bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automatic segmentation of spinal cord lesions in MS: A robust tool for axial T2-weighted MRI scans
Authors: Naga Karthik Enamundram , McGinnis Julian , Wurm Ricarda , Ruehling Sebastian , Graf Robert , Valosek Jan , Benveniste Pierre-Louis , Lauerer Markus , Talbott Jason , Bakshi Rohit , Tauhid Shahamat , Shepherd Timothy , Berthele Achim , Zimmer Claus , Hemmer Bernhard , Rueckert Daniel , Wiestler Benedikt , Kirschke Jan S. , Cohen-Adad Julien , Mühlau Mark 
Published: January 2025

AbstractDeep learning models have achieved remarkable success in segmenting brain white matter lesions in multiple sclerosis (MS), becoming integral to both research and clinical workflows. While brain lesions have gained significant attention in MS research, the involvement of spinal cord lesions in MS is relatively understudied. This is largely owed to the variability in spinal cord magnetic resonance imaging (MRI) acquisition protocols, high individual anatomical differences, the complex morphology and size of spinal cord lesions - and lastly, the scarcity of labeled datasets required to develop robust segmentation tools. As a result, automatic segmentation of spinal cord MS lesions remains a significant challenge. Although some segmentation tools exist for spinal cord lesions, most have been developed using sagittal T2-weighted (T2w) sequences primarily focusing on cervical spines. With the growing importance of spinal cord imaging in MS, axial T2w scans are becoming increasingly relevant due to their superior sensitivity in detecting lesions compared to sagittal acquisition protocols. However, most existing segmentation methods struggle to effectively generalize to axial sequences due to differences in image characteristics caused by the highly anisotropic spinal cord scans. To address these challenges, we developed a robust, open-source lesion segmentation tool tailored specifically for axial T2w scans covering the whole spinal cord. We investigated key factors influencing lesion segmentation, including the impact of stitching together individually acquired spinal regions, straightening the spinal cord, and comparing the effectiveness of 2D and 3D convolutional neural networks (CNNs). Drawing on these insights, we trained a multi-center model using an extensive dataset of 582 MS patients, resulting in a dataset comprising an entirety of 2,167 scans. We empirically evaluated the model’s segmentation performance across various spinal segments for lesions with varying sizes. Our model significantly outperforms the current state-of-the-art methods, providing consistent segmentation across cervical, thoracic and lumbar regions. To support the broader research community, we integrate our model into the widely-used Spinal Cord Toolbox (v7.0 and above), making it accessible via the command sct deepseg-task seg sc ms lesion axial t2w -i <path-to-image.nii.gz>.
Atrophy in multiple system atrophy relates to mitochondrial and oligodendrocytic processes
Authors: Chougar Lydia , Tremblay Christina , Delva Aline , Filiatrault Marie , Vo Andrew , Hansen Justine Y. , Farahani Asa , Misic Bratislav , Khalafi Parsa , Castonguay Charles-Etienne , Rouleau Guy , Corvol Jean-Christophe , Vidailhet Marie , Degos Bertrand , Grabli David , Lehéricy Stéphane , Dagher Alain , Rahayel Shady 
Published: January 2025

AbstractObjectiveTo investigate the gene expression and neurobiological underpinnings of brain atrophy in multiple system atrophy (MSA) using imaging transcriptomics and PET-based molecular annotation.MethodsWe derived brain atrophy measurements from the T1-weighted MRI scans of 65 patients with MSA and 181 age- and sex-matched healthy controls. Using postmortem data from the Allen Human Brain Atlas, partial least square (PLS) regression was used to identify gene expression components associated with atrophy. Gene enrichment analyses were performed to investigate the biological processes with enriched genes in regions showing atrophy. Annotation mapping was used to identify the neurochemical systems whose density maps matched atrophy in MSA.ResultsAtrophy in MSA was found to primarily affect deep brain regions, including the cerebellar white matter, pons, putamen, olive nuclei, and substantia nigra. PLS regression on deep brain region atrophy identified two gene expression latent variables, explaining 27.5% of the covariance. Regions with greater atrophy overexpressed genes related to the mitochondrial respiratory chain, particularly proton transmembrane transport and complex I assembly. In addition, cell type analysis revealed that regions with atrophy overexpressed genes related to oligodendrocytes. These patterns were distinct from those found in Parkinson’s disease. Atrophic regions in MSA also displayed less serotonin and GABA receptors and more acetylcholine and noradrenaline receptors.InterpretationRegions showing atrophy in MSA show specific features, namely overexpression of genes related to mitochondrial function and oligodendrocytes and distinct neurochemical patterns. This study highlights some of the biological and neurochemical mechanisms underlying selective vulnerability of brain regions in MSA.
A pivot-tether model for nucleosome recognition by the chromosomal passenger complex
Authors: Ruza Reinis R. , Chung Chyi Wei , Gold Danny B.H. , Serena Michela , Roberts Emile , Gruneberg Ulrike , Barr Francis A. 
Published: January 2025

AbstractSpatial restriction of Aurora B to centromeres during prometaphase and metaphase enables it to phosphorylate proteins necessary for spindle assembly checkpoint signalling and biorientation of chromosomes on the mitotic spindle. Aurora B binding to T3-phosphorylated histone H3 (H3pT3) nucleosomes requires a multivalent targeting module, the chromosomal passenger complex (CPC), consisting of survivin, borealin, and INCENP. To shed light on how these components mediate CPC localisation during prometaphase and metaphase, we determined the structure of the CPC targeting module in complex with haspin-phosphorylated H3pT3-nucleosomes by cryo-electron microscopy. This structure shows how the N-terminus of borealin and the survivin BIR domain act as pivot and flexible tethering points, respectively, to increase CPC affinity for H3pT3 nucleosomes without limiting it to a specific orientation. We demonstrate that this flexible, yet constrained pivot-tether arrangement is important for the control of spindle assembly checkpoint signalling by Aurora B.
Impact of cross-validation designs on cattle behavior prediction using machine learning and deep learning models with tri-axial accelerometer data
Authors: Wang Jin , Yu Ziwen , Chebel Ricardo C. , Yu Haipeng 
Published: January 2025

1AbstractAssessing cattle behaviors provides insights into animal health, welfare, and productivity to support on-farm management decisions. Wearable accelerometers offer an alternative approach to traditional human evaluation, providing a more objective and efficient method for predicting cattle behavior. Random cross-validation (CV) is commonly used to evaluate behavior prediction by splitting data into training and testing sets, but it can yield inflated results when records from the same animal are included in both sets. Block CV splits data by block effects, offering a more realistic evaluation but remains underexplored for predicting multi-class imbalanced cattle behavior. Additionally, deep learning (DL) models have not been fully explored for behavior prediction compared to machine learning (ML) models. The objectives of this study were to examine the impact of CV designs on multi-class imbalanced cattle behavior prediction and to compare the performance of ML and DL models. Three ML and two DL models were used to predict the four behaviors of six beef cows from a public tri-axial accelerometer dataset, with model performance evaluated using both hold-out and leave-cow-out CV designs representing random and block CV, respectively. In hold-out CV, ML models achieved accuracies of 0.94 to 0.96 and F1 scores of 0.93 to 0.95, while DL models achieved accuracies of 0.9 to 0.92 and F1 scores of 0.89 to 0.91. In the leave-cow-out CV, ML models obtained accuracies of 0.72 to 0.82 and F1 scores of 0.64 to 0.82, whereas DL models obtained accuracies of 0.76 to 0.82 and F1 scores of 0.64 to 0.76. Generally, ML models outperformed DL models in the hold-out CV, but the multi-layer perceptron DL model demonstrated comparable or superior performance in the leave-cow-out CV. All models performed better with hold-out CV than leave-cow-out CV. Our results suggest that CV designs can affect behavior prediction performance. While a random CV produces seemingly good predictions, these results can be artificially inflated by the data partition. A block CV that strategically partitions data could be a more appropriate design.
Evidence of inbreeding depression on stature in Brown Swiss cattle
Authors: He Qiongyu , Deuber Jessica , Seefried Franz R. , Pausch Hubert , Kadri Naveen 
Published: January 2025

AbstractBackgroundSmall effective population size and the disproportionately large use of few genetically superior bulls in artificial insemination lead to extensive runs of homozygosity and an increased risk of homozygosity for deleterious alleles in domestic cattle, which may cause inbreeding depression. The adverse effects of inbreeding on phenotypic performance are well established, but the genetic variants contributing to inbreeding depression remain largely unknown. This study aimed to analyse the impacts of inbreeding on stature (measured as height at the sacral bone) in a cohort of 15,306 Brown Swiss (BS) cows that have imputed genotypes at 20 million sequence variants and stature measurements as height at the sacral bone.ResultsThe average genomic inbreeding coefficient of the 15,306 BS cows estimated from runs of homozygosity (ROH) was 0.369 (± 0.022). We found a loss in stature, decreasing from a height of 0.076 cm at the sacral bone per 1% increase in inbreeding (p = 1.94e-09). Contributions to inbreeding depression were significant for long (> 2 Mb), medium (0.1 – 2 Mb), and short (50 kb – 0.1 Mb) ROH (p = 1.29e-12, p = 3.20e-04 and p = 1.77e-06, respectively), suggesting that both ancient and recent inbreeding have negative effects on stature. Non-additive association testing identified a novel recessive quantitative trait locus (QTL) for stature on chromosome 25 with the most significantly (p = 2.35e-21) associated SNP residing at 14,535,327 bp. Cows homozygous for the alternate allele of the top associated SNP were 2 cm shorter than heterozygous and reference allele homozygotes. Fine mapping of the QTL identified a splice donor variant (rs447836030 at 25:14,515,474) of the geneABCC6encoding ATP binding cassette subfamily C member 6 which causes exon skipping as both a positional and functional candidate causal variant.ConclusionsOur study reveals evidence for inbreeding depression on stature in a large cohort of BS cattle. We also uncover a recessive QTL that decreases stature through non-additive association testing. This QTL harbors a high-impact variant affecting a splice donor site ofABCC6which leads to exon skipping, thereby possibly contributing to inbreeding depression. Accumulating non-lethal deleterious alleles in ROH may reduce the overall fitness of the BS cattle population.
Extracellular polymeric substance degradation shapes microbial community diversity
Authors: Pontrelli Sammy , Villi Kian Bigovic , Sichert Andreas , Trouillon Julian , Rutz Adriano , Landry Zachary , Rüdisser Simon H. , Stocker Roman , Sauer Uwe 
Published: January 2025

AbstractCompetition for and exchange of nutrients play crucial roles in shaping microbial community function and dynamics. Although cross-feeding of small metabolites is known to drive carbon exchange among species, the importance of self-produced extracellular polymeric substances (EPS)— which include proteins, polysaccharides, DNA, and humic-like substances— remains less understood. Utilizing chitin-degrading microbial isolates and natural seawater communities, we found that 4–7% of the carbon from chitin degradation is converted into EPS, accounting for nearly a quarter of the exuded carbon. Different sources of EPS were found to select for distinct microbial communities. Through enzyme assays and untargeted metabolomics, we demonstrated that secreted enzymes degrade EPS in multiple steps that influence community diversity: larger oligomers are initially utilized by specialized degraders, while the subsequent breakdown into smaller oligomers, monosaccharides, and amino acids supports non-specialized consumers. These findings highlight the role of EPS as a significant carbon source exchanged between microbes, fueling metabolically diverse populations and enriching our understanding of carbon-mediated microbial interactions.
Convergent flow-mediated mesenchymal force drives embryonic foregut constriction and splitting
Authors: Yan Rui , Hoffmann Ludwig A. , Oikonomou Panagiotis , Li Deng , Lee ChangHee , Gill Hasreet , Mongera Alessandro , Nerurkar Nandan L. , Mahadevan L. , Tabin Clifford J. 
Published: January 2025

AbstractThe transformation of a two-dimensional epithelial sheet into various three-dimensional structures is a critical process in generating the diversity of animal forms. Previous studies of epithelial folding have revealed diverse mechanisms driven by epithelium-intrinsic or -extrinsic forces. Yet little is known about the biomechanical basis of epithelial splitting, which involves extreme folding and eventually a topological transition breaking the epithelial tube. Here, we leverage tracheal-esophageal separation (TES), a critical and highly conserved morphogenetic event during tetrapod embryogenesis, as a model system for interrogating epithelial tube splitting both in vivo and ex vivo. Comparing TES in chick and mouse embryos, we identified an evolutionarily conserved, compressive force exerted by the mesenchyme surrounding the epithelium, as being necessary to drive epithelial constriction and splitting. The compressive force is mediated by localized convergent flow of mesenchymal cells towards the epithelium. We further found that Sonic Hedgehog (SHH) secreted by the epithelium functions as an attractive cue for mesenchymal cells. Removal of the mesenchyme, inhibition of cell migration, or loss of SHH signaling all abrogate TES, which can be rescued by externally applied pressure. These results unveil the biomechanical basis of epithelial splitting and suggest a mesenchymal origin of tracheal-esophageal birth defects.
Co-translational assembly promotes functional diversification of paralogous proteins
Authors: Mallik Saurav , Cisneros Angel F. , Landry Christian R. , Levy Emmanuel D. 
Published: January 2025

ABSTRACTHomomeric proteins are ubiquitous and mediate myriads of cellular functions. When a gene encoding a homomer duplicates, the resulting paralogs can either form distinct homomers, or evolve into a heteromer containing both paralogs. While such events have extensively shaped proteomes, the molecular mechanisms driving these fates and their associated functional consequences remain largely unknown. Here, we conducted a comprehensive phylogenomic analysis tracing gene duplication histories of 7,377 human paralogs across the eukaryotic lineage and identified their fates using protein interaction data. Simulations and data analyses show that cellular constraints must act as barriers to disfavor heteromerization and promote homomerization. We found that multiple cellular and molecular constraints can serve as barriers, including the lack of co-expression and co-localization. The main barrier, however, is co-translational assembly, which naturally promotes the self-assembly of each paralog from its corresponding mRNA, thus hindering heteromerization. We further established that heteromerization constrains functional divergence, with homomeric paralogs exhibiting stronger signatures of adaptive evolution and functional divergence compared to heteromeric paralogs. Together, these findings identify key biochemical and cellular properties that explain protein function diversification following gene duplication.One Sentence SummaryCo-translational assembly drives the selective homo-oligomerization of paralogs, which in turn promotes their functional divergence.Graphical Abstract
Shallow-angle intracranial cannula for repeated infusion and in vivo imaging with multiphoton microscopy
Authors: Hou Steven S. , Yang Joyce , Kwon Yeseo , Pian Qi , Tang Yijing , Dauphinais Christine A. , Calvo-Rodriguez Maria , El Khatib Mirna , Vinogradov Sergei A. , Sakadzic Sava , Bacskai Brian J. 
Published: January 2025

ABSTRACTMultiphoton microscopy serves as an essential tool for high-resolution imaging of the living mouse brain. To facilitate optical access to the brain during imaging, the cranial window surgery is commonly used. However, this procedure restricts physical access above the imaging area and hinders the direct delivery of imaging agents and drugs. To overcome this limitation, we have developed a cannula delivery system that enables the implantation of a low-profile cannula nearly parallel to the brain surface at angles as shallow as 8 degrees, while maintaining compatibility with multiphoton microscopy. To validate this approach, we perform direct infusion and imaging of various fluorescent cell markers in the brain. Additionally, we successfully demonstrate tracking of degenerating neurons over time in Alzheimer’s disease mice using Fluoro-Jade C. Furthermore, we show longitudinal imaging of brain tissue partial pressure of oxygen using a phosphorescent oxygen sensor. Our developed technique should enable a wide range of new longitudinal imaging studies in the mouse brain.
A synaptic-astrocytic proteomic signature associated with synaptopathy in Alzheimer’s Disease
Authors: Griffiths Jessica , Schneegans Eléonore , Whitwell Harry , Qiu Zhen , Notman Beverley , Cheung Dorcas , Willumsen Nanet , Matthews Paul M , Grant Seth G N , Jackson Johanna S 
Published: January 2025

AbstractSynapse loss is the greatest correlate of cognitive impairment in Alzheimer’s Disease (AD) and offers a therapeutic avenue alongside disease-modifying therapies. However, the events preceding synapse loss in the human condition have not been well characterised. In this study, we describe a pseudotemporal profile of alterations in the synaptic proteome prior to excitatory synapse loss in humanpost-mortembrain AD tissue using synapse proteomics and synaptome mapping techniques. In a region with early-stage disease pathology, the most predominant changes were pre-synaptic and featured changes in metabolism and exocytosis. In a mid-stage disease state, alongside initial synapse loss, there was a dominance of inhibitory synaptic changes. In a region with late-stage disease pathology and profound synapse loss, post-synaptic changes were most prevalent with a range of canonical synaptic transmission pathways reduced and differential excitatory synapse subtype pathology. Synapse loss was associated with changes in astrocytic proteins which were enriched for those at peri-synaptic astrocytic processes, including an upregulation of complement activation and endocytosis; a signature that differed from the astrocyte cytosolic proteome. Taken together, this provides evidence of a cascade of events leading to synapse loss with multiple points for therapeutic intervention to alleviate cognitive decline in AD. Data are available via ProteomeXchange with identifier PXD056052.
Hard processes in multi-TeV ion collisions
Authors: Fuks Benjamin , Marougkas Fotios , Ruiz Richard , Sztandera Alicja 
Published: January 2025

Motivated by the ion-collision program at the Large Hadron Collider, plans for its high-luminosity upgrade, and ongoing discussions for multi-TeV future hadron colliders, we systematically investigate hard-scattering, Standard Model processes in many-TeV ion-ion collisions. We focus on the symmetric beam configurations Pb208−Pb208, Xe131−Xe131, C12−C12, and pp, and we catalog total and fiducial cross sections for dozens of processes, ranging from associated-Higgs and multiboson production to associated-top pair production, at next-to-leading order in QCD for nucleon-nucleon collision energies from sNN=1 to 100 TeV. We report the residual scale uncertainties at this order as well as the uncertainties originating from fits of nuclear parton densities. We also discuss the propagation of nuclear dynamics (as encoded in nuclear parton densities) into parton luminosities and ultimately into predictions for cross sections. Finally, we report on the emergence of trends and the reliability of extrapolating cross sections across different nuclei. For Pb-Pb collisions at a hypothetical Future Circular Collider with sNN=39  TeV, O(108) weak bosons, O(105) diboson pairs, O(104) WH and ZH pairs, O(103) triboson events, O(105) high-pT photons events, and O(107) tt¯ pairs can be produced with L=33  nb−1 of data. At sNN=5.52  TeV, one can expect O(10–106) single, multiboson, and top events per 1  nb−1. Decay rates and experimental selection/acceptance rates will impact final event yields and merit further study; as an illustrative example, we focus on select diboson and triboson channels in lead-lead collisions and discuss their observability at the high-luminosity phase of the Large Hadron Collider and the Future Circulate Collider.

Published by the American Physical Society
2025
Anisotropic signatures of electron hydrodynamics
Authors: Estrada-Álvarez Jorge , Domínguez-Adame Francisco , Díaz Elena 
Published: January 2025

Electron hydrodynamics refers to the transport regime where electrons collectively behave like a fluid. Its realization requires pure materials, some of which, such as bilayer graphene or PdCoO2, are anisotropic so that different in-plane transport directions can be defined. Collective electron flow also benefits from geometrically engineered devices because it is highly dependent on the nonuniformity of the electron flow. Here we analyze carrier transport in anisotropic materials where remarkable effects emerge after the proper directional design of the device. Simulations based on the Boltzmann transport equation demonstrate that electrical properties are clearly different when the device is set in the easy or the hard transport directions, namely, when the transport channel is aligned or not aligned to the group velocity at the Fermi level, respectively. Most importantly, the standard signatures of viscous electron flow, such as Poiseuille flow, superballistic conduction, and the formation of whirlpools, are enhanced when the anisotropic device operates in the hard transport directions. As a result, we demonstrate that electron hydrodynamics leads to a different route for efficient charge transport in the hard in-plane transport directions.

Published by the American Physical Society
2025