Papers

Mentalization - the ability to infer others' beliefs and intentions to guide one's own choices - is a key cognitive function underlying human social interactions. Large language models (LLMs) demonstrate behaviour consistent with humans on theory-of-mind tasks, yet whether these models can guide adaptive behaviour through mentalization is unknown. Here we use two economic games with cognitive computational modeling to uncover the latent strategies underlying mentalization in LLMs. We tested individual LLM agents across four model families, DeepSeek, GPT-4.1, GPT-5 and Gemini 2.0 Flash (N = 2,099), against opponents of varying sophistication and examined whether a prompting strategy designed to elicit strategic reasoning improved performance. We benchmarked results against human participants (N = 251) as a comparative measure. Across both games, LLMs showed clear behavioural and computational signatures of mentalizing that differed markedly by model provider and size. Strategic prompting generally improved performance by inducing more sophisticated reasoning, yet the extent of the benefit differed across the two tasks. Last, GPT-5 agents flexibly adapted their recursive depth of reasoning to increasingly sophisticated opponents, demonstrating superior performance to human participants. Collectively, we demonstrate different capacities for mentalization across LLMs, and highlight cognitive computational modeling as a formal method for assessing comparative intelligence across humans and machines.

With activity against multidrug-resistant pathogens and mechanisms distinct from conventional antibiotics, antimicrobial peptides (AMPs) offer a promising approach to combating antibiotic-resistant infections. However, their potency varies substantially across pathogen species, making accurate prediction of the minimum inhibitory concentration (MIC) for specific peptide-pathogen pairs essential for prioritizing candidates before costly experimental validation. Existing predictors are trained mainly on a few well-represented pathogens and rarely exploit biological relationships across species, limiting their generalization to low-resource and unseen pathogens. We introduce PathoMIC, the largest and most pathogen-diverse unified dataset for quantitative antimicrobial peptide activity prediction, containing 74,751 experimentally reported MIC measurements across 424 pathogen species. PathoMIC integrates peptide sequences, standardized MIC values, pathogen descriptions, and taxonomic relationships to facilitate knowledge transfer across related species. We establish few-shot and zero-shot cross-species evaluation protocols and develop a knowledge-enhanced framework that leverages pathogen descriptions and taxonomy. The framework yields substantial improvements for low-resource species with limited supervision, while gains for entirely unseen species remain modest, highlighting the difficulty of zero-shot cross-species MIC prediction. PathoMIC provides a standardized foundation for cross-species activity modeling and pathogen-specific virtual screening. Code is available at https://anonymous.4open.science/r/PathoMIC-546D/.

Dementia comprises biologically heterogeneous disorders, yet current risk assessment provides limited insight into how subtype-specific risk emerges and diverges before clinical diagnosis. We developed NetMoint, a multimodal framework integrating partially observed plasma proteomic, structural magnetic resonance imaging and cerebral haemodynamic phenotypes to predict individualized risks of Alzheimer's disease (AD), vascular dementia (VD) and frontotemporal dementia (FTD) across 1-, 5-, 10- and 20-year horizons. Among 104,120 UK Biobank participants free of dementia at baseline, NetMoint achieved mean area under the receiver operating characteristic curve (AUC) values of 0.937, 0.930 and 0.932 for AD, VD and FTD, respectively. The biological determinants of prediction shifted with time, from structural brain vulnerability at shorter horizons towards circulating molecular signatures at longer horizons, with distinct subtype-specific biological profiles. Multi-horizon risk profiling identified distinct temporal trajectories of dementia susceptibility. Among participants who subsequently developed AD, 0.7% followed a persistently very-high-risk trajectory, with predicted risk reaching 53.50% at 20 years, whereas 8.3% of those who developed FTD followed an increasing very-high-risk trajectory, reaching 67.17%. These high-risk trajectories were marked by distinct molecular signatures, with lower TGFB1 characterizing the AD group and higher NDRG1 the FTD group. In an independent ADNI-to-UK Biobank analysis, AD risk prediction remained informative after harmonization to 138 shared features, with an AUC of 0.741 at 20 years. Together, these findings establish a multimodal framework for trajectory-resolved dementia risk stratification, identifying small but high-risk populations within dementia subtypes and linking their divergent risk trajectories to distinct molecular signatures.

In the tumor microenvironment, a cell's state is influenced by cell-cell interactions (CCIs) with neighboring cells in its niches. Identifying dysregulated CCIs that are associated with pathogenic processes pinpoints targets for drug discovery. Imaging-based spatial transcriptomics and single-cell RNA sequencing provide, respectively, single-cell spatial information and transcriptome-wide measurements needed to study CCIs, but neither modality provides both. Existing spatial transcriptomics foundation models also cannot effectively learn from spatially resolved single-cell data with full-transcriptome coverage, explicitly infer the CCI mechanisms driving cell state-niche associations, or be interpretable enough to support direct biological interpretations. Here, we present GITIII-scale, a hierarchical, interpretable pan-cancer spatial transcriptomics foundation model for TME representation learning that investigates cell state-niche associations and their underlying ligand-receptor (LR) signaling pathways. GITIII-scale uses transformers to model interactions between pairs of cells at defined spatial distances, an interpretable single-layer graph transformer without a feed-forward network to decompose how each gene in a receiver cell is influenced by each neighboring sender cell, and a graph transformer to generate cellular-neighborhood embeddings. Trained on our assembled pan-cancer database of specimen-matched scRNA-seq and imaging-based spatial transcriptomics datasets, GITIII-scale generated TME embeddings that recovered niche-associated state changes more accurately than existing spatial transcriptomics foundation models in cancer types unseen during training. A case study of an unseen breast cancer dataset further demonstrated the model's interpretability by identifying potentially drug-targetable LR pathways associated with endothelial overgrowth and tumorigenesis.

Wearable electrocardiogram (ECG) and photoplethysmogram (PPG) sensors are complementary but individually fragile: motion artifact, poor contact, and sensor dropout can degrade one or both signals. Fusion strategies that assume both modalities are equally trustworthy can become less reliable than a single clean modality under degradation. We present CardioFusion-AI, a framework whose signal-processing front end, including R-peak and systolic-peak detection, an Orphanidou-type signal-quality index, and beat-by-beat pulse transit time estimation, is validated on 53 real intensive-care recordings (848 windows; heart-rate mean absolute error 1.61 bpm for ECG and 2.78 bpm for PPG) and a real annotated fetal ECG database (R-peak F1 0.89-0.98). We then conduct a controlled synthetic degradation study comparing eight ECG-PPG fusion strategies across six degradation regimes spanning graded corruption and complete modality loss, using five independent training seeds. Attention fusion achieved the lowest descriptive overall error (1.66+/-0.43 bpm). Both adaptive gates reallocated weight toward the healthy modality under complete modality loss, but showed near-zero correlation between gate weight and signal quality under graded degradation (r = 0.10-0.24). Signal-quality conditioning produced a specific improvement under missing-PPG conditions (1.56+/-0.59 bpm), approaching the 1.48 bpm unimodal ceiling. With only five training seeds, no pairwise comparison survives Holm-corrected significance testing; effect sizes and confidence intervals are therefore reported. These results indicate that modality availability and modality quality are functionally distinct problems for adaptive fusion.

In the Derrida–Higgs model of sympatric speciation, a sexually reproducing population with finite binary genomes can mate only when the genetic overlap between two individuals exceeds a threshold $q_{\min}$. Depending on the genome length $L$, the population either remains genetically connected or fragments into reproductively isolated species. A central problem is therefore to predict the critical genome length $L_c$ at which fragmentation begins. At finite $L$, fluctuations broaden the overlap distribution and allow genetically distant regions of the population to remain connected. A previously proposed transient variance criterion captures this effect, but its evaluation requires numerical iteration of coupled moment equations. Here we first correct the unrestricted moment equations by removing a previously implicit assumption and then derive an explicit closed form expression for $L_c$. The resulting formula shows that the critical genome length is determined, at the time the mean overlap reaches $q_{\min}$, by the competition between deterministic separation from the unrestricted equilibrium and the transient genealogical variance of the overlap distribution. This expression permits a systematic asymptotic analysis. When the deterministic contribution dominates, $L_c$ becomes essentially independent of the population size $M$ and scales as $\mu^{-2}$. When the transient genealogical variance dominates, $L_c$ grows as $M^{3/2}$ or as $\sqrt{M}/\mu$, depending on how $M$ and the mutation rate $\mu$ jointly vary. Simulations support all predicted behaviors. Our results identify transient genealogical variance as the principal mechanism linking finite genome fluctuations to the onset of reproductive fragmentation and provide a practical analytical prediction for the critical genome length.

The coordinated movement of animal groups is one of the most widespread social behaviors, which are generally attributed to high-order cognitive processing in the brain. Yet, collective coordination can seemingly emerge from rapid, local interactions between individuals, suggesting the existence of decentralized mechanisms of online coordination that remain to be identified. Here, we show that a low-order spinal sensorimotor circuit is required for real-time social coordination during schooling in zebrafish. Central to this circuit are intraspinal proprioceptive neurons that detect local body bending and deliver direct, curvature-based inhibition to precisely time the locomotor network. Combining electrophysiology, calcium imaging, optogenetics, and behavioral analysis, we show that this circuit encodes both self-generated (egocentric) and neighbor-induced (allocentric) body bending signals, enabling fish to match the phase of their swimming to the wakes of their neighbors (vortex phase matching). In a neuromechanical model and physical robot, this single feedback loop is sufficient to generate vortex phase matching and to lower the energetic cost of swimming. Disrupting this circuit uncouples neighboring fish and abolishes schooling behavior. These results show that a spinal circuit dynamically synchronizes individuals through simple, local interactions, revealing how low-order mechanisms can drive the emergence of coordinated group behavior.

There is growing international interest in generative AI (GenAI) literacy and its assessment among high school students, but objective assessment in this population remains underdeveloped. This article reports the iterative development and validation of the GenAI Literacy Test (GenAIT), an 18-item multiple-choice test measuring high school students' conceptual knowledge about GenAI, with content spanning technical, practical, and human-impact domains. Expert review of relevance, clarity, and comprehensiveness provided evidence of content validity. In a large-scale survey of 7432 Estonian high school students, we evaluated the psychometric functioning of the Estonian-language GenAIT using confirmatory factor analysis, classical test theory, and item response theory. Results supported approximate unidimensionality, broadly adequate reliability for group-level research (marginal reliability = .72, KR-20 = .69), and good fit of a three-parameter logistic model (RMSEA = .013, TLI = .987, CFI = .990, SRMSR = .021). Measurement precision was sufficient for the majority of students but varied substantially across the latent trait, with lower precision for lower scoring students. GenAIT is therefore more suitable for group-level research than high-stakes individual classification. GenAIT scores were unrelated to perceived usefulness and perceived ease of use, and negatively associated with LLM use frequency, suggesting that frequent use and favorable perceptions of AI should not be treated as proxies for conceptual understanding.

Communication typically relies on a shared code, and any change to it must be coordinated between senders and receivers to avoid a breakdown of communication. The honeybee waggle dance illustrates this problem: species with horizontal combs point directly at a food source, while species with vertical combs cannot point directly and instead reference the dance to gravity, decoded against the position of the sun. We model the rise of the first of these codes and its evolutionary transition to the second in populations of bee-like agents, with selection acting at the level of colonies. In a horizontal-comb model, we find that direct pointing evolves readily when food is moderately hard to find by random search alone, whether because sites are few and large or many and small. Communication fails to evolve when food is too sparse to spark dances or so abundant that it is found without signaling. Adding an exogenous benefit for vertical combs, we then find that the transition to the gravity-referenced code is driven mainly by the magnitude of this benefit and by the mutation scale, with the coupling between sender and receiver mutations playing a further role when the mutation scale is low. Given a favorable confluence of these factors, the transition proceeds reliably and without a breakdown of communication. Outside that confluence it remains possible, though rarer, across a much wider range of settings.

Continuous-time Markov chains (CTMCs) provide the backbone for modeling discrete stochastic dynamics across applied, physical, and biological sciences. Their integration with modern gradient-based machine learning, however, is limited by the hard categorical event selection intrinsic to Gillespie-type simulation algorithms. We exploit the affine state update to obtain the exact one-step conditional-mean sensitivity by differentiating normalized reaction propensities. We pair this backward rule with exact forward trajectories to define the propensity straight-through (PST) estimator. At the trajectory level, we show that one-step sensitivities composed across events can depart from the exact multistep sensitivity. We derive the resulting per-step discrepancy in closed form and prove that it vanishes identically for affine downstream dependence. PST matches the accuracy of Gumbel-Softmax straight-through across all benchmarks: reversible dimerization (0.06% error), a genetic oscillator (1.7% error), a 50-task repressilator suite (0.17% median error), and patch-clamp ion-channel recordings ($R^2$ = 0.988). Under matched settings, PST converges 3.0-fold faster on the oscillator and 2.1-fold faster on the ion channel. At deep-learning scale, PST trains a 203,796-parameter stochastic reaction network with hard sampling, reaching 98.22% MNIST digit classification accuracy. By differentiating an exact conditional mean rather than a relaxed sample, PST offers a temperature- and Gumbel-free path to scalable gradient-based learning through exact stochastic trajectories.

Strongly connected components (SCCs) characterize modular structure in directed networks but are fragile to single node failures. We study strongly biconnected components (SBCs), which are the set of nodes in which every node pair remains mutually reachable after the removal of any single node, as a more robust notion of connectivity. Using a generating function formalism, we derive the size of the giant SBC and analyze its percolation behavior under random node and link removal. We show that the giant SBC emerges at the same threshold as the giant SCC but grows more slowly due to stricter connectivity requirements. We also applied our theoretical framework to real-world biological networks including gene regulatory networks and neural connectome. Our framework provides insight into the interplay between connectivity, redundancy, and robustness in complex directed systems.

Recently, there has been a growing adoption of protein language models (PLMs) in biomedical science. Their embeddings provide a rich numerical representation of protein sequences which achieve state-of-the-art performance on several downstream tasks including protein fitness prediction. However, PLM embeddings are not directly interpretable and, thereby, it remains unclear what features they encode. To gain insight into which biochemical properties of the protein are driving the prediction, we leverage an orthogonal projection technique that removes linear effects of known tabular features from embeddings and extend it to high-order and interaction effects. In this way, we remove the effects of interpretable biochemical features from PLM embeddings. In an ablation study, we show that this leads to a decrease in performance for a downstream classifier trained only on the embeddings to predict protein fitness. In an additional evaluation, we find that these biochemical features explain a substantial part of the variance in the predictions of this classifier. Hence, we can show that PLM embeddings encode patterns correlated with biochemical properties and quantify their contribution to predicting protein fitness. This computationally efficient approach is not limited to the features or embeddings considered here and is readily transferable to problem settings beyond protein fitness prediction.

Phylogenetic trees are used in evolutionary biology to represent the evolutionary history of a collection of taxa. As we have incomplete information about any evolutionary history, recovering trees from partial information is a focus of phylogenetic combinatorics. However, in some cases the available data does not describe a single phylogenetic tree. We consider recovery of pairs of phylogenetic trees from their combined subtrees with $k$ leaves, which we call a $k$-bucket. We establish the exact cases in which these pairs of trees are recoverable from their subtrees with a single leaf removed, both when just considering the structure of the trees, and when additionally considering the set of taxa on the leaves. We also consider recovery of pairs of trees with labelled leaves from their rooted triples, and establish that they are recoverable up to a sequence of subtree swaps.

We describe a systematic approach for spawning and aggregating multi-class cryo-EM reconstruction jobs. This approach formalizes standard ad hoc strategies of iterative classification and filtering typically used by practitioners to sort impure, heterogeneous samples. To our knowledge, this is the first method that can successfully perform ab initio reconstruction on datasets containing dozens of distinct species. We obtain 97% accuracy on ab initio reconstruction of a 45-class subset of Tomotwin-100, 75% accuracy on the full Tomotwin-100 dataset, and demonstrate recovery of ribosomal assembly states from an unfiltered experimental cryo-EM dataset. Our approach's capability scales with compute and lays the foundation for automated cryo-EM workflows in modern experimental settings.

Artificial intelligence (AI) promises to accelerate biological research by automating computational analyses. Yet the ability of AI agents to execute on computational biology at the scale of complete research studies has not been systematically evaluated. Here we introduce BixBench3, a benchmark that measures the capacity of AI agents to process raw biological data through to scientific results. We designed BixBench3 tasks to mirror the delegation of work from a scientist to an agent: the scientist chooses the research question and high-level methods, then delegates implementation of all analyses to the agent. In each task, an agent receives a research objective, methodological guidance, and raw data derived from a published scientific study, and must execute a sequence of analyses to achieve the research objective. The data artifacts resulting from these analyses, such as peak call matrices or differential expression tables, are programmatically graded against the corresponding artifacts generated and reported in the original study. Across 20 BixBench3 tasks encompassing the generation of 138 unique artifacts, we find that 13 frontier models achieve scores ranging from 0.00 for Gemini 3.1 Flash Lite to 0.48 for GPT 5.6 Sol. Agents perform worse on tasks with larger raw datasets (0.36 on tasks with <100 GB versus 0.10 on tasks with >100 GB) and on analyses requiring more sequential steps (0.36 at 1-2 steps vs 0.24 at 3+). On average, agents use 6.8 hours, 102 million tokens, and \$43 to complete each task, with the longest attempts consuming 24 hours, 1.07 billion tokens, and \$525. Notably, the highest-scoring agents used fewer tokens and were cheaper than less performant options. These results reveal that LLMs vary substantially in their ability to (1) execute multiple sequential analysis steps coherently, (2) manage large quantities of raw data, and (3) work across scientific domains.

Histology and transcriptomics provide complementary views of tissue biology, capturing spatial morphology and molecular activity, respectively. Pathology foundation models (PFMs) learn rich morphological representations from H&E images, yet strong downstream performance alone does not establish whether these representations encode biologically meaningful and robust molecular information. We present a **training-free framework for auditing biological alignment in frozen PFMs** using spatially paired histology and transcriptomics from HEST-1k, evaluated on **240 samples spanning three organs**. Multiple frozen PFMs are used to extract H&E representations, while gene expression is aggregated into biologically interpretable pathway-level programs. We use TabPFN as a pretrained probe to quantify the extent to which these molecular programs can be decoded from frozen image representations without task-specific gradient updates. Beyond predictive performance, our audit examines whether pathway decodability generalizes across tissue sections, patient groups, and tissue types; whether representations exhibit section-level or other shortcut dependencies; and whether predictions remain stable under small image perturbations and context resampling. This multi-tissue evaluation distinguishes molecular programs that are consistently encoded from those that are tissue-specific, unstable, or shortcut-sensitive. Our framework therefore provides a systematic approach for assessing not only **what biological information pathology foundation models encode, but also how reliably that information persists under clinically relevant sources of variation**.

Objective: Recent studies demonstrate that functional connectomes contain subject-specific signatures, or fingerprints, that can identify individuals across repeated sessions and tasks. Existing methods mostly rely on edge-level features that are sensitive to noise, difficult to interpret, and limited in their ability to generalize across tasks and datasets. Methods: We propose a multiscale community-based functional connectome fingerprinting framework that characterizes each individual by the mesoscale structure of their functional networks. We introduce a signed multilayer community detection framework that incorporates both correlated and anti-correlated brain activity to identify subject-specific community structures across tasks and sessions. Graph-theoretic metrics are then computed from the resulting joint community structures to derive low-dimensional community-level fingerprint representations. Results: The proposed framework is evaluated on 810 healthy control subjects from the Human Connectome Project (HCP). The results show that community-based fingerprints provide a reliable and interpretable substrate for individualized brain characterization across sessions and tasks. Conclusion: Mesoscale community structure provides meaningful and discriminative subject-specific fingerprints. Significance: The proposed framework offers a promising foundation for precision neuroimaging and personalized neuroscience applications.

Natural language driven autonomous co-scientist workflows involve a fundamental trade-off between flexibility and reasoning at the expense of determinism, reproducibility, and observability. Such agents increasingly must communicate across institutional boundaries, where federation topology can shape latency and cost. We systematically evaluated these tradeoffs using a controlled ablation on a production agentic platform for science. We use a verifiable task: given a protein sequence, we ask an agent to confidently characterize its function by routing across common tools. We compare federation topology, classic RL vs LLM-driven harnesses, language model, and prompt expertise. We also stratify results by protein novelty. We find that the choice of LLM dominated prediction quality far more than topology or prompting (Opus ~92%-94% vs o4-mini ~40%-50%). The PPO policy was nearly as accurate as the best LLM (88%) at zero token cost, fastest latency, and perfect consistency, but yields no reasoning trace. Expert prompted LLMs reached the highest accuracy but were high-cost and less consistent; prompt dependence was largest when the task was hardest. Federation imposed a negligible penalty on performance. These results offer actionable guidance for deploying agents for scientific workflows: for routine, verifiable tasks, a cheap deterministic policy delivers near-frontier accuracy with complete reproducibility, while flexible LLM reasoning is best reserved for open-ended discovery.

RNA inverse folding asks for an RNA sequence whose prescribed secondary structure is the unique maximum-base-pair compatible fold. In the four-letter Watson-Crick model (A-U and C-G pairs only, no pseudoknots, and zero minimum base-pair span), Hales et al. introduced a separated-coloring certificate and an even-odd device, while Boury et al. generalized this to modulo-$m$ separability, gave an $O(n 2^m)$ decision algorithm, and guaranteed designability when every helix has length at least 3. We prove that the guarantee still holds when a motif-free target has at most two maximal helices of length 2, no maximal helix of length 1, and all remaining helices of length at least 3. The proof builds on Boury et al.'s local helix-coloring transfers and adds a global counting argument showing that the demands created by at most two short helices can always be coordinated. This is a structural success guarantee for the existing modulo-2 algorithm, not a new general decision capability. The resulting coloring yields an explicit sequence whose every distinct compatible noncrossing fold has fewer pairs. No claim is made for nearest-neighbor thermodynamic energy models. The theorem and supporting lemmas are formalized in Lean 4 against pinned Mathlib and reproduced from a frozen public artifact; the kernel-reported axiom set is $\{\mathrm{propext},\mathrm{Classical.choice},\mathrm{Quot.sound}\}$. The work was developed with foundational generative-AI assistance under the author's direction and has not yet received independent human expert review.

Frozen hematology foundation-model (FM) embeddings reach near-saturated in-domain white-blood-cell (WBC) accuracy, but clinical deployment demands reliability across scanners, sites, stains and preparation pipelines. We audit 15 frozen encoders (hematology, pathology, and general vision) across four public single-cell acquisition domains along two axes: accuracy robustness and calibration. In-domain linear-probe macro-F1 is saturated (0.98-0.997), yet cross-dataset macro-F1 drops 34-72% and rankings re-order: DinoBloom-L, the in-domain best, falls to 10th of 15 on the most-shifted target (MLL23) at the benchmark's shared 224-px input, behind RedDino and several general and pathology encoders. Rank transfer is probe-dependent: 1-NN retrieval is more stable on average than a source-fitted linear head (median $\rho$ 0.65 vs 0.45), but neither probe universally predicts target robustness. Calibration also collapses: source-trained probes are nearly calibrated in-domain (expected calibration error, ECE, 0.004) but confidently wrong off-domain (ECE 0.35), and source-fitted temperature scaling transfers poorly. We further audit pretraining exposure and identify MLL23 as DinoBloom's internal cohort; because DinoBloom's only held-out dataset is also our source domain, this benchmark cannot isolate exposure from scanner-associated shift. Label-free adaptation and marginal-entropy-based model selection appear safe under balanced evaluation but fail under realistic WBC class-prior shift. Class-Balanced Re-standardization (CBR), a training-free pseudo-label-balanced feature normalization, improves all evaluated target-prior scenario means and partially improves calibration, although encoder-level exceptions and residual miscalibration remain. Hematology FM benchmarks must therefore jointly audit accuracy, calibration, exposure, and class-prior robustness.

In the present study, we investigated a large dataset of normal adult corneal topographies in an exploratory attempt to identify the natural groupings of their 3D shapes, with the practical clinical aim of categorizing the shape of a future generation of biosynthetic corneal implants. Because of the wide range of shapes among normal corneas, we needed to identify a limited number of normal corneal shape categories to guide the conception of different implants to match the patient's own corneal shape category. At this stage of our research, we focused on the anterior surface, which exhibits greater variation in a normal population and is responsible for most of the refractive power of the eye. The corneal surface 3D data used were the anterior elevation maps taken from corneal topographies. Clustering corneal topography elevation maps was performed to reveal the normal corneal shape categories. To facilitate groupings, corneal data had their dimensionality reduced by Zernike polynomial modeling. The resulting clusters were evaluated using different clustering scores, representations and statistical cluster comparisons. While several hard and soft linear and nonlinear clustering methods were tested in this way, k-means proved to be sufficient for this task. The best number of clusters was three and they were primarily differentiated according to corneal curvature (Zernike defocus coefficient). These clusters were related to established clinical parameters, confirming that the algorithm extracted relevant information based solely on the normal 3D shape of corneas.

Cortical computation is strikingly low-dimensional: a handful of latent variables, carried in a neural population's activity, steer the higher-dimensional responses of individual neurons. Our aim is sample efficiency-models that decode well from limited data and at small parameter budgets. In a standard Transformer layer, the feed-forward block applies the same operator to every token. We suggest a von-Neumann inspired hypothesis of efficient computation as an alternative for neural decoding: a controller decodes an instruction and then executes a token-specific operator; the usual realization-a soft mixture of experts-only blends their outputs, not operators. We introduce a von-Neumann State-Space Transformer (VN-SST), a memory-augmented Transformer whose feed-forward block is a low-rank instruction bank: a shared base operator plus a small set of learned low-rank instructions, from which a per-token code synthesizes the weight matrix actually used at that token. The code is read from a low- dimensional projection of a carried state-space memory, so a slow latent trajectory acts as an instruction pointer-mirroring how low-dimensional dynamics may route cortical computation. On three motor-cortex neural-decoding benchmarks, VN-SST is far more data-efficient than a modern Transformer, each jointly predicting spikes and decoding behavior. This model wins by a wide margin on the scarcest benchmark, leads on the other two, and turns longer context into rising rather than falling accuracy. We evaluated that the network compresses a large instruction bank to a few bits per token, so program capacity acts as a control channel, not an accuracy lever. The same model is also more parameter-efficient on two small text benchmarks used for language modeling (LLMs), suggesting a generic mechanism.

The entropy production rate (EPR) quantifies irreversibility of a nonequilibrium steady state, yet standard formulas obscure how a complex interaction network generates it. For multivariate Ornstein-Uhlenbeck dynamics on such networks, we express the EPR as a quadratic form in antisymmetric matrices measuring the nonreciprocity of aggregate directed walks at every length, and, equivalently, as two weighted-walk quantities: pairs of directed walks sharing both endpoints, and directed closed walks. For diagonalizable interactions, an exact correspondence translates these walk quantities into eigenvalues and biorthogonal eigenvector overlaps. Across dense, sparse, and deep acyclic random interactions satisfying matched-walk conditions, the mean EPR per node universally follows the square-root law $\phi_*(g)=1-\sqrt{1-g^2}$, where $g \in [0,1)$ parametrizes the interaction strength. Deep acyclic interaction matrices are nilpotent, with all eigenvalues fixed at zero for every $g$, yet, as their depth increases, their mean EPR per node approaches $\phi_*(g)$. Thus, the square-root law arises from directed walk properties, rather than from a shared spectral density or specific network topology.

Prenatal maternal distress has been linked to differences in offspring brain and behavioural development, but is rarely framed computationally. Predictive-processing (PP) accounts hold that perception, cognition, and action arise from the interplay of incoming input and internally generated predictions, governed in part by precision. We reappraised eleven publications from two non-clinical prenatal cohorts for a coherent PP-compatible developmental pattern. Eight Leuven publications spanned adolescence to adulthood: externally cued response inhibition was largely preserved, whereas differences emerged when task goals, stimulus relevance, expected outcomes, and response policies had to be generated or maintained endogenously. At age 28, higher prenatal anxiety was associated with lower radial and mean diffusivity in the left superior posterior corona radiata, lower Vocabulary scores, weaker medial prefrontal to left inferior frontal connectivity, and greater unpleasantness of induced dyspnoea. Three Tilburg ERP publications covered infancy and early childhood: higher prenatal anxiety was associated with increased processing of repeated standard tones, of fearful over happy vocalizations, and of neutral over pleasant or unpleasant pictures. Maternal mindfulness, the only positive prenatal characteristic examined, showed the opposite association for the repeated standard, suggesting that positive and distress-related states may act differently on shared mechanisms. Across cohorts, findings were compatible with differences in how relevance and processing resources are allocated to predictable, threat-related, ambiguous, contextual, feedback-related, and bodily information. Because these publications did not formally estimate precision, prediction errors, or priors, we treat them as hypothesis-supporting rather than a formal test of the account.

Spatially resolved biology requires representations that preserve biological neighborhood structure rather than only exact cross-modal correspondences. Existing histology–transcriptomics objectives can emphasize instance-level matching even when non-paired spots share molecular or spatial context. We introduce BioKERN, a multimodal spatial representation-learning framework that incorporates biological structure as an explicit, learnable inductive bias. BioKERN constructs a training-time biological kernel by combining transcriptomic similarity and spatial proximity, then uses it to provide graded neighborhood supervision and regularize embedding geometry. Evaluation uses a fixed, model-independent biological neighborhood definition shared by all methods. Across Mouse Brain Visium and Human Liver GSE240429, BioKERN consistently improves biological-neighborhood retrieval over BLEEP in both single- and multi-scale settings. Controlled shared-architecture experiments show that most of the improvement arises from biological-kernel regularization rather than increased model capacity. These results support explicit biological geometry as an interpretable inductive bias for multimodal learning in spatial biology.

Most lunar surface conditions are incredibly harsh for microbial survival. High ultraviolet radiation, temperatures, and energetic particle radiation limit survival over most unprotected lunar surfaces, particularly in equatorial regions where all previous crewed exploration occurred. However, whether these harsh conditions are widespread at lunar poles has not been examined considering topographical effects. Here, we show that recent microorganism survivability data and lunar surface remote sensing reveal likely survivable niches in lunar polar regions. Analysis of topography and latitude-driven surface conditions using remote sensing data and high-resolution illumination models indicates the lunar south pole possesses significant regions with persistent low temperatures and ultraviolet flux. Comparing these conditions to survivability data of specific microorganisms, we find significant lunar polar areas likely possess surface conditions amenable to microbial survival. Our findings suggest lunar polar regions may be less hostile to microbial survival than previously assumed. This does not encompass growth likelihood, but survival in a cryptobiotic state where growth would be possible if habitable conditions were present. Potential microbial survivability at lunar poles is particularly significant given many examined microbes will likely be transported to the Moon during crewed lunar south pole exploration planned in numerous near-term missions. Thoughtfully planning exploration and tracking its impact is key to limiting and understanding potential unintended life transfer to the Moon.

Evolution in changing environments requires both reliable expression of the currently favored phenotype, as quantified by penetrance, and the capacity to reach alternative phenotypes through mutation. Previous studies suggest that high penetrance may restrict such mutational access. However, because these studies focus on evolved genotypes and local mutational neighborhoods, they cannot determine whether this local constraint limits mutational adaptability under environmental change. Such adaptability depends on a genotype's position relative to high-fitness regions for other environments. Addressing this question requires reconstructing the full probability distribution over phenotypes for every genotype and the resulting environment-specific fitness landscapes across genotype space. Such reconstruction is generally infeasible because genotype and phenotype spaces grow combinatorially. Here, an abstract model of stochastic genotype-phenotype mapping, inspired by interacting spins in statistical physics, permits exhaustive reconstruction of the map. We find that high-penetrance genotypes tend to occupy the interior of environment-specific high-fitness regions and are mutationally robust, whereas lower-penetrance genotypes tend to lie near their boundaries and have greater mutational access to high-fitness regions for alternative environments. This global geometry generates a trade-off between penetrance and mutational adaptability. In evolutionary simulations, stronger phenotypic noise in a fixed environment increases the selective advantage of reliable expression, thereby favoring high penetrance and mutational robustness. Frequent environmental change instead favors mutational accessibility at the expense of penetrance. Thus, penetrance and adaptability are opposing consequences of the same global geometry, with environmental conditions determining their evolutionary balance.

Wearable device data enables continuous health monitoring, but suffers from structured missingness: features sharing a physical sensor drop out together. Deep imputation methods such as BRITS and SAITS have seen limited evaluation on multimodal physiological data under realistic missingness, and existing benchmarks use random-point holdout protocols that incorrectly assume missingness is independent across features and time. Using data from a person with epilepsy recorded on a Garmin smartwatch, we develop an evaluation protocol that mines contiguous missing-run templates from training data, stratifies them by per-feature gap-length quantiles, and injects them as block masks with preserved co-missingness structure. A matched training protocol exposing models to the same missingness distribution reduces BRITS's severe-gap MAE by 43%, demonstrating the potential benefit of the proposed evaluation and training protocol within this single-participant dataset. We further extend BRITS with time-of-day encoding and a circadian harmonic channel. No single model dominates: linear interpolation is optimal for slow-moving features over short gaps; extended BRITS achieves lower MAE on dynamic cardiac features in moderate and severe gaps; and SAITS better preserves the ground-truth distribution by Jensen-Shannon distance despite higher MAE. Ultimately, model rankings strongly depend on evaluation designs. By exposing how traditional evaluation methods obscure true model capabilities, our transferable protocol establishes critical steps towards developing better imputation strategies for future multi-sensor wearable datasets.

Reproducibility of heart rate variability (HRV) analysis is limited by differences in preprocessing and computational conventions across software platforms. We developed HRV Studio, an open-source PyQt6-based desktop application integrating transparent HRV analysis with automated quality-control (QC) diagnostics. Validation included large-scale agreement with NeuroKit2, targeted Kubios benchmarking, spectral-method comparison, synthetic perturbation testing, recording-duration sensitivity analysis, and arrhythmia-focused QC stress testing. HRV Studio showed near-identical agreement for the widely used time-domain indices RMSSD and SDNN under matched conditions. In the primary five-minute NeuroKit2 comparison, frequency-domain median relative errors were 1.35% for LF, 0.18% for HF, and 1.41% for LF/HF, while VLF remained more convention-sensitive (37.79%). Nonlinear Poincaré indices also demonstrated high consistency. Sequence-harmonized Kubios benchmarking confirmed near-identical agreement for time-domain and nonlinear indices and strong agreement for most frequency-domain measures. Extended ten-minute analyses reproduced the same overall pattern with lower disagreement for some convention-sensitive spectral outputs. Synthetic and arrhythmia stress tests maintained 100% numerical stability while consistently triggering QC warnings. Overall, HRV Studio provides a transparent and reproducible platform for HRV research, with strong cross-platform consistency when NN sequences, preprocessing, and analytical conventions are harmonized. Stress-test results indicate computational robustness rather than clinical validation.

Facial attractiveness has been linked to statistical regularities such as symmetry and averageness, suggesting that beauty may depend on the ease with which a face is perceived. We empirically test this hypothesis by training variational autoencoders on four face datasets without attractiveness supervision and evaluating their representations on the 597 faces from the Chicago Face Database. Across models, human attractiveness ratings closely aligns with the direction defined by the VAE evidence lower bound (ELBO) in rate-distortion space. Independently learned latent spaces contain an attractiveness direction that transfers strongly across random initializations and training data. We also find that attractive faces are more prototypical in both shape and latent space. Our results connect classic accounts of aesthetics with learned generative models and provide empirical support for a variational interpretation of the processing fluency theory of aesthetic pleasure.