bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expanding the Phenotypic Spectrum of SPG7 Rare Damaging Variants: Insights From a Hungarian Cohort
Authors: Jimoh Idris Janos , Balicza Peter , Szlepak Tamas , Csaban Dora , Gal Aniko , Geresi Adrienn , Grosz Zoltan , Palasti Agnes , Boczan Judit , Klivenyi Peter , Molnar Maria Judit 
Published: February 2025

ABSTRACTMitochondria‐associated paraplegin dysfunction is primarily linked to spastic paraplegia; however, genetic alterations in SPG7 have been associated with a broader spectrum of clinical symptoms. To identify disease‐causing variants in the SPG7 gene, 437 patients with spastic ataxia, mitochondrial dysfunction‐associated symptoms, or motoneuron lesions detected by EMG have been tested. We aimed to assess the clinical spectrum and determine the frequency of damaging variants within patient groups, particularly those less studied. Using ACMG criteria, we identified 10 pathogenic or likely pathogenic variants, 5 variants of uncertain significance with predicted damaging effects, and a probable risk factor variant in 58 patients. We identified 25 biallelic and 33 monoallelic cases. The most common variant was p. Leu78Ter (N = 23), followed by p. Ala510Val (N = 21). The point prevalence of SPG7‐associated conditions in Hungary in 2024 is 0.46 per 100 000. In addition to well‐characterized cohorts, SPG7 alterations were frequently identified in cohorts with multisystemic mitochondrial disease and lower motoneuron lesions. Multiple mtDNA deletions and histological abnormalities were consistently observed across all groups. In monoallelic cases, no evidence of a digenic effect involving AFG3L2 was found. Both autosomal dominant and recessive inheritance patterns were documented, with monoallelic cases typically presenting with a milder phenotype.
Enhancing Foreign Language Learning Through Social Media Applications: A Fuzzy Analytic Hierarchy Process Approach
Authors: Geng Yanping , Alshahrani Reem , Mujlid Hana Mohammed 
Published: February 2025

ABSTRACTThe Fuzzy Analytic Hierarchy Process (FAHP) was employed to evaluate and rank language‐learning applications based on criteria such as engagement, interactivity, feedback, content quality and usability. A pairwise comparison matrix was constructed, fuzzy logic was applied to convert qualitative judgements into numerical values, and these values were normalised to calculate crisp weights for each criterion. These weights assessed and ranked five popular language‐learning apps: Duolingo, Busuu, Babbel, Memrise and Tandem. The results show Duolingo ranking highest with an aggregate score of 20.912, demonstrating superior performance across all criteria. Busuu and Babbel followed with scores of 18.541 and 18.485, respectively, while Memrise and Tandem scored 17.260 and 17.024. The FAHP methodology effectively addresses uncertainty in the evaluation process, offering a structured and reliable framework for users and educators to select the most suitable language‐learning tool.
Distinct mechanisms linking romantic attachment dimensions to harsh discipline among Chinese parents of young children
Authors: Jin Zhou , Ye Minjie , Lu Hui , Chen Lanyue , Chen Wenyue , Yang Hongsheng , Chang Lei , Wang Deborah Baofeng , Wu Yili 
Published: February 2025

AbstractObjectiveThis study aims to explore the mediating role of parental reflective functioning (PRF) and parental sense of competence (PSC) in the effect of romantic attachment on harsh discipline among Chinese parents of young children through both variable‐ and person‐centered approaches.BackgroundHarsh discipline is a negative parenting practice that has detrimental impacts on children. Evidence showed that parents' insecure romantic attachment may contribute to the use of harsh discipline, whereas the psychological mechanism underlying this association remains unclear.MethodParticipants were 489 Chinese parents of children aged 0 to 5 years. Validated scales were used to assess romantic attachment, PRF (assessed by the prementalizing modes dimension), PSC, and harsh discipline. Mediation analysis and latent profile analysis were conducted.ResultsPSC mediated the relationship between attachment avoidance and harsh discipline, whereas PRF and PSC played a chain‐mediating role between attachment anxiety and harsh discipline. By using the person‐centered approach, three profiles of attachment were identified: secure (46.8%), dismissive (23.9%), and fearful (29.2%). Compared to secure profile, PRF and PSC sequentially mediated the link between dismissive/fearful profile of attachment and harsh discipline.ConclusionsThe mediating roles of PRF and PSC elucidated psychological mechanisms for the impact of romantic attachment on harsh parenting, particularly among couples with dismissive and fearful attachment.ImplicationsImproving PRF and PSC is crucial for preventing harsh parenting among insecurely attached couples.
High crystallinity CSP bioceramics with excellent mechanicals for 3D printed bone regeneration repairing
Authors: Zhou Chenliang , Chen Wei , Liang Yiran , Zhang Jiali , Huang Li , Chen Zhili , Cheng Xiangyu , Zhang Yunxiang , Zhang Qinfang 
Published: February 2025

AbstractLarge bone defects caused by disease, physiological deformation, and accidental injury present significant challenges for clinical bone tissue repair. Calcium silicon phosphate (CSP)‐based bioceramics are widely used for clinical bone defect repair with the advantages of biocompatibility and osteogenic properties. However, poor mechanical strength limits their load‐bearing applications. In this work, a novel CSP‐based bioceramic, Nagelschmidtite (Nagel, Ca7Si2P2O16), was fabricated by the molten salt synthesis (MSS), sol‒gel, and solid‐state reaction methods. Materials characterization revealed the Nagel powders fabricated from the MSS method possess high crystallinity, uniform particle size distribution, and smooth particle surfaces, and their disks exhibited low porosity and high density. Benefiting from the above characterizations, the mechanical strength of the MSS sample was enhanced by roughly 6.07 times relative to the sol‒gel sample. Meanwhile, the stable degradation performance and bone mineralization ability mean that MSS samples have the potential for direct application with load‐bearing sites. Furthermore, MSS Nagel can be used to support three dimensional (3D)‐printed scaffolds of various shapes. These findings demonstrate that Nagel bioceramics, produced with high crystallinity through the MSS method, are highly promising as 3D‐printed biomaterials for applications in bone tissue regeneration.
Competitive Entry in the Market for Branded Generic Drugs
Authors: Wattal Vasudha 
Published: February 2025

ABSTRACTI analyze the determinants of lead time (the time lag between the first‐mover's product release and the competitor's market entry) and its consequences for product prices, competition, and consumers. I investigate the case for the Indian branded generic pharmaceutical sector where substantial variation in lead time is observed. I show that overall entry is linked with product market profitability, but entry timing may be strategically related with both originator and competitor firm experience. This appears relevant for those products more likely to build up brand loyalty. I also show that lead time, once its potential endogeneity is accounted for, appears to increase the originator's post‐entry market shares, but has no effect on prices. These findings indicate that market segmentation based on price sensitivity appears less likely in the presence of brand name prescriptions. To enable price competition, there is a need for quality assurance among otherwise substitutable generic drugs.
MiR‐33‐Mediated Regulation of Autophagy and Inflammation in CIK Cells Through Atg5
Authors: Yang Lulu , Lin Mengjun , Zhao Weifang , Zhang Yuru , Xu Xinxin , Cao Xianglin , Nie Guoxing , Lu Ronghua 
Published: February 2025

ABSTRACTMicroRNA‐33 (miR‐33) plays a critical role in the regulation of autophagy and inflammatory responses. In this study, C. idella kidney (CIK) cells were transfected with a miR‐33 mimic or inhibitor and Atg5 was overexpressed or silenced to elucidate the regulatory mechanism of miR‐33. Our findings revealed that the miR‐33 mimic significantly decreased the expression of LC3B (a marker of autophagy activation), and the level of autophagy‐related genes (Beclin‐1, Atg5 and LC3‐1) was also significantly downregulated (p < 0.05). Additionally, the miR‐33 mimic promoted the secretion of proinflammatory factors, including TNF‐α, IL‐6, IL‐12 and IL‐1β (p < 0.05). In contrast, the miR‐33 inhibitor significantly enhanced LC3B protein expression and increased the relative expression of Beclin‐1 and Atg5 (p < 0.05). The secretion of proinflammatory factors (TNF‐α, IL‐6 and IL‐12) was significantly reduced (p < 0.05). These results suggested that inhibition of miR‐33 could induce the initiation of autophagy and attenuate the inflammatory response in CIK cells. Furthermore, we identified Atg5 as a direct target gene of miR‐33. Overexpression of Atg5 significantly upregulated the levels of Beclin‐1, Atg5, Atg4C and LC3‐1, along with a reduction in the secretion of proinflammatory factors (TNF‐α, IL‐12 and IL‐1β). Besides, the activities of superoxide dismutase (SOD) and catalase (CAT) were significantly increased (p < 0.05). Conversely, interference with Atg5 expression caused significant downregulation in the expression levels of Beclin‐1, Atg5, Atg12, Atg4C and LC3‐1, resulting in increased secretion of TNF‐α, IL‐12 and IL‐1β and decreased activity of acid phosphatase (ACP) and SOD (p < 0.05). Taken together, these results suggested that inhibition of miR‐33 expression could promote the initiation of autophagy and attenuate the inflammation in CIK cells through targeting Atg5. This study not only enhances the understanding of the mechanism by which miR‐33 regulates autophagy and inflammation in fish but also provides a theoretical foundation and novel insights to improve disease management in the fish aquaculture industry.
Plant–microbiome interactions and their impacts on plant adaptation to climate change
Authors: Zeng Qing , Hu Hang‐Wei , Ge An‐Hui , Xiong Chao , Zhai Chang‐Chun , Duan Gui‐Lan , Han Li‐Li , Huang Si‐Yun , Zhang Li‐Mei 
Published: February 2025

ABSTRACTPlants have co‐evolved with a wide range of microbial communities over hundreds of millions of years, this has drastically influenced their adaptation to biotic and abiotic stress. The rapid development of multi‐omics approaches has greatly improved our understanding of the diversity, composition, and functions of plant microbiomes, but how global climate change affects the assembly of plant microbiomes and their roles in regulating host plant adaptation to changing environmental conditions is not fully known. In this review, we summarize recent advancements in the community assembly of plant microbiomes, and their responses to climate change factors such as elevated CO2 levels, warming, and drought. We further delineate the research trends and hotspots in plant–microbiome interactions in the context of climate change, and summarize the key mechanisms by which plant microbiomes influence plant adaptation to the changing climate. We propose that future research is urgently needed to unravel the impact of key plant genes and signal molecules modulated by climate change on microbial communities, to elucidate the evolutionary response of plant–microbe interactions at the community level, and to engineer synthetic microbial communities to mitigate the effects of climate change on plant fitness.
Uncertainties in interfacial excess calculations from atom probe tomography data
Authors: Tegg Levi , Cairney Julie M. 
Published: February 2025

AbstractAtom probe tomography can be used to measure the excess of solute chemical species at internal interfaces, but common protocols do not usually consider the compositional uncertainty of the (usually dilute) solute. Here, general models are derived for the composition profile of a solute segregated to the interface between two grains or phases. This model is fit to experimental data, with the cumulative compositional uncertainty included in the calculation of the interfacial excess. It is shown that the relative uncertainty in the interfacial excess can be large for dilute solutes, even when segregation is obvious in the concentration profile. Different methods for estimating the extent of the boundary provide different estimates for the interfacial excess and its uncertainty. Some strategies are provided for the minimisation of uncertainties in typical data, though ultimately, a typical calculation will be limited by compositional uncertainty arising from the relatively few solute counts in the region‐of‐interest.
Melatonin Deficits Result in Pathologic Metabolic Reprogramming in Differentiated Neurons
Authors: Jauhari Abhishek , Monek Adam C. , Suofu Yalikun , Amygdalos Olivia R. , Singh Tanisha , Baranov Sergei V. , Carlisle Diane L. , Friedlander Robert M. 
Published: February 2025

ABSTRACTDifferentiation from neural progenitor to mature neuron requires a metabolic switch, whereby mature neurons become almost entirely dependent upon oxidative phosphorylation (OXPHOS) for ATP production. Although more efficient with respect to ATP production, OXPHOS produces additional reactive oxygen species, as compared to glycolysis; thus, endogenous mechanisms to quench free radicals are essential for the maintenance of neuronal health. Melatonin is synthesized in neuronal mitochondria and has a dual role as a free radical scavenger and as an inhibitor of mitochondrial‐triggered cell death and proinflammatory pathways. Previously, we showed that loss of endogenous melatonin induced mitochondrial DNA (mtDNA) and cytochrome c (CytC) release triggering pathological inflammation and cell death pathways, respectively. Here we find that in mature neurons, but not undifferentiated neuronal cells, melatonin deficiency altered metabolic reprogramming in aralkylamine N‐acetyltransferase knockout (AANAT‐KO) neurons as compared with neurons expressing AANAT. Interestingly, there are no differences in neural progenitors regardless of AANAT status. In addition, AANAT‐KO deficiency elevated BAK and BAX levels in AANAT‐KO neurons. Further, we found that exogenous melatonin treatment of AANAT‐KO cells during differentiation into mature neurons rescued metabolic reprogramming defects and restored normal BAK/BAX levels. Thus, we demonstrated that the metabolic reprogramming and subsequent consequences of the switch to OXPHOS that normally occurs during neuronal maturation are compromised by melatonin deficiency and rescued by melatonin supplementation.
DNA Methylation and Target Gene Expression in Fatty Liver Progression From Simple Steatosis to Advanced Fibrosis
Authors: Li Jin , Liu Xiaoqin , Tran Tran T. , Lee Miryoung , Tsai Robert Y. L. 
Published: February 2025

ABSTRACTBackground and AimMetabolic dysfunction‐associated steatotic liver diseases (MASLD), also known as non‐alcoholic fatty liver diseases (NAFLD), have become a leading risk factor for hepatocellular carcinoma (HCC) in Western countries. NAFLD progresses from simple steatosis to HCC, with advanced liver fibrosis (ALF) and metabolic dysfunction‐associated steatohepatitis (MASH) or non‐alcoholic steatohepatitis (NASH) representing the two preceding high‐risk stages.MethodsWe analysed changes in the DNA methylation landscape from simple steatosis to ALF or NASH and determined their relevance in gene regulation and HCC survival. Methylomic datasets generated from applying the Illumina 450K BeadChip on human MASLD/NAFLD liver samples were analysed using integrative data analyses to identify differentially methylated regions (DMRs) associated with ALF (F3/4 vs. F0/1) or non‐fibrotic NASH (NASH‐F0/1 vs. NAFLD‐F0/1).ResultsGene Set Enrichment Analysis (GSEA) of genes associated with fibrosis‐DMRs showed enrichment in xenobiotic metabolism, UV response and hypoxia pathways. Expression of 25 DMR‐associated genes showed significant associations with HCC survival outcomes, including 16 genes with fibrosis‐DMRs and 2 with NASH‐DMRs mapped to their promoter regions. Binding motifs of seven transcription factors (TFs) were enriched in fibrosis‐DMRs. Four DMR‐associated genes (ESR1, TYW3, CLGN and TUBB) displayed an inverse relationship between promoter methylation and gene expression during human MASLD progression, which was further validated in a mouse MASLD model.ConclusionsWe propose a model in which changes in promoter DNA methylation during NAFLD progression regulate gene expression, impacting HCC survival outcomes.
Sperm Whales—Island Specialists, Are They on the Way to Extinction? Systematic Literature Review in a Global Context
Authors: Barteneva‐Vitry Svetlana , Appadoo Chandani , Plön Stephanie 
Published: February 2025

ABSTRACTBackgroundSperm whale population units, resident off inhabited islands, are an important source of ecosystem services for local communities and may be subject to greater anthropogenic pressures than their oceanic conspecifics.AimsThe objectives of this review were to identify sperm whale‐island specialists' habitats around the world and to assess the level of anthropogenic pressure on such nearshore populations. The hypothesis was that sperm whales with this ecological specialisation are rare and that the negative impacts they experience living close to inhabited shores may be also exacerbated by Anthropogenic Allee effect.Materials & MethodsThis study was conducted using a systematic literature review, following the principles recommended by the PRISMA guidelines, with a scoping of records of the presence of sperm whale social units in the territorial waters of countries around the world published between 2003 and 2023.Results & DiscussionA review of 422 relevant research papers revealed only two places in the world where sperm whales with an island ecological specialisation exist, and there are negative trends in both. Such population units experience cumulative anthropogenic pressures 1.7–1.8 times higher than oceanic ones. The charisma and media popularity of sperm whales, combined with the rarity of observation sites for this species, may increase pressure, potentially accelerating their extinction (Anthropogenic Allee Effect). The results of the study are presented in the form of a narrative synthesis, tables and a map.ConclusionDetermining the ecological specialisation of sperm whale population units should be a key component of management at both the local and species level. Exploitation of ecosystem services provided by island specialists should be strictly regulated in favour of sustainability, in order to preserve this rare ecological type.
Dilemma in the Treatment of Sports Injuries in Athletes: Tendon Overuse, Muscle Strain, and Tendon Rupture
Authors: Kjær Michael , Petersen Jesper , Dünweber Michael Ries , Andersen Jesper Løvind , Engebretsen Lars , Magnusson Stig Peter 
Published: February 2025

ABSTRACTInjuries to the musculoskeletal system are frequent in elite sports and they are detrimental to athletic performance. This can be due to, for example, (1) overuse disorders of tendon (tendinopathy) that not only lower the training efficiency but also, in many cases, are career‐ending for the athlete due to pain; (2) acute muscle strain injury that both causes prolonged absence from competition and results in many re‐injuries; or (3) tendon rupture that, apart from a very long rehabilitation period, will also result in many athletes never resuming their original high level of competitive sports. For all three injury examples, several evidence‐based prevention programs and treatments are available, and yet the incidence of these injuries remains high and single treatments often provide only partial recovery. In this paper, we highlight the current treatments of these three conditions and focus on the unsolved dilemmas that exist in these sports injuries.
Diversification and evolution of serine/arginine‐rich splicing factors in plants
Authors: Guo Mingxi , Liang Chao , Cui Mingyang , Luo Linlin , Gao Zhongtian , Chen Haolang , Xie Qi , Cui Jie , Liu Lin , Mo Beixin , Gao Lei 
Published: February 2025

SUMMARYIn plants, serine/arginine‐rich splicing factors (SRSFs) play an essential role in pre‐mRNA splicing, influencing growth and stress response. The present study investigated the evolution and diversification of SR proteins in plants by phylogenetic analysis. First, we identified 1650 SR proteins from 132 plant species. Large‐scale phylogenetic analysis divided these SR proteins into nine subfamilies: SR, RS, SC, SCL, RSZ, RS2Z, SR45, SR45a, and a newly discovered RSZ‐like subfamily. The analysis also suggested that SR proteins of animals and plants originated from an ancient SR gene of a common ancestor of eukaryotes and showed that RSZ‐like subfamily diverged in fern. We also found the presence of the newly discovered RSZ‐like subfamily in ferns, gymnosperms, and angiosperms as a sister group of SR45 and SR45a, indicating a common ancestor. In addition, we detected deletion of the N‐terminal RS domain in a few members of SR45 and SR45a of plants. These findings provide novel insights into the phylogeny of the SR gene family in plants, emphasizing their crucial function as a splicing factor.
AI‐Assisted Tailored Intervention for Nurse Burnout: A Three‐Group Randomized Controlled Trial
Authors: Baek Gumhee , Cha Chiyoung 
Published: February 2025

ABSTRACTBackgroundHigh‐stress environments, heavy workloads, and the emotional demands of patient care, which are common challenges faced by nurses, are factors that can lead to burnout. Shift work can make traditional burnout interventions costly and difficult to implement. Artificial intelligence (AI) could offer solutions that are less constrained by time, resources, and labor.AimTo investigate the effectiveness of an AI‐assisted intervention in reducing nurse burnout.MethodsA single‐blind, three‐group, randomized controlled trial of 120 nurses (40 per group) was conducted from June 2023 to July 2023. The AI‐assisted tailored intervention included two 2‐week programs, delivering one of four programs to the intervention group: mindfulness meditation, acceptance commitment therapy, storytelling and reflective writing, or laughter therapy. The experimental group received tailored programs based on demographic and work‐related characteristics, job stress, stress response, coping strategy, and burnout dimensions (client‐related, personal, and work‐related). Control Group 1 self‐selected their programs, while Control Group 2 was provided with online information on burnout reduction. Primary outcomes, client‐related, personal, and work‐related burnout, were measured at baseline, week 2, and week 4. Secondary outcomes, job stress, stress responses, and coping strategies, were assessed at baseline and week 4. Data were analyzed using ANOVA, repeated measures ANOVA, and the Scheffé test for post hoc analysis.ResultsThe experimental group showed significant reductions in client‐related burnout (F = 7.725, p = 0.001) and personal burnout (F = 10.967, p < 0.0001) compared to the other groups. Significant effects of time and time × group interactions were observed for client‐related and personal burnout, with time effects noted for work‐related burnout. Stress response reduction was highest in Control Group 1, followed by the experimental group and Control Group 2 (F = 3.07, p = 0.017).Linking Evidence to ActionAI algorithms could provide tailored programs to mitigate nurse burnout, particularly in client‐related and personal burnout. Reducing nurse burnout could contribute to the quality of care.Trial RegistrationThis trial is registered with the Clinical Research Information Service (KCT0008546)