bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective validation of a seizure diary forecasting falls short
Authors: Goldenholz Daniel M. , Eccleston Celena , Moss Robert , Westover M. Brandon 
Published: January 2024

AbstractOBJECTIVERecently, a deep learning AI model forecasted seizure risk using retrospective seizure diaries with higher accuracy than random forecasts. The present study sought to prospectively evaluate the same algorithm.METHODSWe recruited a prospective cohort of 46 people with epilepsy; 25 completed sufficient data entry for analysis (median 5 months). We used the same AI method as in our prior study. Group-level and individual-level Brier Skill Scores (BSS) compared random forecasts and simple moving average forecasts to the AI.RESULTSThe AI had an AUC of 0.82. At the group level, the AI outperformed random forecasting (BSS=0.53). At the individual level, AI outperformed random in 28% of cases. At the group and individual level, the moving average outperformed the AI. If pre-enrollment (non-verified) diaries (with presumed under-reporting) were included, the AI significantly outperformed both comparators. Surveys showed most did not mind poor quality LOW-RISK or HIGH-RISK forecasts, yet 91% wanted access to these forecasts.SIGNIFICANCEThe previously developed AI forecasting tool did not outperform a very simple moving average forecasting this prospective cohort, suggesting that the AI model should be replaced.Key pointsA previously developed e-diary based AI seizure forecasting tool was prospectively tested. Although by some metrics the tool was successful, the overall AI performance was unacceptably low.It was much easier to outperform a random forecast; it was much harder to outperform a moving average forecast.Using unverified diaries can skew forecasting metrics in favor of underperforming tools.
Neural Network-Assisted Humanization of COVID-19 Hamster scRNAseq Data Reveals Matching Severity States in Human Disease
Authors: Friedrich Vincent D , Pennitz Peter , Wyler Emanuel , Adler Julia M , Postmus Dylan , Alves Luiz Gustavo Teixeira , Prigann Julia , Pott Fabian , Vladimirova Daria , Hoefler Thomas , Goekeri Cengiz , Landthaler Markus , Goffinet Christine , Saliba Antoine-Emmanuel , Scholz Markus , Witzenrath Martin , Trimpert Jakob , Kirsten Holger , Nouailles Geraldine 
Published: January 2024

AbstractTranslating findings from animal models to human disease is essential for dissecting disease mechanisms, developing and testing precise therapeutic strategies. The coronavirus disease 2019 (COVID-19) pandemic has highlighted this need, particularly for models showing disease severity-dependent immune responses. Single-cell transcriptomics (scRNAseq) is well poised to reveal similarities and differences between species at the molecular and cellular level with unprecedented resolution. However, computational methods enabling detailed matching are still scarce. Here, we provide a structured scRNAseq-based approach that we applied to scRNAseq from blood leukocytes originating from humans and hamsters affected with moderate or severe COVID-19. Integration of COVID-19 patient data with two hamster models that develop moderate (Syrian hamster,Mesocricetus auratus) or severe (Roborovski hamster,Phodopus roborovskii) disease revealed that most cellular states are shared across species. A neural network-based analysis using variational autoencoders quantified the overall transcriptomic similarity across species and severity levels, showing highest similarity between neutrophils of Roborovski hamsters and severe COVID-19 patients, while Syrian hamsters better matched patients with moderate disease, particularly in classical monocytes. We further used transcriptome-wide differential expression analysis to identify which disease stages and cell types display strongest transcriptional changes. Consistently, hamster’s response to COVID-19 was most similar to humans in monocytes and neutrophils. Disease-linked pathways found in all species specifically related to interferon response or inhibition of viral replication. Analysis of candidate genes and signatures supported the results. Our structured neural network-supported workflow could be applied to other diseases, allowing better identification of suitable animal models with similar pathomechanisms across species.Key PointsNeural networks can successfully match disease states between animal models and humans using single-cell data as shown for COVID-19Moderately diseased patients best matched Syrian hamster cells; severely diseased patients best matched Roborovski hamster neutrophils
Analgesic targets identified in mouse sensory neuron somata and terminal pain translatomes
Authors: Bangash M. Ali , Cubuk Cankut , Iseppon Federico , Haroun Rayan , Luiz Ana P. , Arcangeletti Manuel , Gossage Samuel J. , Santana-Varela Sonia , Cox James J. , Lewis Myles J. , Wood John N. , Zhao Jing 
Published: January 2024

AbstractThe relationship between transcription and protein expression is complex. We identified polysome-associated RNA transcripts in the somata and central terminals of mouse sensory neurons in control, painful (+ Nerve Growth Factor (NGF)) and pain-free conditions (Nav1.7 null mice). The majority (98%) of translated transcripts are shared between male and female mice in both the somata and terminals. Some transcripts are highly enriched in the somata or terminals. Changes in the translatome in painful and pain-free conditions include novel and known regulators of pain pathways. Antisense knockdown of selected somatic and terminal polysome-associated transcripts that correlate with pain states diminished pain behaviour. Terminal-enriched transcripts encoding synaptic proteins (e.g. Synaptotagmin), non-coding RNAs, transcription factors (e.g. Znf431), proteins associated with trans-synaptic trafficking (HoxC9), GABA generating enzymes (Gad1 and Gad2) and neuropeptides (Penk). Thus, central terminal translation may well be a significant regulatory locus for peripheral input from sensory neurons.
EMG-to-torque models for exoskeleton assistance: a framework for the evaluation ofin situcalibration
Authors: Quesada Lucas , Verdel Dorian , Bruneau Olivier , Berret Bastien , Amorim Michel-Ange , Vignais Nicolas 
Published: January 2024

AbstractIn the field of robotic exoskeleton control, it is critical to accurately predict the intention of the user. While surface electromyography (EMG) holds the potential for such precision, current limitations arise from the absence of robust EMG-to-torque model calibration procedures and a universally accepted model. This paper introduces a practical framework for calibrating and evaluating EMG-to-torque models, accompanied by a novel nonlinear model. The framework includes anin situprocedure that involves generating calibration trajectories and subsequently evaluating them using standardized criteria. A comprehensive assessment on a dataset with 17 participants, encompassing single-joint and multi-joint conditions, suggests that the novel model outperforms the others in terms of accuracy while conserving computational efficiency. This contribution introduces an efficient model and establishes a versatile framework for EMG-to-torque model calibration and evaluation, complemented by a dataset made available. This further lays the groundwork for future advancements in EMG-based exoskeleton control and human intent detection. This work has been submitted to the IEEE for possible publication. Copyright may be transferred without notice, after which this version may no longer be accessible.
Response-locked theta dissociations reveal potential feedback signal following successful retrieval
Authors: Smith Devyn E. , Wheelock Justin R. , Long Nicole M. 
Published: January 2024

AbstractSuccessful memory retrieval relies on memory processes to access an internal representation and decision processes to evaluate and respond to the accessed representation, both of which are supported by fluctuations in theta (4-8Hz) activity. However, the extent to which decision making processes are engaged following a memory response is unclear. Here, we recorded scalp electroencephalography (EEG) while human participants performed a recognition memory task. We focused on response-locked data, allowing us to investigate the processes that occur prior to and following a memory response. We replicate previous work and find that prior to a memory response theta power is greater for identification of previously studied items (hits) relative to rejection of novel lures (correct rejections; CRs). Following the memory response, the theta power dissociation ‘flips’ whereby theta power is greater for CRs relative to hits. We find that the post-response ‘flip’ is more robust for hits that are committed quickly, potentially reflecting a positive feedback signal for strongly remembered experiences. Our findings suggest that there are potentially distinct processes occurring before and after a memory response that are modulated by successful memory retrieval.
Erroneous compensation for long-latency feedback delays as origin of Essential Tremor Running title: Erroneous delay compensation as origin of ET
Authors: Blondiaux Florence , Colmant Lise , Lebrun Louisien , Hanseeuw Bernard , Crevecoeur Frédéric 
Published: January 2024

AbstractEssential tremor (ET), a movement disorder characterized by involuntary oscillations of the limbs during movement, remains to date not well understood. It has been recently suggested that the tremor originates from impaired delay compensation, affecting movement representation and online control. Here we tested this hypothesis directly with ET patients (N=24) and neurologically intact (NI) volunteers (N=28) in an upper limb postural perturbation task. After maintaining their hand in a visual target, participants experienced perturbations of unpredictable direction and magnitude, and were instructed to counter the perturbation and steer their hand back to the starting position. In comparison with NI volunteers, ET patients’ early muscular responses (Short and Long-Latency Responses, 20-50 ms and 50-100 ms respectively) were preserved or even slightly increased. However, they exhibited perturbation-dependent deficits when stopping and stabilizing their hand in the final target supporting the hypothesis that the tremor was generated by the feedback controller. We show in a computational model that errors in delay compensation accumulating over time produced the same small increase in initial feedback response followed by oscillations that scaled with the perturbation magnitude as observed in ET population. Our experimental results therefore validate the computational hypothesis that inaccurate delay compensation in long-latency pathways could be the origin of the tremor.Significance StatementEssential Tremor origin remains poorly understood. In the present study, we focused on motor impairments associated with feedback control. Following a mechanical perturbation applied to their arm, patients’ short and initial long-latency stretch responses were preserved. However, we observed clear impairments during the stabilization phase that scaled with the perturbation magnitude. These results were reproduced in a computational model where delay compensation was inaccurate, suggesting that the origin of the tremor may lie in an underestimation of the delays impacting the internal monitoring of the motor commands.Conflict of interestThe authors declare no competing financial interests.
Subtle, but Perceptible, Sexual Dichromatism and Disassortative Mating Based on Plumage Reflectance in Black Terns (Chlidonias niger)
Authors: Baldassarre Daniel T. , Davis Kristina M. , Shealer David A. 
Published: January 2024

AbstractIn birds, sexual selection on plumage often leads to sexual dichromatism and male ornamentation. However, even in drab species with no obvious sexual dichromatism, both sexes may still use plumage for mate choice. A previous study found weak sexual size dimorphism in North American Black Terns (Chlidonias niger surinamensis), but no assortative mating based on morphology. However, the relevance of plumage variation to mate choice is yet untested. Here, using reflectance spectrometry and avian visual modeling revealed that Black Tern males and females exhibited a subtle but significant difference in brightness (males darker). Importantly, the achromatic contrast between the sexes should be perceptible during mate choice. Moreover, there was evidence of disassortative mating for plumage color, but not brightness: more black and saturated birds paired with more gray and unsaturated birds. There was no relationship between plumage color or brightness and body mass. This finding suggests that visual signals unrelated to body condition may be relevant to Black Tern mate choice. The pattern of disassortative mating was unexpected, and potential benefits of choosing a mate dissimilar from oneself are discussed. This study highlights the importance of considering the avian visual system when studying plumage variation elusive to human observers.
RiboGraph: An interactive visualization system for ribosome profiling data at read length resolution
Authors: Chacko Jonathan , Ozadam Hakan , Cenik Can 
Published: January 2024

AbstractSummaryRibosome profiling is a widely-used technique for measuring ribosome occupancy at nucleotide resolution. However, the need to analyze this data at nucleotide resolution introduces unique challenges in data visualization and analyses. In this study, we introduce RiboGraph, a dedicated visualization tool designed to work with .ribo files, a specialized and efficient format for ribosome occupancy data. Unlike existing solutions that rely on large alignment files and time-consuming preprocessing steps, RiboGraph operates on a purpose designed compact file type and eliminates the need for data preprocessing. This efficiency allows for interactive, real-time visualization at ribosome-protected fragment length resolution. By providing an integrated toolset, RiboGraph empowers researchers to conduct comprehensive visual analysis of ribosome occupancy data.Availability and ImplementationSource code, step-by-step installation instructions and links to documentation are available on GitHub:https://github.com/ribosomeprofiling/ribograph. On the same page, we provide test files and a step-by-step tutorial highlighting the key features of RiboGraph.
Timing and Amplitude of Catch-up Saccades to Accelerating Targets
Authors: Doré Sydney , Coutinho Jonathan , Brooks Emma , Khan Aarlenne Z , Lefèvre Philippe , Blohm Gunnar 
Published: January 2024

AbstractTo track moving targets, humans move their eyes using both saccades and smooth pursuit. If pursuit eye movements fail to accurately track the moving target, catch-up saccades are initiated to rectify the tracking error. It is well known that retinal position and velocity errors determine saccade timing and amplitude, but the extent to which retinal acceleration error influences these aspects is not well quantified. To test this, 13 adult human participants performed an experiment where they pursued accelerating / decelerating targets. During ongoing pursuit, we introduced a randomly sized target step to evoke a catch-up saccade and analyzed its timing and amplitude. We observed that retinal acceleration error was a statistically significant predictor of saccade amplitude and timing. A multiple linear regression supported our hypothesis that retinal acceleration errors influence saccade amplitude in addition to the influence of retinal position and velocity errors. We also found that saccade latencies were shorter when retinal acceleration error increased the tracking error and vice versa. In summary, our findings support a model in which retinal acceleration error is used to compute a predicted position error ∼100ms into the future to trigger saccades and determine saccade amplitude.Significance statementWhen visually tracking object motion, humans combine smooth pursuit and saccadic eye movements to maintain the target image on the fovea. Retinal position and velocity errors are known to determine catch-up saccade amplitude and timing, however it is unknown if retinal acceleration error is also used to predict future target position. This study provides evidence of a small but statistically significant contribution of retinal acceleration error in determining saccade amplitude and timing.
A mass cytometry approach to track the evolution of T cell responses during infection and immunotherapy by paired T cell receptor repertoire and T cell differentiation state analysis
Authors: Castillo Jesse Garcia , DeBarge Rachel , Mende Abigail , Tenvooren Iliana , Marquez Diana M. , Straub Adrian , Busch Dirk H. , Spitzer Matthew H. , DuPage Michel 
Published: January 2024

AbstractT cell receptor (TCR) recognition followed by clonal expansion is a fundamental feature of adaptive immune responses. Here, we developed a mass cytometric (CyTOF) approach combining antibodies specific for different TCR Vα– and Vβ-chains with antibodies against T cell activation and differentiation proteins to identify antigen-specific expansions of T cell subsets and assess aspects of cellular function. This strategy allowed for the identification of expansions of specific Vβ and Vα chain expressing CD8+and CD4+T cells with varying differentiation states in response toListeria monocytogenes, tumors, and respiratory influenza infection. Expanded Vβ chain expressing T cells could be directly linked to the recognition of specific antigens fromListeria, tumor cells, or influenza. In the setting of influenza infection, we showed that the common therapeutic approaches of intramuscular vaccination or convalescent serum transfer altered the clonal diversity and differentiation state of responding T cells. Thus, we present a new method to monitor broad changes in TCR specificity paired with T cell differentiation during adaptive immune responses.
Incorporating temporal information during feature engineering bolsters emulation of spatio-temporal emergence
Authors: Cain Jason Y. , Evarts Jacob I. , Yu Jessica S. , Bagheri Neda 
Published: January 2024

AbstractMotivationEmergent biological dynamics derive from the evolution of lower-level spatial and temporal processes. A long-standing challenge for scientists and engineers is identifying simple low-level rules that give rise to complex higher-level dynamics. High-resolution biological data acquisition enables this identification and has evolved at a rapid pace for both experimental and computational approaches. Simultaneously harnessing the resolution and managing the expense of emerging technologies—e.g. live cell imaging, scRNAseq, agent-based models—requires a deeper understanding of how spatial and temporal axes impact biological systems. Effective emulation is a promising solution to manage the expense of increasingly complex high-resolution computational models. In this research, we focus on the emulation of a tumor microenvironment agent-based model to examine the relationship between spatial and temporal environment features, and emergent tumor properties.ResultsDespite significant feature engineering, we find limited predictive capacity of tumor properties from initial system representations. However, incorporating temporal information derived from intermediate simulation states dramatically improves the predictive performance of machine learning models. We train a deep-learning emulator on intermediate simulation states and observe promising enhancements over emulators trained solely on initial conditions. Our results underscore the importance of incorporating temporal information in the evaluation of spatio-temporal emergent behavior. Nevertheless, the emulators exhibit inconsistent performance, suggesting that the underlying model characterizes unique cell populations dynamics that are not easily replaced.AvailabilityAll source codes for the agent-based model, emulation, and analyses are publicly available atgithub.com/bagherilab/ARCADE,github.com/bagherilab/emulation, andgithub.com/bagherilab/emulation_analysis, respectively.Contactnbagheri@uw.edu
Secreted Particle Information Transfer (SPIT) – A Cellular Platform forIn VivoGenetic Engineering
Authors: Charlesworth Carsten T. , Homma Shota , Suchy Fabian , Wang Sicong , Bhadhury Joydeep , Amaya Anais K. , Camarena Joab , Zhang Jinyu , Tan Tze Kai , Igarishi Kyomi , Nakauchi Hiromitsu 
Published: January 2024

ABSTRACTA multitude of tools now exist that allow us to precisely manipulate the human genome in a myriad of different ways. However, successful delivery of these tools to the cells of human patients remains a major barrier to their clinical implementation. Here we introduce a new cellular approach forin vivogenetic engineering,SecretedParticleInformationTransfer (SPIT) that utilizes human cells as delivery vectors forin vivogenetic engineering. We demonstrate the application of SPIT for cell-cell delivery of Cre recombinase and CRISPR-Cas9 enzymes, we show that genetic logic can be incorporated into SPIT and present the first demonstration of human cells as a delivery platform forin vivogenetic engineering in immunocompetent mice. We successfully applied SPIT to genetically modify multiple organs and tissue stem cellsin vivoincluding the liver, spleen, intestines, peripheral blood, and bone marrow. We anticipate that by harnessing the large packaging capacity of a human cell’s nucleus, the ability of human cells to engraft into patients’ long term and the capacity of human cells for complex genetic programming, that SPIT will become a paradigm shifting approach forin vivogenetic engineering.
Morphologically defined substages of tail morphogenesis inC. elegansmales
Authors: Kiontke Karin , Fernandez Porfirio , Woronik Alyssa , Fitch David H. A. 
Published: January 2024

AbstractBackgroundSex-specific morphogenesis occurs inC. elegansin the vulva of the hermaphrodite and in the male tail during the last larval stage. Temporal progression of vulva morphogenesis has been described in fine detail. However, a similar precise description of male tail morphogenesis was lacking.ResultsWe here describe morphogenesis of the male tail at time points matching vulva development with special focus on morphogenesis of the tail tip. Using fluorescent reporters, we follow changes in cell shapes, cell fusions, nuclear migration, modifications in the basement membrane and formation of a new apical extracellular matrix at the end of the tail.ConclusionOur analysis answers two open questions about tail tip morphogenesis (TTM) by showing that one of the four tail tip cells, hyp11, remains separate while the other cells fuse with each other and with two additional tail cells to form a ventral tail syncytium. This fusion begins early during TTM but is only completed towards the end of the process. This work provides a framework for future investigations of cell-biological factors that drive male tail morphogenesis.