co‐isolated during EV‐isolation.
Ultrasound Predicts Drug‐Induced Sleep Endoscopy Findings Using Machine Learning Models
Authors: Jones Samuel E. , Aw Natalie , Acord Molly , Miller Sarah , Sidelnikov Danielle , Haft Sunny J. , Restaino Stephen M. 
Published: January 2025

ObjectivesUltrasound is a promising low‐risk imaging modality that can provide objective airway measurements that may circumvent limitations of drug‐induced sleep endoscopy (DISE). This study was devised to identify ultrasound‐derived anatomical measurements that could accurately predict collapse pattern and location based on the VOTE criteria (VOTE: Velum, Oropharynx, Tongue, and Epiglottis).MethodsUltrasonography was performed on 20 adult patients of various airway subsites while awake and sedated with concurrent endoscopy performed during drug‐induced sleep. Measurements were obtained from the ultrasonographic images, and percent collapse (Pc) was estimated then graded using a standard VOTE score. Generalized Least Squares regression (GLS) was used to establish models predictive of Pc on a continuous scale, while multiple machine learning (ML) models were trained to predict each VOTE score (binary, >50% collapse) from ultrasound measurements.ResultsMeasurements of multiple ultrasonographic airway subsites demonstrated associations with endoscopic collapse using Kendall Tau correlation. The GLS models showed moderate to strong correlation between multiple ultrasound features and Pc (R2adj 0.53–0.82) across all VOTE subsites. ML models accurately predicted binarized VOTE scores from ultrasound measurements in four out of five VOTE subsites (F1 score >0.65), while the VOTE subsite with the most accurately predicted collapse was lateral velum collapse with an F1 score of 0.93 averaged across all models.ConclusionsUltrasound is a reliable imaging modality and can identify features of airway collapse during drug‐induced sleep. Regression (GLS) and ML models show promise in predicting severity of collapse during DISE with analysis of airway ultrasonographic measurements.Level of Evidence3 Laryngoscope, 2025
Brain Age as a New Measure of Disease Stratification in Huntington's Disease
Authors: Abeyasinghe Pubu M. , Cole James H. , Razi Adeel , Poudel Govinda R. , Paulsen Jane S. , Tabrizi Sarah J. , Long Jeffrey D. , Georgiou‐Karistianis Nellie 
Published: January 2025

AbstractBackgroundDespite advancements in understanding Huntington's disease (HD) over the past two decades, absence of disease‐modifying treatments remains a challenge. Accurately characterizing progression states is crucial for developing effective therapeutic interventions. Various factors contribute to this challenge, including the need for precise methods that can account for the complex nature of HD progression.ObjectiveThis study aims to address this gap by leveraging the concept of the brain's biological age as a foundation for a data‐driven clustering method to delineate various states of progression. Brain‐predicted age, influenced by somatic expansion and its impact on brain volumes, offers a promising avenue for stratification by stratifying subgroups and determining the optimal timing for interventions.MethodsTo achieve this, data from 953 participants across diverse cohorts, including PREDICT‐HD, TRACK‐HD, and IMAGE‐HD, were meticulously analyzed. Brain‐predicted age was computed using sophisticated algorithms, and participants were categorized into four groups based on CAG and age product score. Unsupervised k‐means clustering with brain‐predicted age difference (brain‐PAD) was then employed to identify distinct progression states.ResultsThe analysis revealed significant disparities in brain‐predicted age between HD participants and controls, with these differences becoming more pronounced as the disease progressed. Brain‐PAD demonstrated a correlation with disease severity, effectively identifying five distinct progression states characterized by significant longitudinal disparities.ConclusionsThese findings highlight the potential of brain‐PAD in capturing HD progression states, thereby enhancing prognostic methodologies and providing valuable insights for future clinical trial designs and interventions. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Novel De Novo Intronic Variant of SYNGAP1 Associated With the Neurodevelopmental Disorders
Authors: Xie Wuming , Liao Baoqiong , Shuai Mei , Liu Rutian , Hong Min , He Shuwen 
Published: January 2025

ABSTRACTBackgroundSYNGAP1 encodes a Ras/Rap GTPase‐activating protein that is predominantly expressed in the brain with the functional roles in regulating synaptic plasticity, spine morphogenesis, and cognition function. Pathogenic variants in SYNGAP1 have been associated with a spectrum of neurodevelopmental disorders characterized by developmental delays, intellectual disabilities, epilepsy, hypotonia, and the features of autism spectrum disorder. The aim of this study was to identify a novel SYNGAP1 gene variant linked to neurodevelopmental disorders and to evaluate the pathogenicity of the detected variant.MethodsA novel de novo intronic variant in SYNGAP1 was identified by Whole exome sequencing (WES) and confirmed by Sanger sequencing. Minigene assays were conducted to assess whether the intronic variant in SYNGAP1 influenced the normal splicing of mRNA.ResultsA novel de novo intronic variant in SYNGAP1 (c.3582+2T>G) was indentified with clinical features suggestive of neurodevelopmental related disorders. Minigene splicing analysis demonstrated that this noncanonical splice site variant led to the activation of a cryptic acceptor splice site. Consequently, 101 base pairs of intron 16 were aberrantly retained in the mRNA, leading to a frameshift. This frameshift resulted in the introduction of a premature stop codon (TGA) in the coding sequence and the production of a truncated SYNGAP1 protein, potentially leding to loss of function and subsequent disruption of its biological roles.ConclusionOur findings highlight the significance of de novo pathogenic SYNGAP1 variants at the intron 16/exon 17 junction in the SYNGAP1‐related neurodevelopmental disorders, providing novel insights into the genetic basis and diagnosis of these disabilities.