bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accurate diagnosis of high-risk pulmonary nodules using a non-invasive epigenetic biomarker test
Authors: Chen Pei-Hsing , Tsai Tung-Ming , Lu Tzu-Pin , Lu Hsiao-Hung , Pamart Dorian F. , Kotronoulas Aristotelis , Herzog Marielle , Micallef Jacob V. , Hsu Hsao-Hsun , Chen Jin-Shing 
Published: December 2024

ABSTRACTBackgroundAccurate non-invasive tests to improve the early detection and diagnosis of lung cancer are urgently needed, given that large tumors may metastasize or be resistant to treatment. However, no regulatory-approved blood tests are available for the early detection of lung cancer. We aimed to improve the classification of pulmonary nodules to identify malignant ones in a high-prevalence patient group.MethodsA study involving 806 participants with undiagnosed nodules larger than 5 mm, identified via CT imaging, focused on assessing nucleosome levels and histone modifications in circulating blood. Nodules were classified as malignant or benign. A logistic regression analysis was performed. For model development, the data were randomly divided into training (n = 483) and validation (n = 121) datasets. The model’s performance was then evaluated using a separate testing dataset (n = 202).ResultsAmong patients, 755 (93.7%) had a tissue diagnosis. The overall malignancy rate in the cohort was 80.4%. For all datasets, the AUCs were as follows: training, 0.74; validation, 0.86; and test, 0.79 (accuracy range: 0.80–0.88). Sensitivity showed consistent results across all datasets (0.91, 0.95, and 0.93, respectively), whereas specificity ranged from 0.37 to 0.64. For smaller nodules (5–10 mm), the model recorded accuracy values of 0.76, 0.88, and 0.85. Sensitivity values of 0.91, 1.00, and 0.94 further highlight the robust diagnostic capability of the model. The performance of the model across the RADS categories was evaluated, and it demonstrated consistent accuracy.ConclusionOur EB panel detected non-small cell lung cancer early in a high-risk patient group with high sensitivity and accuracy. The EB model was particularly effective in identifying high-risk lung nodules, including small, part-solid, and non-solid nodules, and provided further evidence for external validation.SynopsisAn epigenetic biomarker (EB) model demonstrated high sensitivity and accuracy for early lung cancer detection in 806 patients with pulmonary nodules. It performed well across imaging types and stages, including small nodules, reducing false negatives in minimally invasive surgery.
Social determinants of cognitive aging trajectories across 39 countries
Authors: Gilles Victor , Salouhou Syrine , Vallée Rémi , Spiers Hugo , Hornberger Michael , Garnier-Crussard Antoine , Coutrot Antoine 
Published: December 2024

AbstractDistinguishing between normal and pathological cognitive aging is challenging because there is no typical older person. Some people in their eighties have cognitive abilities similar to many 30-year-olds, while others experience significant cognitive decline at a much younger age. The variation in age-related cognitive decline is not arbitrary. Several non-modifiable (e.g. genetic) and potentially modifiable (e.g. high blood pressure, smoking, and hearing loss) risk factors are associated with faster cognitive aging. Beyond these individual-level risk factors, a growing body of evidence has identified associations between cognitive impairment and social, economic, and environmental factors. These associations are even more pronounced in developing countries, notably because of greater disparities in education and socioeconomic status. However, people from these countries are rarely studied in scientific research: a citizen of a high-income country is 37 times more likely to appear in a study in top medical journals than a citizen of a low-income country. Here, we examine the association between sociodemographic factors and cognitive aging trajectories among 715,295 participants in 46 countries. Cognition is assessed using Sea Hero Quest, a spatial navigation video game that predicts spatial ability in the real world. We find that the social, economic, and environmental well-being of older adults, as measured by the Global AgeWatch Index (GAWI), is negatively associated with age-related decline in spatial ability. In particular, the GAWI Health and Environment subscores are strongly correlated with the effect of age on wayfinding performance. We also found that gender differences in spatial navigation skills increase with age, and even more so in countries with greater gender inequality, as estimated by the Gender Inequality Index. Our results show that cognitive aging must be understood as a dynamic, heterogeneous process that is strongly linked to potentially modifiable environmental and social factors.
ARID1A-induced transcriptional reprogramming rewires signalling responses to drug treatment in melanoma
Authors: Barker Charlie George , Sharma Sumana , Santos Ana Mafalda , Nikolakopoulos Konstantinos-Stylianos , Velentzas Athanassios D. , Völlmy Franziska I. , Minia Angeliki , Pliaka Vicky , Altelaar Maarten , Wright Gavin J , Alexopoulos Leonidas G. , Stravopodis Dimitrios J. , Petsalaki Evangelia 
Published: December 2024

AbstractResistance to BRAF and MAPK inhibitors is a significant challenge in melanoma treatment, driven by adaptive and acquired mechanisms that allow tumour cells to evade therapy. Here, we examined early signalling responses to single and combined BRAF and MAPK inhibition in a BRAFV600E, drug-sensitive melanoma cell line and a drug-resistant ARID1A-knockout (KO) derivative. ARID1A, frequently mutated in melanoma, is associated with resistance and immune evasion. Using an innovative systems biology approach that integrates transcriptomics, proteomics, phosphoproteomics, and functional kinomics through matrix factorization and network analysis, we identified key signalling alterations and resistance mechanisms.We found that ARID1A-KO cells exhibited transcriptional rewiring, sustaining MAPK1/3 and JNK activity post-treatment, bypassing feedback sensitivity observed in parental cells. This rewiring suppressed PRKD1 activation, increased JUN activity—a central resistance network node—and disrupted PKC dynamics through elevated basal RTKs (e.g., EGFR, ROS1) and Ephrin receptor activity post-treatment. ARID1A mutations also reduced HLA-related protein expression and enriched extracellular matrix components, potentially limiting immune infiltration and reducing immunotherapy efficacy. Our graph-theoretical multi-omics approach uncovered novel resistance-associated signalling pathways, identifying PRKD1, JUN, and NCK1 as critical nodes. While receptor activation redundancies complicate single-target therapies, they also present opportunities for combination strategies.This study highlights ARID1A’s role in reshaping signalling and immune interactions, offering new insights into melanoma resistance mechanisms. By identifying actionable targets, including JUN and immune pathways, we provide a foundation for developing integrated therapeutic strategies to overcome resistance in BRAF/MAPK inhibitor-treated melanoma.One sentence summaryThis study reveals how ARID1A-mediated transcriptional rewiring drives resistance to MAPK inhibitors in melanoma by altering signalling pathways, immune interactions, and receptor dynamics, highlighting potential targets for combinatorial therapies.
CCR1 inhibition sensitizes multiple myeloma cells to glucocorticoid therapy
Authors: Luyckx Bert , Van Trimpont Maaike , Declerck Fien , Staessens Eleni , Verhee Annick , T’Sas Sara , Eyckerman Sven , Offner Fritz , Van Vlierberghe Pieter , Goossens Steven , Clarisse Dorien , De Bosscher Karolien 
Published: December 2024

AbstractGlucocorticoids (GC) are cornerstone drugs in the treatment of multiple myeloma (MM). Because MM cells exploit the bone marrow microenvironment to obtain growth and survival signals, resistance to glucocorticoid-induced apoptosis emerges, yet the underlying mechanisms remain poorly characterized. Here, we identify that the chemokine receptor CCR1, together with its main ligand CCL3, plays a pivotal role in reducing the glucocorticoid sensitivity of MM cells. We show that blocking CCR1 signaling with the antagonist BX471 enhances the anti-MM effects of the glucocorticoid dexamethasone in MM cell lines, primary patient material and a myeloma xenograft mouse model. Mechanistically, the drug combination shifts the balance between pro- and antiapoptotic proteins towards apoptosis and deregulates lysosomal proteins. Our findings suggest that CCR1 may play a role in glucocorticoid resistance, as the GC-induced downregulation of CCR1 mRNA and protein is blunted in a GC-resistance onset model. Moreover, we demonstrate that inhibiting CCR1 partially reverses this resistance, providing a promising strategy for resensitizing MM cells to GC treatment.
From calamity to infestation: linking windstorm tree damage to bark beetle outbreak through forest structure and meteorological analysis
Authors: Torresani Michele , Tognetti Roberto 
Published: December 2024

AbstractIn recent years, we have witnessed worldwide, an increase in natural forest disturbances, particularly windstorms, which have caused significant direct and indirect forest damages, often triggering largescale bark beetle outbreaks. In this study, we investigated the interaction between windstorm-induced tree damage and subsequent bark beetle outbreaks in the northeastern Italian Alps (Province of Belluno and Bolzano), focusing on the 2018 Vaia windstorm and the successive bark beetle infestation started in 2021. Additionally, we aimed to determine whether this potential correlation is influenced by forest structural characteristics such as forest height heterogeneity (HH), forest density, and forest mean height using LiDAR data, or by meteorological factors (mean temperature and cumulative precipitation) through in-situ spatialized information.Our research findings, based on a methodology centered on spatial interactions, indicate a potential link between the bark beetle outbreaks and the windstorm event Vaia occurred three years before. Our results suggest that forest structural variables are, in most of the cases, significantly similar across all areas affected by the bark beetle. This similarity is observed both in forests impacted by the Vaia windstorm and in otherPicea abiesforests not affected by the windstorm, indicating that these forest structural variables may not be a trigger for the bark beetle outbreak. Our findings do not show a clear and consistently significant difference in meteorological conditions. This variability can be attributed to the specific areas affected by the Vaia windstorm, which are predominantly mountainous regions characterized by distinct temperatures and precipitation compared to the rest of the provinces. When analyzing the combined influence of structural and meteorological variables in both study areas, our results indicate that none of these factors were ultimately significant predictors of the interaction between bark beetle infestations and areas affected by the Vaia windstorm. Our study suggests that, as climate change increases the frequency and severity of these disturbances, adaptable forest management framework to enhance forest resilience and sustainability are needed, helping forests to better withstand and recover from future natural disturbances.
A Comparative Study of Muscular, Vestibular, and Haptic Stimulation on Dream Incorporation
Authors: Peters Emma , Pöhlmann Jakob , Wang Xinlin , Dresler Martin , Erlacher Daniel 
Published: December 2024

AbstractThe connection between the dreamed body and the real physical body remains a subject of ongoing investigation. This study explored how the dreamed body responds to somatosensory stimulation of the physical body, aiming to shed light on the sensory processes that shape our dreaming experiences. We employed a novel within-subject design to compare the incorporation of three different types of bodily stimuli—electrical muscular, galvanic vestibular, and haptic vibration—into dream content, alongside a control sham condition for each stimulus. In total, 24 participants spent one adaptation night, followed by three consecutive test nights in the sleep laboratory. REM awakenings, after sham or stimulation periods, were carried out for dream report collection. In total, 165 dream reports were collected across conditions. While dream incorporation was observed across the three stimulation methods, it occurred equally in both the stimulation and sham conditions for all three modalities. These findings highlight broader methodological challenges in dream incorporation research and raise concerns about potential confounding factors affecting the interpretation of results. Future research with larger sample sizes is needed to detect smaller effect sizes and fully understand the influence of these somatosensory stimuli on dream content. This study employed a rigorous experimental approach to exploring dream incorporation and addressed many methodological challenges in this area. We further suggest areas of improvement to optimize dream incorporation of different sensory modalities.Graphical Abstract
Large effect life-history genomic regions are associated with functional morphological traits in Atlantic salmon
Authors: Aykanat Tutku , Debes Paul V. , Jansouz Shadi , Gueguen Lison , House Andrew H. , Ruokolainen Annukka , Erkinaro Jaakko , Pritchard Victoria L. , Primmer Craig R. , Bolstad Geir H. 
Published: December 2024

AbstractUnderstanding pleiotropic architectures of phenotypes is instrumental for identifying the functional basis of adaptive genetic variation in the wild. Life-history variation may have a morphological basis that mediates resource acquisition and allocation pathways, but identifying the underlying genetic basis of such traits is challenging. In this study, using Atlantic salmon juveniles reared in common garden conditions, we test if two life-history associated loci in Atlantic salmon, six6andvgll3,are also associated with functional morphological traits. These loci had previously shown to exhibit strong signals of adaptation and are highly correlated with age at maturity. Here, we show that genetic variation at thevgll3locus is linked to variation in morphological traits that underlie swimming performance, along a trade-off axis between efficient cruising and maneuvering, while the genetic variation at thesix6locus was linked to variation in body-head proportions suggesting the potential functional importance of these traits for resource acquisition efficiency. However, the direction of changes in morphological traits associated with late-vs. early-maturing alleles was not always consistent with the expected direction of an effect to maturation timing. Our results reveal a complex morphological landscape associated with the genetic variation in these loci, possibly as a result of pleiotropy or linkage across these genomic regions.
Localized Delivery of Growth Factors from Microparticles Modulate Osteogenic and Chondrogenic Gene Expression in Growth Factor-dependent Manner in anex vivoChick Embryonic Bone Model
Authors: Rashidi Hassan , Cox Helen C. , Qutachi Omar , Moulding Dale , White Lisa J. , Smith Emma L. , Kanczler Janos M. , Rojo Luis , Rotherham Michael , Henstock James R. , Stevens Molly M. , El Haj Alicia J. , Oreffo Richard O.C. , Shakesheff Kevin M. , Rose Felicity R.A.J. 
Published: December 2024

AbstractGrowth factors play a crucial role in regulating various cellular functions, including proliferation and differentiation. Consequently, the biomaterial-based delivery of exogenous growth factors presents a promising strategy in regenerative medicine to manage the healing process and restore tissue function. For effective therapeutic applications, it is essential that these active compounds are precisely targeted to the site of regeneration, with release kinetics that align with the slow pace of tissue growth. We have developed an ex vivo model utilizing a developing embryonic chick bone, and using PLGA based microparticles as controlled-release systems, allowing for the investigation of spatiotemporal effects of growth factor delivery on cell differentiation and tissue formation. Our findings demonstrate that BMP2 and FGF2 can significantly alter cell morphology and zonally pattern collagen deposition within the model, but only when the growth factor presentation rate is carefully regulated. Furthermore, the growth factor-dependent responses observed underscore the potential of this model to explore the interactions between cells and the growth factors released from biomaterials in an approach which can be applied for bone tissue engineering.
Ancient sedimentary DNA shows more than 5000 years of continuous beaver occupancy in Grand Teton National Park
Authors: Baker D. Nevé , Larsen Darren J. , Fairfax Emily , Muscott Amelia P. , Shapiro Beth , Crump Sarah E. 
Published: December 2024

AbstractBeaver-based restoration is emerging as a cost-effective conservation and climate adaptation strategy, but efforts are constrained by limited knowledge of pre-colonial beaver distribution and their long-term ecosystem impacts. Here, we apply sedimentary ancient DNA (sedaDNA) techniques to investigate the history of beaver occupancy at three lakes in Grand Teton National Park, Wyoming over the last ∼10 ka, as well as interactions with the local plant community. We documented a dynamic history of beaver presence in two sub-alpine lakes (Taggart and Jenny Lakes) and demonstrate no history of beaver occupancy at the higher-elevation alpine lake (Lake Solitude). Beavers were first detected at Jenny Lake around 7.2 ka and intermittently thereafter. At nearby Taggart Lake, beavers were first detected at ∼5.9 ka and continuously from 5.2 ka onwards. Vegetation metabarcoding revealed a shift in plant community coinciding with beaver establishment in these two sub-alpine lakes, as well as an increase in taxonomic diversity. These changes coincide with regional trends towards wetter conditions. Notably, beavers persist at Taggart Lake during inferred droughts, indicating a potential role in maintaining wetlands through extended periods of climatic stress. Our results demonstrate sedaDNA as a powerful, novel technique for reconstructing past beaver occupancy dynamics.
Constant-pH MD Simulations of Lipids
Authors: Trollmann Marius F.W. , Rossetti Paolo , Böckmann Rainer A. 
Published: December 2024

AbstractConstant pH Molecular Dynamics (CpHMD) simulations represent a cutting-edge computational approach for studying biological systems with remarkable realism. Recent advancements have enhanced the accessibility and efficiency of CpHMD, significantly reducing the performance overhead compared to traditional constant-protonation MD simulations. This chapter guides the reader through the application of CpHMD to investigate the pH-dependent behavior of Cationic Ionizable Lipids (CILs) — a critical component of Lipid Nanoparticles (LNPs), which are among the most promising platforms for drug delivery. LNPs, including those employed in mRNA-based vaccines, played a pivotal role in the global response to the SARS-CoV-2 pandemic, underscoring their potential in modern medicine. The chapter begins with a comprehensive introduction to the fundamental concepts of LNPs and provides a step-by-step protocol for setting up simulations of membranes containing CILs to calculate their apparent pKa. This parameter is crucial for governing thein vivobehavior of LNPs, where precise control is essential to optimize delivery efficiency while minimizing toxicity. By showcasing the ability of CpHMD simulations to unravel the intricate relationship between pH-dependent protonation, membrane structure, and lipid distribution, this chapter highlights their potential to inform the rational design of novel LNP formulations.
Multiple within species comparisons show Tanganyikan cichlid fish have larger brains in less structurally complex habitats
Authors: Ma Bin , Li Weiwei , Song Zitan , Fischer Stefan , Lein Etienne , Jungwirth Arne , Jordan Alex 
Published: December 2024

AbstractMany studies have found a link between higher habitat structural complexity and increased relative brain size in vertebrates. Here we explore this relationship in a multi-species comparison, comparing ten species of wild cichlids that differ in their social and territorial behaviour, but which occur across four ecologically similar but structurally diverse rocky habitats. This design allows us to perform repeated intra-specific comparisons, avoiding confounds associated with comparisons across species boundaries. We sampled 147 fish, analysing brain size and architecture while controlling for body mass and species-specific variability and compared this with habitat complexity, quantified using underwater video and three-dimensional reconstructions. Our results challenge the Clever Foraging Hypothesis (CFH), which posits that greater habitat complexity correlates with larger brain sizes. Contrary to CFH, fish from the least complex habitat had significantly larger brains. Additionally, brain architecture analysis indicated a significant enlargement of the cerebellum in fish from less complex habitats, whereas the hypothalamus showed a non-significant negative trend. Taken together, these results indicate that lower habitat complexity may impose higher cognitive demands on spatial memory and navigation due to limited refuges and increased predation risk. This study highlights the need to reconsider the assumed linear positive relationship between environmental complexity and brain development, suggesting that simpler environments might also impose significant cognitive and ecological challenges that drive brain evolution. Our findings underscore the importance of considering intra-species variability and the specific ecological and cognitive demands of different habitats in studies of brain evolution.
Plipastatin is a shared good byBacillus subtilisduring combatingFusariumspp
Authors: Stannius Rune Overlund , Kovács Ákos T. 
Published: December 2024

AbstractBacillus subtilisa Gram-positive soil dwelling bacterium known for its wide range of bioactive secondary metabolites. The lipopeptide plipastatin produced by mostB. subtilisisolates have been shown to exhibit potent anti-fungal activity against plant pathogenic fungi. While the effect of these anti-fungal compounds are well studied in the context of biocontrol, much less is known of their role in the environment, which also harbor non-producing strains of these compounds.Fusariumspecies produce multiple antibacterial compounds resulting in dysbiosis of the plant-associated microbiome and inhibiting plant beneficial bacteria likeB. subtilis. While plipastatin is expected to be important for survival ofB. subtilis, not all isolates carry the biosynthetic gene cluster for plipastatin suggesting that the protective effect of plipastatin might be shared. In this study, we investigated the protective effect of plipastatin againstFusarium oxysporumin a co-culture using a producer and a non-producer isolate of plipastatin. We tested the survival of single and co-cultured strains underFusariumchallenge in liquid media and solid agar plates to dissect the influence of spatial structure. Our results highlights that plipastatin protects the non-producer strain in a density dependent manner.