bluuebunny/crossref_metadata_2025_split huggingface dataset:
Over a Century of Infectious Disease Surveillance in Canada: Introducing the Canadian Disease Incidence Dataset (CANDID)
Authors: Earn David J. D. , MacKinnon Gabrielle , Manzin Samara , Roswell Michael , Cygu Steve , Shi Chyunfung , Bolker Benjamin M. , Dushoff Jonathan , Walker Steven C. 
Published: December 2024

AbstractBackgroundCanadian notifiable disease surveillance provides data on the incidence of communicable diseases, dating back to the late 19th century. The Public Health Agency of Canada offers summaries of these data (from 1924–2022) through an online portal. These summaries provide historical context for Canadian health researchers, but lack information on intra-annual and inter-provincial patterns. Sub-annual and sub-national data can be found in published documents, or requested from archives of government agencies, but are only available in typewritten or handwritten hard copies. We digitized and collated these data sources to create a resource for epidemiology and public health.MethodsWe manually entered data from scans of hard copies into spreadsheets resembling the originals, facilitating accurate transcription through easier cross-checking. We developed open-source pipelines to harmonize these spreadsheets into CSV files that blend data across sources.ResultsWe assembled and processed 1,631,380 incidence values from 1903–2021. Focusing on sub-annual and sub-national data and removing redundancy yielded 934,009 weekly, monthly, or quarterly incidence values broken down by province/territory, containing 139 diseases. We give two examples of sub-annual and sub-national patterns: strong annual cycles of poliomyelitis that peaked simultaneously across provinces, and spatially heterogeneous resurgence of whooping cough in the 1990s.InterpretationCanada’s history of infectious disease surveillance has produced a detailed record of sub-annual and sub-national disease incidence patterns that remains largely unexplored. This important record is now available as the Canadian Disease Incidence Dataset (CANDID), hosted on a publicly accessible website along with the pipelines used to create it and scans of the original sources.
Differential fMRI neural synchrony associated with migraine during emotionally arousing naturalistic stimuli
Authors: Klamer Keva , Craig Joshua , Haines Christina , Sullivan KiAnna , Seres Peter , Ekstrand Chelsea 
Published: December 2024

AbstractMigraine is a common neurological disorder that impacts approximately 12% of the general population and is characterized by moderate to severe headaches, nausea, mood changes, and fatigue. It impacts lower-level visual and auditory processing, causing hypersensitivities that lead to heightened audiovisual multisensory integration. However, the impact of migraine on the processing of complex, audiovisual stimuli is still unclear. Additionally, migraine may induce hypersensitivities to emotional arousal and valence, though the relative significance of these factors remains unknown. The current study seeks to identify how migraine impacts synchronous neural processing of complex, audiovisual stimuli, and how this differs based on the emotional arousal and valence of the stimulus. To do so, we collected functional magnetic resonance imaging data from 17 migraineurs and 25 healthy controls during the passive viewing of three audiovisual films of differing emotional arousal and valence. We identified that, in response to high arousal emotional stimuli, the migraine group showed greater neural synchrony in regions associated with multisensory integration, including the posterior superior temporal gyrus. In response to the negative valence film, the migraine group had heightened neural synchrony in bilateral cuneus and the right angular gyrus. These findings suggest that migraine involves hypersensitivity to audiovisual movies as a function of both emotional arousal and valence, with high arousal driving greater synchrony in multisensory integration and negative valence enhancing synchrony in peripheral visual processing. Overall, this research highlights distinct pathways through which emotional stimuli impacts neural processing in migraine.
Generation of antigen-specific paired chain antibody sequences using large language models
Authors: Wasdin Perry T. , Johnson Nicole V. , Janke Alexis K. , Held Sofia , Marinov Toma M. , Jordaan Gwen , Vandenabeele Léna , Pantouli Fani , Gillespie Rebecca A. , Vukovich Matthew J. , Holt Clinton M. , Kim Jeongryeol , Hansman Grant , Logue Jennifer , Chu Helen Y. , Andrews Sarah F. , Kanekiyo Masaru , Sautto Giuseppe A. , Ross Ted M. , Sheward Daniel J. , McLellan Jason S. , Abu-Shmais Alexandra A. , Georgiev Ivelin S. 
Published: December 2024

AbstractThe traditional process of antibody discovery is limited by inefficiency, high costs, and low success rates. Recent approaches employing artificial intelligence (AI) have been developed to optimize existing antibodies and generate antibody sequences in a target-agnostic manner. In this work, we present MAGE (Monoclonal Antibody GEnerator), a sequence-based Protein Language Model (PLM) fine-tuned for the task of generating paired human variable heavy and light chain antibody sequences against targets of interest. We show that MAGE can generate novel and diverse antibody sequences with experimentally validated binding specificity against SARS-CoV-2, an emerging avian influenza H5N1, and respiratory syncytial virus A (RSV-A). MAGE represents a first-in-class model capable of designing human antibodies against multiple targets with no starting template.
Local activation of Cxcl12a signaling controls olfactory placode morphogenesis in zebrafish embryos
Authors: Zilliox Marie , Letort Gaëlle , Sanchez David , Rouviere Christian , Dufourcq Pascale , Gaits-Iacovoni Frédérique , Pizzoccaro Anne , Roussier-Michon Violaine , Blader Patrick , Batut Julie 
Published: December 2024

AbstractMorphogenesis and cell-type differentiation are highly coordinated in sensory organs to ensure their function. Morphogenesis of the olfactory epithelium (OE) in zebrafish provides a unique model to study this process as undifferentiated cells aligned around the anterior neural plate mature into clusters of early olfactory neurons across a short time scale. While the Cxcl12a/Cxcr4b signaling pathway drives this process, what constraints on pathway activation apply during morphogenesis are unclear. We developed a mathematical model recapitulating Cxcl12a-mediated OE morphogenesis. Restoring Cxcl12a expression in mutants for the ligand rescues correct morphogenesis both in silico and in vivo. However, where expression of the ligand is restored is crucial for rescue, a point not predicted by our model and suggesting an unexpected level of pathway activation control. Analysis of a Cxcr4b activation reporter supports this idea. We concluded that mosaic and heterochronic Cxcl12a activation along the anteroposterior axis sculpts the olfactory epithelium.
Radiation damage behavior of soft matter in ultrafast cryo-electron microscopy (cryo-UEM)
Authors: Zhao Yimin , Qi Chen , Zhu Chunhui , Zhu Yun , Zhang Yongzhao , Gu Tongnian , Tian Huanfang , Wang Wentao , Huang Siyuan , Yang Huaixin , Li Jianqi , Sun Fei 
Published: December 2024

AbstractWhether time-modulated pulsed-electron imaging in ultrafast electron microscopy (UEM) can mitigate the electron radiation damage that occurs to samples, is still controversial. The effectiveness of such mitigation effect and relevant potential application in cryo-EM remain to be explored. Herein, we built an ultrafast cryo-EM (cryo-UEM) device based on an ultrafast laser system. Using such equipment and the saturated aliphatic hydrocarbon compounds (C44H90), the fading curves of diffraction intensity and corresponding critical electron doses (Ne) of the samples were carefully measured under different imaging modes, temperatures, imaging dose rates and pulsed repetition rates. Our experimental results show that, the fading curves andNevalues of the C44H90crystals are uncorrelated with the imaging electron dose rates and do not show dependence on the dose-rate effect. As the temperature decreased, theNevalues of the sample increased, indicating the cryoprotective effect on radiation damage to the samples. Surprisingly, at a constant temperature, the fading curves andNevalues of the sample in multi-electrons-packet and near-single-electron-packet pulsed modes are all approximately the same as those in conventional continuous electron-beam mode, even when the results are obtained at different pulsed repetition rates. These results show that the time-modulated pulsed electron beam does not seem to mitigate the electron radiation damage that occurs on samples. Our findings offer new insights and experimental basis for the radiation damage behavior of samples under electron beams, and provide guidance and inspiration for elucidating the fundamental principles of radiation damage.
Development of a flexible 3D printed TPU-PVC microfluidic devices for organ-on-a-chip applications
Authors: Abdalkader Rodi Kado , Konishi Satoshi , Fujita Takuya 
Published: December 2024

ABSTRACTThe development of cost-effective, flexible, and scalable microfluidic devices is crucial for advancing organ-on-a-chip (OoC) technology for drug discovery and disease modeling applications. In this study, we present a novel 3D-printed flexible microfluidic device (3D- FlexTPU-MFD) fabricated through a one-step fused deposition modeling (FDM) process using thermoplastic polyurethane (TPU) as the printing filament and polyvinyl chloride (PVC) as the bonding substrate. The device’s compatibility was evaluated with various cell types, including human primary myoblasts, human primary endothelial cells (HUVEC), and human iPSC- derived optic vesicle (OV) organoids. Myoblasts cultured within the device exhibited high viability, successful differentiation, and the formation of aligned myotube bundles, outperforming conventional well-plate cultures. Additionally, iPSC-derived OV organoids- maintained viability, displayed neurite outgrowth, and sustained expression of the eye marker PAX6. These results demonstrate that the 3D-FlexTPU-MFD effectively supports cell growth, differentiation, and alignment, making it a promising platform for tissue modeling and OoC applications in future.
Large-scale infra-slow dynamics of extracellular potentials linked to synchronous states revealed by graphene neural probes
Authors: Garcia-Cortadella R. , Cisneros-Fernandez J. , Schwesig G. , Shahidi A. , Umurzakova A. , Schäfer N. , Aguilar J. , Masvidal-Codina E. , Del Corro E. , Moahrlok R. , Kurnoth M. , Paetzold J. , Loeffler H. , Jeschke C. , Meents J. , Illa X. , Serra-Graells F. , Guimerà-Brunet A. , Garrido J. A. , Sirota A. 
Published: December 2024

AbstractBrain states exhibit slow transitions that are coordinated by slowly varying homeostatic and neuromodulatory factors. These slow dynamics modulate neuronal excitability, giving rise to brain state-specific synchronous oscillatory patterns across brain regions. Such synchronous states could be reflected in local infra-slow variations in the extracellular potential, providing new insights into the organisation of spontaneous brain dynamics beyond the established fast time scales. However, mapping of the LFP across brain regions with high spatio-temporal resolution remains challenging, with the infra-slow component particularly elusive. To overcome these limitations, we developed neural probes based on arrays of up to 512 multiplexed graphene transistors, which enable DC-coupled, high-density, and large-scale recordings of surface and depth activity in freely behaving rats. Analysis of cortex-wide oscillation dynamics improves segmentation, provides new insights into global brain states and allows detection of the local oscillatory states. Brain state transitions related to changes in neuronal synchrony are found to correlate with topographically structured infra-slow dynamics. Furthermore, transregional infra-slow waves during non-REM sleep are globally coupled to diverse sleep spindle oscillatory modes independent of their localization while slow oscillations locally modulate spindle occurrence. This study shows that spatio-temporal patterns of infra-slow and slow LFP parallel the spatially organized oscillatory dynamics, reflecting the interplay between sub-cortical inputs and cortical excitability across brain states.
Abundant non-inclusion α-synuclein pathology in Lewy body-negative LRRK2-mutant cases
Authors: Jensen Nanna Møller , Vitic Zagorka , Antorini Mia R. , Bruun Viftrup Tobias , Parkkinen Laura , Jensen Poul Henning 
Published: December 2024

AbstractLewy body diseases are common neurodegenerative diseases, including Parkinson’s disease (PD) and dementia with Lewy bodies, which lead to both motor and non-motor symptoms. They are neuropathologically characterized by loss of neuromelanized neurons in the substantia nigra pars compacta and α-synuclein-immunopositive inclusions (Lewy bodies) in several types of neurons in the brain. A fraction of monogenic PD cases, however, represent a conundrum, as they can present with clinical Lewy body disease but do not have Lewy bodies upon neuropathological examination. For LRRK2, the presence or absence of Lewy bodies is not related to any specific mutation in the gene and different clinical presentation and neuropathology can be present even in the same family.Here, we present the first evidence of widespread α-synuclein accumulation detected with proximity ligation assay (PLA) using the MJFR14-6-4-2 antibody in six Lewy body-negative LRRK2 cases and compare the levels with five patients with neuropathologically-verified Lewy body disease cases and six healthy controls. We show that non-inclusion, aggregated α-synuclein PLA signal is dominant in the LRRK2 cases, while Lewy-like PLA signal is predominant in late-stage Lewy body disease. Furthermore, LRRK2 cases displayed prominent PLA signal in pontocerebellar tracts and inferior olivary nuclei in the brainstem, which was not seen in idiopathic PD cases. These results suggest that Lewy-body negative LRRK2-related PD is not associated with a lack of α-synuclein aggregation in neurons but rather a deficiency in the formation of inclusions.
Experimental evolution of a pathogen confronted with innate immune memory increases variation in virulence
Authors: Korša Ana , Baur Moritz , Schulz Nora K.E. , Anaya-Rojas Jaime M. , Mellmann Alexander , Kurtz Joachim 
Published: December 2024

AbstractUnderstanding the drivers and mechanisms of virulence evolution is still a major goal of evolutionary biologists and epidemiologists. Theory predicts that the way virulence evolves depends on the balance between the benefits and costs it provides to pathogen fitness. Additionally, host responses to infections, such as resistance or tolerance, play a critical role in shaping virulence evolution. But, while the evolution of pathogens has been traditionally studied under the selection pressure of host adaptive immunity, less is known about their evolution when confronted to simpler and less effective forms of immunity such as immune priming. In this study, we used a well-established insect model for immune priming – red flour beetles and their bacterial pathogenBacillus thuringiensis tenebrionis –to test whether this form of innate immune memory favors the evolution of higher virulence. Through controlled experimental evolution of the pathogen in primed versus non-primed hosts, we found no change in average virulence after eight selection cycles in primed host. However, we found a significant increase in the variation of virulence (i.e., host-killing ability) among independent pathogen lines evolved in primed host, and bacteria were unable to evolve resistance against host priming. Whole genome sequencing revealed increased activity in the bacterial mobilome (prophages and plasmids). Expression of the Cry toxin – a well-known virulence factor – was linked to evolved differences in copy number variation of thecry-carrying plasmid, though this did not correlate directly with virulence. These findings highlight that innate immune memory can drive variability in pathogen traits, which may favor adaptation to variable environments. This underscores the need to consider pathogen evolution in response to innate immune memory when applying these mechanisms in medicine, aquaculture, pest control, and insect mass production.
Transcriptional responses toin vitromacrocyclic lactone exposure inToxocara canislarvae using RNA-seq
Authors: Quintana Theresa A. , Brewer Matthew T. , Chelladurai Jeba R. Jesudoss 
Published: December 2024

AbstractToxocara canis, the causative agent of zoonotic toxocariasis in humans, is a parasitic roundworm of canids with a complex lifecycle. While macrocyclic lactones (MLs) are successful at treating adultT. canisinfections when used at FDA-approved doses in dogs, they fail to kill somatic third-stage larvae. In this study, we profiled the transcriptome of third-stage larvae derived from larvated eggs and treatedin vitrowith 10 µM of the MLs – ivermectin and moxidectin with Illumina sequencing. We analyzed transcriptional changes in comparison with untreated control larvae. In ivermectin-treated larvae, we identified 608 differentially expressed genes (DEGs), of which 453 were upregulated and 155 were downregulated. In moxidectin-treated larvae, we identified 1,413 DEGs, of which 902 were upregulated and 511 were downregulated. Notably, many DEGs were involved in critical biological processes and pathways including transcriptional regulation, energy metabolism, neuronal structure and function, physiological processes such as reproduction, excretory/secretory molecule production, host-parasite response mechanisms, and parasite elimination. We also assessed the expression of known ML targets and transporters, including glutamate-gated chloride channels (GluCls), and ATP-binding cassette (ABC) transporters, subfamily B, with a particular focus on P-glycoproteins (P-gps). We present gene names for previously uncharacterizedT. canisGluCl genes using phylogenetic analysis of nematode orthologs to provide uniform gene nomenclature. Our study revealed that the expression ofTca-glc-3and six ABCB genes, particularly four P-gps, were significantly altered in response to ML treatment. Compared to controls,Tca-glc-3,Tca-Pgp-11.2, andTca-Pgp-13.2were downregulated in ivermectin-treated larvae, whileTca-abcb1,Tca-abcb7,Tca-Pgp-11.2, andTca-Pgp-13.2were downregulated in moxidectin-treated larvae. Conversely,Tca-abcb9.1andTca-Pgp-11.3were upregulated in moxidectin-treated larvae. These findings suggest that MLs broadly impact transcriptional regulation inT. canislarvae.
Contributions of temporal and spatial masking signals in perception of sequential visual events
Authors: Buonocore Antimo , Cuomo Maria , Maresca Martina , Fracasso Alessio 
Published: December 2024

AbstractAccurate perception of time and space is essential for moment-to-moment interactions with our surroundings. This process requires flexibility, as it integrates information from our actions and the external context. Probing the visual system during the updating process reveals spatiotemporal distortions, where sequential stimuli appear closer in time and space than they are. These effects occur perisaccadically or when a visual mask follows the stimuli. The study investigated whether non-overlapping visual masks could influence temporal inversion judgments (TOJs), suggesting that a temporal signal might act as an anchor during updating. In Experiment 1, participants judged the temporal order of two stimuli under three conditions: no mask, a full-field mask, or a partial mask avoiding stimuli’s locations. Compared to no mask, both masks triggered TOJs when presented within 30 milliseconds of the second stimulus. In a control experiment, delaying mask onset by 30 milliseconds eliminated the inversion effect. In Experiment 2, TOJs were observed for both ipsilateral and contralateral masks, suggesting that long range inhibitory signals might also contribute to the effect. Together, these findings indicate that temporal inversions can occur with non-overlapping stimuli masks configuration, pointing to a non-spatial signal related to mask timing as the underlying mechanism.
Critical periods support representation learning in a model of cortical processing
Authors: Delrocq Ariane , Wu Zihan , Bellec Guillaume , Gerstner Wulfram 
Published: December 2024

AbstractExposure of the brain to multiple stimuli drives the development of cortical representations, likely controlled by rules of synaptic plasticity. However, the type of developmental plasticity rules that lead to high-level representations of objects are unknown. Here we study a generalized Hebbian plasticity model that includes a predictive component. The learning rule uses only quantities that are locally available at the site of the synapse, is consistent with recent plasticity experiments in pyramidal neurons, and, as opposed to backpropagation learning, does not need a detailed feedback architecture. Our model shows that limiting plasticity in time to critical periods of development improves the quality and stability of sensory representation across different cortical areas described as layers of an artificial neural network. Our model achieves state-of-the-art performance for bio-plausible plasticity models on both an abstract hierarchical object database and a large image dataset designed for unsupervised learning.
Multiomics plasticity in seed traits of pan-genome wheat cultivars
Authors: Bose Utpal , Winkler Jana Barbro , Sorg Elisa , Mitu Shahida A. , Huber Gregor , Koller Robert , Beale David J. , Dawson Amanda L. , Escobar-Correas Sophia , Biswas Bhabananda , Rahman Mohammad M. , Stockwell Sally , Byrne Keren , Broadbent James , Neerukonda Manjusha , Buegger Franz , Sigalas Alexandros , Mayer Klaus F. X. , Schuppan Detlef , Pozniak Curtis , Colgrave Michelle L. , Spannagl Manuel , Juhász Angéla , Schnitzler Jörg-Peter 
Published: December 2024

AbstractThe molecular basis of cultivar-level variations in polyploid wheat that enables environmental adaptation while maintaining yield and quality in polyploid wheat remains poorly understood. We conducted a detailed phenotypic assessment and multiomics analysis of nine pan-genome polyploid wheat cultivars grown under control and drought conditions. We aimed to investigate the subgenome-level variations, cultivar differences and biochemical mechanisms affecting plant fitness under moderate drought stress. Intrinsic water use efficiency, grain yield, and grain protein content and quality differed among cultivars, supporting the plasticity of drought stress responses. Biased proteome and metabolome abundance changes in response to moderate drought stress during the vegetative stage indicate different strategies for the utilization of homeologous protein isoforms assigned to the A, B, and D subgenomes. Drought effects were detected at the protein level, but significant changes were observed in central carbon pathway metabolites and micronutrient profiles. The subgenomic localization of seed storage proteins highlight differences in nutrient reservoir accumulation and emphasizes the enhanced role of S-rich prolamins in the stress response. Subgenomic variations define cultivar phenotypes by producing molecules that accumulate and enable the underlying trade-offs between environmental adaptation and yield- or quality-related traits. These variations can be used to select crops with increased stress resistance without compromising yield.