bluuebunny/crossref_metadata_2025_split huggingface dataset:
AI-based Detection of Central Retinal Artery Occlusion within 4.5 hours on Standard Fundus Photographs
Authors: Gungor Ayse , Sarbout Ilias , Gilbert Aubrey L. , Hamann Steffen , Lebranchu Pierre , Hobeanu Cristina , Gohier Philippe , Vignal-Clermont Catherine , Dumitrascu Oana M. , Cohen Salomon-Yves , Lagrèze Wolf A. , Feltgen Nicolas , van der Heide Frank , Lamirel Cédric , Jonas Jost B. , Obadia Michael , Racoceanu Daniel , Milea Dan 
Published: December 2024

AbstractBackgroundPrompt diagnosis of acute central retinal artery occlusion (CRAO) is crucial for therapeutic management and secondary prevention of associated neurological co-morbidities. However, most stroke centers lack on-site ophthalmic expertise prior to considering fibrinolytic treatments. We aimed to develop, train, and test a deep learning system (DLS) able to accurately detect hyper-acute CRAO on retinal color fundus photographs, during the critical treatment window of 4.5 hours after visual loss. We also evaluated the diagnostic performance of the DLS within 24 hours after visual loss, aiming to improve secondary prevention of stroke after CRAO.MethodsOur retrospective, multicenter, multiethnic study included 1,322 color fundus photographs from 771 patients with various causes of acute visual loss, including CRAO, central retinal vein occlusion, non-arteritic anterior ischemic optic neuropathy, and healthy controls. Photographs were collected from 9 expert neuro-ophthalmology centers in 6 countries, including 3 randomized clinical trials. Training was performed on 1,039 photographs (517 patients), followed by testing on two datasets to discriminate CRAO cases at (i) hyper-acute stage (54 photographs, 54 patients) and (ii) within 24 hours after visual loss (110 photographs, 109 patients).ResultsThe DLS achieved an area under the receiver operating characteristic curve (AUC) of 0.96 (95% confidence interval [CI], 0.95-0.98), a sensitivity of 92.6% (95% CI, 87.0-98.0), and a specificity of 85.0% (95% CI, 81.8-92.8) for detecting CRAO at hyper-acute stage, with similar results for CRAO diagnosis within 24 hours. The DLS outperformed neurologists on a subset of testing dataset at hyper-acute stage (120 photographs from 120 patients).ConclusionsA DLS can accurately detect hyper-acute CRAO on retinal photographs within a time-window compatible with urgent fibrinolysis. Delayed diagnosis (24h) did not alter the ability of the DLS to accurately identify CRAO. If further validated, such systems could improve patient selection for fibrinolytic trials and optimize secondary stroke prevention.Clinical Trial Registration:URL:https://www.clinicaltrials.gov; Unique identifier:NCT06390579.
SpaceExpress: a method for comparative spatial transcriptomics based on intrinsic coordinate systems of tissues
Authors: Kim Yeojin , Ojha Abhishek , Schrader Alex , Lee Juyeon , Wu Zijun , Traniello Ian M , Robinson Gene E , Han Hee Sun , Zhao Sihai D , Sinha Saurabh 
Published: December 2024

ABSTRACTSpatial transcriptomics (ST) technologies have enabled new explorations into the spatial organization of tissues and their functional implications. However, one of the most fundamental analyses – comparative analysis of spatial gene expression across phenotypes – remains a formidable challenge. We introduce SpaceExpress, a novel statistical tool for detecting phenotype-associated changes in spatial expression patterns. SpaceExpress employs a neural network to embed multiple ST samples in a common latent space, enabling robust cross-sample comparisons despite structural and technical variations. It then uses spline regression to test differential spatial expression of genes between conditions, with rigorous false discovery control and handling of multiple replicates per condition. It includes visualization tools to help interpret spatial pattern differences. We demonstrate the tool’s effectiveness on synthetic and real ST datasets, revealing mechanistic insights into behavior-related neurogenomic changes in honey bees and mice. Our work extends the highly influential paradigm of differential gene expression analysis to spatial omics.
Modification of the microstructure of the CERN- CLEAR-VHEE beam at the picosecond scale modifies ZFE morphogenesis but has no impact on hydrogen peroxide production
Authors: Kacem Houda , Kunz Louis , Korysko Pierre , Ollivier Jonathan , Tsoutsou Pelagia , Martinotti Adrien , Rieker Vilde , Bateman Joseph , Farabolini Wilfrid , Baldacchino Gérard , Loo Billy W. , Limoli Charles L. , Dosanjh Manjit , Corsini Roberto , Vozenin Marie-Catherine 
Published: December 2024

AbstractFLASH has emerged as a significant breakthrough for the future of radiation oncology, as it reduces complications while preserving the tumor killing efficacy. To define the beam parameters for future clinical translation, Very High Energy Electrons (VHEE) delivered at CLEAR and able to reach deep seated tumors were used in conjunction with a FLASH-validated Intermediate Energy Electron (IIE) beam and a 160-225 keV X-ray beam, collectively able to deliver dose rates spanning from 1 Gy/min to 1011Gy/s. High-throughput chemical assays were used to investigate radiochemical effects of FLASH, while zebrafish embryos served as a model to evaluate its impact on biological outcomes and morphogenesis. This study is the first comprehensive exploration investigating the impact of a large range of dose rates and various temporal parameters from early physico-chemical events to a complex biological system. Data derived at CLEAR revealed that the intensity of the bunch is a critical factor for observing the sparing effect of FLASH and uncovered an unforeseen biological response when electrons are delivered over the picosecond timescale. Present data also suggests that scanning with high intensity beamlets will be optimal for the future clinical translation of FLASH.HighlightsTo investigate the physics parameters required to trigger the FLASH sparing effect, CLEAR/VHEE/CERN beam macro/microstructure was varied. We show that delivery at the picosecond scale:-reduces alteration in the morphogenesis of zebrafish embryos, but-has no impact on secondary hydrogen peroxide production,Graphical abstract
Bioengineered yeast tethered respiratory supercomplexes reveal mechanisms governing efficient substrate utilization
Authors: Eldeeb Mazzen H. , Cosner Zoe , Carlstrom Andreas , Mays Jeffri-Noelle , Rodriguez Gabriella F. , Berndtsson Jens , Ott Martin , Fontanesi Flavia 
Published: December 2024

ABSTRACTThe mitochondrial respiratory chain (MRC) enzymatic complexes, essential for aerobic energy transduction in eukaryotic cells, are organized into evolutionarily conserved higher-order structures known as supercomplexes (SCs). The elucidation of the physiological relevance of respiratory SCs is essential for our understanding of mitochondrial function and cellular bioenergetics, yet it has been severely hampered by the limited availability of experimental models isolating SC formation as the sole variable. In the yeastSaccharomyces cerevisiae, where SCs are formed by the association of complexes III and IV into III2IV1and III2IV2configurations, compelling evidence suggests that SCs confer a competitive advantage by facilitating cytochromecdiffusion along the SC surface and enhancing respiratory rates. However, the significance of the proposed MRC plasticity and the role of distinct SC conformations in substrate utilization remain unresolved, leaving critical gaps in our understanding of mitochondrial bioenergetics and the adaptive evolution of energy transduction. To address these open questions, we engineered a yeast strain expressing a covalently linked III2IV2SC, whose high-resolution structure is virtually identical to wild-type. Exclusive expression of this tethered SC supports robust overall respiratory activity but selectively affects mitochondrial respiration of cytosolically-generated NADH. This is attributable to the preferential interaction of distinct SC species with mitochondrial NADH dehydrogenases. We propose that in yeast mitochondria, substrate-driven formation of defined respirasome-like SC organizations contributes to the optimization of electron fluxes across the MRC and support metabolic plasticity.
Non-continuous neuromodulation in awake, unrestrained felines increases bladder capacity
Authors: Ortiz-Lopez Miguel , Ouyang Zhonghua , Kotkar Anagha , Willen Maeve , Liu Richard , Olszewski Jordan , Stevens Miriam , Kennedy Eric , Offutt Sarah J. , Bittner Katie C. , Zirpel Lance , Bruns Tim M. 
Published: December 2024

AbstractObjectiveNeuromodulation is a standard therapy for bladder symptoms such as overactive bladder. Previous studies have demonstrated that non-continuous stimulation can increase bladder capacity, and that bladder pressure can be estimated from dorsal root ganglia (DRG) neural activity in anesthetized animal models. Our goal is to determine if non-continuous neuromodulation elicits similar bladder capacity effects as continuous neuromodulation and if bladder pressure can be estimated from DRG signals in an awake, unrestrained animal model.ApproachWe performed aseptic, chronic implant surgeries with seven adult, male felines. Three animals were used to establish procedures, three for experimental testing, and one did not yield data. Bipolar stimulating electrodes were placed on the ipsilateral pudendal nerve and sacral nerve. Microelectrode arrays were inserted in two ipsilateral sacral DRG. Two single-lumen catheters were implanted in the bladder dome for recording bladder pressure and infusing saline. Fixed-sequence, repeated bladder fills were performed in three awake test felines to evaluate the bladder capacity during no-stimulation, non-continuous stimulation, and continuous stimulation at either the pudendal or sacral nerve. Non-continuous stimulation was performed based on increases in bladder pressure estimated from DRG recordings or when 50% of the average no-stimulation bladder capacity was reached.Main resultsWe observed similar bladder capacity increases for non-continuous stimulation (122 ± 32% of no-stimulation control) as for continuous stimulation (121 ± 33%) in the three test animals. Non-continuous stimulation paradigms reduced stimulation time by 44% on average. Median correlation coefficients of 0.46 and 0.64 (maximum 0.93) between neural activity and bladder pressure were obtained for awake trials with bladder units in two animals.SignificanceThis study demonstrated the feasibility of using non-continuous neuromodulation to increase bladder capacity in awake, unrestrained felines and for decoding bladder pressure from DRG recordings. Further studies are needed to optimize non-continuous stimulation timing for clinical translation.
The Plantae Visualization Platform: a comprehensive web-based tool for the integration, visualization, and analysis of omic data across plant and related species
Authors: Santiago Antonio , Orduña Luis , Fernández José David , Vidal Álvaro , de Martín-Agirre Iñigo , Lisón Purificación , Vidal Elena A. , Navarro-Payá David , Matus José Tomás 
Published: December 2024

AbstractThe increasing availability of omic data from non-model plant species has created a need for centralized, user-friendly platforms that maximize the utility of these datasets. Here, we introduce PlantæViz, a web-based tool designed for the integration, visualization, and analysis of multi-omic data across a wide range of plant species. PlantæViz offers advanced functionalities including gene co-expression and regulatory networks, gene expression atlases, cistrome visualization and metabolomics-transcriptomics integration, providing a robust framework for hypothesis generation and biological interpretation. A suite of GeneCards applications tailored to each plant species provide both community curated and automatic functional annotation information. One of the main features of the platform is its big data approach, whereby large volumes of publicly available transcriptomic data have been processed and displayed, i.e. over 58,000 transcriptomic samples are included in total. In addition, a particular effort in the automatic classification and standardization of omic metadata through regular expressions and data mining has been made, with over 90% of transcriptomic runs being successfully classified according to sample tissue. This data has been used to build gene networks through computationally intensive approaches using different methods. PlantæViz connects genomic and functional understanding between model and non-model plant species and aims to expand its catalog of species in the future. Further developments will include the integration of enhanced data types, and novel tools to further support plant research across diverse biological contexts.
Kinase Plasticity in Response to Vandetanib Enhances Sensitivity to Tamoxifen and Identifies Co-Treatment Strategies in Estrogen Receptor Positive Breast Cancer
Authors: Kakati Rasha T. , Whitman Austin A. , Haase Santiago , Szenasi Attila T. , Thai Christine HNC , Brunk Elizabeth , Okumu Denis O. , East Michael P. , Perou Charles M. , Johnson Gary L. , Spanheimer Philip M. 
Published: December 2024

ABSTRACTResistance to endocrine therapy (ET) is common in estrogen receptor (ER) positive breast cancer. Multiple studies have demonstrated that upregulation of MAPK signaling pathways contributes to ET resistance. Herein we show that vandetanib treatment enhances sensitivity to ET in ET-sensitive and –resistant ER+ breast cancer models. Using a CRISPR knockout model, we demonstrate that vandetanib effects are partially mediated by RET receptor tyrosine kinase. Vandetanib treatment alters the gene expression program of ER+ breast cancer cells resulting in a less proliferative and more estrogen responsive Luminal-A like character. Tyrosine kinase network reprogramming was assessed using multiplexed kinase inhibitor beads-mass spectrometry (MIB/MS) assay to identify adaptive resistance mechanisms to vandetanib treatment, which identified upregulation of HER2 activity. Co-treatment to inhibit HER2 with lapatinib enhanced sensitivity to vandetanib, demonstrating biologic activity of HER2 upregulation. Finally, we use our operating room-to-laboratory assay that measures drug response in individual primary tumor cells in short term cultures to demonstrate conserved gene expression changes, including increased HER2 activity signatures, in vandetanib treated cells, and identify features associated with vandetanib response. These results support future investigation of RET targeting strategies considering reprogrammed networks, such as activated HER2, in patients with ET resistant ER+ breast cancer.
Supplementing floral resources does not mitigate the negative effects of urbanisation on cavity-nesting bees and wasps
Authors: Ellis Emilie E. , Campbell Stuart A. , Edmondson Jill L. 
Published: December 2024

AbstractCavity-nesting bees and wasps provide essential ecosystem services such as pollination and pest control. Within urban environments, it is likely that cavity-nesting insects are using greenspaces to forage for food and nesting resources, and thus may benefit from urban greenspace management interventions, such as the addition of flower patches and “bee hotels” (trap nests).In contrast to the relatively large body of work demonstrating the effects of wildflower provisioning on bees in an agricultural context, there have been few studies testing the benefits of floral provisioning, or the relative importance of nest site and food constraints on urban cavity-nesting bees and wasps. Consequently, we lack an empirical evidence base for optimising and informing conservation interventions for these taxa.To understand how the addition of floral resources influences cavity-nesting insect communities, we conducted a 2-year study in urban greenspaces used for horticulture (allotments). We manipulated floral and nesting resources by adding nectar-rich flower patches and artificial trap nests, and compared nest colonisation by cavity-nesting bees and wasps in sites with floral additions and where no additions were made. Our sites were configured along an urbanisation gradient, allowing us to examine how surrounding urbanisation influenced these patterns.Contrary to our predictions, we found no significant difference in trap nest uptake in sites where floral resources were added, compared to control sites. However, cavity-nesting insect abundance showed a 6-fold decrease over our urbanisation gradient. The addition of floral resources did not mitigate the negative effects of urbanisation on cavity-nesting insects.Synthesis and Applications:Although enhancing floral resources in urban systems is a recognised strategy for conserving key pollinators such as social bees, our findings suggest that this approach alone does not address the challenges faced by cavity-nesting bees or wasps in urban landscapes. Our results suggest that accounting for the diversity of resource requirements and incorporating landscape-scale analysis is essential to ensure local conservation interventions will benefit a diversity of insect communities.
TEAD switches interacting partners along neural progenitor lineage progression to execute distinct functions
Authors: Perry Charles H. , Lavado Alfonso , Thulabandu Venkata , Ramirez Cody , Paré Joshua , Dixit Rajiv , Mishra Akhilesh , Yang Jiyuan , Yu Jiyang , Cao Xinwei 
Published: December 2024

AbstractThe TEAD family of transcription factors are best known as the DNA-binding factor in the Hippo pathway, where they act by interacting with transcriptional coactivators YAP and TAZ (YAP/TAZ). Despite the importance of the Hippo pathway, the in vivo functions of TEAD in mammals have not been well established. By comparing mouse mutants lacking TEAD1 and TEAD2 (TEAD1/2) to those lacking YAP/TAZ, we found that TEAD1/2 have both YAP/TAZ-dependent and -independent functions during ventral telencephalon development. TEAD1/2 loss and YAP/TAZ loss similarly disrupt neuroepithelial apical junctions. However, the impacts of their losses on progenitor lineage progression are essentially opposite: Whereas YAP/TAZ loss depletes early progenitors and increases later progenitors—consistent with their established function in promoting progenitor self-renewal and proliferation, TEAD1/2 loss expands early progenitors and reduces late progenitors, indicating that TEAD1/2 promote lineage progression. We further show that TEAD1/2 promote neural progenitor lineage progression by, at least in part, inhibiting Notch signaling and by cooperating with Insulinoma-associated 1 (INSM1). Orthologs of TEAD and INSM1 have been shown to cooperatively regulate neuronal cell fate decisions in worms and flies. Our study reveals a remarkable evolutionary conservation of the function of this transcription factor complex during metazoan neural development.
A Large Language Model Guides the Affinity Maturation of Variant Antibodies Generated by Combinatorial Optimization
Authors: Ashraf Faisal Bin , Zhang Zihao , Paco Karen , Mendivil Mariana P. , Lay Jordan A. , Ray Animesh , Lonardi Stefano 
Published: December 2024

AbstractMachine learning-based antibody design and optimization by computational affinity maturation is emerging as a promising approach to combating infectious diseases. This has been possible because of significant advances in artificial intelligence methods and a surge in experimental datasets on antigen-antibody interaction. The ability of an antibody to bind an antigen with sufficient strength (measured bybinding affinity, the inverse of the equilibrium dissociation constant) and specificity are critical properties in the design of neutralizing antibodies. Here we introduce Ab-Affinity, a new large language model in conjunction with a genetic algorithm and simulated annealing for diversity generation and fitness optimization, which can accurately predict the binding affinity of specific antibodies against a target peptide within the SARS-CoV-2 spike protein. When trained on large datasets of existing antibodies that bind to certain antigens, we show that Ab-Affinity can generate novel antibodies with more than a 160-fold enhancement in binding affinities over those obtained experimentally. The predicted biophysical properties of the synthetic antibodies demonstrate their robustness. Molecular docking and molecular dynamics simulation of the binding interactions of the best candidate synthetic antibodies showed enhanced interactions and stability on the target peptide epitope. In general, antibodies generated by Ab-Affinity appear to be superior to those obtained with other existing computational methods.
A long-distance inhibitory system regulates haustoria numbers in parasitic plants
Authors: Kokla Anna , Leso Martina , Simura Jan , Wärdig Cecilia , Hayashi Marina , Nishii Naoshi , Tsuchiya Yuichiro , Ljung Karin , Melnyk Charles W. 
Published: December 2024

AbstractThe ability of parasitic plants to withdraw nutrients from their hosts depends on the formation of an infective structure known as the haustorium. How parasites regulate their haustoria numbers is poorly understood, and here, we uncovered that existing haustoria in the facultative parasitic plantsPhtheirospermum japonicumandParentucellia viscosasuppressed the formation of new haustoria on distant roots. UsingPhtheirospermum japonicum,we found that this effect depended on the formation of mature haustoria and could be induced through the application of external nutrients. To understand the molecular basis of this root plasticity, we analyzed hormone response and found that existing infections upregulated cytokinin responsive genes first at the haustoria and then more distantly inPhtheirospermumshoots. We observed that infections increased endogenous cytokinin levels inPhtheirospermumroots and shoots, and this increase appeared relevant since local treatments with exogenous cytokinins blocked the formation of both locally and distantly formed haustoria. In addition, local overexpression of a cytokinin degrading enzyme inPhtheirospermumprevented this systemic inter-haustoria repression and increased haustoria numbers locally. We propose that a long-distance signal produced by haustoria negatively regulates future haustoria, and inPhtheirospermum, such a signaling system is mediated by a local increase in cytokinin to regulate haustoria numbers and balance nutrient acquisition.
Order matters: Autocorrelation of temperature dictates extinction risk in populations with nonlinear thermal performance
Authors: Robey Alison J. , Vasseur David A. 
Published: December 2024

AbstractForecasting the risks caused by climate change often relies upon combining species’ thermal performance curves with expected statistical distributions of experienced temperatures, without consideration for the order in which those temperatures occur. Such averaging approaches may obscure the disproportionate impacts that extreme events like heatwaves have on fitness and survival. In this study, we instead incorporate thermal performance curves with population dynamical modeling to elucidate the relationship between the sequence of temperature events – driven by temporal autocorrelation – and extinction risk. We show that the permutation of temperatures determines the extent of risk; as thermal regimes grow warmer, more variable, and more autocorrelated, the risk of extinction grows non-linearly and is driven by interactions among our three treatment variables. Given that the mean, variance, and autocorrelation of temperatures are changing in nuanced ways across the globe, understanding these interactions is paramount for forecasting risk. Using empirical data from a benchmarked set of thermal performance curves, we demonstrate how extinction risk is impacted by the change in mean, variance, and autocorrelation, while controlling for seasonal and diurnal cycling. Our results and modeling approach offer new tools for testing the robustness of thermal performance curves and emphasize the importance of looking beyond temporally-blind metrics, like mean population size or average thermal distributions, for forecasting impending extinction risks.