bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of Serum Folate and Vitamin B12levels with Cardiovascular Mortality among Non-diabetic Population
Authors: Chen Zijun , Cheng Dian , Wang Xuecheng 
Published: January 2025

ABSTRACTBackgroundWhile studies have examined the associations between folate, vitamin B12, and cardiovascular mortality in high-risk populations, evidence regarding these associations in non-diabetic population remains limited. This study aimed to assess the associations of serum folate and vitamin B12levels with cardiovascular mortality in a large, nationally representative cohort of US non-diabetic adults.Methods and ResultsData were extracted from the National Health and Nutrition Examination Survey (NHANES) cycles from 1999 to 2006 and 2011 to 2014. Multivariate logistic regression and restricted cubic spline (RCS) analyses were used to evaluate the associations between serum folate, vitamin B12and cardiovascular mortality. A two-piecewise logistic regression model was employed to identify the inflection points of serum folate and vitamin B12levels on cardiovascular mortality. Among 19,402 US adults, the mean age was 43.9 ± 18.6 years, 9,749 (50.2%) were male, and 8,438 (43.5%) were non-Hispanic White. With a median follow-up of 159 months (IQR: 82.0-193.0 months), 928 cardiovascular deaths were documented. After fully adjusting for potential confounders, a significant inverse association was observed between serum folate levels and cardiovascular mortality. The RCS analysis revealed non-linear associations between serum folate (Pfor nonlinearity = 0.02), vitamin B12levels (Pfor nonlinearity = 0.04), and the risk of cardiovascular mortality. Specifically, serum folate levels below 19.50 ng/mL and serum vitamin B12levels at or above 436.52 pg/mL were both linked to an increased risk of cardiovascular mortality. Stratified and sensitivity analyses confirmed the robustness of these associations.ConclusionsThis study demonstrated that low serum folate levels and high vitamin B12levels were associated with an increased risk of cardiovascular mortality in non-diabetic individuals. These findings provide evidence supporting the potential of serum folate and vitamin B12levels as biomarkers for cardiovascular mortality risk estimation, pending further validation in other independent cohorts.
Carotid endarterectomy is associated with lower rates of reintervention compared to carotid stenting
Authors: Adkar Shaunak S. , George Elizabeth L. , Zheng Xinyan , Sorondo Sabina M. , Fereydooni Arash , Dossabhoy Shernaz , Stern Jordan R. 
Published: January 2025

AbstractObjectivesPerioperative outcomes for carotid endarterectomy (CEA) and transfemoral carotid artery stenting (TFCAS) have been well studied. Less is known about the durability and reintervention rates of each, particularly in the era of transcarotid artery revascularization (TCAR). We sought to compare real-world rates of ipsilateral reintervention, stroke, and death in patients undergoing CEA, TFCAS, and TCAR.MethodsThe Vascular Quality Initiative (VQI) was matched to Medicare claims via the Vascular Implant Surveillance and Implantation Network (VISION) database to identify patients who had primary carotid revascularization from December 2016 to December 2019 in a n observational cohort study. The primary outcome was ipsilateral reintervention; secondary outcomes included stroke and mortality. After 1:1 greedy matching using propensity scores, patients who underwent CEA and carotid artery stenting (CAS) via either transcarotid or transfemoral approach were compared using time-dependent Cox regression models. A separate propensity matched analysis was then performed to compare TFCAS and TCAR. Kaplan-Meier curves were compared using log rank tests.ResultsAfter propensity matching (N=27,944 patients), we compared 4705 patients in each group. Risk of re-intervention was increased within 6 months for CAS (HR: 1.97; 95% CI: 1.11-3.50; p<0.05), but not beyond 6 months (HR: 1.08; 95% CI: 0.62-1.89; p=0.79). The incidence of stroke prior to discharge was increased in patients undergoing CAS (5.4% v. 1.0%; p<0.0001) and mortality hazard with CAS was increased both within 6 months (HR:1.69; 95% CI: 1.38- 2.07; p<0.0001) and beyond 6 months (HR: 1.52; 95% CI: 1.27-1.81; p<0.0001). When comparing TFCAS and TCAR (n=2115 per group), there was a significantly increased risk of re- intervention for TFCAS beyond 6 months (HR: 2.31, 95% CI: 1.05-5.11, p <0.05).ConclusionsCEA portends a lower risk of reintervention than CAS, particularly within the first 6 months after revascularization. On subgroup analysis of stenting modalities, TCAR had a lower hazard of longer-term reintervention compared to TFCAS.
Characterising the periodontal granulation tissue using scRNAseq
Authors: Zhu Wentao , Fung Kathy , Dhami Pawan , Sharpe Paul , Krivanek Jan , Nibali Luigi , Zhang Cheng , Neves Vitor C.M. 
Published: January 2025

AbstractAimsOur research investigated the cellular composition and molecular mechanisms of periodontal granulation tissue using single-cell RNA sequencing (scRNA-seq), aiming to enhance the understanding of periodontal disease pathogenesis and identify potential targets for regenerative therapies.Materials and MethodsGranulation tissue samples were collected from patients undergoing periodontal surgery. Fresh tissues were processed into single-cell suspensions and subjected to scRNA-seq. The data were integrated with existing datasets from healthy gingiva and periodontal ligament. Computational analyses were performed, and validation through immunofluorescence staining.ResultsTen distinct cell clusters were identified across the samples. Granulation tissue exhibited a higher abundance of immune cells compared to healthy tissues. A novel endothelial cell subpopulation, exclusive to granulation tissue, was discovered, characterized by NOTCH3 expression and involvement in ossification pathways. Additionally, granulation tissue Fibroblast subpopulations demonstrated a progenitor-like state, characterized by extracellular matrix reorganization and low differentiation, similar to cancer-associated fibroblasts.Conclusion(s)This study advances the understanding of periodontal disease by characterizing key regulatory cell populations within granulation tissue. The identification of the novel endothelial subpopulation offers new insights into the disease’s pathogenesis and presents potential targets for regenerative therapies. These findings suggest opportunities for developing biomaterials that modulate specific cellular pathways to improve periodontal disease treatment.
Using high-dimensional immunophenotyping for mapping immune cell composition in rapid cryopreserved liquid biopsies
Authors: Pedersen JG , Jordt JCL , Thorborg E , Dietz LL , Winther-Larsen A , Gammelgaard KR , Jakobsen MR 
Published: January 2025

AbstractLiquid biopsies, such as a blood sample, are non-invasive and simple ways to monitor biomarkers in clinical settings. For cancer immunotherapy settings a major clinical goal is to identify host immunological biomarkers that can be used to monitor progression of disease, treatment efficacy, or even adverse effects. Here, the profiling and validation of blood circulating immune cells may allow continuously survey on how the immune system alters during disease progress and treatment. However, such practice will require proper sampling and development of a robust high-dimensional phenotypic analysis.Here, we designed a 37-marker spectral flow cytometry assay with the purpose of conducting high-dimensional immunophenotyping as monitoring the immune status in patients. The assay was developed to profile all major immune cell compartments, their differentiation as well as activation markers, including numerous checkpoint markers. Importantly, we validated this assay in context of how liquid biopsies should be processed to ensure minimal effect of cryopreservation compared to immunophenotyping of a freshly acquired blood sample. Our work highlights important considerations for which phenotypic alternations can be introduced with different cryopreservation methods. Essentially, we identified a fast and simple processing pipeline where cryopreservation of immune cells showed minimal changes in the immunophenotyping profile. This approach can certainly be implemented in clinical settings and will help diagnostic clinical sites with a strong and validated tool applicable for monitoring individual patients’ immunological status.
The first complete mitochondrial genome of the endangered spotted eagle rayAetobatus ocellatus
Authors: Marín Alan 
Published: January 2025

AbstractThe complete mitochondrial genome of the endangered spotted eagle rayAetobatus ocellatuswas determined for the first time using Next Generation Sequencing (NGS) reads mined from the Sequence Read Archive (SRA) of the GenBank database (BioSample SAMN31811701, collection site: Bohol Island, Philippines). The spotted eagle ray mitogenome (GenBank accession pending) has 20,217 bp in length displaying a typical vertebrate mitogenome organization (13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and a control region). A phylogenetic analysis based on the nucleotide sequence information of 13 protein-coding genes from different related species confirmed the species status ofA. ocellatusas an Indo-West Pacific species, which was formerly described asA. narinariwhose current accepted distribution is restricted to the Atlantic Ocean.
Misophonia Symptoms Severity is Attributed to Impaired Flexibility and Heightened Rumination
Authors: Black Vivien , Allen J.D. , Aazh Hashir , Johnson Sheri L. , Erfanian Mercede 
Published: January 2025

AbstractMisophonia is a disorder involving sensitivity to certain sounds and related stimuli. Here, we explore the relationship between misophonia and affective flexibility, which describes cognitive shifting abilities in the face of emotion-evoking stimuli. Previous evidence suggests impaired subjective cognitive flexibility in misophonia, but this relationship has not been confirmed behaviourally or in emotionally-salient contexts. The secondary aim of this study is to test the potential association between misophonia and cognitive flexibility, building upon findings from previous research. The third objective is to examine the relationship between misophonia and rumination, a maladaptive cognitive process characterized by repetitive negative thinking and linked to both cognitive and affective inflexibility. One hundred and forty participants completed the recently developed Memory and Affective Flexibility Task (MAFT), designed to assess affective flexibility, as well as a battery of self-report measures to evaluate misophonia severity, cognitive flexibility and rumination. Results suggested an inverse relationship between affective flexibility as measured by switch accuracy, but not reaction time, and misophonia severity. Cognitive flexibility was also inversely associated with misophonia severity, but notably didnotattribute to task-based affective flexibility, suggesting two independent constructs both involved in misophonia manifestation. Rumination associated positively with misophonia severity and inversely with cognitive flexibility, but not affective flexibility. Taken together, these findings highlight a unique cognitive profile of misophonia, characterized by rigidity at the psychological level through cognitive inflexibility and rumination, as well as at the executive-function level in terms of affective switching difficulties.
Conditional Universal Differential Equations Simultaneously Capture Population Level Dynamics and Inter-individual Variation in Human C-peptide Production
Authors: de Rooij Max , van Riel Natal A.W. , O’Donovan Shauna D. 
Published: January 2025

AbstractUniversal differential equations (UDEs) are an emerging approach in biomedical systems biology, integrating physiology-driven mathematical models with machine learning for data-driven model discovery in areas where knowledge of the underlying physiology is limited. However, current approaches to training UDEs do not directly accommodate heterogeneity in the underlying data. As a data-driven approach, UDEs are also vulnerable to overfitting and consequently cannot sufficiently generalise to heterogeneous populations. We propose a conditional UDE (cUDE) where we assume that the structure and weights of the embedded neural network are common across individuals, and introduce a conditioning parameter that is allowed to vary between individuals. In this way, the cUDE architecture can accommodate inter-individual variation in data while learning a generalisable network representation. We demonstrate the effectiveness of the cUDE as an extension of the UDE framework by training a cUDE model of c-peptide production. We show that our cUDE model can accurately describe postprandial c-peptide levels in individuals with normal glucose tolerance, impaired glucose tolerance, and type 2 diabetes mellitus. Furthermore, we show that the conditional parameter captures relevant inter-individual variation. Subsequently, we use symbolic regression to derive a generalisable analytical expression for c-peptide production.
Action mechanism of a novel agrichemical quinofumelin againstFusarium graminearum
Authors: Xiu Qian , Yin Xiaoru , Chen Yuanyuan , Zhang Ziyang , Mao Yushuai , Wang Tianshi , Zhang Jie , Zhou Mingguo , Duan Yabing 
Published: January 2025

AbstractModern fungicides have made significant contributions to crop disease management, but the development of resistant fungal strains has caused their failure in disease control. Therefore, developing fungicides with novel action mechanisms is the most effective measure to manage resistance. Quinofumelin, a novel quinoline fungicide, exhibits exceptional antifungal activity against phytopathogens. However, there is currently no available information on its mechanism of action. Here, we used transcriptome and metabolome analysis to observe a co-enrichment pattern of differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) within pyrimidine biosynthesis pathway (PBP), identifying down-regulation of dihydroorotate dehydrogenase (DHODH). Exogenous UMP, uridine or uracil (metabolites in PBP) successfully restored quinofumelin-induced inhibition of mycelial growth inFusarium graminearumandFusarium asiaticum. Additionally, the deletion ofFgDHODHIIwas determined to be lethal; however, mycelial growth of ΔFgDHODHII mutants could be restored by adding UMP, uridine or uracil. These findings indicate that the deficiencies inFgDHODHIIare functionally equivalent to complete inhibition of its activity by quinofumelin. Finally, molecular docking, surface plasmon resonance (SPR) and microscale thermophoresis (MST) results strongly support the precise interaction between quinofumelin and FgDHODHII. Collectively, these findings provide compelling evidence for the involvement ofde novouracil biosynthesis as mechanism of action for quinofumelin while identifying FgDHODHII as its specific target.
One-shot normative modelling of whole-brain functional connectivity
Authors: Kobbersmed Janus R. L. , Gohil Chetan , Marquand Andre , Vidaurre Diego 
Published: January 2025

AbstractMany brain diseases and disorders lack objective measures of brain function as indicators of pathology, which has recently spurred the use of normative modelling in neuroimaging. Normative models characterize the normal variation of brain measurements given sex and age, thereby allowing identification of abnormalities as deviations from normal. Normative modelling of brain function is typically based on predicting functional connectivity (FC) between each pair of brain regions. But the human brain is an extremely integrated organ, and brain disease often has widespread effects that are not well captured by piecemeal analyses, i.e. connection by connection. We propose Functional Connectivity Integrative Normative Modelling (FUNCOIN), developing a whole-brain normative model of FC from a large resting-state fMRI data set that captures whole-network-level changes associated with sex and age. This model can significantly, and substantially, uncover abnormal FC patterns in Parkinson’s disease patients even on scans up to 5.5 years before diagnosis.
Engineered antimicrobial scaffolds protect bone marrow mesenchymal stem cell-Based Implants from bacterial infections
Authors: Khalid Ahmed Alani Mohanad , Ali Mujahid Khalaf , Alani Basma Kh. 
Published: January 2025

ABSTRACTBone marrow mesenchymal stem cell (BM-MSC)-based implants is a promising method for bone regeneration. Implant failures are often caused by their susceptibility to bacterial infections. The aim of this study is to develop and evaluate antimicrobial scaffolds designed to protect BM-MSC-based implants from bacterial colonization while promoting bone repair. Biocompatible polycaprolactone (PCL) scaffolds were fabricated with incorporated antimicrobial agents, including silver nanoparticles (AgNPs) and vancomycin, using electrospinning and surface coating techniques. The scaffolds were characterized for morphology, mechanical properties, and antimicrobial release profiles. The findings of in vitro studies revealed that the scaffolds effectively inhibited bacterial growth (>90% reduction in CFUs) and biofilm formation forStaphylococcus aureusandEscherichia coli, without affecting BM-MSC viability or osteogenic potential. In vivo implantation on a rat femoral defect model showed that antimicrobial scaffolds significantly reduced bacterial load and enhanced bone regeneration, with micro-CT showing 65% bone volume compared to 35% in controls. Histological analysis confirmed active osteogenesis and infection control. These findings showed the potential of antimicrobial scaffolds as a dual-functional platform for bone tissue engineering. Future research can explore scaffold optimization for different applications and examine their efficacy against multi-drug-resistant bacteria to broaden clinical relevance.
Genetic background sets the trajectory of cancer evolution
Authors: Aitken Sarah J. , Connor Frances , Feig Christine , Rayner Tim F. , Lukk Margus , Luft Juliet , Aitken Stuart , Arnedo-Pac Claudia , Hayes James F. , Nicholson Michael D. , Sundaram Vasavi , Verburg Jan C. , Connelly John , Anderson Craig J. , Behm Mikaela , Campbell Susan , Daunesse Maëlle , Ewing Ailith , Kaiser Vera B. , Kentepozidou Elissavet , Pich Oriol , Redmond Aisling M. , Santoyo-Lopez Javier , Sentís Inés , Talmane Lana ,   Liver Cancer Evolution Consortium, Flicek Paul , López-Bigas Núria , Semple Colin A. , Taylor Martin S. , Odom Duncan T. 
Published: January 2025

AbstractHuman cancers are heterogeneous. Their genomes evolve from genetically diverse germlines in complex and dynamic environments, including exposure to potential carcinogens. This heterogeneity of humans, our environmental exposures, and subsequent tumours makes it challenging to understand the extent to which cancer evolution is predictable. Addressing this limitation, we re-ran early tumour evolution hundreds of times in diverse, inbred mouse strains, capturing genetic variation comparable to and beyond that found in human populations. The sex, environment, and carcinogenic exposures were all controlled and tumours comprehensively profiled with whole genome and transcriptome sequencing. Within a strain, there was a high degree of consistency in the mutational landscape, a limited range of driver mutations, and all strains converged on the acquisition of a MAPK activating mutation with similar transcriptional disruption of that pathway. Despite these similarities in the phenotypic state of tumours, different strains took markedly divergent paths to reach that state. This included pronounced biases in the precise driver mutations, the strain specific occurrence of whole genome duplication, and differences in subclonal selection that reflected both cancer susceptibility and tumour growth rate. These results show that interactions between the germline genome and the environment are highly deterministic for the trajectory of tumour genome evolution, and even modest genetic divergence can substantially alter selection pressures during cancer development, influencing both cancer risk and the biology of the tumour that develops.
High density EEG and deep learning improves outcome prediction on the first day of coma after cardiac arrest
Authors: Pelentritou Andria , Gruaz Lucas , Iten Manuela , Haenggi Matthias , Zubler Frederic , Rossetti Andrea O , De Lucia Marzia 
Published: January 2025

AbstractWe assessed outcome prediction of comatose patients using a deep learning analysis applied to resting EEG on the first and second day after cardiac arrest (CA), and its added value to clinical prognosis. We recorded 62-channel resting-state EEG in comatose patients after CA across three Swiss hospitals during the first (N=165) and second (N=100) coma day. Patient outcome was classified as favorable if the best Cerebral Performance Category was 1-2. A convolutional neural network provided a predicted probability for favorable outcome for each patient’s and recording day’s 62-channel and 19-channel EEG. Predictive performance was additionally evaluated on an external 19-channel dataset collected outside Switzerland (N=60). The deep learning prediction was compared to EEG-based clinical markers - according to the American Clinical Neurophysiology Society -, brainstem reflexes and motor responses. On the first day, patient outcome was predicted with an accuracy of 0.94±0.03 for 62 channels and 0.90±0.03 and 0.87 for 19 channels using the Swiss and external dataset, respectively. High outcome prediction (0.98 accuracy) was observed when considering only patients with uncertain prognosis based on clinical assessment. The second day was less predictive, with an accuracy of 0.72±0.05. The estimated outcome prediction correlated with spectral power on the first day for favorable (r =0.38, p=0.01) and unfavorable (r=-0.28, p=0.02) outcome patients, and was consistent with clinical markers (p<0.0001), except brainstem reflexes. On the first day of coma in CA patients, a deep learning analysis of resting-state high-density EEG provides accurate outcome prediction, superior to lower-density EEG, and complements clinical markers.Graphical abstract