bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating bioinformatics and machine learning to identify AhR-related gene signatures for prognosis and tumor microenvironment modulation in melanoma
Authors: Li Qianru , Li Heli 
Published: January 2025

BackgroundThe Aryl Hydrocarbon Receptor (AhR) pathway significantly influences immune cell regulation, impacting the effectiveness of immunotherapy and patient outcomes in melanoma. However, the specific downstream targets and mechanisms by which AhR influences melanoma remain insufficiently understood.MethodsMelanoma samples from The Cancer Genome Atlas (TCGA) and normal skin tissues from the Genotype-Tissue Expression (GTEx) database were analyzed to identify differentially expressed genes, which were intersected with a curated list of AhR-related pathway genes. Prognostic models were subsequently developed, and feature genes were identified. Advanced methodologies, including Gene Set Enrichment Analysis (GSEA) and immune cell infiltration analysis, were employed to explore the biological significance of these genes. The stability of the machine learning models and the relationship between gene expression and immune infiltrating cells were validated using three independent melanoma datasets. A mouse melanoma model was used to validate the dynamic changes of the feature genes during tumor progression. The relationship between the selected genes and drug sensitivity, as well as non-coding RNA interactions, was thoroughly investigated.ResultsOur analysis identified a robust prognostic model, with four AhR-related genes (MAP2K1, PRKACB, KLF5, and PIK3R2) emerging as key contributors to melanoma progression. GSEA revealed that these genes are involved in primary immunodeficiency. Immune cell infiltration analysis demonstrated enrichment of CD4+ naïve and memory T cells, macrophages (M0 and M2), and CD8+ T cells in melanoma, all of which were associated with the expression of the four feature genes. Importantly, the diagnostic power of the prognostic model and the relevance of the feature genes were validated in three additional independent melanoma datasets. In the mouse melanoma model, Map2k1 and Prkacb mRNA levels exhibited a progressive increase with tumor progression, supporting their role in melanoma advancement.ConclusionsThis study presents a comprehensive analysis of AhR-related genes in melanoma, highlighting MAP2K1, PRKACB, KLF5, and PIK3R2 as key prognostic markers and potential therapeutic targets. The integration of bioinformatics and machine learning provides a robust framework for enhancing prognostic evaluation in melanoma patients and offers new avenues for the development of treatments, particularly for those resistant to current immunotherapies.
Improving students' performance via case-based e-learning
Authors: Ertl Sebastian , Wadowski Patricia P. , Löffler-Stastka Henriette 
Published: January 2025

BackgroundThe integration of interdisciplinary clinical reasoning and decision-making into the medical curriculum is imperative. Novel, high-quality e-learning environments, encompassing virtual clinical and hands-on training, are essential. Consequently, we evaluated the efficacy of a case-based e-learning approach.MethodThe impact of a case-based interdisciplinary e-learning environment with an integrated question/feedback system on medical students' academic performance was examined in a cross-sectional sample of different study years, longitudinally matched per academic year. Differences between the groups were analyzed through an unpaired t-test.ResultsThe exam results of students who participated in the e-learning course (n = 296) were compared with those of all students at the university (n = 5,800). A statistically significant (p-value &lt; 0.01) improvement in students' final examination grades was observed through intensive training on the offered platform.ConclusionsOur analyses demonstrated the positive influence of a case-based e-learning approach within the Viennese medical curriculum.
Real world efficacy and safety of the advanced hybrid closed-loop system MiniMed 780G (SmartGuard) in children under 7 years of age
Authors: López-López Sara , Díaz-Martín Cristina , García-de Pablo Inés , Ovejero-Garcia María Teresa , Garnier-Rodríguez María Beatriz , Molina-Suárez Ruth , Ontoria-Betancort Cristina , Sáez-Gallego Blanca , Domínguez-García Ángela , Quinteiro-González Sofía , Travieso-Suárez Lourdes , Cabrera-Guedes María Fátima , Nóvoa-Medina Yeray 
Published: January 2025

ObjectiveTo evaluate the safety and efficacy of the Medtronic 780G SmartGuard™ AID system in children under 7 years of age with type 1 diabetes (T1D).MethodsRetrospective analysis of data from children living with T1D under 7 years of age using the MiniMed 780G™ across three pediatric endocrinology units in the Canary Islands. Metabolic control parameters were analyzed from 14 days of pretreatment to 12 months of follow-up.ResultsThe study included 61 children under 7 years of age, 35 in Group 1 and 26 in Group 2. In Group 1, there was a significant increase in time in range (TIR) (13%, p = 0,000), along with a significant decrease in time above range (TAR) (7% for TAR1 and 3% for TAR2; p = 0,000). These improvements persisted for up to 1 year of follow-up. In Group 2, there was a significant increase in the TIR (7%; p = 0,000) and a significant decrease in the TAR (7%; p = 0,000 for TAR1 and 6.5%; p = 0,001 for TAR2). These improvements persisted for up to 6.5 months of follow-up. No significant changes were observed in the time below range (TBR) or variation coefficient (CV) in either group. No events of severe hypoglycemia or diabetic ketoacidosis occurred. Efficacy and safety were maintained in children with a TDD &lt;8 units/day.ConclusionThe use of the Medtronic 780G™ SmartGuard™ system in children under 7 years of age with T1D is effective and safe, with benefits persisting for up to 6–12 months. The safety profile is maintained in children receiving a TDD &lt;8 units/day.
Relationship between maternal pre-pregnancy BMI and neonatal birth weight in pregnancies with gestational diabetes mellitus: a retrospective cohort study
Authors: Liao Qiuping , Yu Tiantian , Chen Jiajia , Zheng Xiuqiong , Zheng Lianghui , Yan Jianying 
Published: January 2025

AimThe aim of this study was to explore the association between maternal pre-pregnancy body mass index (BMI) and neonatal birth weight in pregnancies with gestational diabetes mellitus (GDM).MethodsThis was a retrospective cohort study conducted between January 2019 and June 2020 at a university hospital in Fuzhou, China.ResultsPre-pregnancy BMI was used to categorize 791 pregnant women as underweight (3.03%), normal weight (51.71%), overweight (32.74%), and obese (12.52%). Among the 791 babies, 11.63% were small for gestational age (SGA), 77.37% were normal weight, and 11.00% were large for gestational age (LGA). The rate of the SGA babies increased with higher pre-pregnancy BMI. The percentage of LGA babies was higher in women who were overweight or obese compared to those of normal weight. Neonatal birth weight displayed a significantly increasing trend with increasing maternal pre-pregnancy BMI when maternal pre-pregnancy BMI was less than 27.78 kg/m2 [β = 0.03, 95% CI (0.01, 0.04); p = 0.0052 &lt; 0.05] when maternal pre-pregnancy BMI was greater than 27.78 kg/m2, neonatal birth weight decreased as maternal pre-pregnancy BMI increased [β = −0.01, 95% CI (−0.04, 0.01); p = 0.3555].ConclusionThe incidence of SGA and LGA babies was higher in the women with GDM who were overweight or obese before pregnancy. The data suggest that different management strategies should be implemented for pregnant women with a pre-pregnancy BMI below 27.78 kg/m2 and above 27.78 kg/m2, particularly in cases of GDM. These findings highlight the importance of providing information, offering preconception counseling, and delivering health education on weight management to ensure healthy pregnancies.
High perioperative lactate levels as a potential predictor for severe acute kidney injury following aortic arch surgery
Authors: Wang Dongxu , Yang Chen , Wang Han , Ye Mengmeng , Xue Chao , Wang Weiguang , Yu Bo , Ren Kai , Jin Zhenxiao , Yu Shiqiang , Duan Weixun 
Published: January 2025

BackgroundAcute type A aortic dissection (ATAAD) is a life-threatening condition that often requires total aortic arch replacement (TAR) combined with frozen elephant trunk (FET) implantation. Despite advancements in surgical techniques and preoperative management, postoperative acute kidney injury (AKI) remains a prevalent complication that significantly affects patient prognosis, particularly severe AKI. The aim of this study was to investigate the predictive value of perioperative lactate levels in severe postoperative AKI after TAR.MethodsA cohort analysis of 328 patients who underwent TAR with frozen elephant trunk implantation at Xijing Hospital, Xi’an, China, between September 2019 and September 2023 was conducted. Patients were categorized according to AKI severity into non-AKI, mild-AKI, and severe-AKI cohorts, and lactate levels were measured at nine perioperative time points. The primary endpoint was severe AKI (Kidney Disease: Improving Global Outcomes stage 3). Uni-and multivariate logistic regression analyses were performed to identify risk factors for severe AKI. Subgroup analysis substantiated the robustness of lactate levels in predicting severe AKI.ResultsIn total, 45.4% of patients developed mild AKI postoperatively and 20.7% developed severe AKI. Patients with severe postoperative AKI exhibited higher preoperative lactate levels. Multivariate stepwise backward logistic regression analysis identified lactate levels at 12 h postoperatively ([Lacpo12h], cutoff value: 3.3 mmol/L; sensitivity: 63.2%; specificity: 72.3%) as an independent predictor of severe AKI. The subgroup analysis underscored the consistent predictive capacity of Lacpo12h. The 30-day mortality rate was markedly elevated in the severe-AKI cohort, with deceased patients exhibiting a significantly higher Lacpo12h.ConclusionAmong patients with acute type A aortic dissection undergoing TAR, high perioperative lactate levels were closely associated with postoperative AKI. Lacpo12h is a reliable and effective predictor of severe postoperative AKI, highlighting its clinical utility in risk stratification and management strategies.
Increased platelet aggregation in hepatic tissue of metabolic-associated fatty liver disease—an observational study
Authors: Fan Rongshan , Li Yandong , Du Zeng 
Published: January 2025

ObjectiveThe study aimed to observe the quantity of platelet aggregation in the hepatic tissue of patients with metabolic-associated fatty liver disease (MAFLD) and its relationship with hepatic inflammation, fibrosis, and fatty degeneration.MethodsClinical data of 55 patients with MAFLD and 25 patients without MAFLD, admitted to the Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine from December 2020 to May 2022, were retrospectively analyzed. Liver tissue obtained by liver biopsy underwent routine pathological examination. Immunohistochemical staining with CD63 antibody was performed to label platelets in the liver tissue. Clinical, liver pathology, and immunohistochemical staining data of the study subjects were statistically analyzed using unpaired t-test.ResultsThe quantity of platelet aggregation in the hepatic tissue was higher in MAFLD patients than in non-MAFLD patients and was related to the degree of hepatic inflammation but not to the degree of hepatic fibrosis or fatty degeneration.ConclusionThe quantity of platelet aggregation in hepatic tissue was increased in patients with MAFLD and was related to the degree of hepatic inflammation,
Anti-caries effect of a novel elastic silicone appliance material incorporating sodium fluoride
Authors: Yu Shuxing , Zhang Lingyu , Ma Qizhao , Zhou Jing , Liu Yaqi , Zou Jing , Zhang Qiong 
Published: January 2025

IntroductionThis study developed an elastic silicone appliance material incorporating sodium fluoride (NaF) and evaluated its mechanical properties, biocompatibility, antibacterial effects, and remineralization potential.MethodsSilicone components A and B were combined with varying concentrations of NaF (0.5, 1, 1.5, 2, and 2.5%), thoroughly mixed, and transferred into molds. After drying and curing, the resulting orthodontic appliance was retrieved from the mold and underwent finishing processes, followed by the assessment of its mechanical properties, cytotoxicity, and antibacterial impact. Additionally, the impact of this novel silicone appliance material on salivary biofilm’s activity and acid production was evaluated in samples from children with severe early childhood caries (S-ECC). The hardness of demineralized and remineralized bovine enamel was measured.ResultsIncorporating NaF (0.5, 1, and 1.5%) resulted in no cytotoxic effects, with cell viability &gt;85%. The fluoride release rate initially increased over 14 days, followed by a gradual decline, maintaining a steady release for approximately 28 days. Incorporating 1.5% NaF preserved the mechanical properties and exhibited specific antibacterial properties that inhibited the growth, biofilm formation, and acid production activity of Streptococcus mutans (S. mutans) and saliva biofilms from S-ECC children. Furthermore, all concentrations of the samples helped improve enamel hardness loss.DiscussionThe novel silicone appliance material incorporating NaF exhibited antibacterial, fluoride releasing, and enamel remineralization properties while maintaining its physical and chemical integrity without cytotoxic effects.
Identification and validation of reference genes for quantitative gene expression analysis under 409 and 415 nm antimicrobial blue light treatment
Authors: Kruszewska-Naczk Beata , Grinholc Mariusz , Rapacka-Zdonczyk Aleksandra 
Published: January 2025

IntroductionReverse transcription quantitative real-time polymerase chain reaction Q7 (RT‒qPCR) is a commonly used tool for gene expression quantification. Because the qPCR method depends on several variables that can influence the analysis process, stably expressed genes should be selected for relative gene expression studies. To date, there is insufficient information on the selection of appropriate reference genes for antimicrobial photodynamic inactivation (aPDI) and antimicrobial blue light (aBL) treatment. Therefore, the purpose of the present study was to determine the most stable reference gene under treatment with aBL under sublethal conditions and to evaluate differences in the expression of the selected gene after aBL treatment in comparison to the nontreated control.MethodsSelection of stable reference genes was performed using 4 programs: BestKeeper, geNorm, NormFinder and RefFinder under 409 and 415 nm aBL treatment.ResultsThe results revealed that the gene encoding the integration host factor β subunit (ihfB) in Escherichia coli was the most stably expressed gene after both 409 and 415 nm aBL treatment. Three programs, RefFinder, geNorm, and NormFinder, indicated that this gene had the most stable expression in comparison to the other reference gene candidates. The next best candidates were cysG, uidA, and gyrA. NormFinder revealed ihfB as the single gene and cysG - gyrA as the combination of reference genes with the best stability.DiscussionUniversal reference genes are characterized by stable expression that remains consistent across various stress conditions. Consequently, it is essential to evaluate reference genes for each specific stress factor under investigation. In the case of aBL at different wavelengths, we identified genes that maintain stable expression following irradiation.
Identification and validation of five ferroptosis-related molecular signatures in keloids based on multiple transcriptome data analysis
Authors: Sun Zhen , Qin Yonghong , Zhang Xuanfen 
Published: January 2025

IntroductionKeloids are a common skin disorder characterized by excessive fibrous tissue proliferation, which can significantly impact patients’ health. Ferroptosis, a form of regulated cell death, plays a crucial role in the development of fibrosis; however, its role in the mechanisms of keloid formation remains poorly understood.MethodsThis study aimed to identify key genes associated with ferroptosis in keloid formation. Data from the NCBI GEO database, including GSE145725, GSE7890, and GSE44270, were analyzed, comprising a total of 24 keloid and 17 normal skin samples. Additionally, single-cell data from GSE181316, which included 8 samples with complete expression profiles, were also evaluated. Differentially expressed genes were identified, and ferroptosis-related genes were extracted from the GeneCards database. LASSO regression was used to select key genes associated with keloids. Validation was performed using qRT-PCR and Western blot (WB) analysis on tissue samples from five keloid and five normal skin biopsies.ResultsA total of 471 differentially expressed genes were identified in the GSE145725 dataset, including 225 upregulated and 246 downregulated genes. Five ferroptosis-related genes were selected through gene intersection and LASSO regression. Two of these genes were upregulated, while three were downregulated in keloid tissue. Further analysis through GSEA pathway enrichment, GSVA gene set variation, immune cell infiltration analysis, and single-cell sequencing revealed that these genes were primarily involved in the fibrotic process. The qRT-PCR and WB results confirmed the expression patterns of these genes.DiscussionThis study provides novel insights into the molecular mechanisms of ferroptosis in keloid formation. The identified ferroptosis-related genes could serve as potential biomarkers or therapeutic targets for treating keloids.
Nerve repair with polylactic acid and inosine treatment enhance regeneration and improve functional recovery after sciatic nerve transection
Authors: Cardoso Fellipe Soares dos Santos , Maria Guilherme dos Santos , Pestana Fernanda Marques , Cardoso Ricardo , Ramalho Bruna dos Santos , Heringer Luiza dos Santos , Taboada Tiago Bastos , Martinez Ana Maria Blanco , de Almeida Fernanda Martins 
Published: January 2025

BackgroundFollowing transection, nerve repair using the polylactic acid (PLA) conduit is an effective option. In addition, inosine treatment has shown potential to promote nerve regeneration. Therefore, this study aimed to investigate the regenerative potential of inosine after nerve transection and polylactic acid conduit repair.MethodsC57/Black6 mice were subjected to sciatic nerve transection, repair with PLA conduit, and intraperitoneal injection of saline or inosine 1 h after injury and daily for 1 week. To assess motor and sensory recovery, functional tests were performed before and weekly up to 8 weeks after injury. Following, to evaluate the promotion of regeneration and myelination, electroneuromyography, morphometric analysis and immunohistochemistry were then performed.ResultsOur results showed that the inosine group had a greater number of myelinated nerve fibers (1,293 ± 85.49 vs. 817 ± 89.2), an increase in neurofilament high chain (NFH) and myelin basic protein (MBP) immunolabeling and a greater number of fibers within the ideal g-ratio (453.8 ± 45.24 vs. 336.6 ± 37.01). In addition, the inosine group presented a greater adenosine A2 receptor (A2AR) immunolabeling area. This resulted in greater compound muscle action potential amplitude and nerve conduction velocity, leading to preservation of muscle and neuromuscular junction integrity, and consequently, the recovery of motor and sensory function.ConclusionOur findings suggest that inosine may enhance regeneration and improve both motor and sensory function recovery after nerve transection when repaired with a poly-lactic acid conduit. This advances the understanding of biomaterials and molecular treatments.
Association between deep gray matter iron deposition and clinical symptoms in Parkinson’s disease: a quantitative susceptibility mapping study
Authors: Zhao Hui , Ji Qiu-Hong , Jia Zhong-Zheng , Shen Li-Hua 
Published: January 2025

PurposeThis study aimed to assess the association between motor and non-motor symptoms of Parkinson’s disease (PD) and iron accumulation within the deep gray matter of the brain by Quantitative Susceptibility Mapping (QSM).MethodsFifty-six PD patients and twenty-nine healthy controls were recruited in this study. According to the Hoehn and Yahr (H-Y) stage score, PD patients were divided into early stage (H-Y ≤ 2) and advanced stage (H-Y &gt; 2) groups. Specifically, the Regions of Interest (ROIs) encompassed the substantia nigra (SN), red nucleus (RN), caudate nucleus (CN), globus pallidus (GP) and putamen (PT). Meanwhile, various rating scales were used to assess the clinical symptoms of PD.ResultsCompared to healthy controls (HCs), PD patients showed a significant increase in magnetic susceptibility values (MSVs) within the SN and GP. Further comparisons indicated that the MSVs of the SN, PT, GP and CN are all higher in advanced stages than in early stages. Significant positive correlations were observed between the MSVs of the SN and scores on the UPDRS-III, HAMA, and HAMD (r = 0.310, p = 0.020; r = 0.273, p = 0.042; r = 0.342, p = 0.010, respectively). Likewise, the MSVs of the GP demonstrated notable correlations with HAMA and HAMD scores (r = 0.275, p = 0.040; r = 0.415, p = 0.001). Additionally, a significant correlation was found between the MSVs of the PT and HAMD scores (r = 0.360, p = 0.006). Furthermore, we identified a significant negative correlation between MMSE scores and the MSVs of both the PT and GP (r = −0.268, p = 0.046; r = −0.305, p = 0.022).ConclusionOur study revealed that QSM possesses the capability to serve as a biomarker for PD. Significant correlations were found between clinical features and the iron deposition in the nigrostriatal system.