bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circular genetic structure of the Abies nephrolepis species complex shaped by the circular landform of Northeast Asia
Authors: Kwak Myounghai , Nakamura Koh , Xiang Qiaoping , Wen Jun , Lee Eun Sil , Hong Jaram , Kovtonyuk Nataliya , Kryukova Maria , Korchagina Olga , Koo Kyung Ah , Iwaizumi Masakazu G. , Lee Byoung Yoon , Kokubugata Goro , Zhang Xianchun , Lebedev Dmitry 
Published: April 2024

AbstractAimPinaceae have been noted for their tendency towards reticulation as a result of interspecific hybridization. Here, we demonstrated the phylogeographic dynamics of the native Northeast Asian sub‐alpine conifer, Abies nephrolepis species complex (ANSC), evolving in circular overlaps along the Northeast Asian landform, which functions as a corridor with the sea, thus acting as a geographic barrier.LocationNortheast Asia: the Korean Peninsula, Japanese Archipelago, Russian Far East and northeastern China.TaxonAbies nephrolepis species complex (Family Pinaceae, Genus Abies, Section Balsamea, Abies nephrolepis, A. koreana, A. veitchii and A. sachalinensis).MethodsA total of 728 individuals from 38 ANSC populations were analysed using multiplexed inter‐simple sequence repeat genotyping by sequencing to capture variations in biparental nuclear genomes. Eight mitochondrial regions and eight chloroplast regions of each individual were sequenced using the MiSeq platform and Sanger sequencing. Species distribution models were generated.ResultsBayesian clustering with 507 nuclear single nucleotide polymorphisms and the discrepancy between cytoplasmic and nuclear genome lineages implied contemporary and ancient connections between neighbouring species in the form of circular overlap. This genetic connectivity was supported by principal component analysis. Strong correlations between genetic distance and geographic distance were observed, suggesting that gene flow occurs through a continuous chain around the sea. We also found that gene flow direction and intensity changed over time, with support from palaeodistribution modelling.ConclusionPast hybridization events were captured in cytoplasmic genomes, generating heterogeneity across maternal ancestries. This intensive phylogeographic study demonstrates speciation with incomplete reproductive isolation (continuous gene flow) among neighbouring species with an alteration of the direction and intensity of gene flow due to climate change. The divergence of ANSC due to repeated isolation and reconnection caused by heterogenous physiological environments and climate fluctuation provides a model to solve evolutionary scenarios for reticulate evolution in Pinaceae and other plants.
The plasma miRNome and venous thromboembolism in high‐grade glioma: miRNA Sequencing of a nested case–control cohort
Authors: Erhart Friedrich , Widhalm Georg , Kiesel Barbara , Hackl Matthias , Diendorfer Andreas , Preusser Matthias , Rössler Karl , Thaler Johannes , Pabinger Ingrid , Ay Cihan , Riedl Julia 
Published: April 2024

AbstractPatients with high‐grade gliomas are at high risk of venous thromboembolism (VTE). MicroRNAs (miRNAs) are small non‐coding RNAs with multiple roles in tumour biology, haemostasis and platelet function. Their association with VTE risk in high‐grade glioma has not been comprehensively mapped so far. We thus conducted a nested case–control study within 152 patients with WHO grade IV glioma that had been part of a prospective cohort study on VTE risk factors. At inclusion a single blood draw was taken, and patients were thereafter followed for a maximum of 2 years. During that time, 24 patients (16%) developed VTE. Of the other 128 patients, we randomly selected 24 age‐ and sex‐matched controls. After quality control, the final group size was 21 patients with VTE during follow‐up and 23 without VTE. Small RNA next‐generation sequencing of plasma was performed. We observed that hsa‐miR‐451a was globally the most abundant miRNA. Notably, 51% of all miRNAs showed a correlation with platelet count. The analysis of miRNAs differentially regulated in VTE patients—with and without platelet adjustment—identified potential VTE biomarker candidates such as has‐miR‐221‐3p. Therewith, we here provide one of the largest and deepest peripheral blood miRNA datasets of high‐grade glioma patients so far, in which we identified first VTE biomarker candidates that can serve as the starting point for future research.
Pathway‐based stratification of gliomas uncovers four subtypes with different TME characteristics and prognosis
Authors: Huang Ruoyu , Han Bo , Zhang Ying , Yang Jingchen , Wang Kuanyu , Liu Xing , Wang Zhiliang 
Published: April 2024

AbstractIncreasing evidences have found that the interactions between hypoxia, immune response and metabolism status in tumour microenvironment (TME) have clinical importance of predicting clinical outcomes and therapeutic efficacy. This study aimed to develop a reliable molecular stratification based on these key components of TME. The TCGA data set (training cohort) and two independent cohorts from CGGA database (validation cohort) were enrolled in this study. First, the enrichment score of 277 TME‐related signalling pathways was calculated by gene set variation analysis (GSVA). Then, consensus clustering identified four stable and reproducible subtypes (AFM, CSS, HIS and GLU) based on TME‐related signalling pathways, which were characterized by differences in hypoxia and immune responses, metabolism status, somatic alterations and clinical outcomes. Among the four subtypes, HIS subtype had features of immunosuppression, oxygen deprivation and active energy metabolism, resulting in a worst prognosis. Thus, for better clinical application of this acquired stratification, we constructed a risk signature by using the LASSO regression model to identify patients in HIS subtype accurately. We found that the risk signature could accurately screen out the patients in HIS subtype and had important reference value for individualized treatment of glioma patients. In brief, the definition of the TME‐related subtypes was a valuable tool for risk stratification in gliomas. It might serve as a reliable prognostic classifier and provide rational design of individualized treatment, and follow‐up scheduling for patients with gliomas.
Integrated analysis highlights the significance role of ITGAL in lung adenocarcinoma
Authors: Xiao Zengtuan , Nian Zhe , Zhang Mengzhe , Liu Zuo , Liu Zhe , Zhang Zhenfa 
Published: April 2024

AbstractIntegrin alpha L (ITGAL), a member of the integrin family, is associated with carcinogenesis and immune regulation. However, the biological functions of ITGAL in lung adenocarcinoma (LUAD) remain poorly understood. In this study, we utilized the TCGA dataset to analyse ITGAL mRNA expression in LUAD and examined its correlation with clinical prognosis. Three‐dimensional (3D) Matrigel culture, 5‐bromodeoxyuridine (BrdU) ELISA, wound‐healing migration and cell adherence assays were used to demonstrate the potential role of ITGAL in LUAD progression. Additionally, we analysed single‐cell sequencing data of LUAD to determine the expression and biological function of ITGAL. Our research revealed that the expression of ITGAL in LUAD samples is an independent predictor of prognosis. Patients with high expression of ITGAL had significantly better overall survival (OS), progression‐free survival (PFS) and disease‐specific survival (DSS) compared to the low‐expression group. Meanwhile, the expression of ITGAL suppressed malignant progression in LUAD cells. Functional enrichment analyses showed that ITGAL was significantly correlated with cell immune response and immune checkpoint, consistent with the analysis of single‐cell sequencing in paired samples of normal and tumour. Furthermore, we confirmed that ITGAL expression affect the tumour microenvironment (TME) through regulation of the expression of cytokines in NK cells of LUAD. In summary, ITGAL is a prognostic biomarker for LUAD patients, and it repressed malignant progression in LUAD cells. Moreover, ITGAL expression also enhanced the effect of immunotherapy and may be an important target in LUAD therapy.
The role of autophagy in odontogenesis, dental implant surgery, periapical and periodontal diseases
Authors: İnan Sevinç , Barış Emre 
Published: April 2024

AbstractAutophagy is a cellular process that is evolutionarily conserved, involving the sequestration of damaged organelles and proteins into autophagic vesicles, which subsequently fuse with lysosomes for degradation. Autophagy controls the development of many diseases by influencing apoptosis, inflammation, the immune response and different cellular processes. Autophagy plays a significant role in the aetiology of disorders associated with dentistry. Autophagy controls odontogenesis. Furthermore, it is implicated in the pathophysiology of pulpitis and periapical disorders. It enhances the survival, penetration and colonization of periodontal pathogenic bacteria into the host periodontal tissues and facilitates their escape from host defences. Autophagy plays a crucial role in mitigating exaggerated inflammatory reactions within the host's system during instances of infection and inflammation. Autophagy also plays a role in the relationship between periodontal disease and systemic diseases. Autophagy promotes wound healing and may enhance implant osseointegration. This study reviews autophagy's dento‐alveolar effects, focusing on its role in odontogenesis, periapical diseases, periodontal diseases and dental implant surgery, providing valuable insights for dentists on tooth development and dental applications. A thorough examination of autophagy has the potential to discover novel and efficacious treatment targets within the field of dentistry.
Deferoxamine topical cream superior to patch in rescuing radiation‐induced fibrosis of unwounded and wounded skin
Authors: Berry Charlotte E. , Abbas Darren B. , Griffin Michelle , Lintel Hendrik , Guo Jason , Kameni Lionel , Churukian Andrew A. , Fazilat Alexander Z. , Chen Kellen , Gurtner Geoffrey C. , Longaker Michael T. , Momeni Arash , Wan Derrick C. 
Published: April 2024

AbstractTopical patch delivery of deferoxamine (DFO) has been studied as a treatment for this fibrotic transformation in irradiated tissue. Efficacy of a novel cream formulation of DFO was studied as a RIF therapeutic in unwounded and excisionally wounded irradiated skin. C57BL/6J mice underwent 30 Gy of radiation to the dorsum followed by 4 weeks of recovery. In a first experiment, mice were separated into six conditions: DFO 50 mg cream (D50), DFO 100 mg cream (D100), soluble DFO injections (DI), DFO 1 mg patch (DP), control cream (Vehicle), and irradiated untreated skin (IR). In a second experiment, excisional wounds were created on the irradiated dorsum of mice and then divided into four treatment groups: DFO 100 mg Cream (W‐D100), DFO 1 mg patch (W‐DP), control cream (W‐Vehicle), and irradiated untreated wounds (W‐IR). Laser Doppler perfusion scans, biomechanical testing, and histological analysis were performed. In irradiated skin, D100 improved perfusion compared to D50 or DP. Both D100 and DP enhanced dermal characteristics, including thickness, collagen density and 8‐isoprostane staining compared to untreated irradiated skin. D100 outperformed DP in CD31 staining, indicating higher vascular density. Extracellular matrix features of D100 and DP resembled normal skin more closely than DI or control. In radiated excisional wounds, D100 facilitated faster wound healing and increased perfusion compared to DP. The 100 mg DFO cream formulation rescued RIF of unwounded irradiated skin and improved excisional wound healing in murine skin relative to patch delivery of DFO.
Identification and characterization of novel genetic variants in the first Chinese family of mucopolysaccharidosisIIIC(Sanfilippo C syndrome)
Authors: Zhao Hongjun , Wang Lijing , Zhang Mengfei , Wang Huakun , Zhang Sizhe , Wu Junjiao , Tang Yu 
Published: April 2024

AbstractMucopolysaccharidosis type IIIC (MPS IIIC) is one of inherited lysosomal storage disorders, caused by deficiencies in lysosomal hydrolases degrading acidic mucopolysaccharides. The gene responsible for MPS IIIC isHGSNAT, which encodes an enzyme that catalyses the acetylation of the terminal glucosamine residues of heparan sulfate. So far, few studies have focused on the genetic landscape of MPS IIIC in China, where IIIA and IIIB were the major subtypes. In this study, we utilized whole‐exome sequencing (WES) to identify novel compound heterozygous variants in theHGSNATgene from a Chinese patient with typical MPS IIIC symptoms: c.743G>A; p.Gly248Glu and c.1030C>T; p.Arg344Cys. We performed in silico analysis and experimental validation, which confirmed the deleterious pathogenic nature of both variants, as evidenced by the loss of HGSNAT activity and failure of lysosomal localization. To the best of our knowledge, the MPS IIIC is first confirmed by clinical, biochemical and molecular genetic findings in China. Our study thus expands the spectrum of MPS IIIC pathogenic variants, which is of importance to dissect the pathogenesis and to carry out clinical diagnosis of MPS IIIC. Moreover, this study helps to depict the natural history of Chinese MPS IIIC populations.
Comprehensive analysis of the interaction of antigen presentation during anti‐tumour immunity and establishment of AIDPS systems in ovarian cancer
Authors: Sun Wenhuizi , Xu Ping , Gao Kefei , Lian Wenqin , Sun Xiang 
Published: April 2024

AbstractThere are hundreds of prognostic models for ovarian cancer. These genes are based on different gene classes, and there are many ways to construct the models. Therefore, this paper aims to build the most stable prognostic evaluation system known to date through 101 machine learning strategies. We combined 101 algorithm combinations with 10 machine learning algorithms to create antigen presentation‐associated genetic markers (AIDPS) with outstanding precision and steady performance. The inclusive set of algorithms comprises the elastic network (Enet), Ridge, stepwise Cox, Lasso, generalized enhanced regression model (GBM), random survival forest (RSF), supervised principal component (SuperPC), Cox partial least squares regression (plsRcox), survival support vector machine (Survival‐SVM). Then, in the train cohort, the prediction model was fitted using a leave‐one cross‐validation (LOOCV) technique, which involved 101 different possible combinations of prognostic genes. Seven validation data sets (GSE26193, GSE26712, GSE30161, GSE63885, GSE9891, GSE140082 and ICGC_OV_AU) were compared and analysed, and the C‐index was calculated. Finally, we collected 32 published ovarian cancer prognostic models (including mRNA and lncRNA). All data sets and prognostic models were subjected to a univariate Cox regression analysis, and the C‐index was calculated to demonstrate that the antigen presentation process should be the core criterion for evaluating ovarian cancer prognosis. In a univariate Cox regression analysis, 22 prognostic genes were identified based on the expression profiles of 283 genes involved in antigen presentation and the intersection of genes (p < 0.05). AIDPS were developed by our machine learning‐based integration method, which was applied to these 22 genes. One hundred and one prediction models are fitted using the LOOCV framework, and the C‐index is calculated for each model across all validation sets. Interestingly, RSF + Lasso was the best model overall since it had the greatest average C‐index and the highest C‐index of any combination of models tested on the validated data sets. In comparing external cohorts, we found that the C‐index correlated AIDPS method using the RSF + Lasso method in 101 prediction models was in contrast to other features. Notably, AIDPS outperformed the vast majority of models across all data sets. Antigen‐presenting anti‐tumour immune pathways can be used as a representative gene set of ovarian cancer to track the prognosis of patients with cancer. The antigen‐presenting model obtained by the RSF + Lasso method has the best C‐INDEX, which plays a key role in developing antigen‐presenting targeted drugs in ovarian cancer and improving the treatment outcome of patients.
The adjunctive effect of polydeoxyribonucleotide on bone formation in alveolar ridge preservation: A pre‐clinical in vivo study
Authors: Ko Young‐Chang , Lee Jungwon , Urban Istvan , Seol Yang‐Jo , Lee Yong‐Moo , Koo Ki‐Tae 
Published: April 2024

AbstractAimThis study investigated the adjunctive effect of polydeoxyribonucleotide (PDRN) on bone formation in alveolar ridge preservation (ARP) sockets.Materials and MethodsBoth mandibular second, third and fourth premolars of eight beagle dogs were randomly divided into ARP and ARP/PDRN groups. Following tooth extraction, ARP procedures were conducted using collagenized alloplastic graft material and bilayer collagen membrane soaked with normal saline (ARP group) or PDRN (ARP/PDRN group) for 10 min before application. Both groups were also randomly allocated to 2‐, 4‐ or 12‐week healing subgroups. The primary endpoint of this study was to compare histomorphometric differences between ARP and ARP/PDRN. The secondary endpoints of this study were to compare micro‐CT analysis and three‐dimensional volumetric measurement between the two groups.ResultsIn the histomorphometric analysis, the ARP/PDRN group exhibited greater new bone formation at coronal, middle and total position compared with the ARP group at 2‐week healing. The number of newly formed blood vessels was higher in the ARP/PDRN group than in the ARP group at 2‐ and 4‐week healing. In micro‐CT analysis, the mean new bone volume/total bone volume between ARP and ARP/PDRN was statistically significant at 2‐week healing. Ridge volume alterations were significantly decreased in the ARP/PDRN group during entire healing time compared with the ARP group, especially on the buccal side.ConclusionsThe application of PDRN in ARP might provide additional benefits for early bone regeneration and maintenance of buccal ridge volume.
The relationship between type, timing and duration of exposure to adverse childhood experiences and adolescent self‐harm and depression: findings from three UK prospective population‐based cohorts
Authors: Farooq Bushra , Russell Abigail E. , Howe Laura D. , Herbert Annie , Smith Andrew D.A.C. , Fisher Helen L. , Baldwin Jessie R. , Arseneault Louise , Danese Andrea , Mars Becky 
Published: April 2024

BackgroundAdverse childhood experiences (ACEs) are well‐established risk factors for self‐harm and depression. However, despite their high comorbidity, there has been little focus on the impact of developmental timing and the duration of exposure to ACEs on co‐occurring self‐harm and depression.MethodsData were utilised from over 22,000 children and adolescents participating in three UK cohorts, followed up longitudinally for 14–18 years: the Avon Longitudinal Study of Parents and Children (ALSPAC), the Millennium Cohort Study (MCS) and the Environmental Risk (E‐Risk) Longitudinal Twin Study. Multinomial logistic regression models estimated associations between each ACE type and a four‐category outcome: no self‐harm or depression, self‐harm alone, depression alone and self‐harm with co‐occurring depression. A structured life course modelling approach was used to examine whether the accumulation (duration) of exposure to each ACE, or a critical period (timing of ACEs) had the strongest effects on self‐harm and depression in adolescence.ResultsThe majority of ACEs were associated with co‐occurring self‐harm and depression, with consistent findings across cohorts. The importance of timing and duration of ACEs differed across ACEs and across cohorts. For parental mental health problems, longer duration of exposure was strongly associated with co‐occurring self‐harm and depression in both ALSPAC (adjusted OR: 1.18, 95% CI: 1.10–1.25) and MCS (1.18, 1.11–1.26) cohorts. For other ACEs in ALSPAC, exposure in middle childhood was most strongly associated with co‐occurring self‐harm and depression, and ACE occurrence in early childhood and adolescence was more important in the MCS.ConclusionsEfforts to mitigate the impact of ACEs should start in early life with continued support throughout childhood, to prevent long‐term exposure to ACEs contributing to risk of self‐harm and depression in adolescence.
Redescription and molecular characterization of Loxocephalus luridus Eberhard, 1862 based on Czech populations: Implications for order Loxocephalida Jankowski, 1980
Authors: Bourland William , Pomahač Ondřej , Poláková Kateřina , Čepička Ivan 
Published: April 2024

AbstractThe phylogenetic and taxonomic affinities of lineages currently assigned to the non‐monophyletic ciliate order Loxocephalida Jankowski (1980) within subclass Scuticociliatia Small (1967) remain unresolved. In the current study, we redescribe the morphology of the type species, Loxocephalus luridus Eberhard (1862) based on two Czech populations and include the first scanning and transmission electron microscopy images of the species. We provide the first 18S rRNA gene sequences for L. luridus and consider its phylogenetic position. Our results support the separation of Dexiotricha from Loxocephalus; however, the former genus is recovered as non‐monophyletic. The monophyly of genus Dexiotricha and that of Loxocephalus + Dexiotricha is rejected. Loxocephalus luridus, together with Dexiotricha species, nests within a fully supported clade with Conchophthirus species, long presumed to belong to the Pleuronematida. Haptophrya is recovered as sister to this clade. The monophyly of the Astomatia Schewiakoff (1896) including Haptophrya is rejected. No clear morphologic synapomorphy is identified for the fully supported clade consisting of Haptophrya, Dexiotricha, Loxocephalus, and Conchophthirus.
Sensitivity analysis on stormwater management response to land cover dynamics and urban expansion of developing City in Lake Hawassa watershed, Ethiopia
Authors: Kassay Abreham Birhane , Tuhar Abraham Woldemichael , Ulsido Mihret Dananto 
Published: April 2024

AbstractHawassa is a rapidly developing city in Lake Hawassa watershed of Ethiopia. Analyzing the effect of land cover dynamics on surface runoff remains imperative to adaptive urban stormwater management. This study quantified spatial variation of land cover and sensitivity of stormwater management response. Historical 30 years of daily annual rainfall, three satellite imageries, DEM, and hydrological soil group data were analyzed. A statistical‐based combined approach of geospatial techniques and Soil Conservation Service‐Curve Number (SCS‐CN) model was employed. CN and surface runoff depth for the delineated urban watersheds were determined. The result revealed that the built‐up area increased by 30.9 km2, where the rate varies spatially. The variation of impervious land cover explains 58.6% of change in CN with coefficient of 0.352. While CN is inversely correlated with agricultural and vegetation land cover variations. The finding suggests CN explains 96.78% of the change in surface runoff with a significant correlation coefficient of 3.91. The proposed integrated model approach justifies the potential to reorganize the relationship between the spatial effect of land cover variation on surface runoff at the urban watersheds. Thus, suitable local‐specific solutions can be devised for effective management of flood risk and optimize the drainage system of urban areas.