bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrographic Seizure Characteristics and Electrographic Status Epilepticus Prediction
Authors: Fung France W. , Parikh Darshana S. , Donnelly Maureen , Xiao Rui , Topjian Alexis A. , Abend Nicholas S. 
Published: January 2024

Purpose:
We aimed to characterize electrographic seizures (ES) and electrographic status epilepticus (ESE) and determine whether a model predicting ESE exclusively could effectively guide continuous EEG monitoring (CEEG) utilization in critically ill children.

Methods:
This was a prospective observational study of consecutive critically ill children with encephalopathy who underwent CEEG. We used descriptive statistics to characterize ES and ESE, and we developed a model for ESE prediction.

Results:
ES occurred in 25% of 1,399 subjects. Among subjects with ES, 23% had ESE, including 37% with continuous seizures lasting >30 minutes and 63% with recurrent seizures totaling 30 minutes within a 1-hour epoch. The median onset of ES and ESE occurred 1.8 and 0.18 hours after CEEG initiation, respectively. The optimal model for ESE prediction yielded an area under the receiver operating characteristic curves of 0.81. A cutoff selected to emphasize sensitivity (91%) yielded specificity of 56%. Given the 6% ESE incidence, positive predictive value was 11% and negative predictive value was 99%. If the model were applied to our cohort, then 53% of patients would not undergo CEEG and 8% of patients experiencing ESE would not be identified.

Conclusions:
ESE was common, but most patients with ESE had recurrent brief seizures rather than long individual seizures. A model predicting ESE might only slightly improve CEEG utilization over models aiming to identify patients at risk for ES but would fail to identify some patients with ESE. Models identifying ES might be more advantageous for preventing ES from evolving into ESE.
Small non-coding RNA content in plasma-derived extracellular vesicles distinguish ataxic SCA3 mutation carriers from pre-ataxic and control subjects
Authors: Santana Magda M , Silva Patrick , Pinto Maria M , Gaspar Laetitia , Nobre Rui , Duarte Sónia , Marques Tânia Monteiro , Gama-Carvalho Margarida , Januário Cristina , Cunha Inês , Ribeiro Joana Afonso , Hübener-Schmid Jeannette , Infante Jon , Raposo Mafalda , Lima Manuela , Garcia-Moreno Hector , Giunti Paola , van de Warrenburg Bart , Synofzik Matthis , Faber Jennifer , Klockgether Thomas ,   ESMI Study Group, Pereira de Almeida Luís 
Published: January 2024

AbstractSpinocerebellar ataxia type 3 (SCA3), a neurodegenerative disorder caused by a CAG expansion in theATXN3gene, is the most common spinocerebellar ataxia subtype worldwide. Currently, there is no therapy to stop or prevent disease progression. Promising therapeutic strategies are emerging, but their translation into clinical practice requires sensitive and reliable biomarkers. Blood circulating extracellular vesicles constitute a promising source of biomarkers with potential to track alterations of the central nervous system due to their ability to cross the blood brain barrier.Here, we perform sequencing analysis of small RNAs from plasma-derived extracellular vesicles from SCA3 mutation carriers (10 pre-ataxic and 10 ataxic) and 12 control subjects to identify potential RNA biomarker candidates for this disease.Data showed that plasma-derived extracellular vesicles from ataxic SCA3 mutation carriers are enriched in mitochondrial, nuclear, and nucleolar RNA biotypes compared to pre-ataxic and control subjects. Moreover, ataxic mutation carriers could be discriminated from control and pre-ataxic subjects based on the miRNAs or piRNAs content, but not tRNA. Furthermore, we identified a subset of differentially expressed miRNAs and piRNAs that clearly differentiate ataxic mutation carriers from pre-ataxic and control subjects.These findings open new avenues for further investigation on the role of these RNAs in the pathogenesis of SCA3 and their potential as biomarkers for this disease.
PEMPS: A Phylogenetic Software Tool to Model the Evolution of Metabolic Pathways
Authors: McCloskey Nicholas S. , Mammedova Ayna , Liberles David A. 
Published: January 2024

AbstractBackgroundMetabolic pathways support the enzyme flux that converts input chemicals into energy and cellular building blocks. With a constant rate of input, steady-state flux is achieved when metabolite concentrations and reaction rates remain constant over time. Individual genes undergo mutation, while selection acts on higher level functions of the pathway, such as steady-state flux where applicable. Modeling the evolution of metabolic pathways through mechanistic sets of ordinary differential equations is a piece of the genotype-phenotype map model for interpreting genetic variation and inter-specific differences. Such models can generate distinct compensatory changes and adaptive changes from directional selection, indicating single nucleotide polymorphisms and fixed differences that could affect phenotype. If used for inference, this would ultimately enable detection of selection on metabolic pathways as well as inference of ancestral states for metabolic pathway function.ResultsA software tool for simulating the evolution of metabolic pathways based upon underlying biochemistry, phylogenetics, and evolutionary considerations is presented. The Python program, Phylogenetic Evolution of Metabolic Pathway Simulator (PEMPS), implements a mutation-selection framework to simulate the evolution of the pathway over a phylogeny by interfacing with COPASI to calculate the steady-state flux of the metabolic network, introducing mutations as alterations in parameter values according to a model, and calculating a fitness score and corresponding probability of fixation based on the change in steady-state flux value(s). Results from simulations are consistent witha prioriexpectations of fixation probabilities and systematic change in model parameters.ConclusionsThe PEMPS program simulates the evolution of a metabolic pathway with a mutation-selection modeling framework based on criteria like steady-state flux that is designed to work with SBML-formatted kinetic models, and Newick-formatted phylogenetic trees. The Python software is run on the Linux command line and is available athttps://github.com/nmccloskey/PEMPS.
Antigen-display exosomes provide adjuvant-free protection against SARS-CoV-2 disease at nanogram levels of spike protein
Authors: Guo Chenxu , Sachithanandham Jaiprasath , Zhong William , Craney Morgan , Villano Jason , Pekosz Andrew , Gould Stephen J. 
Published: January 2024

AbstractAs the only bionormal nanovesicle, exosomes have high potential as a nanovesicle for delivering vaccines and therapeutics. We show here that the loading of type-1 membrane proteins into the exosome membrane is induced by exosome membrane anchor domains, EMADs, that maximize protein delivery to the plasma membrane, minimize protein sorting to other compartments, and direct proteins into exosome membranes. Using SARS-CoV-2 spike as an example and EMAD13 as our most effective exosome membrane anchor, we show that cells expressing a spike-EMAD13 fusion protein produced exosomes that carry dense arrays of spike trimers on 50% of all exosomes. Moreover, we find that immunization with spike-EMAD13 exosomes induced strong neutralizing antibody responses and protected hamsters against SARS-CoV-2 disease at doses of just 0.5-5 ng of spike protein, without adjuvant, demonstrating that antigen-display exosomes are particularly immunogenic, with important implications for both structural and expression-dependent vaccines.
Wild bird mass mortalities in eastern Canada associated with the Highly Pathogenic Avian Influenza A(H5N1) virus, 2022
Authors: Avery-Gomm Stephanie , Barychka Tatsiana , English Matthew , Ronconi Robert , Wilhelm Sabina I. , Rail Jean-François , Cormier Tabatha , Beaumont Matthieu , Bowser Campbell , Burt Tori V. , Collins Sydney , Duffy Steven , Giacinti Jolene A. , Gilliland Scott , Giroux Jean-François , Gjerdrum Carina , Guillemette Magella , Hargan Kathryn E. , Jones Megan , Kennedy Andrew , Kusalik Liam , Lair Stéphane , Lang Andrew S. , Lavoie Raphael , Lepage Christine , McPhail Gretchen , Montevecchi William A. , Parsons Glen J. , Provencher Jennifer F. , Rahman Ishraq , Robertson Gregory J. , Seyer Yannick , Soos Catherine , Ward Christopher R. E. , Wells Regina , Wight Jordan 
Published: January 2024

AbstractIn 2022, a severe outbreak of clade 2.3.4.4b Highly Pathogenic Avian Influenza (HPAI) H5N1 virus resulted in unprecedented mortality among wild birds in eastern Canada. Tens of thousands of birds were reported sick or dead, prompting a comprehensive assessment of mortality spanning the breeding season between April 1 and September 30, 2022. Mortality reports were collated from federal, Indigenous, provincial, and municipal agencies, the Canadian Wildlife Health Cooperative, non-governmental organizations, universities, and citizen science platforms. A scenario analysis was conducted to refine mortality estimates, accounting for potential double counts from multiple sources under a range of spatial and temporal overlap. Correcting for double counting, an estimated 40,966 wild birds were reported sick or dead in eastern Canada during the spring and summer of 2022. Seabirds and sea ducks, long-lived species that are slow to recover from perturbations, accounted for 98.7% of reported mortalities. Mortalities were greatest among Northern Gannets(Morus bassanus; 26,193), Common Murres (Uria aalge; 8,133), and American Common Eiders (Somateria mollissima dresseri;1,945), however, these figures underestimate total mortality as they exclude unreported deaths on land and at sea. In addition to presenting mortality estimates, we compare mortalities with known population sizes and trends and make an initial assessment of whether population-level impacts are possible for the Northern Gannet, a species that has suffered significant global mortality, and two harvested species, Common Murre and American Common Eider, to support management decisions. We hypothesize that population-level impacts in eastern Canada are possible for Northern Gannets and American Common Eiders but are unlikely for Common Murres. This study underscores the urgent need for further research to understand the broader ecological ramifications of the HPAI outbreak on wild bird populations.
SanA is an inner membrane protein mediating the early stages of Salmonella infection
Authors: Aleksandrowicz Adrianna , Kolenda Rafał , Thurston Teresa L M , Grzymajło Krzysztof 
Published: January 2024

AbstractBacterial membrane proteins, crucial for the interaction with the environment, encompass various functional molecules such as SanA. SanA is pivotal for the physicochemical properties of the bacterial membrane, influencingSalmonella’s antibiotic resistance and infection phenotype. Previous studies identified a link betweensanAmutation and increasedSalmonellainvasiveness, but the mechanisms underlying this phenomenon remain largely unexplored. Therefore, our research investigates SanA’s role duringSalmonellainfection, examining its expression pattern, localization within the cell, and association withSalmonellaPathogenicity Island I (SPI-I). Using subcellular fractionation and Western Blotting we revealed that SanA is predominantly located in the inner membrane. Additionally, we utilized transcriptional fusion to monitor SanA expression under various environmental conditions. We observed that SanA plays a significant role during the late exponential and early stationary growth phase and remains important 24 hours after the bacteria enter host cells. Moreover, our invasion assays demonstrated that deletion ofsanAin bacteria grown to early stationary phase significantly enhances their invasiveness, partly due to increased SPI-I expression, which is regulated in a nutrient availability-dependent manner. Our results highlight SanA’s essential role inSalmonella’s response to environmental stress, critical for its entry and survival in hostile environments. This research underscores the importance of inner membrane proteins in bacterial pathogenicity, particularly in the initial stages of infection.
Distribution of calbindin-positive neurons across areas and layers of the marmoset cerebral cortex
Authors: Atapour Nafiseh , Rosa Marcello G. P. , Bai Shi , Bednarek Sylwia , Kulesza Agata , Saworska Gabriela , Worthy Katrina H. , Majka Piotr 
Published: January 2024

SummaryThe calcium-binding protein calbindin is selectively expressed in specific neuronal populations of the cerebral cortex, including major classes of inhibitory interneurons. We have charted the distribution of calbindin-positive (CB+) neurons across areas and layers of the entire marmoset cortex using a combination of immunohistochemistry, AI-based image segmentation, 3-dimensional reconstruction, and cytoarchitecture-aware registration. CB+neurons formed 10-20% of the cortical neuronal population, occurring in higher proportions in areas corresponding to low hierarchical levels of processing, such as sensory cortices. Although CB+neurons concentrated in the supragranular layers, there were clear trends in laminar distribution: the relative density in infragranular layers increased with hierarchical level, and the density in layer 4 was lowest in areas involved in sensorimotor integration and action planning. These results reveal new aspects of the cytoarchitectural organization of the primate cortex and demonstrate an efficient approach to mapping the full distribution of neurochemically distinct cell types throughout the brain, readily applicable to most mammalian species and parts of the nervous system.
High-resolution metabolite imaging: luteolinidin accumulates at the host-cyanobiont interface during cold-acclimation inAzollasymbioses
Authors: Güngör Erbil , Bartels Benjamin , Bolchi Giorgio , Heeren Ron M.A. , Ellis Shane R. , Schluepmann Henriette 
Published: January 2024

AbstractAquatic ferns of the genusAzolla(Azolla) form highly productive symbioses with filamentous cyanobacteria fixing N2in their leaf cavities,Nostoc azollae. Stressed symbioses characteristically turn red due to 3-deoxyanthocyanin (DA) accumulation, rare in angiosperms and of unknown function. To reveal DA functions upon cold acclimation and recovery, we integrated laser-desorption-ionization mass-spectrometry-imaging (LDI-MSI), a newA. filiculoidesgenome-assembly and annotation, and dual RNA-sequencing into phenotypic analyses of the symbioses.Azolla sp.Anzali recovered even when cold-induced DA-accumulation was inhibited by abscisic acid. Cyanobacterial filaments generally disappeared upon cold acclimation, andN. azollaetranscript profiles were unlike those of resting stages formed in cold-resistant sporocarps, yet filaments re-appeared in leaf cavities of newly formed green fronds upon cold-recovery.The high transcript accumulation upon cold acclimation ofAfDFR1encoding a flavanone 4-reductase activein vitrosuggested that the enzyme of the first step in the DA-pathway may regulate accumulation of DAs in different tissues. However, LDI-MSI highlighted the necessity to describe metabolite accumulation beyond class assignments as individual DA and caffeoylquinic acid metabolites accumulated differentially. For example, luteolinidin accumulated in epithelial cells, including those lining the leaf cavity, supporting a role for the former in the symbiotic interaction during cold acclimation.Summary statementDuring cold acclimation inAzollasymbioses, individual compounds from the same phenolic class accumulated in different host tissues: luteolinidin associated with biotic interactions at the symbiosis interface whilst apigenidin with photooxidative stress mitigation in the mesophyll.
Neural representations of predicted events: Evidence from time-resolved EEG decoding
Authors: Li Ai-Su , Theeuwes Jan , van Moorselaar Dirk 
Published: January 2024

AbstractThrough statistical learning, humans are able to extract temporal regularities, using the past to predict the future. Evidence suggests that learning relational structures makes it possible to anticipate the imminent future; yet, the neural dynamics of predicting the future and its time-course remain elusive. To examine whether future representations are denoted in a temporally discounted fashion, we used the high-temporal-resolution of electroencephalography (EEG). Observers were exposed to a fixed sequence of events at four unique spatial positions within the display. Using multivariate pattern analyses trained on independent pattern estimators, we were able to decode the spatial position of dots within full sequences, and within randomly intermixed partial sequences wherein only a single dot was presented. Crucially, within these partial sequences, subsequent spatial positions could be reliably decoded at their expected moment in time. These findings highlight the dynamic weight changes within the assumed spatial priority map and mark the first implementation of EEG to decode predicted, yet critically omitted events.Impact statementUtilizing high-temporal-resolution EEG, the dynamic weight changes of assumed spatial priority map were visualized by decoding the spatial position of expected, yet omitted, events at their expected moment in time.
Surface colonization byFlavobacterium johnsoniaepromotes its survival in a model microbial community
Authors: Magesh Shruthi , Hurley Amanda I. , Nepper Julia F. , Chevrette Marc G. , Schrope Jonathan H. , Li Chao , Beebe David J. , Handelsman Jo 
Published: January 2024

ABSTRACTFlavobacterium johnsoniaeis a ubiquitous soil and rhizosphere bacterium, but despite its abundance, the factors contributing to its success in communities are poorly understood. Using a model microbial community,TheHitchhikersOf the Rhizosphere (THOR), we determined the effects of colonization on fitness ofF. johnsoniaein the community. Insertion sequencing (INSeq), a massively parallel transposon mutant screen, on sterile sand identified 25 genes likely to be important for surface colonization. We constructed in-frame deletions of nine candidate genes predicted to be involved in cell membrane biogenesis, motility, signal transduction, and transport of amino acids and lipids. All mutants poorly colonized sand, glass, and polystyrene and produced less biofilm than the wild type, indicating the importance of the targeted genes in surface colonization. Eight of the nine colonization-defective mutants were also unable to form motile biofilms, or zorbs, thereby suggesting that the affected genes play a role in group movement and linking stationary and motile biofilm formation genetically. Furthermore, we showed that deletion of colonization genes inF. johnsoniaeaffected its behavior and survival in THOR on surfaces, suggesting that the same traits are required for success in a multispecies microbial community. Our results provide insight into the mechanisms of surface colonization byF. johnsoniaeand form the basis for further understanding its ecology in the rhizosphere.IMPORTANCEMicrobial communities direct key environmental processes through multispecies interactions. Understanding these interactions is vital for manipulating microbiomes to promote health in human, environmental, and agricultural systems. However, microbiome complexity can hinder our understanding of the underlying mechanisms in microbial community interactions. As a first step towards unraveling these interactions, we explored the role of surface colonization in microbial community interactions using THOR, a genetically tractable model community of three bacterial species,Flavobacterium johnsoniae,Pseudomonas koreensis,andBacillus cereus.We identifiedF. johnsoniaegenes important for surface colonization in solitary conditions and in the THOR community. Understanding the mechanisms that promote success of bacteria in microbial communities brings us closer to targeted manipulations to achieve outcomes that benefit agriculture, the environment, and human health.
Macrophages drive the earliest anti-tumoral response to BCG therapy by directly killing bladder cancer through TNF signaling
Authors: Martinez-Lopez Mayra , de Almeida Cátia Rebelo , Fontes Marcia , Mendes Raquel Valente , Kaufmann Stefan H.E. , Fior Rita 
Published: January 2024

ABSTRACTThe Bacillus Calmette-Guérin (BCG) vaccine is the cancer immunotherapy longest in use. Despite its effectiveness in bladder cancer (BC), its initial mechanisms of action remain largely unknown. Therefore, proper diagnostic assessments to identify patients who will not respond to treatment or develop resistance are lacking. Here, we set-out to unravel the earliest innate cellular mechanisms involved in BCG-induced clearance of tumors. We show that BCG induces a massive recruitment of macrophages to the tumor microenvironment and modulates their morphology and behavior towards a proinflammatory phenotype, while also promoting macrophage fusion-like events. We demonstrate that macrophages directly induce apoptosis and clearance of cancer cells through TNF-signaling and that they are indispensable for this antitumoral response since their depletion completely abrogates the BCG-anti tumor effect. Contrary to the general concept that macrophage antitumoral activities uniquely rely on stimulating an effective adaptive response, we demonstrate that macrophages alone can directly induce tumor killing and clearance; revealing an additional step to the BCG-induced tumor immunity model, that was not previously considered. In addition, we also provide proof-of-concept experiments demonstrating the potential of this uniquein vivopreclinical model to test new innate immunomodulators.
The vitals for steady nucleation maps of spontaneous spiking coherence in autonomous two-dimensional neuronal networks
Authors: Zendrikov Dmitrii , Paraskevov Alexander 
Published: January 2024

AbstractThin pancake-like neuronal networks cultured on top of a planar microelectrode array have been extensively tried out in neuroengineering, as a substrate for the mobile robot’s control unit, i.e., as a cyborg’s brain. Most of these attempts failed due to intricate self-organizing dynamics in the neuronal systems. In particular, the networks may exhibit an emergent spatial map of steady nucleation sites (“n-sites”) of spontaneous population spikes. Being unpredictable and independent of the surface electrode locations, the n-sites drastically change local ability of the network to generate spikes. Here, using a spiking neuronal network model with generative spatiallyembedded connectome, we systematically show in simulations that the number, location, and relative activity of spontaneously formed n-sites (“the vitals”) crucially depend on the samplings of three distributions: 1) the network distribution of neuronal excitability, 2) the distribution of connections between neurons of the network, and 3) the distribution of maximal amplitudes of a single synaptic current pulse. Moreover, blocking the dynamics of a small fraction (about 4%) of non-pacemaker neurons having the highest excitability was enough to completely suppress the occurrence of population spikes and their n-sites. This key result is explained theoretically. Remarkably, the n-sites occur taking into account only short-term synaptic plasticity, i.e., without a Hebbian-type plasticity. As the spiking network model used in this study is strictly deterministic, all simulation results can be accurately reproduced. The model, which has already demonstrated a very high richness-to-complexity ratio, can also be directly extended into the three-dimensional case, e.g., for targeting peculiarities of spiking dynamics in cerebral (or brain) organoids. We recommend the model as an excellent illustrative tool for teaching network-level computational neuroscience, complementing a few benchmark models.