Purpose: Facial expression production and perception in autism spectrum disorder (ASD) suggest potential presence of behavioral biomarkers that may stratify individuals on the spectrum into prognostic or treatment subgroups. Construct validity and group discriminability have been recommended as criteria for identification of candidate stratification biomarkers. Methods: In an online pilot study of 11 children and young adults diagnosed with ASD and 11 age- and gender-matched neurotypical (NT) individuals, participants recognize and mimic static and dynamic facial expressions of 3D avatars. Webcam-based eye-tracking (ET) and facial video tracking (VT), including activation and asymmetry of action units (AUs) from the Facial Action Coding System (FACS) are collected. We assess validity of constructs for each dependent variable (DV) based on the expected response in the NT group. Then, the Boruta statistical method identifies DVs that are significant to group discriminability (ASD or NT). Results: We identify one candidate ET biomarker (percentage gaze duration to the face while mimicking static 'disgust' expression) and 14 additional DVs of interest for future study, including 4 ET DVs, 5 DVs related to VT AU activation, and 4 DVs related to AU asymmetry in VT. Based on a power analysis, we provide sample size recommendations for future studies. Conclusion: This pilot study provides a framework for ASD stratification biomarker discovery based on perception and production of facial expressions.

The global decline in bee populations poses significant risks to agriculture, biodiversity, and environmental stability. To bridge the gap in existing data, we introduce ApisTox, a comprehensive dataset focusing on the toxicity of pesticides to honey bees (Apis mellifera). This dataset combines and leverages data from existing sources such as ECOTOX and PPDB, providing an extensive, consistent, and curated collection that surpasses the previous datasets. ApisTox incorporates a wide array of data, including toxicity levels for chemicals, details such as time of their publication in literature, and identifiers linking them to external chemical databases. This dataset may serve as an important tool for environmental and agricultural research, but also can support the development of policies and practices aimed at minimizing harm to bee populations. Finally, ApisTox offers a unique resource for benchmarking molecular property prediction methods on agrochemical compounds, facilitating advancements in both environmental science and cheminformatics. This makes it a valuable tool for both academic research and practical applications in bee conservation.

In this work, we study a class of hybrid dynamical systems called hybrid gene regulatory networks (HGRNs) which was proposed to model gene regulatory networks. In HGRNs, there exist well-behaved trajectories that reach a fixed point or converge to a limit cycle, as well as chaotic trajectories that behave non-periodic or indeterministic. In our work, we investigate these irregular behaviors of HGRNs and present theoretical results about the decidability of the reachability problem, the probability of indeterministic behavior of HGRNs, and chaos especially in 2-dimensional HGRNs.

The human brain receives complex inputs when performing cognitive tasks, which range from external inputs via the senses to internal inputs from other brain regions. However, the explicit inputs to the brain during a cognitive task remain unclear. Here, we present an input identification framework for reverse engineering the control nodes and the corresponding inputs to the brain. The framework is verified with synthetic data generated by a predefined linear system, indicating it can robustly reconstruct data and recover the inputs. Then we apply the framework to the real motor-task fMRI data from 200 human subjects. Our results show that the model with sparse inputs can reconstruct neural dynamics in motor tasks ($EV=0.779$) and the identified 28 control nodes largely overlap with the motor system. Underpinned by network control theory, our framework offers a general tool for understanding brain inputs.

Ligand-receptor interactions constitute a fundamental mechanism of cell-cell communication and signaling. NicheNet is a well-established computational tool that infers ligand-receptor interactions that potentially regulate gene expression changes in receiver cell populations. Whereas the original publication delves into the algorithm and validation, this paper describes a best practices workflow cultivated over four years of experience and user feedback. Starting from the input single-cell expression matrix, we describe a "sender-agnostic" approach which considers ligands from the entire microenvironment, and a "sender-focused" approach which only considers ligands from cell populations of interest. As output, users will obtain a list of prioritized ligands and their potential target genes, along with multiple visualizations. In NicheNet v2, we have updated the data sources and implemented a downstream procedure for prioritizing cell-type-specific ligand-receptor pairs. Although a standard NicheNet analysis takes less than 10 minutes to run, users often invest additional time in making decisions about the approach and parameters that best suit their biological question. This paper serves to aid in this decision-making process by describing the most appropriate workflow for common experimental designs like case-control and cell differentiation studies. Finally, in addition to the step-by-step description of the code, we also provide wrapper functions that enable the analysis to be run in one line of code, thus tailoring the workflow to users at all levels of computational proficiency.

A central question for cognitive science is to understand how humans process visual objects, i.e, to uncover human low-dimensional concept representation space from high-dimensional visual stimuli. Generating visual stimuli with controlling concepts is the key. However, there are currently no generative models in AI to solve this problem. Here, we present the Concept based Controllable Generation (CoCoG) framework. CoCoG consists of two components, a simple yet efficient AI agent for extracting interpretable concept and predicting human decision-making in visual similarity judgment tasks, and a conditional generation model for generating visual stimuli given the concepts. We quantify the performance of CoCoG from two aspects, the human behavior prediction accuracy and the controllable generation ability. The experiments with CoCoG indicate that 1) the reliable concept embeddings in CoCoG allows to predict human behavior with 64.07\% accuracy in the THINGS-similarity dataset; 2) CoCoG can generate diverse objects through the control of concepts; 3) CoCoG can manipulate human similarity judgment behavior by intervening key concepts. CoCoG offers visual objects with controlling concepts to advance our understanding of causality in human cognition. The code of CoCoG is available at \url{https://github.com/ncclab-sustech/CoCoG}.

Hierarchically modular organization is a canonical network topology that is evolutionarily conserved in the nervous systems of animals. Within the network, neurons form directional connections defined by the growth of their axonal terminals. However, this topology is dissimilar to the network formed by dissociated neurons in culture because they form randomly connected networks on homogeneous substrates. In this study, we fabricated microfluidic devices to reconstitute hierarchically modular neuronal networks in culture (in vitro) and investigated how non-random structures, such as directional connectivity between modules, affect global network dynamics. Embedding directional connections in a pseudo-feedforward manner suppressed excessive synchrony in cultured neuronal networks and enhanced the integration-segregation balance. Modeling the behavior of biological neuronal networks using spiking neural networks (SNNs) further revealed that modularity and directionality cooperate to shape such network dynamics. Finally, we demonstrate that for a given network topology, the statistics of network dynamics, such as global network activation, correlation coefficient, and functional complexity, can be analytically predicted based on eigendecomposition of the transition matrix in the state-transition model. Hence, the integration of bioengineering and cell culture technologies enables us not only to reconstitute complex network circuitry in the nervous system but also to understand the structure-function relationships in biological neuronal networks by bridging theoretical modeling with in vitro experiments.

With an increasing presence of science throughout all parts of society, there is a rising expectation for researchers to effectively communicate their work and, equally, for teachers to discuss contemporary findings in their classrooms. While the community can resort to an established set of teaching aids for the fundamental concepts of most natural sciences, there is a need for similarly illustrative experiments and demonstrators in neuroscience. We therefore introduce Lu.i: a parametrizable electronic implementation of the leaky-integrate-and-fire neuron model in an engaging form factor. These palm-sized neurons can be used to visualize and experience the dynamics of individual cells and small spiking neural networks. When stimulated with real or simulated sensory input, Lu.i demonstrates brain-inspired information processing in the hands of a student. As such, it is actively used at workshops, in classrooms, and for science communication. As a versatile tool for teaching and outreach, Lu.i nurtures the comprehension of neuroscience research and neuromorphic engineering among future generations of scientists and in the general public.

This report enlists 13 functional conditions cashed out in computational terms that have been argued to be constituent of conscious valenced experience. These are extracted from existing empirical and theoretical literature on, among others, animal sentience, medical disorders, anaesthetics, philosophy, evolution, neuroscience, and artificial intelligence.

Tumor cell migration within the microenvironment is a crucial aspect for cancer progression and, in this context, hypoxia has a significant role. An inadequate oxygen supply acts as an environmental stressor inducing migratory bias and phenotypic changes. In this paper, we propose a novel multi-scale mathematical model to analyze the pivotal role of Snail protein expression in the cellular responses to hypoxia. Starting from the description of single-cell dynamics driven by the Snail protein, we construct the corresponding kinetic transport equation that describes the evolution of the cell distribution. Subsequently, we employ proper scaling arguments to formally derive the equations for the statistical moments of the cell distribution, which govern the macroscopic tumor dynamics. Numerical simulations of the model are performed in various scenarios with biological relevance to provide insights into the role of the multiple tactic terms, the impact of Snail expression on cell proliferation, and the emergence of hypoxia-induced migration patterns. Moreover, quantitative comparison with experimental data shows the model's reliability in measuring the impact of Snail transcription on cell migratory potential. Through our findings, we shed light on the potential of our mathematical framework in advancing the understanding of the biological mechanisms driving tumor progression.

The interactions between tumor cells and the tumor microenvironment (TME) dictate therapeutic efficacy of radiation and many systemic therapies in breast cancer. However, to date, there is not a widely available method to reproducibly measure tumor and immune phenotypes for each patient's tumor. Given this unmet clinical need, we applied multiple instance learning (MIL) algorithms to assess activity of ten biologically relevant pathways from the hematoxylin and eosin (H&E) slide of primary breast tumors. We employed different feature extraction approaches and state-of-the-art model architectures. Using binary classification, our models attained area under the receiver operating characteristic (AUROC) scores above 0.70 for nearly all gene expression pathways and on some cases, exceeded 0.80. Attention maps suggest that our trained models recognize biologically relevant spatial patterns of cell sub-populations from H&E. These efforts represent a first step towards developing computational H&E biomarkers that reflect facets of the TME and hold promise for augmenting precision oncology.

Boolean networks can be viewed as functions on the set of binary strings of a given length, described via logical rules. They were introduced as dynamic models into biology, in particular as logical models of intracellular regulatory networks involving genes, proteins, and metabolites. Since genes can have several modes of action, depending on their expression levels, binary variables are often not sufficiently rich, requiring the use of multi-valued networks instead. The steady state analysis of Boolean networks is computationally complex, and increasing the number of variable values beyond $2$ adds substantially to this complexity, and no general methods are available beyond simulation. The main contribution of this paper is to give an algorithm to compute the steady states of a multi-valued network that has a complexity that, in many cases, is essentially the same as that for the case of binary values. Our approach is based on a representation of multi-valued networks using multi-valued logic functions, providing a biologically intuitive representation of the network. Furthermore, it uses tools to compute lattice points in rational polytopes, tapping a rich area of algebraic combinatorics as a source for combinatorial algorithms for Boolean network analysis. An implementation of the algorithm is provided.