bluuebunny/crossref_metadata_2025_split huggingface dataset:
What are wereallydecoding? Unveiling biases in EEG-based decoding of the spatial focus of auditory attention
Authors: Rotaru Iustina , Geirnaert Simon , Heintz Nicolas , Van de Ryck Iris , Bertrand Alexander , Francart Tom 
Published: July 2023

AbstractObjectiveSpatial auditory attention decoding (Sp-AAD) refers to the task of identifying the direction of the speaker to which a person is attending in a multi-talker setting, based on the listener’s neural recordings, e.g., electroencephalography (EEG). The goal of this study is to thoroughly investigate potential biases when training such Sp-AAD decoders on EEG data, particularly eye-gaze biases and latent trial-dependent confounds, which may result in Sp-AAD models that decode eye-gaze or trial-specific fingerprints rather than spatial auditory attention.ApproachWe designed a two-speaker audiovisual Sp-AAD protocol in which the spatial auditory and visual attention were enforced to be either congruent or incongruent, and we recorded EEG data from sixteen participants undergoing several trials recorded at distinct timepoints. We trained a simple linear model for Sp-AAD based on common spatial patterns (CSP) filters in combination with either linear discriminant analysis (LDA) or k-means clustering, and evaluated them both across- and within-trial.Main resultsWe found that even a simple linear Sp-AAD model is susceptible to overfitting to confounding signal patterns such as eye-gaze and trial fingerprints (e.g., due to feature shifts across trials), resulting in artificially high decoding accuracies. Furthermore, we found that changes in the EEG signal statistics across trials deteriorate the trial generalization of the classifier, even when the latter is retrained on the test trial with an unsupervised algorithm.SignificanceCollectively, our findings confirm that there exist subtle biases and confounds that can strongly interfere with the decoding of spatial auditory attention from EEG. It is expected that more complicated non-linear models based on deep neural networks, which are often used for Sp-AAD, are even more vulnerable to such biases. Future work should perform experiments and model evaluations that avoid and/or control for such biases in Sp-AAD tasks.
A jump-driven self-exciting stochastic fish migration model and its fisheries applications
Authors: Yoshioka Hidekazu , Yamazaki Kazutoshi 
Published: July 2023

ABSTRACTWe introduce a stochastic continuous-time model via a self-exciting process with jumps to describe a seasonal migration event of diadromous fish. The dynamics of the stored population at a point in a river, waiting for their upward migration, increases by the inflow from the downstream/ocean and decreases by the outflow due to their upstream migration. The inflow is assumed to occur at a constant rate until an Erlang-distributed termination time. The outflow is modeled by a self-exciting jump process to incorporate the flocking and social interactions in fish migration. Harvested cases are also studied for fisheries applications. We derive the backward Kolmogorov equations and the associated finite-difference method to compute various performance indices including the mean migration period and harvested populations. Detailed numerical and sensitivity analysis are conducted to study the spring upstream migration of the diadromous AyuPlecoglossus altivelis altivelis.
Solid tumor-on-chip model for efficacy and safety assessment of CAR-T cell therapy
Authors: Maulana Tengku Ibrahim , Teufel Claudia , Cipriano Madalena , Lazarevski Lisa , van den Hil Francijna E. , Orlova Valeria , Koch André , Alb Miriam , Hudecek Michael , Loskill Peter 
Published: July 2023

ABSTRACTThe non-clinical assessment of CAR-T cells demands innovative models that are capable of predicting safety and efficacy in the clinical setting. Here, we present a novel solid tumor-on-chip model that allows CAR-T cell perfusion and integrates the vasculature and tumor lesions to recapitulate key events of CAR-T cell performance including extravasation, tumor infiltration and cytokine release. We assessed CAR-T cells targeting the ROR1 antigen against tumor aggregates that were derived from a breast cancer cell line and primary breast cancer organoids. The data show the temporal kinetic of ROR1 CAR-T cell migration and expansion, lytic activity and cytokine production over the course of 8 days, and reveal a correlation between anti-tumor efficacy and ROR1 antigen density on tumor cells. CAR-modified T cells extravasated faster, infiltrated tumor lesions stronger, persisted longer and in higher numbers than non-CAR modified T cells. Intriguingly, we detected cytokine release levels and kinetics typically observed in patients who developed cytokine release syndrome, and administered dasatinib as a pharmacologic OFF switch to control this inflammatory response. The data illustrate the ability of this tumor-on-chip platform to assess parameters associated withherapeutic outcome and the potential to aid in patient stratification and monitoring of CAR-T cell therapy.
Accurately identifying nucleic-acid-binding sites through geometric graph learning on language model predicted structures
Authors: Song Yidong , Yuan Qianmu , Zhao Huiying , Yang Yuedong 
Published: July 2023

AbstractThe interactions between nucleic acids and proteins are important in diverse biological processes. The high-quality prediction of nucleic-acid-binding sites continues to pose a significant challenge. Presently, the predictive efficacy of sequence-based methods is constrained by their exclusive consideration of sequence context information, whereas structure-based methods are unsuitable for proteins lacKing Known tertiary structures. Though protein structures predicted by AlphaFold2 could be used, the extensive computing requirement of AlphaFold2 hinders its use for genome-wide applications. Based on the recent breaKthrough of ESMFold for fast prediction of protein structures, we have developed GLMSite, which accurately identifies DNA and RNA-binding sites using geometric graph learning on ESMFold predicted structures. Here, the predicted protein structures are employed to construct protein structural graph with residues as nodes and spatially neighboring residue pairs for edges. The node representations are further enhanced through the pre-trained language model ProtTrans. The networK was trained using a geometric vector perceptron, and the geometric embeddings were subsequently fed into a common networK to acquire common binding characteristics. Then two fully connected layers were employed to learn specific binding patterns for DNA and RNA, respectively. Through comprehensive tests on DNA/RNA benchmarK datasets, GLMSite was shown to surpass the latest sequence-based methods and be comparable with structure-based methods. Moreover, the prediction was shown useful for the inference of nucleic-acid-binding proteins, demonstrating its potential for protein function discovery. The datasets, codes, together with trained models are available athttps://github.com/biomed-AI/nucleic-acid-binding.
Predicting Disease-gene Associations through Self-supervised Mutual Infomax Graph Convolution Network
Authors: Xie Jiancong , Rao Jiahua , Xie Junjie , Yang Yuedong 
Published: July 2023

AbstractIlluminating associations between diseases and genes can help reveal the pathogenesis of syndromes and contributes to treatments, but a large number of associations still remained unexplored. To identify novel disease-gene association, many computational methods have been developed using disease and gene related prior knowledge. However, these methods remain of relatively inferior performance due to the limited external data sources and the inevitable noise among the prior knowledge. In this study, we have developed a new method, Self-Supervised Mutual Infomax Graph Convolution Network (MiGCN), to predict disease-gene associations under the guidance of external disease-disease and gene-gene collaborative graphs. The noises within the collaborative graphs were eliminated by maximizing the mutual information between nodes and neighbors through a graphical mutual infomax layer. In parallel, the node interactions were strengthened by a novel informative message passing layer to improve the learning ability of graph neural network. The extensive experiments showed that our model achieves performance improvement over the state-of-art method by more than 8% on AUC. The datasets, source codes and trained models of MiGCN are available athttps://github.com/biomed-AI/MiGCN.
N-acetylcysteine and acetyl-L-carnitine did not prevent acute PTZ-induced seizure in adult and larvae zebrafish
Authors: Chitolina Rafael , Reis Carlos G. , Stahlhofer-Buss Thailana , Linazzi Amanda , Benvenutti Radharani , Marcon Matheus , Herrmann Ana P. , Piato Angelo 
Published: July 2023

AbstractEpilepsy is a prevalent neurological disorder, affecting approximately 1 to 2% of the global population. The hallmark of epilepsy is the occurrence of epileptic seizures, which are characterized by predictable behavioral changes reflecting the underlying neural mechanisms of the disease. Unfortunately, around 30% of patients do not respond to the current available pharmacological treatments. Consequently, it is crucial to explore alternative therapeutic options for managing these seizures. Two potential candidates for attenuating seizures are N-acetylcysteine (NAC) and Acetyl-L-carnitine (ALC), as they have shown promising neuroprotective effects through the modulation of the neurotransmitter glutamate. Therefore, this study aims to assess the effects of varying concentrations (0.1, 1.0, and 10 mg/L) of NAC and ALC on acute PTZ-induced seizures in zebrafish, in both adult and larval stages. The evaluation of behavioral parameters such as seizure intensity and latency to the crisis can provide insights into the efficacy of these substances. However, our results indicate that both drugs at any of the tested concentrations were not able to reduce PTZ-induced epileptic seizures. On the other hand, the administration of diazepam demonstrated a notable reduction in seizure intensity and an increase in latencies to higher scores of epileptic seizures. Consequently, we conclude that, under the conditions employed in this study, NAC and ALC do not exhibit any significant effects on acute seizures in zebrafish.
Day and night posture of the bluegill sunfish (Lepomis macrochirus)
Authors: Fath Michael , Tytell Eric D. 
Published: July 2023

AbstractMany animals assume characteristic postures when resting or sleeping. These postures are often stable and can be maintained passively, thus reducing the energy cost for maintaining an unstable posture. For example, many tetrapods lay prone on the ground and some negatively buoyant fishes are also able to rest on the substrate. Other fishes rest suspended in the water column. Counterintuitively, hovering this way can be of similar energetic cost to swimming. Even if the fish is perfectly neutrally buoyant, any displacement between its center of mass and center of buoyancy will produce destabilizing pitching torques that the fish must constantly work to counteract if they wish to maintain that posture. We hypothesized that a neutrally buoyant fish could rest at an equilibrium – a posture at which no destabilizing torques are produced by the body --to minimize the metabolic costs associated with hovering. Specifically, we studied the bluegill sunfish (Lepomis macrochirus), which is unstable in a horizontal posture. However, by pitching their bodies up or down they may be able to attain a less costly equilibrium posture, one which vertically aligns their center of mass and center of buoyancy. To test this hypothesis, we measured pitch angle of bluegill over the course of 24 hours. We also measured the pitch angles of the body that correspond to stable and unstable equilibria. We found that the stable equilibrium was a belly-up posture, and the unstable equilibrium is a dorsal side up posture pitched 53±26° head-down. The fish rested at a head-down pitch of -10.7±0.4° degrees, which is significantly steeper than the average pitch during the day of -3.4±0.8° degrees head down. These results show that bluegill do not rest at unstable or stable equilibrium. However, they do rest closer to unstable equilibrium at night than during the day. This may allow them to decrease destabilizing torques generated from the relative locations of the COM and COB while maintaining maneuverability.
Chemo-Mechanical Regulation of Tau Phosphorylation Following Traumatic Brain Injuries
Authors: Kant Aayush , Medhekar Nikhil V. , Bhandakkar Tanmay K. 
Published: July 2023

AbstractTraumatic brain injuries are characterized by damage to axonal cytoskeletal proteins. Here, we present a mathematical model predicting the chemo-mechanical disruption of intra-axonal micro-tubule assembly in terms of hyperphosphorylation-led dysfunction of tubulin-binding tau proteins. Intracellular calcium accumulation following a trauma leads to calpain activation, disturbing the downstream kinase-phosphatase activity balance which causes tau hyperphosphorylation. We develop a computational framework, using finite element methods, predicting the spatiotemporal evolution of mechanical stress and ensuing tau hyperphosphorylation in the human brain after traumatic brain injury-inducing loads. We compare our predictions with previously reported experimental and clinical observations to validate the model. Our model provides important insights into the secondary effects of traumatic brain injuries and can be essential in their clinical management.
Origin and diversity ofCapsella bursa-pastorisfrom the genomic point view
Authors: Penin Aleksey A. , Kasianov Artem S. , Klepikova Anna V. , Omelchenko Denis O. , Makarenko Maksim S. , Logacheva Maria D. 
Published: July 2023

AbstractBackgroundCapsella bursa-pastoris, a cosmopolitan weed of hybrid origin, is an emerging model object for the study of early consequences of polyploidy, being a fast growing annual and a close relative ofArabidopsis thaliana. The development of this model is hampered by the absence of a reference genome sequence.Resultswe present here a subgenome-resolved chromosome-scale assembly and a genetic map of the genome ofCapsella bursa-pastoris. It shows that the subgenomes are mostly colinear, with no massive deletions, insertions or rearrangements in any of them. A subgenome-aware annotation reveals the lack of genome dominance – both subgenomes carry similar number of genes. While most chromosomes can be unambiguously recognized as derived from either paternal or maternal parent, we also found homeologous exchange between two chromosomes. It led to an emergence of two hybrid chromosomes; this event is shared between distant populations ofC. bursa-pastoris. The whole-genome analysis of 119 samples belonging toC. bursa-pastorisand its parental speciesC. grandiflora/rubellaandC. orientalisreveals introgression fromC. orientalisbut not fromC. grandiflora/rubella.ConclusionsC. bursa-pastorisdo not show genome dominance. In the earliest stages of evolution of this species a homeologous exchange occurred; its presence in all present-day populations ofC. bursa-pastorisindicates on a single origin of this species. The evidence coming from whole-genome analysis challenges the current view thatC. grandiflora/rubellawas a direct progenitor ofC. bursa-pastoris; we hypothesize that it was an extinct (or undiscovered) species sister toC. grandiflora/rubella.
BERLIN: Basic Explorer for single-cell RNAseq analysis and cell Lineage Determination
Authors: Nobles Gabrielle , Obermayer Alyssa , Yang Ching Yao , Zelenka Tomas , Nugyen Thanh N , Chen Zhihua , Conejo-Garcia Jose , Avram Dorina , Yu Xiaoqing , Chen Y Ann , Shaw Timothy 
Published: July 2023

AbstractSingle-cell RNA sequencing has revolutionized the study of immuno-oncology, cancer biology, and developmental biology by enabling the joint characterization of gene expression and cellular heterogeneity in a single platform. As of July 2023, the Gene Expression Omnibus now contains over 4000 published single-cell data sets, providing an invaluable opportunity for reanalysis to identify new cell types or cellular states as well as their defining transcriptional programs. To facilitate the reprocessing of these public datasets, we have devised a single-cell RNA sequencing analysis framework for data retrieval, quality control, expression normalization, dimension reduction, cell clustering, and data integration. Additionally, we have developed a Shiny App visualization platform that enables the exploration of gene expression, cell type annotations, and cell lineages through a user interface. We performed a re-analysis of single-cell RNAseq data generated from acute myeloid leukemia and tumor-reactive lymphocytes and found our pipeline to faithfully recapitulated the cell type assignment as well as expected lineage trajectories. Altogether, we present BERLIN, a single-cell RNAseq analysis pipeline that facilitates the integration and public dissemination of results from the reanalysis.
Thermospermine is an evolutionarily ancestral phytohormone required for organ development and stress responses in the basal land plantMarchantia polymorpha
Authors: Furumoto Takuya , Yamaoka Shohei , Kohchi Takayuki , Motose Hiroyasu , Takahashi Taku 
Published: July 2023

AbstractThermospermine, a structural isomer of spermine, suppresses auxin-inducible xylem differentiation, whereas spermine is implicated in stress responses in angiosperms. Thermospermine synthase ACAULIS5 (ACL5) is well conserved from algae to land plants, but its physiological function remains elusive in non-vascular plants. Here we focused on MpACL5, a gene in the liverwortMarchantia polymorpha, which rescued the dwarf phenotype of theacl5mutant ofArabidopsis. In the Mpacl5mutants generated by genome editing, growth of the vegetative organ, thallus, and the sexual reproductive organ, gametangiophore, was severely retarded. The mutant gametangiophore exhibited remarkable morphological defects such as short stalks, fasciation, and indeterminate growth; it was formed as a fusion of two gametangiophores and a new gametangiophore was often initiated from the old one. Furthermore, Mpacl5was shown to be hypersensitive to heat and salt stresses. Given the absence of spermine in liverworts includingM. polymorpha, these results reveal that thermospermine has a dual primordial function in organ development and stress responses in the basal land plant lineage, the latter of which may have eventually been assigned to spermine during the land plant evolution.
Patterns of change in nucleotide diversity over gene length
Authors: Ali Farhan 
Published: July 2023

AbstractNucleotide diversity at a site is influenced by the relative strengths of neutral and selective population genetic processes. Therefore, attempts to identify sites under positive selection require an understanding of the expected diversity in its absence. The nucleotide diversity of a gene was previously found to correlate with its length. In this work, I measure nucleotide diversity at synonymous sites and uncover a pattern of low diversity towards the translation initiation site (TIS) of a gene. The degree of reduction in diversity at the TIS and the length of this region of reduced diversity can be quantified as “Effect Size” and “Effect Length” respectively, using parameters of an asymptotic regression model. Estimates of Effect Length across bacteria covaried with recombination rates as well as with a multitude of fast-growth adaptations such as the avoidance of mRNA secondary structure around TIS, the number of rRNAs, and relative codon usage of ribosomal genes. Thus, the dependence of nucleotide diversity on gene length is governed by a combination of selective and non-selective processes. These results have implications for the estimation of effective population size and relative mutation rates based on “silent-site” diversity, and for pN/pS-based prediction of genes under selection.
Targeting the glucose-insulin link in head and neck squamous cell carcinoma induces cytotoxic oxidative stress and inhibits cancer growth
Authors: Mazambani Simbarashe , Choe Joshua H. , Oh Tae-Gyu , Singh Pankaj K. , Kim Jung-whan , Kim Tae Hoon 
Published: July 2023

ABSTRACTReactive oxygen species (ROS) are a double-edge sword in cancers and can both promote pro-tumorigenic signaling and also trigger oxidative stress dependent cell death. Thus, maintaining redox homeostasis to control levels of ROS within a tumor-promoting range elicits critical tumorigenic potential in cancer. Here, we show that head and neck squamous cell carcinoma (HNSCC) is uniquely characterized by its critical dependence on heightened antioxidant capacity facilitated by elevated glucose uptake to maintain survival and proliferation. Using a basal-epithelial-layer-specific GLUT1 knockout mouse model, we establish that targeting GLUT1-mediated glucose utilization in HNSCC cells of origin robustly inhibits HNSCC progression, providing strong genetic evidence that GLUT1 is indeed a targetable metabolic vulnerability. We further demonstrate that disrupting redox homeostasis with prooxidants such as high dose vitamin C and Auranofin induces potent cytotoxicity in HNSCCs by exerting profound oxidative stress when combined with GLUT1 inhibitors. Given the central role of insulin signaling in glucose homeostasis, we additionally show that circulating insulin levels modulate metabolic and oncogenic pathways of HNSCCs, providing a new perspective on events driving and sustaining HNSCC malignancy. These results establish GLUT1 as a viable therapeutic target for HNSCC in combination with prooxidant chemotherapies and define critical dependencies in HNSCC that can be utilized with existing clinical stage drugs for the treatment of HNSCC and potentially other squamous cancers.
Clockor2: Inferring global and local strict molecular clocks using root-to-tip regression
Authors: Featherstone Leo A. , Rambaut Andrew , Duchene Sebastian , Wirth Wytamma 
Published: July 2023

AbstractMolecular sequence data from rapidly evolving organisms are often sampled at different points in time. Sampling times can then be used for molecular clock calibration. The root-to-tip (RTT) regression is an essential tool to assess the degree to which the data behave in a clock-like fashion. Here, we introduce Clockor2, a client-side web application for conducting RTT regression. Clockor2 uniquely allows users to quickly fit local and global molecular clocks, thus handling the increasing complexity of genomic datasets that sample beyond the assumption homogeneous host populations. Clockor2 is efficient, handling trees of up to the order of 104tips, with significant speed increases compared to other RTT regression applications. Although clockor2 is written as a web application, all data processing happens on the client-side, meaning that data never leaves the user’s computer. Clockor2 is freely available athttps://clockor2.github.io/.