bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA‐mediated Ets1 repression in retinal endothelial cells: A novel anti‐angiogenic mechanism in nonproliferative diabetic retinopathy
Authors: Zhao Jianyu , Sun Zewen , Li Zimeng , Xu Mengyu , Tian Aowen , An Zhengwen , Guo Wenbo , He Chang , Dong Ying , Wen Jianping , Yang Jianli , Wang Qing , Chen Peng 
Published: January 2025

AbstractAimsThis study aimed to discover the regulatory mechanisms contributing to angiogenesis in nonproliferative diabetic retinopathy (NPDR).Materials and MethodsThis study employed a case–control design involving type 2 diabetes patients with and without NPDR. We utilised microRNA sequencing to analyse plasma and retina samples from T2D patients, to identify both existing and novel microRNAs relevant to retinal health. An integrative approach combining single‐cell sequencing data from mouse and rat models was used to explore the molecular mechanism in retinal cells under diabetes condition.ResultsWe identified a specific set of circulating microRNAs with strong predictive potential for distinguishing NPDR patients. In addition, a novel microRNA targeting the ETS proto‐oncogene 1 (Ets1), a key regulator of microvascular angiogenesis, was found to be upregulated in the plasma of NPDR patients. Analysis of single‐cell sequencing data suggested that Ets1 expression was downregulated in diabetic endothelial cells and was associated with the repression of Angiopoietin‐1 and phosphoinositide 3‐kinase‐Akt (PI3K‐Akt) signalling pathways, indicating an anti‐angiogenic mechanism in NPDR.ConclusionsThe identification of a novel microRNA involved in the anti‐angiogenic mechanism in NPDR provides new insights into the molecular underpinnings of endothelial dysfunction in diabetic retinopathy. Our retina‐specific circulating microRNA panel has potential utility in risk assessment and early detection of NPDR.
Pedagogical and Methodological Principles for the Development of Artistry of Vocal Performance in the Context of Distance Learning
Authors: Liu Aizhen 
Published: January 2025

ABSTRACTThe objective of this study was to investigate the influence of contemporary pedagogical principles of distance learning on the quality of acquiring artistic skills in the field of vocal arts. The research was conducted based on a sample of 750 first‐year students from the School of Literature and Journalism (Zhengzhou Business University), utilising a random sampling method. The research entailed the implementation of a case study method to facilitate an in‐depth examination of the impact of modern pedagogical principles of distance learning on the quality of acquiring artistic skills in the realm of vocal arts. Pedagogical observation materials were employed in two experimental groups of students for empirical investigation purposes. To obtain statistical data, the method of qualitative analysis was employed and experimental online sessions were conducted from February to April 2023. It has been ascertained that, based on preliminary surveys, the average performance scores for the three groups, as per the mental principle, did not exceed 3.8 points; as per the physical principle, 4.3 points; and as per the aesthetic principle, 4.4 points. This equates to a low and borderline average level of knowledge and signifies the low efficacy of the methodological principles.
The Role of Lifestyle and Environmental Factors in the Pathogenesis of Multiple Myeloma
Authors: Suska Anna , Tyczyńska Agata , Zaucha Jan Maciej , Kopińska Anna , Helbig Grzegorz , Markiewicz Mirosław , Warzybok Katarzyna , Leder Ewa , Grosicki Sebastian , Machaliński Bogusław , Baumert Bartłomiej , Bator Michał , Usnarska‐Zubkiewicz Lidia , Fornagiel Szymon , Ciepłuch Hanna , Waszczuk‐Gajda Anna , Kruczkowska‐Tarantowicz Kamila , Rzepecki Piotr , Hus Marek , Morawska‐Krekora Anna , Raźny Małgorzata , Charliński Grzegorz , Puła Anna , Nita Ewa , Wojciechowska Małgorzata , Krawczyk‐Kuliś Małgorzata , Goldberg Joanna , Woźny Tomasz , Rodzaj Marek , Olejarz Dariusz , Gronau‐Dziurkowska Marlena , Skalniak Ewa , Krzysztoń Janusz , Niezabitowska Karolina , Jurczyszyn Artur 
Published: January 2025

ABSTRACTObjectivesThe study evaluated the impact of lifestyle and environmental exposure on the etiology of multiple myeloma (MM).MethodsA multicenter case–control study was conducted in 20 hematology centers and in 5 outpatient clinics in Poland. The questionnaire on exposure to potential risk factors including sociodemographic data, lifestyle, and environmental factors was completed.ResultsA total of 274 patients with newly diagnosed MM and 208 patients from primary healthcare centers in the control group were enrolled in the study. Regarding lifestyle, sports practiced systematically for at least half a year play a protective role in the development of myeloma (OR = 0.40, 95% CI, 0.28–0.58, p < 0.001). Among environmental factors harmful exposures that increase the likelihood of the development of MM include pesticides (OR = 3.29, p < 0.001), asphalt (OR = 2.42, p = 0.026), coal dust (OR = 2.27, p = 0.004), organic vapors (OR = 2.11, p = 0.001), metal dust (OR = 2.07, p = 0.023), exhaust fumes (OR = 2.03, p < 0.01), and chemicals (OR = 1.80, p < 0.01).ConclusionsThe pathogenesis of MM is complex with the impact of modifiable factors. Lifestyle, with physical activity, seems to play a key role.
Delineating the genetic landscape of Charcot–Marie–tooth disease in Türkiye: Distinct distribution, rare phenotypes, and novel variants
Authors: Cakar Arman , Candayan Ayse , Bagırova Gulandam , Uyguner Zehra Oya , Ceylaner Serdar , Durmus Hacer , Battaloglu Esra , Parman Yesim 
Published: January 2025

AbstractBackgroundCharcot–Marie‐Tooth (CMT) disease is the most common inherited neuropathy. In this study, we aimed to analyze the genetic spectrum and describe phenotypic features in a large cohort from Türkiye.MethodsDemographic and clinical findings were recorded. Patients were initially screened for PMP22 duplication. Targeted sequencing or whole‐exome sequencing was performed in duplication‐negative patients.ResultsOverall, 311 patients from 265 families were included. Demyelinating CMT (67.4%) was more common than axonal (20.5%) and intermediate subtypes (11.7%). PMP22 duplication was the most frequent mutation, followed by pathogenic variants in GJB1, MFN2, SH3TC2, and GDAP1 genes. MPZ‐neuropathy was rare in our cohort (3.0%). Interestingly, CMT4 is the second most common type after CMT1. Lower extremity weakness and foot deformities were the most frequent presenting complaints. Striking clinical features included a high frequency of scoliosis in SH3TC2, peripheral hyperexcitability in HINT1, and central nervous system findings in GJB1. Autosomal recessive CMT subtypes had higher CMTESv2 scores when compared to autosomal dominant ones (12.39 ± 4.81 vs. 8.36 ± 4.15, p: 0.023). Twenty‐one patients used wheelchairs during their last examination. Among them, 16 had an autosomal recessive subtype. Causative variants were identified in 31 genes, including 28 novel pathogenic or likely pathogenic changes.ConclusionsOur findings provided robust data regarding the genetic distribution of CMT in Türkiye, which may pave the path for building population‐specific diagnostic gene panels. Rare autosomal recessive subtypes were relatively frequent in our cohort. By analyzing genotype–phenotype correlations, our data may provide clinical clues for clinicians.
Identification and characterisation of temporal abundance of microRNAs in synovial fluid from an experimental equine model of osteoarthritis
Authors: Walters Marie , Skovgaard Kerstin , Heegaard Peter M. H. , Fang Yongxiang , Kharaz Yalda A. , Bundgaard Louise , Skovgaard Lene T. , Jensen Henrik E. , Andersen Pia H. , Peffers Mandy J. , Jacobsen Stine 
Published: January 2025

AbstractBackgroundMicroRNAs, a class of small noncoding RNAs, serve as post‐transcriptional regulators of gene expression and are present in a stable and quantifiable form in biological fluids. MicroRNAs may influence intra‐articular responses and the course of disease, but very little is known about their temporal changes in osteoarthritis.ObjectivesTo identify miRNAs and characterise the temporal changes in their abundance in SF from horses with experimentally induced osteoarthritis. We hypothesised that the abundance of miRNA would change during disease progression.Study designIn vivo experiments.MethodsRNA extracted from synovial fluid obtained sequentially (Day 0, 28 and 70) from nine horses with experimentally induced osteoarthritis was subjected to small RNA sequencing using the Illumina Hiseq 4000 sequencing platform. Differentially abundant miRNAs underwent further validation and mapping of temporal abundance (Day 0, 14, 17, 21, 28, 35, 42, 49, 56, 63 and 70 days after osteoarthritis induction) by microfluidic reverse transcription quantitative real‐time PCR. Bioinformatic analyses were performed to predict potential biological associations and target genes of the differentially abundant microRNAs.ResultsSmall RNA sequencing revealed 61 differentially abundant microRNAs at an early osteoarthritis stage (Day 28), and subsequent reverse transcription quantitative real‐time PCR analysis validated 20 of these. Significant biological functions of the differentially abundant microRNAs were apoptosis, necrosis, cell proliferation and cell invasion. Following validation, four microRNAs (miRNA‐199b‐3p, miRNA‐139‐5p, miRNA‐1839 and miRNA‐151‐5p) were detected in more than 50% of the synovial fluid samples and had higher abundance in osteoarthritic than in control joints.Main limitationsLimited sample size.ConclusionThis is the first study to determine longitudinal changes in synovial fluid microRNA abundance in an equine model of osteoarthritis. Larger studies are needed in naturally occurring osteoarthritis to interrogate putative changes identified by this study.
Inflammation and response to bacterial infection as potential drivers of equine odontoclastic tooth resorption and hypercementosis: A proteomics insight
Authors: Jensen Anders , Clarke Emily J. , Nugent Zoe , Paice Emily , Gringel Iris , Yamamoto Kazuhiro , Rocchigiani Guido , Peffers Andrew J. , Cooper Lee , Peffers Mandy J. 
Published: January 2025

AbstractBackgroundEquine dental diseases significantly impact a horse's overall health, performance and quality of life. They can result in secondary infections and digestive disturbances, potentially leading to colic. A recently described disease affecting the incisors of horses is equine odontoclastic tooth resorption and hypercementosis (EOTRH). Understanding EOTRH is crucial for early diagnosis, effective management and prevention of its severe consequences.ObjectivesTo determine proteomic differences in incisor cementum in horses with and without clinical EOTRH.Study designComparative and observational clinical study.MethodsTeeth were extracted (N = 5) and cementum was isolated using a diamond wire. Proteins were extracted using an optimised sequential workflow, and trypsin was digested for mass spectrometry. Protein identification and label‐free quantification were undertaken.ResultsIn total 1149 unique proteins were detected in cementum across all samples. We identified four proteins exclusively in EOTRH‐affected cementum. EOTRH samples showed a higher heterogeneity than healthy samples. In total, 54 proteins were increased in EOTRH, and 64 proteins were reduced (adjusted p‐value <0.05). Inflammatory proteins, such as cathepsin G (p = 0.004), neutrophil elastase (p = 0.003), bactericidal permeability‐increasing protein (p = 0.002), azurocidin (p = 0.003) and lactotransferrin (p = 0.002) were all increased in EOTRH. Pathway analysis revealed that antimicrobial peptides (Z score 2.65, p = 1.93E−09) and neutrophil degranulation (Z‐score 1.89, p = 1.7E−04) were commonly up‐regulated canonical pathways.Main limitationsThe sample size was limited. Lack of age‐matched healthy controls.ConclusionEOTRH leads to biochemical changes within the cementum proteome, which are important in explaining the physiological changes occurring in disease. Differentially abundant proteins may represent promising biomarkers for earlier disease detection and the establishment of a cell‐based model could provide further insight into the role these proteins play in hypercementosis and resorption.
Responses of Benthic Carbon Flows in Scandinavian Lakes to Atmospheric Sulphur and Nitrogen Depositions: Potential Influence of Nutrient Limitation
Authors: Belle Simon , Fölster Jens , Goedkoop Willem , Johnson Richard K. 
Published: January 2025

ABSTRACT

Paleolimnological reconstructions of past changes in carbon stable isotopic composition of chironomid head capsules (δ13CHC) were used to quantify the impacts of atmospheric sulphur and nitrogen depositions on carbon processing at the base of lake food webs.

We hypothesised that the impacts of atmospheric nitrogen deposition on carbon flows through food webs are influenced by nutrient limitation, as increasing nitrogen inputs are expected to drive higher primary producer biomass in nitrogen‐limited lakes, thus increasing its availability for benthic consumers.

The δ13CHC values showed significant changes before/after 1960, corresponding to the time of early impacts of atmospheric deposition on water chemistry and biological communities in Scandinavian lakes. These results suggest that atmospheric deposition was a key driver of change in carbon flows through benthic food webs. Furthermore, our study showed that lakes responded differently to atmospheric deposition and that differences in δ13CHC values were largely explained by a combination of nutrient limitation, latitude and water transparency.

Overall, results support the hypothesis that the response of carbon flows through benthic food webs to changes in atmospheric nitrogen deposition differs partly depending on lake nutrient limitation. However, the observed strong collinearity between the explanatory variables complicates the interpretation of the relationships between the temporal changes in benthic carbon flows in response to atmospheric deposition and nutrient limitation.
Threonine and tyrosine kinase (TTK) mRNA and protein expression in breast cancer; prognostic significance in the neoadjuvant setting
Authors: Ashi Abrar , Awaji Aeshah A , Bond Jacquelyn , Johnson Colin A , Shaaban Abeer M , Bell Sandra M 
Published: January 2025

AimsThreonine and tyrosine kinase (TTK) is up‐regulated in triple‐negative breast cancer (TNBC), yet its expression in patients undergoing neoadjuvant chemotherapy (NACT) remains unexplored. This investigation aims to assess TTK protein expression in treatment‐naïve pre‐treatment cores and paired pre‐ and post‐NACT breast cancer (BC) cohorts, as well as its correlation with microcephaly 1 (MCPH1) protein expression.Methods and resultsTranscriptomic data were sourced from the Gene Expression Omnibus microarray database for mRNA expression analysis. TTK protein expression was evaluated using immunohistochemistry staining, employing receiver operating characteristic curve analysis to determine an optimal TTK expression cut‐off point. The association between TTK expression, clinicopathological parameters and survival outcomes was examined. Additionally, MCPH1 protein expression was assessed in a pilot study. Analysis revealed a significantly elevated TTK mRNA expression in BC tissue compared to normal breast tissue, with high TTK mRNA levels predicting reduced overall survival. Notably, TTK protein expression increased significantly post‐NACT in a paired cohort. Conversely, decreased TTK protein expression pre‐NACT was correlated with improved overall survival.ConclusionsHigh TTK and low MCPH1 protein expression was significantly correlated, highlighting TTK's potential as a biomarker for BC and a therapeutic target for MCPH1‐deficient cancer cells.
Temperature dependent scaling behavior and evolution of domain dynamics in low temperature sintered PZN–PZT ceramics
Authors: Baby Anagha , N. Shara Sowmya , N. S. Reshma , S. Susanth , E. K. Sunny , V. Priyadarshini , Thangavelu Karthik 
Published: January 2025

AbstractA comprehensive investigation into the dynamic hysteresis behavior of the low temperature sintered 0.4PZN–0.6PZT ceramics across a wide range of electric field frequency, and temperature was carried out in the present study. Our findings from the electric field and frequency dependent scaling analysis at 303 K revealed distinct domain dynamics having three stages of polarization reversal mechanism with a breakdown frequency (fb) of 5 Hz. Temperature dependent scaling analysis till 503 K showcased the influence of thermal energy especially in the stage‐I and stage‐II of the polarization reversal mechanism resulting in enhanced domain wall mobility with reduced switching time at a lower electric field. The power‐law temperature scaling relations for hysteresis area 〈A〉, remanent polarization (Pr), and coercivity (EC) took the form of A ∝ T 0.1468, Pr ∝ T −0.5577, and EC ∝ T −0.68272, respectively. The decay of the derived exponent values with temperature corresponding to 〈A〉, Pr, and EC was minimal as compared to the other reported soft PZT and lead‐free systems. This study provided information on the influence of temperature toward domain wall motion, domain nucleation, and domain switching, and it will be useful for designing devices that demand high reliability and thermal stability.
Impact of sintering parameters on the microstructure of homogeneous U1‐xCexO2+δ ceramics
Authors: Clavier Nicolas , Massonnet Malvina , Claparede Laurent , Podor Renaud , Imbert Paul‐Henri , Martinez Julien , Dacheux Nicolas 
Published: January 2025

AbstractThe effects of atmosphere and cerium content on the densification and the final microstructure of homogeneous U1‐xCexO2+δ solid solutions (x = 0.10; 0.25; 0.50) were investigated. Dilatometric studies first revealed that while the cerium content only slightly modifies sintering under an Ar/H2 atmosphere, a change of the gas to argon dramatically modifies densification kinetics. As a result, samples prepared under Ar/H2 exhibit a dense microstructure with micrometric grains. Conversely, samples sintered under argon appeared to be less densified but with larger grains. These changes were correlated with the variation of the final O/M stoichiometry (M = U+Ce) and illustrated by the construction of sintering maps. Finally, grain growth was found to be driven by grain boundary motion when the O/M ratio remained close to 2.00, while usual power laws did not apply for most hyper‐stoichiometric samples. The first values of activation energy for the sintering of U1‐xCexO2+δ solid solutions under an Ar/H2 atmosphere were also determined.
Masking Ability of Subtractively and Additively Manufactured Dental Ceramic Restorations: A Systematic Review
Authors: Du Karen , Muao Teuila , Plaksina Polina , Hung Sharon Tsz‐Han , Cameron Andrew B , Choi Joanne Jung Eun 
Published: January 2025

ABSTRACTObjectiveTo conduct a systematic review on the masking ability of subtractively and additively manufactured dental ceramics.Materials and MethodsThe study followed the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement. The electronic search was carried out through MEDLINE, Scopus, and Website of Science databases with a date restriction being from 2001 onwards. Publications in English, in vitro studies, and studies regarding the evaluation of the masking ability of crown materials that were subtractively and additively manufactured were included.ResultsOut of 619 eligible articles, 13 were included. A thickness of 1.5 mm for lithium disilicate (LD) resulted in a dramatic decrease in ∆Eab/∆E00 across all substrates compared to a 1 mm thickness. Low‐translucent LD appeared to have the best masking ability regardless of the shade of the try‐in paste. Layering flowable composite over the substrates improved masking ability. Darker substrates were the hardest to mask no matter the type of restorative material, try‐in paste used, and layering technique. Bilayered restorative materials proved to be superior to monolithic materials regarding masking ability.ConclusionIncreasing the thickness of subtractively manufactured ceramics materials improves the masking ability. 1.5 mm thickness is found to provide the best masking ability for most ceramic materials. Darker substrates prove to be difficult to mask in comparison to lighter substrates and require either thicker materials and/or more opaque cements. Bilayered crowns are recommended for achieving optimal masking while preserving tooth structure. Despite the increasing demand, there is no study available on 3D‐printed (additively manufactured) restoration's masking ability.Clinical SignificanceThis review provides a comparison of masking abilities of multiple subtractively manufactured ceramic materials and highlight the lack of current knowledge on additively manufactured crown materials. It also emphasizes the importance of having a universal approach to interpreting and communicating color changes between collaborative dental professionals to ensure the same shade predictions. In addition, when masking darker shades, clinicians should be aware that alternative material choice or clinical and technical procedures are essential.
A Realist Scoping Review of Community Nutrition Interventions in the UK: Implications for the ‘Nutrition Skills for Life’ Programme
Authors: Lisa Williams J. , Wallace Carolyn , Filipponi Teresa 
Published: January 2025

ABSTRACTBackgroundNutrition Skills for Life (NSFL) provides training and support for communities and organisations to implement Community Nutrition Interventions (CNIs) that meet identified needs. To inform future NSFL evaluation, this scoping review, using a realist approach sought to determine the underpinning initial programme theory (IPT) for how CNIs support socioeconomically disadvantaged (SED) communities to access a healthy diet, as detailed in the protocol doi.org/10.17605/OSF.IO/D56FK.OSF.IO/D56FK.MethodologyReporting standards for realist syntheses (RAMESES) and scoping reviews (PRISMA‐ScR) were used. Four electronic databases and grey literature were searched. Of the 1920 documents identified, 45 were included in the analysis. Data relating to Context, Mechanism and Outcomes were extracted and presented as C‐M‐O configurations (CMOCs). Documents were assessed for relevance to the research question and usefulness in terms of their contribution towards the IPT.ResultsThe IPT, underpinned by the Ottawa Charter for Health Promotion, comprises 17 consolidated CMOCs. These are narratively discussed as follows: understanding community needs; consistent nutrition messages; knowledgeable, skilled, confident practitioners/facilitators and practising new skills.ConclusionsRealist research and analysis of CMOCs provided a deeper understanding of how CNIs can be implemented to support SED communities in accessing a healthy diet. Interventions ‘worked’ when they acknowledged and addressed identified barriers to healthy eating, provided reliable, trusted, easy‐to‐understand nutrition messages, were delivered by confident, knowledgeable practitioners, and facilitated strategies such as meal preparation. Further realist evaluation to refine the IPT could inform the evaluation of other complex public health interventions.