bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unravelling single-cell DNA replication timing dynamics using machine learning reveals heterogeneity in cancer progression
Authors: Josephides Joseph M. , Chen Chun-Long 
Published: February 2025

Abstract
Genomic heterogeneity has largely been overlooked in single-cell replication timing (scRT) studies. Here, we develop MnM, an efficient machine learning-based tool that allows disentangling scRT profiles from heterogenous samples. We use single-cell copy number data to accurately perform missing value imputation, identify cell replication states, and detect genomic heterogeneity. This allows us to separate somatic copy number alterations from copy number changes resulting from DNA replication. Our methodology brings critical insights into chromosomal aberrations and highlights the ubiquitous aneuploidy process during tumorigenesis. The copy number and scRT profiles obtained by analysing >119,000 high-quality human single cells from different cell lines, patient tumours and patient-derived xenograft samples leads to a multi-sample heterogeneity-resolved scRT atlas. This atlas is an important resource for cancer research and demonstrates that scRT profiles can be used to study replication timing heterogeneity in cancer. Our findings also highlight the importance of studying cancer tissue samples to comprehensively grasp the complexities of DNA replication because cell lines, although convenient, lack dynamic environmental factors. These results facilitate future research at the interface of genomic instability and replication stress during cancer progression.
An ontology-based rare disease common data model harmonising international registries, FHIR, and Phenopackets
Authors: Graefe Adam S. L. , Hübner Miriam R. , Rehburg Filip , Sander Steffen , Klopfenstein Sophie A. I. , Alkarkoukly Samer , Grönke Ana , Weyersberg Annic , Danis Daniel , Zschüntzsch Jana , Nyoungui Elisabeth F. , Wiegand Susanna , Kühnen Peter , Robinson Peter N. , Beyan Oya , Thun Sylvia 
Published: February 2025

Abstract
Although rare diseases (RDs) affect over 260 million individuals worldwide, low data quality and scarcity challenge effective care and research. This work aims to harmonise the Common Data Set by European Rare Disease Registry Infrastructure, Health Level 7 Fast Healthcare Interoperability Base Resources, and the Global Alliance for Genomics and Health Phenopacket Schema into a novel rare disease common data model (RD-CDM), laying the foundation for developing international RD-CDMs aligned with these data standards. We developed a modular-based GitHub repository and documentation to account for flexibility, extensions and further development. Recommendations on the model’s cardinalities are given, inviting further refinement and international collaboration. An ontology-based approach was selected to find a common denominator between the semantic and syntactic data standards. Our RD-CDM version 2.0.0 comprises 78 data elements, extending the ERDRI-CDS by 62 elements with previous versions implemented in four German university hospitals capturing real world data for development and evaluation. We identified three categories for evaluation: Medical Data Granularity, Clinical Reasoning and Medical Relevance, and Interoperability and Harmonisation.
Neurocognitive dynamics and behavioral differences of symmetry and asymmetry processing in working memory: insights from fNIRS
Authors: Sztuka Izabela Maria , Kühn Simone 
Published: February 2025

Abstract
Symmetry is a ubiquitous property of the visual world. It facilitates cognitive processing and fosters aesthetic appeal. Despite its importance to aesthetic experience and perceptual prominence, the integration of symmetry in working memory remains underexplored. In our study, participants engaged in a novel working memory task involving both symmetrical and asymmetrical stimuli, while their brain activity was monitored using functional Near Infrared Spectroscopy (fNIRS). The study revealed that symmetry significantly enhances memory performance. Symmetry significantly improves task performance, with symmetrical stimuli leading to higher accuracy and faster recall than asymmetrical ones, especially under high cognitive load. This effect varies with the type of symmetry, with diagonal symmetry being the most effective. Neuroimaging data showed distinct brain activation patterns when participants processed symmetrical stimuli, particularly in the memory-straining condition. Significant differences in brain activity were observed in various brain regions, with lateral occipital, posterior parietal, medial and dorsolateral prefrontal cortices reacting to symmetry with decreased oxygenated hemoglobin (HbO), while in left orbitofrontal (HbO) and right ventrolateral prefrontal cortex (HbO and HbR) hemoglobin concentration increased. Overall, our findings highlight the complex, region-specific brain activation patterns in response to visual symmetry, emphasizing the nuanced role of symmetry in cognitive processing during memory tasks and their potential implication for creative thinking.
Looking outside the box with a pathology aware AI approach for analyzing OCT retinal images in Stargardt disease
Authors: Khateri Parisa , Koottungal Tiana , Wong Damon , Strauss Rupert W. , Janeschitz-Kriegl Lucas , Pfau Maximilian , Schmetterer Leopold , Scholl Hendrik P. N. 
Published: February 2025

Abstract
Stargardt disease type 1 (STGD1) is a genetic disorder that leads to progressive vision loss, with no approved treatments currently available. The development of effective therapies faces the challenge of identifying appropriate outcome measures that accurately reflect treatment benefits. Optical Coherence Tomography (OCT) provides high-resolution retinal images, serving as a valuable tool for deriving potential outcome measures, such as retinal thickness. However, automated segmentation of OCT images, particularly in regions disrupted by degeneration, remains complex. In this study, we propose a deep learning-based approach that incorporates a pathology-aware loss function to segment retinal sublayers in OCT images from patients with STGD1. This method targets relatively unaffected regions for sublayer segmentation, ensuring accurate boundary delineation in areas with minimal disruption. In severely affected regions, identified by a box detection model, the total retina is segmented as a single layer to avoid errors. Our model significantly outperforms standard models, achieving an average Dice coefficient of
$$99\%$$
for total retina and
$$93\%$$
for retinal sublayers. The most substantial improvement was in the segmentation of the photoreceptor inner segment, with Dice coefficient increasing by
$$25\%$$
. This approach provides a balance between granularity and reliability, making it suitable for clinical application in tracking disease progression and evaluating therapeutic efficacy.
Women are worse off in developing and recovering from temporomandibular disorder symptoms
Authors: Lövgren Anna , Vallin Simon , Häggman-Henrikson Birgitta , Kapos Flavia P. , Peck Christopher C. , Visscher Corine M. , Liv Per 
Published: February 2025

Abstract
Decision-making for temporomandibular disorders (TMDs) is reported being a clinical challenge, partly due to uncertainities in assessment of long-term prognosis. Therefore, our aim was to explore variations over time in TMD symptoms and possible sex or age differences. In this cohort study, data were prospectively collected 2010–2017 from the general population in Västerbotten, Northern Sweden. Adults were eligible if they had undergone at least two routine dental check-ups that included screening for TMDs (3Q/TMD) from which states were defined as absence or presence of TMD pain and/or jaw catching/locking. The rate of transitions was estimated between TMD states within a time span of one year. A total of 94,769 individuals were included (49.9% women) with 205,684 repeated visits and 9,006 state transitions recorded over the 8-year period. Compared to men, women had higher rates of transitions from no TMDs to any TMD symptoms. Furthermore, women had a lower rate of transition from TMD pain only to no TMDs. The finding of a poorer prognosis in women, as well as previously reported potential gender differences in pain perception and reporting, reinforces that gender differences should be accounted for in the treatment planning stage for patients with onset of TMDs.
Perceived coercion amongst healthcare workers during the COVID-19 pandemic
Authors: Stoltenberg Andrea S. , Ranieri Veronica , Dahlen Hege Kristine N. , Nastouli Eleni ,   SAFER Investigators, Byott Matt , Edwards Sarah J. L. , Frampton Daniel , Gilson Richard , Hayward Andrew , Heaney Jude , Houlihan Catherine , Lorencatto Fabiana , Manley Ed , Michie Susan , Spyer Moira , Vora Nina , Walker Naomi , Nastouli Eleni , Almvik Roger , Edwards Sarah J. L. , Kamboj Sunjeev K. 
Published: February 2025

Abstract
Direct and prolonged exposure to stress and uncertainty among healthcare workers (HCWs) during the COVID-19 pandemic likely had a significant negative impact on their mental health and general wellbeing. Although the contributors to such distress remain to be fully understood, the construct of perceived coercion appears to be relevant. Among HCWs, perceived coercion is conceptualised as appraisals about lack of control/‘freedom to choose’ and pressure to perform patient-care duties in the context of unprecedented threat of contagion from patients. To improve our understanding of perceived coercion amongst HCWs, we developed a 10-item scale—the Pandemic-specific Perceived Coercion Scale for Healthcare Workers (PPCS-HCW) scale—designed to be adaptable and applicable for use in future mass-contagion emergencies. A preliminary (exploratory) factor analysis (N = 546) showed that relevant items coalesced around three factors—‘internal pressure’, ‘external pressure’ and ‘perceived coercion’, that partly overlap with previous conceptualisations of perceived coercion. The exploratory conceptual and psychometric structure was confirmed in a separate sample of HCWs from the UK and Norway (N = 483). On average, across the three PPCS-HCW scale factors, HCWs showed low levels of perceived coercion (M = 0.22 (95% CI [0.11, 0.33] on a − 3 to + 3 scale). However, cluster analysis identified three groups: low (− 1.09 (95% CI [− 1.20, − 0.99]), moderate (0.17 (95% CI [0.08, 0.25]) and high scoring (1.57 (95% CI [1.47, 1.67]) PPCS-HCW clusters. High scoring participants showed higher levels of psychological distress, avoidance coping and compassion fatigue. In summary, our findings suggest that perceived coercion is a relevant construct in understanding the adverse psychological impact of large-scale contagion emergencies on HCWs.
Prediction of buckling damage of steel equal angle structural members using hybrid machine learning techniques
Authors: Ho Nang Xuan , Le Tien-Thinh , Dinh The-Hung , Nguyen Van-Hai 
Published: February 2025

Abstract
This article deals with prediction of buckling damage of steel equal angle structural members using a surrogate model combining machine learning and metaheuristic optimization technique. In particular, a hybrid Artificial Intelligence (AI)-based model involving Artificial Neural Network (ANN) and Particle Swarm Optimization (PSO) was developed and calibrated for the problem at hand. For this purpose, a database concerning compression tests of steel equal angle structural members was constructed from available resources with geometry variables such as length, width, thickness, mechanical properties of materials such as yield strength and initial imperfections (i.e. residual peak stress and initial geometric imperfections) and critical buckling load of columns. The hybrid PSOANN model was adopted because its prediction capability is higher than the traditional technique – i.e. scaled conjugate gradient (SCG). Indeed, ANN trained by PSO delivered better performance in terms of RMSE, MAE, ErrorStD, R2 and Slope in comparison to ANN trained by SCG, for instance. RMSE decreases from 0.141 to 0.055; MAE decreases from 0.108 to 0.042; R2 increases from 0.749 to 0.959, when switching from ANN alone to hybrid PSOANN, respectively. Moreover, a Partial Dependence (PD) investigation was performed to interpret the “black-box” PSOANN model.
Evaluating the reflux suppression properties of Gaviscon Infant powder with different milk formulations using an in vitro model of the infant stomach
Authors: McLaughlin Fiona , Fisher Jeanine , Atherton Mark , Coyle Cathal 
Published: February 2025

Abstract
Gastroesophageal reflux (GER) is common in babies and infants and is characterized by effortless regurgitation (with or without vomiting), which is a common symptom of other infant conditions, including cow’s milk protein allergy (CMPA). Various milk formulations are commercially available to help manage GER and CMPA symptoms (extensively hydrolyzed [eHF], partially hydrolyzed [pHF], and amino-acid formulas [AAF]). We aimed to understand if an alginate product (Gaviscon Infant powder) worked as intended in the presence of different milk formulations. A previously evaluated artificial infant stomach model simulated an internal pressure-inducing reflux event (five reflux events performed at 5 min intervals). Suppression activity of Gaviscon Infant combined with eHF, pHF, and AAF was assessed by measuring the height that the refluxate event traveled up a tube mimicking the infant esophagus, alongside a benchmark unhydrolyzed formulation (uHF) with Gaviscon Infant and a negative control without Gaviscon Infant. Each experiment was repeated six times per formulation in a random order. Gaviscon Infant combined with each milk formulation produced a lower height of refluxate versus the negative control. When formulations combined with Gaviscon Infant were grouped by category (eHF, pHF, AAF), two or more products from each category showed a lower refluxate height than the benchmark (uHF). There was a significant difference in median refluxate height (p = 0.0011 in Wilcoxon rank sum test) when comparing Gaviscon Infant combined with eHF against Gaviscon Infant combined with pHF, AAF, or uHF (benchmark). Refluxate height did not change significantly between events one and five for each milk formulation combined with Gaviscon Infant. In an artificial infant stomach model, Gaviscon Infant combined with different milk formulations (uHF, eHF, pHF, AAF) produced a lower refluxate height compared with a negative control (uHF without Gaviscon Infant), suggesting that Gaviscon Infant suppresses reflux as intended when used with different milk formulations.
Effect of Bio MTA plus & ProRoot MTA pulp capping materials on the regenerative properties of human dental pulp stem cells
Authors: Ayoub Khaled Mohamed , Nagy Mohamed Mokhtar , Aly Riham Mohamed , El Deen Ghada Nour , El-Batouty Karim 
Published: February 2025

Abstract
The aim of the present study was to investigate the effects of the biological properties of hDPSCs exposed to Bio MTA+ & ProRoot MTA pulp capping materials on the proliferation and odontogenic differentiation of hDPSCs. Human dental pulp stem cells (hDPSCs) were isolated from impacted third molars. Extracts of Bio MTA + and ProRoot MTA were prepared at a 1:1 ratio. The effects of the extracts on hDPSCs cytotoxicity and proliferation were assessed via a CCK-8 assay. Annexin V expression was investigated to assess the effects of both materials on the induction of apoptosis. The effects of ProRoot MTA and Bio MTA + extraction media on the stemness properties of hDPSCs were assessed via real-time quantitative PCR, and the expression of odontogenic markers (RUNX2, DMP1 & DSSP) was analyzed via RT‒PCR Alizarin Red staining. Cells exposed to Bio MTA + had the greatest degree of proliferation. The results of Annexin V staining indicated that Bio MTA + caused the least amount of apoptosis. RUNX2, DMP1 and DSSP were highly expressed by Bio MTA + and indicated successful odontogenic differentiation. Compared with ProRoot MTA, Bio MTA + exhibited an exceptional level of cytocompatibility, as well as advantageous bioactivities, including the preservation of stemness and an increase in the proliferation capacity of hDPSCs. In addition, it demonstrated favorable bioactive properties by stimulating odontogenic differentiation. Bio MTA + offers significant advantages in terms of biocompatibility, bioactivity, and regenerative potential, making it an excellent choice for procedures aimed at preserving or regenerating dental pulp tissue. However, additional research is required to address the lack of in vivo validation, as replicating physiological conditions is crucial for accurately assessing clinical outcomes and comparing them with results obtained from in vitro experiments.
Structured reporting of neuroendocrine tumors in PET/CT using [18F]SiTATE - impact on interdisciplinary communication
Authors: Hinterberger Anna , Trupka Lukas , Kortbein Sophia , Ebner Ricarda , Fink Nicola , Froelich Matthias F. , Nörenberg Dominik , Wängler Carmen , Wängler Björn , Schirrmacher Ralf , Holzgreve Adrien , Brendel Matthias , Corradini Stefanie , Auernhammer Christoph , Rübenthaler Johannes , Grawe Freba 
Published: February 2025

Abstract
Our retrospective single-center study aims to evaluate the impact of structured reporting (SR) using a self-developed template on report quality compared to free-text reporting (FTR) in [18F]SiTATE Positron Emission Tomography/Computer Tomography (PET/CT) for the primary staging and therapy monitoring of patients diagnosed with neuroendocrine tumors (NET). In total 50 patients were included. FTRs and SRs were generated post-examination. All reports were evaluated by a radiologist and a surgeon through a questionnaire to determine their contribution to facilitating clinical decision-making and to assess their completeness, linguistic quality, and overall quality. SR significantly increased the capacity of facilitating therapy decision-making from 32% in FTR to 55% in SR (p < 0.001). Trust in the report was significantly higher in SR with a mean of 5.0 (SD = 0.5) vs. 4.7 (SD = 0.5) for FTR (p < 0.001). SR received significantly higher mean ratings regarding linguistic quality with 4.7 for SR vs. 4.4 for FTR (p = 0.004) and overall report quality with a mean of 4.9 for SR vs. 4.6 for FTR (p < 0.001). Concluding that SR enhances the overall quality of reports in [18F]SiTATE-PET/CTs for NET staging, serving as a tool to streamline clinical decision-making and enhance interdisciplinary communication in the future.
Characterization of the genomic landscape of canine diffuse large B-cell lymphoma reveals recurrent H3K27M mutations linked to progression-free survival
Authors: van der Heiden Anna Darlene , Pensch Raphaela , Agger Sophie , Gardner Heather L. , Hendricks William , Zismann Victoria , Wong Shukmei , Briones Natalia , Turner Bryce , Forsberg-Nilsson Karin , London Cheryl , Lindblad-Toh Kerstin , Arendt Maja Louise 
Published: February 2025

Abstract
Diffuse large B-cell lymphoma (DLBCL) is an aggressive hematopoietic neoplasm that affects humans as well as dogs. While previous studies on canine DLBCL (cDLBCL) have significantly advanced our understanding of the disease, the majority of this research has relied on whole-exome sequencing, which is limited in its ability to detect copy number aberrations and other genomic changes beyond coding regions. Furthermore, many of these studies lack sufficient clinical follow-up data, making it difficult to draw meaningful associations between genetic variants and patient outcomes. Our study aimed to characterize the mutational landscape of cDLBCL using whole-genome sequencing of matched tumor-normal samples obtained from a cohort of 43 dogs previously enrolled in a clinical trial for which longitudinal follow-up was available. We focused on identifying genes that were significantly or recurrently mutated with coding point mutations, copy number aberrations, and their associations with patient outcomes. We identified 26 recurrently mutated genes, 18 copy number gains, and 8 copy number losses. Consistent with prior studies, the most commonly mutated genes included TRAF3, FBXW7, POT1, TP53, SETD2, DDX3X and TBL1XR1. The most prominent copy number gain occurred on chromosome 13, overlapping key oncogenes such as MYC and KIT, while the most frequent deletion was a focal loss on chromosome 26, encompassing IGL, PRAME, GNAZ, RAB36, RSPH14, and ZNF280B. Notably, our set of recurrently mutated genes was significantly enriched with genes involved in epigenetic regulation. In particular, we identified hotspot mutations in two histone genes, H3C8, and LOC119877878, resulting in H3K27M alterations predicted to dysregulate gene expression. Finally, a survival analysis revealed that H3K27M mutations in H3C8 were associated with increased hazard ratios for progression-free survival. No copy number aberrations were associated with survival. These findings underscore the critical role of epigenetic dysregulation in cDLBCL and affirm the dog as a relevant large animal model for interrogating the biological activity of novel histone-modifying treatment strategies.
Bioelectric stimulation outperforms brain derived neurotrophic factor in promoting neuronal maturation
Authors: Diego-Santiago María del Pilar , González María Ujué , Zamora Sánchez Esther María , Cortes-Carrillo Nuria , Dotti Carlos , Guix Francesc Xavier , Mobini Sahba 
Published: February 2025

Abstract
Neuronal differentiation and maturation are crucial for developing research models and therapeutic applications. Brain-derived neurotrophic factor (BDNF) is a widely used biochemical stimulus for promoting neuronal maturation. However, the broad effects of biochemical stimuli on multiple cellular functions limit their applicability in both in vitro models and clinical settings. Electrical stimulation (ES) offers a promising physical method to control cell fate and function, but it is hampered by lack of standard and optimised protocols. In this study, we demonstrate that ES outperforms BDNF in promoting neuronal maturation in human neuroblastoma SH-SY5Y. Additionally, we address the question regarding which ES parameters regulate biological responses. The neuronal differentiation and maturation of SH-SY5Y cells were tested under several pulsed ES regimes. We identified accumulated charge and effective electric field time as novel criteria for determining optimal ES regimes. ES parameters were obtained using electrochemical characterisation and equivalent circuit modelling. Our findings show that neuronal maturation in SH-SY5Y cells correlates with the amount of accumulated charge during ES. Higher charge accumulation (~ 50 mC/h) significantly promotes extensive neurite outgrowth and ramification, and enhances the expression of synaptophysin, yielding effects exceeding those of BDNF. In contrast, fewer charge injection to the culture (~ 0.1 mC/h) minimally induces maturation but significantly increases cell proliferation. Moreover, ES altered the concentration and protein cargo of secreted extracellular vesicles (EV). ES with large enough accumulated charge significantly enriched EV proteome associated with neural development and function. These results demonstrate that each ES regime induces distinct cellular responses. Increased accumulated charge facilitates the development of complex neuronal morphologies and axonal ramification, outperforming exogenous neurotrophic factors. Controlled ES methods are immediately applicable in creating mature neuronal cultures in vitro with minimal chemical intervention.