bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptome‐wide alternative mRNA splicing analysis reveals post‐transcriptional regulation of neuronal differentiation
Authors: Zhou Yuan , Rashad Sherif , Niizuma Kuniyasu 
Published: January 2025

Alternative splicing (AS) plays an important role in neuronal development, function, and disease. Efforts to analyze the transcriptome of AS in neurons on a wide scale are currently limited. We characterized the transcriptome‐wide AS changes in SH‐SY5Y neuronal differentiation model, which is widely used to study neuronal function and disorders. Our analysis revealed global changes in five AS programs that drive neuronal differentiation. Motif analysis revealed the contribution of RNA‐binding proteins (RBPs) to the regulation of AS during neuronal development. We concentrated on the primary alternative splicing program that occurs during differentiation, specifically on events involving exon skipping (SE). Motif analysis revealed motifs for polypyrimidine tract‐binding protein 1 (PTB) and ELAV‐like RNA binding protein 1 (HuR/ELAVL1) to be the top enriched in SE events, and their protein levels were downregulated after differentiation. shRNA knockdown of either PTB and HuR was associated with enhanced neuronal differentiation and transcriptome‐wide exon skipping events that drive the process of differentiation. At the level of gene expression, we observed only modest changes, indicating predominant post‐transcriptional effects of PTB and HuR. We also observed that both RBPs altered cellular responses to oxidative stress, in line with the differentiated phenotype observed after either gene knockdown. Our work characterizes the AS changes in a widely used and important model of neuronal development and neuroscience research and reveals intricate post‐transcriptional regulation of neuronal differentiation.
Sex differences in pain, suicidal ideation, and suicide attempts in patients with migraine
Authors: Kuan Ai Seon , Wang Yen‐Feng , Chen Shih‐Pin , Chuang Yi‐Fang , Wang Shuu‐Jiun 
Published: January 2025

AbstractObjectiveTo examine sex‐specific associations between non‐cephalic pain and suicidal ideation and suicide attempts in patients with migraine, controlling for depression and other risk factors for suicide.BackgroundIn patients with migraine, co‐occurring pain conditions are common and are associated with worse physical and psychosocial function, but the association with suicide has not been determined.MethodsIn this cross‐sectional analysis, we included 10,690 patients with migraine who were consecutively recruited from headache clinics. All participants provided information on sociodemographic status, headache, Widespread Pain Index (WPI), suicidal ideation, and suicide attempts. Relative risks (RRs and 95% confidence intervals [CIs]) for factors associated with suicidal ideation and suicide attempts were calculated.ResultsIn this migraine cohort, more females reported non‐cephalic pain than males (78.7% [6511/8271] vs. 66.7%, [1613/2419]; p < 0.001). The prevalences of suicidal ideation and suicide attempts were higher in female patients than male patients in those aged 20–59 years (p < 0.001), and the differences diminished after the age of 60 years. In female patients, a WPI ≥4 was associated with increased suicidal ideation and suicide attempts, and dysmenorrhea was associated with suicidal ideation (RR 1.27, 95% CI 1.12–1.43), while lower back pain was associated with both suicidal ideation (RR1.35, 95% CI 1.18–1.55) and suicide attempts (RR 1.48, 95% CI 1.19–1.84). In male patients, a WPI ≥2 was associated with increased suicidal ideation, and no individual pain site was associated with suicidal ideation or suicide attempts. In both sexes, there was a dose–response association between the number of pain sites and suicidal ideation and suicide attempts; and pain that had lasted for 2 years and extreme pain intensity were associated with suicide attempts.ConclusionNon‐cephalic pain was associated with suicidal ideation and suicide attempts, with observed differences in pain threshold and individual pain sites found between sexes. Patients with migraine and co‐occurring pain conditions, chronic pain, or extreme pain are distinct subgroups of patients at risk of suicide who require sex‐specific and integrated risk assessment by multidisciplinary teams.
A Meta‐Analysis of Accent Bias in Employee Interviews: The Effects of Gender and Accent Stereotypes, Interview Modality, and Other Moderating Features
Authors: Maindidze Henri T. , Randall Jason G. , Martin‐Raugh Michelle P. , Smith Katrisha M. 
Published: January 2025

ABSTRACTTo address concerns of subtle discrimination against stigmatized groups, we meta‐analyze the magnitude and moderators of bias against non‐standard accents in employment interview evaluations. Results from a multi‐level random‐effects meta‐analysis (unique effects: k = 41, N = 7,596; multi‐level effects accounting for dependencies: k = 120, N = 20,873) demonstrate that standard‐accented (SA) interviewees are consistently favored over non‐standard‐accented (NSA) interviewees (d = 0.46). Accent bias is stronger against women compared to men, particularly when evaluator samples are predominantly female, and was strongly predicted by interviewers' stereotypes of NSA interviewees as less competent and, to a lesser extent, as less warm. Accent bias was not significantly impacted by perceptions of comprehensibility, accentedness, accent type, interview modality, study rigor, or job speaking skill requirements.
The Infant and Toddler Curiosity Questionnaire: A Validated Caregiver‐Report Measure of Curiosity in Children From 5 to 24 Months
Authors: Altmann Elena C. , Bazhydai Marina , Karadağ Didar , Westermann Gert 
Published: January 2025

ABSTRACTHumans are curious. Especially children are known for their drive to explore and learn, which is crucial for developing in and navigating through our complex world. Naturally, some children may be more curious than others, leading to differences in how they structure their own learning experiences, subsequently impacting their developmental trajectories. However, there is a gap in the research field for a reliable measure of such differences early in development. Across three studies, we present the development and assessment of the Infant and Toddler Curiosity Questionnaire (ITCQ), the first caregiver report measure to fill this gap. Items cover observable exploration behaviors in 5‐ to 24‐month‐olds to capture general tendencies of their desire to actively explore their immediate surroundings and are evaluated on a 7‐point Likert‐scale. Exploratory factor analyses and structural equation modeling on a sample of N = 370 UK caregivers led to the final selection of 23 items and provided evidence that the scale allows the reliable computation of an overall curiosity score, with three emergent subscales (Sensory, Investigative, and Interactive) explaining additional variance in the data. Furthermore, the scale had good test‐retest reliability after 7–14 days (N = 67) and related to the child's temperament (N = 75; positively with surgency and effortful control, negatively with negative affect) offering evidence of its validity as a trait measure. Together, these results support the scale's reliability and validity, showcasing the ITCQ as a powerful tool for developmental research.
Risk score stratification of cutaneous melanoma patients based on whole slide images analysis by deep learning
Authors: Bossard Céline , Salhi Yahia , Khammari Amir , Brousseau Maud , Le Corre Yannick , Salhi Sanae , Quéreux Gaëlle , Chetritt Jérôme J. 
Published: January 2025

AbstractBackgroundThere is a need to improve risk stratification of primary cutaneous melanomas to better guide adjuvant therapy. Taking into account that haematoxylin and eosin (HE)‐stained tumour tissue contains a huge amount of clinically unexploited morphological informations, we developed a weakly‐supervised deep‐learning approach, SmartProg‐MEL, to predict survival outcomes in stages I to III melanoma patients from HE‐stained whole slide image (WSI).MethodsWe designed a deep neural network that extracts morphological features from WSI to predict 5‐y overall survival (OS), and assign a survival risk score to each patient. The model was trained and validated on a discovery cohort of primary cutaneous melanomas (IHP‐MEL‐1, n = 342). Performance was tested on two external and independent datasets (IHP‐MEL‐2, n = 161; and TCGA cohort n = 63). It was compared with well‐established prognostic factors. Concordance index (c‐index) was used as a metric.ResultsOn the discovery cohort, the SmartProg‐MEL predicts the 5‐y OS with a c‐index of 0.78 on the cross‐validation data and of 0.72 on the cross‐testing series. In the external cohorts, the model achieved a c‐index of 0.71 and 0.69 for the IHP‐MEL‐2 and TCGA dataset respectively. Furthermore, SmartProg‐MEL was an independent and the most powerful prognostic factor in multivariate analysis (HR = 1.84, p‐value < 0.005). Finally, the model was able to dichotomize patients in two groups—a low and a high‐risk group—each associated with a significantly different 5‐y OS (p‐value < 0.001 for IHP‐MEL‐1 and p‐value = 0.01 for IHP‐MEL‐2).ConclusionThe performance of our fully automated SmartProg‐MEL model outperforms the current clinicopathological factors in terms of prediction of 5‐y OS and risk stratification of cutaneous melanoma patients. Incorporation of SmartProg‐MEL in the clinical workflow could guide the decision‐making process by improving the identification of patients that may benefit from adjuvant therapy.
Performance‐Based Outcome Measures After Hip or Knee Arthroplasty: A Systematic Review and Content Analysis Using the International Classification of Functioning, Disability and Health (ICF)
Authors: Karimijashni Motahareh , Abtahi Forough , Abbasalipour Shokoofih , Dabbagh Armaghan , Ranjbar Parisa , Westby Marie , Ramsay Tim , Beaulé Paul , Poitras Stéphane 
Published: January 2025

ABSTRACTRationalOne of the important considerations to select the appropriate outcome measures is determining if the tool is relevant to patients. Despite the availability of various performance‐based tests to objectively assess function, it is unknown which performance‐based tests best capture important aspects of function after hip or knee arthroplasty.Aims and ObjectivesOur systematic review aimed to identify the existing performance‐based tests used in hip or knee arthroplasty and link the activity component of each test to the modified International Classification of Functioning, Disability and Health (ICF) core set for osteoarthritis (OA).MethodWe searched four databases from inception until April 2024. A performance‐based test was included if an individual performs one or more activities, evaluated by an assessor and resulted in a numerical value. Two reviewers independently screened and extracted data and assessed the included performance‐based tests.ResultsFrom 449 studies included in this review, we identified 28 performance‐based tests which covered 15 categories of OA core set activity and participation. The categories of d4500:walking short distances, d4104:standing and d4103:sitting were the most frequently used, employed in 14, 10 and 10 performance‐based tests, respectively. However, 34 categories of activity and participation were not found in any performance‐based tests. A‐test (‘A’ like Activity or Assessment) had the widest coverage covering 10 out of 49 core set categories. Four performance tests covered four activity and participation categories, one covered three categories, 10 covered two categories and 12 covered one category.ConclusionOur ICF‐based content analysis revealed that the existing performance‐based tests covered certain OA core set activity and participation categories, but overlooked multiple categories. This analysis can serve as a guide for researchers and clinicians in selecting suitable performance‐based tests or a battery of tests to assess function following hip or knee arthroplasty.
Control of Synaptotagmin‐1 Trafficking by SV2A—Mechanism and Consequences for Presynaptic Function and Dysfunction
Authors: Hogg James A. , Cousin Michael A. 
Published: January 2025

ABSTRACTSynaptic vesicle protein 2A (SV2A) is an abundant synaptic vesicle cargo with an as yet unconfirmed role in presynaptic function. It is also heavily implicated in epilepsy, firstly being the target of the leading anti‐seizure medication levetiracetam and secondly with loss of function mutations culminating in human disease. A range of potential presynaptic functions have been proposed for SV2A; however its interaction with the calcium sensor for synchronous neurotransmitter release, synaptotagmin‐1 (Syt1), has received particular attention over the past decade. In this review we will assess the evidence that the primary role of SV2A is to control the expression and localisation of Syt1 at the presynapse. This will integrate biochemical, cell biological and physiological studies where the interaction, trafficking and functional output of Syt1 is altered by SV2A. The potential for SV2A‐dependent epilepsy to be a result of dysfunctional Syt1 expression and localisation is also discussed. Finally, a series of key open questions will be posed that require resolution before a definitive role for SV2A in Syt1 function in health and disease can be confirmed.image
Computational simulation of cranial soft tissue expansion on the cranium during early postnatal growth in humans
Authors: Manson Amy , Jeffery Nathan 
Published: January 2025

AbstractThe importance of interactions between neighbouring rapidly growing tissues of the head during development is recognised, yet this competition for space remains incompletely understood. The developing structures likely interact through a variety of mechanisms, including directly genetically programmed growth, and are mediated via physiological signalling that can be triggered by structural interactions. In this study, we aimed to investigate a different but related potential mechanism, that of simple mechanical plastic deformation of neighbouring structures of the head in response to soft tissue expansion during human postnatal ontogeny. We use computational modelling and normative real‐world data to evaluate the potential for mechanical deformation to predict early postnatal cranial shape changes in humans. We test some aspects of the spatial packing hypothesis applied to the growing brain and masticatory muscles, and their effects on the cranium, with a particular focus on the basicranium and face. A simple finite element model of an early postnatal human cranium, brain and masticatory muscles was created from CT and MRI. Growth of the brain and muscles was simulated using a tissue expansion material. The effect of the expanding soft tissues on the cranium was assessed using geometric morphometrics, comparing the baseline model to simulation results, and also to normative cranial shape data collected from neonatal MRI (0–4 months of age). Findings revealed that cranial shape changes present in the normative sample were consistent with cranial base flexion and were largely allometric (size‐linked). Simulation of brain expansion produced broadly similar shape changes of the basicranium with most growth occurring in the cranial vault, while masticatory muscle expansion produced smaller and more widespread changes throughout the cranium. When simulated together, expansion of the masticatory muscles exerted a constraining effect on the results of brain expansion. Our findings that the simple growth simulations were able to mimic biological growth suggest that the relationship between regions of the developing head may be partly structural within the first few months of postnatal ontogeny in humans.
First insights into the life history of the early Miocene deer Procervulus ginsburgi from Spain
Authors: Cuccu Andrea , Calderón Teresa , Azanza Beatriz , DeMiguel Daniel 
Published: January 2025

AbstractThe small‐sized cervid Procervulus is considered as the most basal member of the Cervidae and one of the earliest ruminants bearing antler‐like appendages. The Iberian Miocene record of this stem‐cervid is extensively documented and largely overlaps with the Miocene Climatic Optimum (MCO), a transient period of global warming of particular interest when comparing present and near future conditions. Despite receiving a substantial amount of attention, histological studies on Procervulus are very scarce and only limited to postcranial remains of Procervulus praelucidus from Germany (MN3). Here we focus for the first time on the dental histology of Procervulus ginsburgi from the Early Miocene Iberian site of Artesilla (MN4, 16.49 Ma), and examine its daily enamel secretion rate (DSR), enamel extension rate (EER) and crown formation time (CFT). Results reveal a brief CTF and high DSR and EER for P. ginsburgi and suggest a fast development at least early in its ontogeny. In addition, the pronounced growth rate of P. ginsburgi emerges as higher than that of the roe deer C. capreolus—documented as an r‐strategist and here examined as a possible extant analog. Overall, our findings point toward a fast life history strategy for P. ginsburgi, which unexpectedly contrasts with that of the 2 million‐year‐older P. praelucidus from Wintershof‐West, with a marked slower growth and maturation. When these results are analyzed together with other evidence, the somewhat drier and more open conditions of Artesilla as a result of the effects of the MCO seem to be the explanation for the different life history and ecology between these Procervulus species. More generally, this study illustrates that life histories within a single genus evolve in response not only to internal constraints but also to the environments, as predicted by the Life History Theory.
Cyclical Change of Partnership Practices in Hybrid Settings
Authors: Weber Christiana , Grewe‐Salfeld Marit , Göbel Markus , Harsman Barbara , Matsuo Yuka , Vogel Rick 
Published: January 2025

AbstractPractice‐driven institutionalism (PDI) is a conceptual lens that explains how practices connect macro‐level phenomena with micro‐level behaviours. Effective practices matter in hybrid organisational settings, such as cross‐sector partnerships, where actors from diverse institutional backgrounds collaborate. Despite its potential, PDI has yet to fully explore the dynamics and interactions among practices, which are essential for understanding their collective and temporal impact in any hybrid setting. Our study addresses this gap through a qualitative multi‐case analysis of three cross‐sector partnerships tackling complex social and environmental challenges. We identify three interconnected sets of partnership practices that help actors navigate the complexities that occur when the logics of business, government, and civil society clash. We reveal a cyclical pattern where collaboration oscillates between motivation and fatigue, driven by these practices. We introduce a conceptual model that transcends the so far static and isolated view on practices, advancing the PDI lens beyond its current limitations. Furthermore, it illuminates the role of the individual in hybrid settings of collaboration.
Clinical outcomes of conversion prosthesis in immediately loaded implants: A retrospective study
Authors: Migus Karolina M. , Bidra Avinash S. , Kuo Chia‐Ling 
Published: January 2025

AbstractPurposeThe primary objective of this retrospective study was to evaluate the survival outcomes of immediately loaded acrylic resin complete arch fixed implant‐supported prosthesis (CAFIP) fabricated from the denture conversion protocol. The secondary objective was to evaluate the early implant survival outcomes associated with these prostheses.Material and MethodsA retrospective chart review was conducted to study the clinical outcomes data of immediately loaded conversion prostheses and immediately loaded implants. All patients who had been treated with immediately loaded acrylic resin CAFIP using the denture conversion protocol over a 9‐year period were included in the study. All dentures were fabricated by conventional processing using compression molded or injection molded techniques. These patients were treated by numerous clinicians but adhering to the same protocol, over the entire 9‐year follow‐up period. Clinical outcome data related to the number of early fractures during the initial implant healing period of 4 months, early implant failures, late fractures (after 4 months), late implant failures (after 4 months), technical complications, number and type of implants placed, the arch in which the implants and prosthesis were placed and the type of opposing dentition were recorded and analyzed. A p‐value < 0.05 was determined to be statistically significant.ResultsA total of 153 prostheses (97 in maxilla, 56 in mandible) in 117 patients (60 males, 57 females) and 768 implants (298 in maxilla, 470 in mandible) were evaluated. All conversion prostheses were followed up for a minimum of 4 months (range of 4–20 months). There were a total of 15 implant failures yielding a survival rate of 98% survival rate during the observation period with the conversion prostheses. Only 3 of the failed implants were associated with a failure (crack or fracture) of the conversion prosthesis (maxilla) during the 4‐month healing period. There were a total of 9 conversion prostheses with cracks or fractures during the 4‐month healing period (early critical complication), yielding a complication‐free survival rate of 94.1%. There were 6 additional early noncritical prosthetic complications such as tooth debonding or chipping during the 4‐month period. Only the early critical prosthetic complication rates comparing maxilla and mandible were statistically significant (p = 0.037).ConclusionsThe findings from this retrospective study revealed a high early survival rate for dental implants (98%) and for the immediately loaded acrylic resin CAFIP fabricated from the denture conversion protocol (94%). There were minimal additional implant failures and noncritical complications related to the conversion prosthesis. The denture conversion protocol is a simple evidence‐based technique and serves as an excellent and predictable method for the immediate loading of dental implants.