Daily Papers

Nucleotide sequences constitute the fundamental genetic basis of biological systems, rendering viral genomic analysis critical for biomedical advancement. Despite progress in biological foundation models, specifically nucleotide foundation models (NFMs), the field lacks a unified standard for viral genomics to facilitate community development and enforce biosecurity constraints. To address this, we introduce ViroBench, the first comprehensive and large-scale benchmark specifically designed for NFMs in viral settings. ViroBench evaluates models across two critical dimensions: biological understanding and latent biosecurity risk, covering 18 diverse scenarios within 4 task types. Extensive evaluation of 66 NFMs across diverse architectures yields three critical conclusions. Firstly, NFMs exhibit a performance degradation in biological understanding under phylogenetic and temporal shifts, indicating weak extrapolation capabilities. Secondly, generation tasks reveal a decoupling between statistical likelihood and biological functional validity, posing latent biosecurity risks. Thirdly, controlled ablation studies reveal that taxonomic diversity in pretraining data outweighs parameter scale. Specifically, a lightweight baseline trained on diverse data achieves a 67.5% performance gain over its original model. Overall, ViroBench provides interpretable, diagnostic evaluations and a reproducible measurement framework for future research on viral nucleotide foundation models. The datasets and code are publicly available at https://github.com/QIANJINYDX/ViroBench.

Predicting spatial gene expression from H&E histology offers a scalable and clinically accessible alternative to sequencing, but realizing clinical impact requires models that generalize across cancer types and capture biologically coherent signals. Prior work is often limited to per-cancer settings and variance-based evaluation, leaving functional relevance underexplored. We introduce HistoPrism, an efficient transformer-based architecture for pan-cancer prediction of gene expression from histology. To evaluate biological meaning, we introduce a pathway-level benchmark, shifting assessment from isolated gene-level variance to coherent functional pathways. HistoPrism not only surpasses prior state-of-the-art models on highly variable genes , but also more importantly, achieves substantial gains on pathway-level prediction, demonstrating its ability to recover biologically coherent transcriptomic patterns. With strong pan-cancer generalization and improved efficiency, HistoPrism establishes a new standard for clinically relevant transcriptomic modeling from routinely available histology.

Medical large language models (LLMs) research often makes bold claims, from encoding clinical knowledge to reasoning like a physician. These claims are usually backed by evaluation on competitive benchmarks; a tradition inherited from mainstream machine learning. But how do we separate real progress from a leaderboard flex? Medical LLM benchmarks, much like those in other fields, are arbitrarily constructed using medical licensing exam questions. For these benchmarks to truly measure progress, they must accurately capture the real-world tasks they aim to represent. In this position paper, we argue that medical LLM benchmarks should (and indeed can) be empirically evaluated for their construct validity. In the psychological testing literature, "construct validity" refers to the ability of a test to measure an underlying "construct", that is the actual conceptual target of evaluation. By drawing an analogy between LLM benchmarks and psychological tests, we explain how frameworks from this field can provide empirical foundations for validating benchmarks. To put these ideas into practice, we use real-world clinical data in proof-of-concept experiments to evaluate popular medical LLM benchmarks and report significant gaps in their construct validity. Finally, we outline a vision for a new ecosystem of medical LLM evaluation centered around the creation of valid benchmarks.

We propose a computationally efficient inferential procedure for longitudinal function-on-function regression. The method follows a marginal three-step approach: (1) fit massive pointwise longitudinal scalar-on-function regression models, (2) smooth the resulting estimates along the bivariate functional domain, and (3) compute confidence bands using either an analytic approach for Gaussian data or a cluster bootstrap for Gaussian or non-Gaussian data. Simulation studies demonstrate that the proposed method achieves accurate estimation and valid inference, while substantially reducing computational burden compared to existing approaches. Methods are motivated by a physical activity intervention trial in older adults where high-dimensional wearable data were collected longitudinally across multiple visits. Our applications reveal significant increases in physical activity in the morning using interpersonal intervention strategies, but not intrapersonal strategies. The proposed methods are implemented in an R package.

Scientific discovery in digital health requires converting continuous physiological signals from wearable devices into clinically actionable biomarkers. We introduce CoDaS (AI Co-Data-Scientist), a multi-agent system that structures biomarker discovery as an iterative process combining hypothesis generation, statistical analysis, adversarial validation, and literature-grounded reasoning with human oversight using large-scale wearable datasets. Across three cohorts totaling 9,279 participant-observations, CoDaS identified 41 candidate digital biomarkers for mental health and 25 for metabolic outcomes, each subjected to an internal validation battery spanning replication, stability, robustness, and discriminative power. Across two independent depression cohorts, CoDaS surfaced circadian instability-related features in both datasets, reflected in sleep duration variability (DWB, ρ= 0.252, p < 0.001) and sleep onset variability (GLOBEM, ρ= 0.126, p < 0.001). In a metabolic cohort, CoDaS derived a cardiovascular fitness index (steps/resting heart rate; ρ= -0.374, p < 0.001), and recovered established clinical associations, including the hepatic function ratio (AST/ALT; ρ= -0.375, p < 0.001), a known correlate of insulin resistance. Incorporating CoDaS-derived features alongside demographic variables led to modest but consistent improvements in predictive performance, with cross-validated ΔR^2 increases of 0.040 for depression and 0.021 for insulin resistance. These findings suggest that CoDaS enables systematic and traceable hypothesis generation and prioritization for biomarker discovery from large-scale wearable data.

Large language models (LLMs) have shown growing promise in biomedical research, particularly for knowledge-driven interpretation tasks. However, their ability to reliably reason from gene-level knowledge to functional understanding, a core requirement for knowledge-enhanced cell atlas interpretation, remains largely underexplored. To address this gap, we introduce SciHorizon-GENE, a large-scale gene-centric benchmark constructed from authoritative biological databases. The benchmark integrates curated knowledge for over 190K human genes and comprises more than 540K questions covering diverse gene-to-function reasoning scenarios relevant to cell type annotation, functional interpretation, and mechanism-oriented analysis. Motivated by behavioral patterns observed in preliminary examinations, SciHorizon-GENE evaluates LLMs along four biologically critical perspectives: research attention sensitivity, hallucination tendency, answer completeness, and literature influence, explicitly targeting failure modes that limit the safe adoption of LLMs in biological interpretation pipelines. We systematically evaluate a wide range of state-of-the-art general-purpose and biomedical LLMs, revealing substantial heterogeneity in gene-level reasoning capabilities and persistent challenges in generating faithful, complete, and literature-grounded functional interpretations. Our benchmark establishes a systematic foundation for analyzing LLM behavior at the gene scale and offers insights for model selection and development, with direct relevance to knowledge-enhanced biological interpretation.

Functional grasping is essential for humans to perform specific tasks, such as grasping scissors by the finger holes to cut materials or by the blade to safely hand them over. Enabling dexterous robot hands with functional grasping capabilities is crucial for their deployment to accomplish diverse real-world tasks. Recent research in dexterous grasping, however, often focuses on power grasps while overlooking task- and object-specific functional grasping poses. In this paper, we introduce FunGrasp, a system that enables functional dexterous grasping across various robot hands and performs one-shot transfer to unseen objects. Given a single RGBD image of functional human grasping, our system estimates the hand pose and transfers it to different robotic hands via a human-to-robot (H2R) grasp retargeting module. Guided by the retargeted grasping poses, a policy is trained through reinforcement learning in simulation for dynamic grasping control. To achieve robust sim-to-real transfer, we employ several techniques including privileged learning, system identification, domain randomization, and gravity compensation. In our experiments, we demonstrate that our system enables diverse functional grasping of unseen objects using single RGBD images, and can be successfully deployed across various dexterous robot hands. The significance of the components is validated through comprehensive ablation studies. Project page: https://hly-123.github.io/FunGrasp/ .

Biological protocols are fundamental to reproducible and safe life science research. While LLMs excel on general tasks, their systematic evaluation on these highly specialized, accuracy-critical, and inherently procedural texts remains limited. In this work, we present BioProBench, the first large-scale, integrated multi-task benchmark for biological protocol understanding and reasoning. While limited benchmarks have touched upon specific aspects like protocol QA, BioProBench provides a comprehensive suite of five core tasks: Protocol Question Answering, Step Ordering, Error Correction, Protocol Generation, and Protocol Reasoning, enabling a holistic evaluation of LLMs on procedural biological texts. Built upon 27K original protocols, it yields nearly 556K high-quality structured instances. We evaluate 12 mainstream open/closed-source LLMs on BioProBench. Experimental results reveal that while top models preform well on surface understanding tasks, struggle significantly with deep reasoning and structured generation tasks like ordering and generation. Furthermore, model comparisons reveal diverse performance: certain open-source models approach closed-source levels on some tasks, yet bio-specific small models lag behind general LLMs, indicating limitations on complex procedural content. Overall, our findings underscore that procedural reasoning within biological protocols represents a significant challenge for current LLMs. BioProBench serves as a standardized framework to diagnose these specific limitations and guide the development of AI systems better equipped for safely automating complex scientific procedures. The code and data are available at: https://github.com/YuyangSunshine/bioprotocolbench and https://huggingface.co/datasets/GreatCaptainNemo/BioProBench.

Morphological traits are physical characteristics of biological organisms that provide vital clues on how organisms interact with their environment. Yet extracting these traits remains a slow, expert-driven process, limiting their use in large-scale ecological studies. A major bottleneck is the absence of high-quality datasets linking biological images to trait-level annotations. In this work, we demonstrate that sparse autoencoders trained on foundation-model features yield monosemantic, spatially grounded neurons that consistently activate on meaningful morphological parts. Leveraging this property, we introduce a trait annotation pipeline that localizes salient regions and uses vision-language prompting to generate interpretable trait descriptions. Using this approach, we construct Bioscan-Traits, a dataset of 80K trait annotations spanning 19K insect images from BIOSCAN-5M. Human evaluation confirms the biological plausibility of the generated morphological descriptions. We assess design sensitivity through a comprehensive ablation study, systematically varying key design choices and measuring their impact on the quality of the resulting trait descriptions. By annotating traits with a modular pipeline rather than prohibitively expensive manual efforts, we offer a scalable way to inject biologically meaningful supervision into foundation models, enable large-scale morphological analyses, and bridge the gap between ecological relevance and machine-learning practicality.

It is desirable for statistical models to detect signals of interest independently of their position. If the data is generated by some smooth process, this additional structure should be taken into account. We introduce a new class of neural networks that are shift invariant and preserve smoothness of the data: functional neural networks (FNNs). For this, we use methods from functional data analysis (FDA) to extend multi-layer perceptrons and convolutional neural networks to functional data. We propose different model architectures, show that the models outperform a benchmark model from FDA in terms of accuracy and successfully use FNNs to classify electroencephalography (EEG) data.

Exposing meaningful and interpretable neural interactions is critical to understanding neural circuits. Inferred neural interactions from neural signals primarily reflect functional interactions. In a long experiment, subject animals may experience different stages defined by the experiment, stimuli, or behavioral states, and hence functional interactions can change over time. To model dynamically changing functional interactions, prior work employs state-switching generalized linear models with hidden Markov models (i.e., HMM-GLMs). However, we argue they lack biological plausibility, as functional interactions are shaped and confined by the underlying anatomical connectome. Here, we propose a novel prior-informed state-switching GLM. We introduce both a Gaussian prior and a one-hot prior over the GLM in each state. The priors are learnable. We will show that the learned prior should capture the state-constant interaction, shedding light on the underlying anatomical connectome and revealing more likely physical neuron interactions. The state-dependent interaction modeled by each GLM offers traceability to capture functional variations across multiple brain states. Our methods effectively recover true interaction structures in simulated data, achieve the highest predictive likelihood with real neural datasets, and render interaction structures and hidden states more interpretable when applied to real neural data.

The vastness of the design space created by the combination of a large number of computational mechanisms, including machine learning, is an obstacle to creating an artificial general intelligence (AGI). Brain-inspired AGI development, in other words, cutting down the design space to look more like a biological brain, which is an existing model of a general intelligence, is a promising plan for solving this problem. However, it is difficult for an individual to design a software program that corresponds to the entire brain because the neuroscientific data required to understand the architecture of the brain are extensive and complicated. The whole-brain architecture approach divides the brain-inspired AGI development process into the task of designing the brain reference architecture (BRA) -- the flow of information and the diagram of corresponding components -- and the task of developing each component using the BRA. This is called BRA-driven development. Another difficulty lies in the extraction of the operating principles necessary for reproducing the cognitive-behavioral function of the brain from neuroscience data. Therefore, this study proposes the Structure-constrained Interface Decomposition (SCID) method, which is a hypothesis-building method for creating a hypothetical component diagram consistent with neuroscientific findings. The application of this approach has begun for building various regions of the brain. Moving forward, we will examine methods of evaluating the biological plausibility of brain-inspired software. This evaluation will also be used to prioritize different computational mechanisms, which should be merged, associated with the same regions of the brain.

Artificial neural networks are being proposed as models of parts of the brain. The networks are compared to recordings of biological neurons, and good performance in reproducing neural responses is considered to support the model's validity. A key question is how much this system identification approach tells us about brain computation. Does it validate one model architecture over another? We evaluate the most commonly used comparison techniques, such as a linear encoding model and centered kernel alignment, to correctly identify a model by replacing brain recordings with known ground truth models. System identification performance is quite variable; it also depends significantly on factors independent of the ground truth architecture, such as stimuli images. In addition, we show the limitations of using functional similarity scores in identifying higher-level architectural motifs.

Unlocking deep, interpretable biological reasoning from complex genomic data is a major AI challenge hindering scientific discovery. Current DNA foundation models, despite strong sequence representation, struggle with multi-step reasoning and lack inherent transparent, biologically intuitive explanations. We introduce BioReason, a pioneering architecture that, for the first time, deeply integrates a DNA foundation model with a Large Language Model (LLM). This novel connection enables the LLM to directly process and reason with genomic information as a fundamental input, fostering a new form of multimodal biological understanding. BioReason's sophisticated multi-step reasoning is developed through supervised fine-tuning and targeted reinforcement learning, guiding the system to generate logical, biologically coherent deductions. On biological reasoning benchmarks including KEGG-based disease pathway prediction - where accuracy improves from 88% to 97% - and variant effect prediction, BioReason demonstrates an average 15% performance gain over strong single-modality baselines. BioReason reasons over unseen biological entities and articulates decision-making through interpretable, step-by-step biological traces, offering a transformative approach for AI in biology that enables deeper mechanistic insights and accelerates testable hypothesis generation from genomic data. Data, code, and checkpoints are publicly available at https://github.com/bowang-lab/BioReason

Images are increasingly becoming the currency for documenting biodiversity on the planet, providing novel opportunities for accelerating scientific discoveries in the field of organismal biology, especially with the advent of large vision-language models (VLMs). We ask if pre-trained VLMs can aid scientists in answering a range of biologically relevant questions without any additional fine-tuning. In this paper, we evaluate the effectiveness of 12 state-of-the-art (SOTA) VLMs in the field of organismal biology using a novel dataset, VLM4Bio, consisting of 469K question-answer pairs involving 30K images from three groups of organisms: fishes, birds, and butterflies, covering five biologically relevant tasks. We also explore the effects of applying prompting techniques and tests for reasoning hallucination on the performance of VLMs, shedding new light on the capabilities of current SOTA VLMs in answering biologically relevant questions using images. The code and datasets for running all the analyses reported in this paper can be found at https://github.com/sammarfy/VLM4Bio.

The brain has computational capabilities that surpass those of modern systems, being able to solve complex problems efficiently in a simple way. Neuromorphic engineering aims to mimic biology in order to develop new systems capable of incorporating such capabilities. Bio-inspired learning systems continue to be a challenge that must be solved, and much work needs to be done in this regard. Among all brain regions, the hippocampus stands out as an autoassociative short-term memory with the capacity to learn and recall memories from any fragment of them. These characteristics make the hippocampus an ideal candidate for developing bio-inspired learning systems that, in addition, resemble content-addressable memories. Therefore, in this work we propose a bio-inspired spiking content-addressable memory model based on the CA3 region of the hippocampus with the ability to learn, forget and recall memories, both orthogonal and non-orthogonal, from any fragment of them. The model was implemented on the SpiNNaker hardware platform using Spiking Neural Networks. A set of experiments based on functional, stress and applicability tests were performed to demonstrate its correct functioning. This work presents the first hardware implementation of a fully-functional bio-inspired spiking hippocampal content-addressable memory model, paving the way for the development of future more complex neuromorphic systems.

Large Language Models (LLMs) are often described as being instances of foundation models - that is, models that transfer strongly across various tasks and conditions in few-show or zero-shot manner, while exhibiting scaling laws that predict function improvement when increasing the pre-training scale. These claims of excelling in different functions and tasks rely on measurements taken across various sets of standardized benchmarks showing high scores for such models. We demonstrate here a dramatic breakdown of function and reasoning capabilities of state-of-the-art models trained at the largest available scales which claim strong function, using a simple, short, conventional common sense problem formulated in concise natural language, easily solvable by humans. The breakdown is dramatic, as models also express strong overconfidence in their wrong solutions, while providing often non-sensical "reasoning"-like explanations akin to confabulations to justify and backup the validity of their clearly failed responses, making them sound plausible. Various standard interventions in an attempt to get the right solution, like various type of enhanced prompting, or urging the models to reconsider the wrong solutions again by multi step re-evaluation, fail. We take these initial observations to the scientific and technological community to stimulate urgent re-assessment of the claimed capabilities of current generation of LLMs, Such re-assessment also requires common action to create standardized benchmarks that would allow proper detection of such basic reasoning deficits that obviously manage to remain undiscovered by current state-of-the-art evaluation procedures and benchmarks. Code for reproducing experiments in the paper and raw experiments data can be found at https://github.com/LAION-AI/AIW

Large language models (LLMs) trained on internet-scale corpora can exhibit systematic biases that increase the probability of unwanted behavior. In this study, we examined potential biases towards synthetic vs. biological technological solutions across four domains (materials, energy, manufacturing, and algorithms). A sample of 5 frontier and 5 open-weight models were measured using 50 curated Bioalignment prompts with a Kelly criterion-inspired evaluation framework. According to this metric, most models were not bioaligned in that they exhibit biases in favor of synthetic (non-biological) solutions. We next examined if fine-tuning could increase the preferences of two open-weight models, Llama 3.2-3B-Instruct and Qwen2.5-3B-Instruct, for biological-based approaches. A curated corpus of ~22M tokens from 6,636 PMC articles emphasizing biological problem-solving was used first to fine-tune Llama 3B with a mixed corpus of continued training and instruction-formatted. This was then extended to Qwen 3B using instruction-formatted only. We found that QLoRA fine-tuning significantly increased the scoring of biological solutions for both models without degrading general capabilities (Holm-Bonferroni-corrected p < 0.001 and p < 0.01, respectively). This suggests that even a small amount of fine-tuning can change how models weigh the relative value of biological and bioinspired vs. synthetic approaches. Although this work focused on small open-weight LLMs, it may be extensible to much larger models and could be used to develop models that favor bio-based approaches. We release the benchmark, corpus, code, and adapter weights.

Large language models (LLMs) are having transformative impacts across a wide range of scientific fields, particularly in the biomedical sciences. Just as the goal of Natural Language Processing is to understand sequences of words, a major objective in biology is to understand biological sequences. Genomic Language Models (gLMs), which are LLMs trained on DNA sequences, have the potential to significantly advance our understanding of genomes and how DNA elements at various scales interact to give rise to complex functions. To showcase this potential, we highlight key applications of gLMs, including functional constraint prediction, sequence design, and transfer learning. Despite notable recent progress, however, developing effective and efficient gLMs presents numerous challenges, especially for species with large, complex genomes. Here, we discuss major considerations for developing and evaluating gLMs.

There is a concerted effort to build domain-general artificial intelligence in the form of universal neural network models with sufficient computational flexibility to solve a wide variety of cognitive tasks but without requiring fine-tuning on individual problem spaces and domains. To do this, models need appropriate priors and inductive biases, such that trained models can generalise to out-of-distribution examples and new problem sets. Here we provide an overview of the hallmarks endowing biological neural networks with the functionality needed for flexible cognition, in order to establish which features might also be important to achieve similar functionality in artificial systems. We specifically discuss the role of system-level distribution of network communication and recurrence, in addition to the role of short-term topological changes for efficient local computation. As machine learning models become more complex, these principles may provide valuable directions in an otherwise vast space of possible architectures. In addition, testing these inductive biases within artificial systems may help us to understand the biological principles underlying domain-general cognition.

Large language models lack persistent, structured memory for long-term interaction and context-sensitive retrieval. Expanding context windows does not solve this: recent evidence shows that context length alone degrades reasoning by up to 85% - even with perfect retrieval. We propose a bio-inspired memory framework grounded in complementary learning systems theory, cognitive behavioral therapy's belief hierarchy, dual-process cognition, and fuzzy-trace theory, organized around three principles: (1) Memory has valence, not just content - pre-computed emotional-associative summaries (valence vectors) organized in an emergent belief hierarchy inspired by Beck's cognitive model enable instant orientation before deliberation; (2) Retrieval defaults to System 1 with System 2 escalation - automatic spreading activation and passive priming as default, with deliberate retrieval only when needed, and graded epistemic states that address hallucination structurally; and (3) Encoding is active, present, and feedback-dependent - a thalamic gateway tags and routes information between stores, while the executive forms gists through curiosity-driven investigation, not passive exposure. Seven functional properties specify what any implementation must satisfy. Over time, the system converges toward System 1 processing - the computational analog of clinical expertise - producing interactions that become cheaper, not more expensive, with experience.

While Large Language Models (LLMs) can generate fluent and convincing responses, they are not necessarily correct. This is especially apparent in the popular decompose-then-verify factuality evaluation pipeline, where LLMs evaluate generations by decomposing the generations into individual, valid claims. Factuality evaluation is especially important for medical answers, since incorrect medical information could seriously harm the patient. However, existing factuality systems are a poor match for the medical domain, as they are typically only evaluated on objective, entity-centric, formulaic texts such as biographies and historical topics. This differs from condition-dependent, conversational, hypothetical, sentence-structure diverse, and subjective medical answers, which makes decomposition into valid facts challenging. We propose MedScore, a new pipeline to decompose medical answers into condition-aware valid facts and verify against in-domain corpora. Our method extracts up to three times more valid facts than existing methods, reducing hallucination and vague references, and retaining condition-dependency in facts. The resulting factuality score substantially varies by decomposition method, verification corpus, and used backbone LLM, highlighting the importance of customizing each step for reliable factuality evaluation by using our generalizable and modularized pipeline for domain adaptation.

We present a smoothly broken power law functional form (that we refer to as a Broken Neural Scaling Law (BNSL)) that accurately models & extrapolates the scaling behaviors of deep neural networks (i.e. how the evaluation metric of interest varies as amount of compute used for training (or inference), number of model parameters, training dataset size, model input size, number of training steps, or upstream performance varies) for various architectures & for each of various tasks within a large & diverse set of upstream & downstream tasks, in zero-shot, prompted, & finetuned settings. This set includes large-scale vision, language, audio, video, diffusion, generative modeling, multimodal learning, contrastive learning, AI alignment, AI capabilities, robotics, out-of-distribution (OOD) generalization, continual learning, transfer learning, uncertainty estimation / calibration, OOD detection, adversarial robustness, distillation, sparsity, retrieval, quantization, pruning, fairness, molecules, computer programming/coding, math word problems, "emergent phase transitions", arithmetic, supervised learning, unsupervised/self-supervised learning, & reinforcement learning (single agent & multi-agent). When compared to other functional forms for neural scaling, this functional form yields extrapolations of scaling behavior that are considerably more accurate on this set. Moreover, this functional form accurately models & extrapolates scaling behavior that other functional forms are incapable of expressing such as the nonmonotonic transitions present in the scaling behavior of phenomena such as double descent & the delayed, sharp inflection points present in the scaling behavior of tasks such as arithmetic. Lastly, we use this functional form to glean insights about the limit of the predictability of scaling behavior. Code is available at https://github.com/ethancaballero/broken_neural_scaling_laws

There is widespread optimism that frontier Large Language Models (LLMs) and LLM-augmented systems have the potential to rapidly accelerate scientific discovery across disciplines. Today, many benchmarks exist to measure LLM knowledge and reasoning on textbook-style science questions, but few if any benchmarks are designed to evaluate language model performance on practical tasks required for scientific research, such as literature search, protocol planning, and data analysis. As a step toward building such benchmarks, we introduce the Language Agent Biology Benchmark (LAB-Bench), a broad dataset of over 2,400 multiple choice questions for evaluating AI systems on a range of practical biology research capabilities, including recall and reasoning over literature, interpretation of figures, access and navigation of databases, and comprehension and manipulation of DNA and protein sequences. Importantly, in contrast to previous scientific benchmarks, we expect that an AI system that can achieve consistently high scores on the more difficult LAB-Bench tasks would serve as a useful assistant for researchers in areas such as literature search and molecular cloning. As an initial assessment of the emergent scientific task capabilities of frontier language models, we measure performance of several against our benchmark and report results compared to human expert biology researchers. We will continue to update and expand LAB-Bench over time, and expect it to serve as a useful tool in the development of automated research systems going forward. A public subset of LAB-Bench is available for use at the following URL: https://huggingface.co/datasets/futurehouse/lab-bench

In recent years, there is strong emphasis on mining medical data using machine learning techniques. A common problem is to obtain a noiseless set of textual documents, with a relevant content for the research question, and developing a Question Answering (QA) model for a specific medical field. The purpose of this paper is to present a new methodology for building a medical dataset and obtain a QA model for analysis of symptoms and impact on daily life for a specific disease domain. The ``Mental Health'' forum was used, a forum dedicated to people suffering from schizophrenia and different mental disorders. Relevant posts of active users, who regularly participate, were extrapolated providing a new method of obtaining low-bias content and without privacy issues. Furthermore, it is shown how to pre-process the dataset to convert it into a QA dataset. The Bidirectional Encoder Representations from Transformers (BERT), DistilBERT, RoBERTa, and BioBERT models were fine-tuned and evaluated via F1-Score, Exact Match, Precision and Recall. Accurate empirical experiments demonstrated the effectiveness of the proposed method for obtaining an accurate dataset for QA model implementation. By fine-tuning the BioBERT QA model, we achieved an F1 score of 0.885, showing a considerable improvement and outperforming the state-of-the-art model for mental disorders domain.

Although large language models (LLMs) are increasingly capable, these capabilities are unevenly distributed: they excel at formal linguistic tasks, such as producing fluent, grammatical text, but struggle more with functional linguistic tasks like reasoning and consistent fact retrieval. Inspired by neuroscience, recent work suggests that to succeed on both formal and functional linguistic tasks, LLMs should use different mechanisms for each; such localization could either be built-in or emerge spontaneously through training. In this paper, we ask: do current models, with fast-improving functional linguistic abilities, exhibit distinct localization of formal and functional linguistic mechanisms? We answer this by finding and comparing the "circuits", or minimal computational subgraphs, responsible for various formal and functional tasks. Comparing 5 LLMs across 10 distinct tasks, we find that while there is indeed little overlap between circuits for formal and functional tasks, there is also little overlap between formal linguistic tasks, as exists in the human brain. Thus, a single formal linguistic network, unified and distinct from functional task circuits, remains elusive. However, in terms of cross-task faithfulness - the ability of one circuit to solve another's task - we observe a separation between formal and functional mechanisms, suggesting that shared mechanisms between formal tasks may exist.

Large language models (LLMs) have emerged as powerful tools for analyzing complex datasets. Recent studies demonstrate their potential to generate useful, personalized responses when provided with patient-specific health information that encompasses lifestyle, biomarkers, and context. As LLM-driven health applications are increasingly adopted, rigorous and efficient one-sided evaluation methodologies are crucial to ensure response quality across multiple dimensions, including accuracy, personalization and safety. Current evaluation practices for open-ended text responses heavily rely on human experts. This approach introduces human factors and is often cost-prohibitive, labor-intensive, and hinders scalability, especially in complex domains like healthcare where response assessment necessitates domain expertise and considers multifaceted patient data. In this work, we introduce Adaptive Precise Boolean rubrics: an evaluation framework that streamlines human and automated evaluation of open-ended questions by identifying gaps in model responses using a minimal set of targeted rubrics questions. Our approach is based on recent work in more general evaluation settings that contrasts a smaller set of complex evaluation targets with a larger set of more precise, granular targets answerable with simple boolean responses. We validate this approach in metabolic health, a domain encompassing diabetes, cardiovascular disease, and obesity. Our results demonstrate that Adaptive Precise Boolean rubrics yield higher inter-rater agreement among expert and non-expert human evaluators, and in automated assessments, compared to traditional Likert scales, while requiring approximately half the evaluation time of Likert-based methods. This enhanced efficiency, particularly in automated evaluation and non-expert contributions, paves the way for more extensive and cost-effective evaluation of LLMs in health.

Foundation models (FMs) have exhibited remarkable performance across a wide range of downstream tasks in many domains. Nevertheless, general-purpose FMs often face challenges when confronted with domain-specific problems, due to their limited access to the proprietary training data in a particular domain. In biomedicine, there are various biological modalities, such as molecules, proteins, and cells, which are encoded by the language of life and exhibit significant modality gaps with human natural language. In this paper, we introduce BioMedGPT, an open multimodal generative pre-trained transformer (GPT) for biomedicine, to bridge the gap between the language of life and human natural language. BioMedGPT allows users to easily ``communicate'' with diverse biological modalities through free text, which is the first of its kind. BioMedGPT aligns different biological modalities with natural language via a large generative language model, namely, BioMedGPT-LM. We publish BioMedGPT-10B, which unifies the feature spaces of molecules, proteins, and natural language via encoding and alignment. Through fine-tuning, BioMedGPT-10B outperforms or is on par with human and significantly larger general-purpose foundation models on the biomedical QA task. It also demonstrates promising performance in the molecule QA and protein QA tasks, which could greatly accelerate the discovery of new drugs and therapeutic targets. In addition, BioMedGPT-LM-7B is the first large generative language model based on Llama2 in the biomedical domain, therefore is commercial friendly. Both BioMedGPT-10B and BioMedGPT-LM-7B are open-sourced to the research community. In addition, we publish the datasets that are meticulously curated for the alignment of multi-modalities, i.e., PubChemQA and UniProtQA. All the models, codes, and datasets are available at https://github.com/PharMolix/OpenBioMed.

Legged locomotion is a challenging task in the field of robotics but a rather simple one in nature. This motivates the use of biological methodologies as solutions to this problem. Central pattern generators are neural networks that are thought to be responsible for locomotion in humans and some animal species. As for robotics, many attempts were made to reproduce such systems and use them for a similar goal. One interesting design model is based on spiking neural networks. This model is the main focus of this work, as its contribution is not limited to engineering but also applicable to neuroscience. This paper introduces a new general framework for building central pattern generators that are task-independent, biologically plausible, and rely on learning methods. The abilities and properties of the presented approach are not only evaluated in simulation but also in a robotic experiment. The results are very promising as the used robot was able to perform stable walking at different speeds and to change speed within the same gait cycle.

Biomedical Foundation Models (FMs) are rapidly transforming AI-enabled healthcare research and entering clinical validation. However, their susceptibility to learning non-biological technical features -- including variations in surgical/endoscopic techniques, laboratory procedures, and scanner hardware -- poses risks for clinical deployment. We present the first systematic investigation of pathology FM robustness to non-biological features. Our work (i) introduces measures to quantify FM robustness, (ii) demonstrates the consequences of limited robustness, and (iii) proposes a framework for FM robustification to mitigate these issues. Specifically, we developed PathoROB, a robustness benchmark with three novel metrics, including the robustness index, and four datasets covering 28 biological classes from 34 medical centers. Our experiments reveal robustness deficits across all 20 evaluated FMs, and substantial robustness differences between them. We found that non-robust FM representations can cause major diagnostic downstream errors and clinical blunders that prevent safe clinical adoption. Using more robust FMs and post-hoc robustification considerably reduced (but did not yet eliminate) the risk of such errors. This work establishes that robustness evaluation is essential for validating pathology FMs before clinical adoption and demonstrates that future FM development must integrate robustness as a core design principle. PathoROB provides a blueprint for assessing robustness across biomedical domains, guiding FM improvement efforts towards more robust, representative, and clinically deployable AI systems that prioritize biological information over technical artifacts.

In this paper, we propose a real-world benchmark for studying robotic learning in the context of functional manipulation: a robot needs to accomplish complex long-horizon behaviors by composing individual manipulation skills in functionally relevant ways. The core design principles of our Functional Manipulation Benchmark (FMB) emphasize a harmonious balance between complexity and accessibility. Tasks are deliberately scoped to be narrow, ensuring that models and datasets of manageable scale can be utilized effectively to track progress. Simultaneously, they are diverse enough to pose a significant generalization challenge. Furthermore, the benchmark is designed to be easily replicable, encompassing all essential hardware and software components. To achieve this goal, FMB consists of a variety of 3D-printed objects designed for easy and accurate replication by other researchers. The objects are procedurally generated, providing a principled framework to study generalization in a controlled fashion. We focus on fundamental manipulation skills, including grasping, repositioning, and a range of assembly behaviors. The FMB can be used to evaluate methods for acquiring individual skills, as well as methods for combining and ordering such skills to solve complex, multi-stage manipulation tasks. We also offer an imitation learning framework that includes a suite of policies trained to solve the proposed tasks. This enables researchers to utilize our tasks as a versatile toolkit for examining various parts of the pipeline. For example, researchers could propose a better design for a grasping controller and evaluate it in combination with our baseline reorientation and assembly policies as part of a pipeline for solving multi-stage tasks. Our dataset, object CAD files, code, and evaluation videos can be found on our project website: https://functional-manipulation-benchmark.github.io

Images of the natural world, collected by a variety of cameras, from drones to individual phones, are increasingly abundant sources of biological information. There is an explosion of computational methods and tools, particularly computer vision, for extracting biologically relevant information from images for science and conservation. Yet most of these are bespoke approaches designed for a specific task and are not easily adaptable or extendable to new questions, contexts, and datasets. A vision model for general organismal biology questions on images is of timely need. To approach this, we curate and release TreeOfLife-10M, the largest and most diverse ML-ready dataset of biology images. We then develop BioCLIP, a foundation model for the tree of life, leveraging the unique properties of biology captured by TreeOfLife-10M, namely the abundance and variety of images of plants, animals, and fungi, together with the availability of rich structured biological knowledge. We rigorously benchmark our approach on diverse fine-grained biology classification tasks, and find that BioCLIP consistently and substantially outperforms existing baselines (by 17% to 20% absolute). Intrinsic evaluation reveals that BioCLIP has learned a hierarchical representation conforming to the tree of life, shedding light on its strong generalizability. Our code, models and data will be made available at https://github.com/Imageomics/bioclip.

We study the problem of optimizing biological sequences, e.g., proteins, DNA, and RNA, to maximize a black-box score function that is only evaluated in an offline dataset. We propose a novel solution, bootstrapped training of score-conditioned generator (BootGen) algorithm. Our algorithm repeats a two-stage process. In the first stage, our algorithm trains the biological sequence generator with rank-based weights to enhance the accuracy of sequence generation based on high scores. The subsequent stage involves bootstrapping, which augments the training dataset with self-generated data labeled by a proxy score function. Our key idea is to align the score-based generation with a proxy score function, which distills the knowledge of the proxy score function to the generator. After training, we aggregate samples from multiple bootstrapped generators and proxies to produce a diverse design. Extensive experiments show that our method outperforms competitive baselines on biological sequential design tasks. We provide reproducible source code: https://github.com/kaist-silab/bootgen{https://github.com/kaist-silab/bootgen}.

Recent advancements in biological research leverage the integration of molecules, proteins, and natural language to enhance drug discovery. However, current models exhibit several limitations, such as the generation of invalid molecular SMILES, underutilization of contextual information, and equal treatment of structured and unstructured knowledge. To address these issues, we propose BioT5, a comprehensive pre-training framework that enriches cross-modal integration in biology with chemical knowledge and natural language associations. BioT5 utilizes SELFIES for 100% robust molecular representations and extracts knowledge from the surrounding context of bio-entities in unstructured biological literature. Furthermore, BioT5 distinguishes between structured and unstructured knowledge, leading to more effective utilization of information. After fine-tuning, BioT5 shows superior performance across a wide range of tasks, demonstrating its strong capability of capturing underlying relations and properties of bio-entities. Our code is available at https://github.com/QizhiPei/BioT5{Github}.

With the advancement of AI capabilities, AI reviewers are beginning to be deployed in scientific peer review, yet their capability and credibility remain in question: many scientists simply view them as probabilistic systems without the expertise to evaluate research, while other researchers are more optimistic about their readiness without concrete evidence. Understanding what AI reviewers do well, where they fall short, and what challenges remain is essential. However, existing evaluations of AI reviewers have focused on whether their verdicts match human verdicts (e.g., score alignment, acceptance prediction), which is insufficient to characterize their capabilities and limits. In this paper, we close this gap through a large-scale expert annotation study, in which 45 domain scientists in Physical, Biological, and Health Sciences spent 469 hours rating 2,960 individual criticisms (each targeting one specific aspect of a paper) from human-written and AI-generated reviews of 82 Nature-family papers on correctness, significance, and sufficiency of evidence. On a composite of all three dimensions, a reviewing agent powered by GPT-5.2 scores above each paper's top-rated human reviewer (60.0% vs. 48.2%, p = 0.009), while all three AI reviewers (including Gemini 3.0 Pro and Claude Opus 4.5) exceed the lowest-rated human across every dimension. AI reviewers' accurate criticisms are also more often rated significant and well-evidenced, and surface a distinct 26% of issues no human raises. However, AI reviewers overlap far more than humans do (21% vs. 3% for cross-reviewer pairs), and exhibit 16 recurring weaknesses humans do not share, such as limited subfield knowledge, lack of long context management over multiple files, and overly critical stance on minor issues. Overall, our results position current AI reviewers as complements to, not substitutes for, human reviewers.

Large language models (LLMs) are increasingly applied in scientific research, offering new capabilities for knowledge discovery and reasoning. In single-cell biology, however, evaluation practices for both general and specialized LLMs remain inadequate: existing benchmarks are fragmented across tasks, adopt formats such as multiple-choice classification that diverge from real-world usage, and rely on metrics lacking interpretability and biological grounding. We present SC-ARENA, a natural language evaluation framework tailored to single-cell foundation models. SC-ARENA formalizes a virtual cell abstraction that unifies evaluation targets by representing both intrinsic attributes and gene-level interactions. Within this paradigm, we define five natural language tasks (cell type annotation, captioning, generation, perturbation prediction, and scientific QA) that probe core reasoning capabilities in cellular biology. To overcome the limitations of brittle string-matching metrics, we introduce knowledge-augmented evaluation, which incorporates external ontologies, marker databases, and scientific literature to support biologically faithful and interpretable judgments. Experiments and analysis across both general-purpose and domain-specialized LLMs demonstrate that (i) under the Virtual Cell unified evaluation paradigm, current models achieve uneven performance on biologically complex tasks, particularly those demanding mechanistic or causal understanding; and (ii) our knowledge-augmented evaluation framework ensures biological correctness, provides interpretable, evidence-grounded rationales, and achieves high discriminative capacity, overcoming the brittleness and opacity of conventional metrics. SC-Arena thus provides a unified and interpretable framework for assessing LLMs in single-cell biology, pointing toward the development of biology-aligned, generalizable foundation models.

While large language models (LLMs) have proven to be effective on a large variety of tasks, they are also known to hallucinate information. To measure whether an LLM prefers factually consistent continuations of its input, we propose a new benchmark called FIB(Factual Inconsistency Benchmark) that focuses on the task of summarization. Specifically, our benchmark involves comparing the scores an LLM assigns to a factually consistent versus a factually inconsistent summary for an input news article. For factually consistent summaries, we use human-written reference summaries that we manually verify as factually consistent. To generate summaries that are factually inconsistent, we generate summaries from a suite of summarization models that we have manually annotated as factually inconsistent. A model's factual consistency is then measured according to its accuracy, i.e.\ the proportion of documents where it assigns a higher score to the factually consistent summary. To validate the usefulness of FIB, we evaluate 23 large language models ranging from 1B to 176B parameters from six different model families including BLOOM and OPT. We find that existing LLMs generally assign a higher score to factually consistent summaries than to factually inconsistent summaries. However, if the factually inconsistent summaries occur verbatim in the document, then LLMs assign a higher score to these factually inconsistent summaries than factually consistent summaries. We validate design choices in our benchmark including the scoring method and source of distractor summaries. Our code and benchmark data can be found at https://github.com/r-three/fib.

Benchmarks shape scientific conclusions about model capabilities and steer model development. This creates a feedback loop: stronger benchmarks drive better models, and better models demand more discriminative benchmarks. Ensuring benchmark reliability is therefore essential for trustworthy evaluation and meaningful progress. In this work, we study benchmark reliability from a distributional perspective and introduce benchmark harmony, which measures how uniformly a model's performance is distributed across the subdomains of a benchmark. We posit that high harmony is a desirable benchmark property, indicating that the aggregate metric reflects uniform competence across subdomains. Across 19 multiple-choice benchmarks and five model families, we map each benchmark onto a mean-variance plane of harmony computed across models, where high mean and low variance signal more reliable evaluation. Our analysis shows that less harmonious benchmarks can give misleading results, since overall accuracy may be disproportionately influenced by specific subdomains. For instance, ARC-Easy is overwhelmed by questions on Biological Concepts, overshadowing other critical subdomains such as Geography, Physics, Chemistry, and Environmental Science. By recommending that harmony should be reported alongside accuracy, we reframe evaluation from simple performance averages to a more robust, distributionally reliable measurement of performance.

Natural language inference (NLI) is critical for complex decision-making in biomedical domain. One key question, for example, is whether a given biomedical mechanism is supported by experimental evidence. This can be seen as an NLI problem but there are no directly usable datasets to address this. The main challenge is that manually creating informative negative examples for this task is difficult and expensive. We introduce a novel semi-supervised procedure that bootstraps an NLI dataset from existing biomedical dataset that pairs mechanisms with experimental evidence in abstracts. We generate a range of negative examples using nine strategies that manipulate the structure of the underlying mechanisms both with rules, e.g., flip the roles of the entities in the interaction, and, more importantly, as perturbations via logical constraints in a neuro-logical decoding system. We use this procedure to create a novel dataset for NLI in the biomedical domain, called BioNLI and benchmark two state-of-the-art biomedical classifiers. The best result we obtain is around mid 70s in F1, suggesting the difficulty of the task. Critically, the performance on the different classes of negative examples varies widely, from 97% F1 on the simple role change negative examples, to barely better than chance on the negative examples generated using neuro-logic decoding.

Predicting gene function from its DNA sequence is a fundamental challenge in biology. Many deep learning models have been proposed to embed DNA sequences and predict their enzymatic function, leveraging information in public databases linking DNA sequences to an enzymatic function label. However, much of the scientific community's knowledge of biological function is not represented in these categorical labels, and is instead captured in unstructured text descriptions of mechanisms, reactions, and enzyme behavior. These descriptions are often captured alongside DNA sequences in biological databases, albeit in an unstructured manner. Deep learning of models predicting enzymatic function are likely to benefit from incorporating this multi-modal data encoding scientific knowledge of biological function. There is, however, no dataset designed for machine learning algorithms to leverage this multi-modal information. Here we propose a novel dataset and benchmark suite that enables the exploration and development of large multi-modal neural network models on gene DNA sequences and natural language descriptions of gene function. We present baseline performance on benchmarks for both unsupervised and supervised tasks that demonstrate the difficulty of this modeling objective, while demonstrating the potential benefit of incorporating multi-modal data types in function prediction compared to DNA sequences alone. Our dataset is at: https://hoarfrost-lab.github.io/BioTalk/.

Practical identifiability is a critical concern in data-driven modeling of mathematical systems. In this paper, we propose a novel framework for practical identifiability analysis to evaluate parameter identifiability in mathematical models of biological systems. Starting with a rigorous mathematical definition of practical identifiability, we demonstrate its equivalence to the invertibility of the Fisher Information Matrix. Our framework establishes the relationship between practical identifiability and coordinate identifiability, introducing a novel metric that simplifies and accelerates the evaluation of parameter identifiability compared to the profile likelihood method. Additionally, we introduce new regularization terms to address non-identifiable parameters, enabling uncertainty quantification and improving model reliability. To guide experimental design, we present an optimal data collection algorithm that ensures all model parameters are practically identifiable. Applications to Hill functions, neural networks, and dynamic biological models demonstrate the feasibility and efficiency of the proposed computational framework in uncovering critical biological processes and identifying key observable variables.

In the development of science, accurate and reproducible documentation of the experimental process is crucial. Automatic recognition of the actions in experiments from videos would help experimenters by complementing the recording of experiments. Towards this goal, we propose FineBio, a new fine-grained video dataset of people performing biological experiments. The dataset consists of multi-view videos of 32 participants performing mock biological experiments with a total duration of 14.5 hours. One experiment forms a hierarchical structure, where a protocol consists of several steps, each further decomposed into a set of atomic operations. The uniqueness of biological experiments is that while they require strict adherence to steps described in each protocol, there is freedom in the order of atomic operations. We provide hierarchical annotation on protocols, steps, atomic operations, object locations, and their manipulation states, providing new challenges for structured activity understanding and hand-object interaction recognition. To find out challenges on activity understanding in biological experiments, we introduce baseline models and results on four different tasks, including (i) step segmentation, (ii) atomic operation detection (iii) object detection, and (iv) manipulated/affected object detection. Dataset and code are available from https://github.com/aistairc/FineBio.

Biomedical researchers increasingly rely on large-scale structured databases for complex analytical tasks. However, current text-to-SQL systems often struggle to map qualitative scientific questions into executable SQL, particularly when implicit domain reasoning is required. We introduce BiomedSQL, the first benchmark explicitly designed to evaluate scientific reasoning in text-to-SQL generation over a real-world biomedical knowledge base. BiomedSQL comprises 68,000 question/SQL query/answer triples grounded in a harmonized BigQuery knowledge base that integrates gene-disease associations, causal inference from omics data, and drug approval records. Each question requires models to infer domain-specific criteria, such as genome-wide significance thresholds, effect directionality, or trial phase filtering, rather than rely on syntactic translation alone. We evaluate a range of open- and closed-source LLMs across prompting strategies and interaction paradigms. Our results reveal a substantial performance gap: GPT-o3-mini achieves 59.0% execution accuracy, while our custom multi-step agent, BMSQL, reaches 62.6%, both well below the expert baseline of 90.0%. BiomedSQL provides a new foundation for advancing text-to-SQL systems capable of supporting scientific discovery through robust reasoning over structured biomedical knowledge bases. Our dataset is publicly available at https://huggingface.co/datasets/NIH-CARD/BiomedSQL, and our code is open-source at https://github.com/NIH-CARD/biomedsql.

Vision Language Models (VLMs) are increasingly used for tasks like medical report generation and visual question answering. However, fluent diagnostic text does not guarantee safe visual understanding. In clinical practice, interpretation begins with pre-diagnostic sanity checks: verifying that the input is valid to read (correct modality and anatomy, plausible viewpoint and orientation, and no obvious integrity violations). Existing benchmarks largely assume this step is solved, and therefore miss a critical failure mode: a model can produce plausible narratives even when the input is inconsistent or invalid. We introduce MedObvious, a 1,880-task benchmark that isolates input validation as a set-level consistency capability over small multi-panel image sets: the model must identify whether any panel violates expected coherence. MedObvious spans five progressive tiers, from basic orientation/modality mismatches to clinically motivated anatomy/viewpoint verification and triage-style cues, and includes five evaluation formats to test robustness across interfaces. Evaluating 17 different VLMs, we find that sanity checking remains unreliable: several models hallucinate anomalies on normal (negative-control) inputs, performance degrades when scaling to larger image sets, and measured accuracy varies substantially between multiple-choice and open-ended settings. These results show that pre-diagnostic verification remains unsolved for medical VLMs and should be treated as a distinct, safety-critical capability before deployment.

Modern life sciences research is increasingly relying on artificial intelligence approaches to model biological systems, primarily centered around the use of machine learning (ML) models. Although ML is undeniably useful for identifying patterns in large, complex data sets, its widespread application in biological sciences represents a significant deviation from traditional methods of scientific inquiry. As such, the interplay between these models and scientific understanding in biology is a topic with important implications for the future of scientific research, yet it is a subject that has received little attention. Here, we draw from an epistemological toolkit to contextualize recent applications of ML in biological sciences under modern philosophical theories of understanding, identifying general principles that can guide the design and application of ML systems to model biological phenomena and advance scientific knowledge. We propose that conceptions of scientific understanding as information compression, qualitative intelligibility, and dependency relation modelling provide a useful framework for interpreting ML-mediated understanding of biological systems. Through a detailed analysis of two key application areas of ML in modern biological research - protein structure prediction and single cell RNA-sequencing - we explore how these features have thus far enabled ML systems to advance scientific understanding of their target phenomena, how they may guide the development of future ML models, and the key obstacles that remain in preventing ML from achieving its potential as a tool for biological discovery. Consideration of the epistemological features of ML applications in biology will improve the prospects of these methods to solve important problems and advance scientific understanding of living systems.

It is known that human speech and certain animal vocalizations can convey meaningful content because we can decipher the content that a given utterance does convey. This paper explores an alternative approach to determining whether a signal is meaningful, one that analyzes only the signal itself and is independent of what the conveyed meaning might be. We devise a method that takes a waveform as input and outputs a score indicating its degree of `meaningfulness`. We cluster contiguous portions of the input to minimize the total description length, and then take the length of the code of the assigned cluster labels as meaningfulness score. We evaluate our method empirically, against several baselines, and show that it is the only one to give a high score to human speech in various languages and with various speakers, a moderate score to animal vocalizations from birds and orcas, and a low score to ambient noise from various sources.

Claims made by individuals or entities are oftentimes nuanced and cannot be clearly labeled as entirely "true" or "false" -- as is frequently the case with scientific and political claims. However, a claim (e.g., "vaccine A is better than vaccine B") can be dissected into its integral aspects and sub-aspects (e.g., efficacy, safety, distribution), which are individually easier to validate. This enables a more comprehensive, structured response that provides a well-rounded perspective on a given problem while also allowing the reader to prioritize specific angles of interest within the claim (e.g., safety towards children). Thus, we propose ClaimSpect, a retrieval-augmented generation-based framework for automatically constructing a hierarchy of aspects typically considered when addressing a claim and enriching them with corpus-specific perspectives. This structure hierarchically partitions an input corpus to retrieve relevant segments, which assist in discovering new sub-aspects. Moreover, these segments enable the discovery of varying perspectives towards an aspect of the claim (e.g., support, neutral, or oppose) and their respective prevalence (e.g., "how many biomedical papers believe vaccine A is more transportable than B?"). We apply ClaimSpect to a wide variety of real-world scientific and political claims featured in our constructed dataset, showcasing its robustness and accuracy in deconstructing a nuanced claim and representing perspectives within a corpus. Through real-world case studies and human evaluation, we validate its effectiveness over multiple baselines.

Immunotherapy is an effective precision medicine treatment for several cancers. Imaging signatures of the underlying genome (radiogenomics) in glioblastoma patients may serve as preoperative biomarkers of the tumor-host immune apparatus. Validated biomarkers would have the potential to stratify patients during immunotherapy clinical trials, and if trials are beneficial, facilitate personalized neo-adjuvant treatment. The increased use of whole genome sequencing data, and the advances in bioinformatics and machine learning make such developments plausible. We performed a systematic review to determine the extent of development and validation of immune-related radiogenomic biomarkers for glioblastoma. A systematic review was performed following PRISMA guidelines using the PubMed, Medline, and Embase databases. Qualitative analysis was performed by incorporating the QUADAS 2 tool and CLAIM checklist. PROSPERO registered CRD42022340968. Extracted data were insufficiently homogenous to perform a meta-analysis. Results Nine studies, all retrospective, were included. Biomarkers extracted from magnetic resonance imaging volumes of interest included apparent diffusion coefficient values, relative cerebral blood volume values, and image-derived features. These biomarkers correlated with genomic markers from tumor cells or immune cells or with patient survival. The majority of studies had a high risk of bias and applicability concerns regarding the index test performed. Radiogenomic immune biomarkers have the potential to provide early treatment options to patients with glioblastoma. Targeted immunotherapy, stratified by these biomarkers, has the potential to allow individualized neo-adjuvant precision treatment options in clinical trials. However, there are no prospective studies validating these biomarkers, and interpretation is limited due to study bias with little evidence of generalizability.

Large language models (LLMs) perform increasingly well on biology benchmarks, but it remains unclear whether they uplift novice users -- i.e., enable humans to perform better than with internet-only resources. This uncertainty is central to understanding both scientific acceleration and dual-use risk. We conducted a multi-model, multi-benchmark human uplift study comparing novices with LLM access versus internet-only access across eight biosecurity-relevant task sets. Participants worked on complex problems with ample time (up to 13 hours for the most involved tasks). We found that LLM access provided substantial uplift: novices with LLMs were 4.16 times more accurate than controls (95% CI [2.63, 6.87]). On four benchmarks with available expert baselines (internet-only), novices with LLMs outperformed experts on three of them. Perhaps surprisingly, standalone LLMs often exceeded LLM-assisted novices, indicating that users were not eliciting the strongest available contributions from the LLMs. Most participants (89.6%) reported little difficulty obtaining dual-use-relevant information despite safeguards. Overall, LLMs substantially uplift novices on biological tasks previously reserved for trained practitioners, underscoring the need for sustained, interactive uplift evaluations alongside traditional benchmarks.

The discovery of novel materials and functional molecules can help to solve some of society's most urgent challenges, ranging from efficient energy harvesting and storage to uncovering novel pharmaceutical drug candidates. Traditionally matter engineering -- generally denoted as inverse design -- was based massively on human intuition and high-throughput virtual screening. The last few years have seen the emergence of significant interest in computer-inspired designs based on evolutionary or deep learning methods. The major challenge here is that the standard strings molecular representation SMILES shows substantial weaknesses in that task because large fractions of strings do not correspond to valid molecules. Here, we solve this problem at a fundamental level and introduce SELFIES (SELF-referencIng Embedded Strings), a string-based representation of molecules which is 100\% robust. Every SELFIES string corresponds to a valid molecule, and SELFIES can represent every molecule. SELFIES can be directly applied in arbitrary machine learning models without the adaptation of the models; each of the generated molecule candidates is valid. In our experiments, the model's internal memory stores two orders of magnitude more diverse molecules than a similar test with SMILES. Furthermore, as all molecules are valid, it allows for explanation and interpretation of the internal working of the generative models.

Misinformation in healthcare, from vaccine hesitancy to unproven treatments, poses risks to public health and trust in medical systems. While machine learning and natural language processing have advanced automated fact-checking, validating biomedical claims remains uniquely challenging due to complex terminology, the need for domain expertise, and the critical importance of grounding in scientific evidence. We introduce CER (Combining Evidence and Reasoning), a novel framework for biomedical fact-checking that integrates scientific evidence retrieval, reasoning via large language models, and supervised veracity prediction. By integrating the text-generation capabilities of large language models with advanced retrieval techniques for high-quality biomedical scientific evidence, CER effectively mitigates the risk of hallucinations, ensuring that generated outputs are grounded in verifiable, evidence-based sources. Evaluations on expert-annotated datasets (HealthFC, BioASQ-7b, SciFact) demonstrate state-of-the-art performance and promising cross-dataset generalization. Code and data are released for transparency and reproducibility: https: //github.com/PRAISELab-PicusLab/CER.

Backpropagation (BP), a foundational algorithm for training artificial neural networks, predominates in contemporary deep learning. Although highly successful, it is often considered biologically implausible. A significant limitation arises from the need for precise symmetry between connections in the backward and forward pathways to backpropagate gradient signals accurately, which is not observed in biological brains. Researchers have proposed several algorithms to alleviate this symmetry constraint, such as feedback alignment and direct feedback alignment. However, their divergence from backpropagation dynamics presents challenges, particularly in deeper networks and convolutional layers. Here we introduce the Product Feedback Alignment (PFA) algorithm. Our findings demonstrate that PFA closely approximates BP and achieves comparable performance in deep convolutional networks while avoiding explicit weight symmetry. Our results offer a novel solution to the longstanding weight symmetry problem, leading to more biologically plausible learning in deep convolutional networks compared to earlier methods.

Recent approximations to backpropagation (BP) have mitigated many of BP's computational inefficiencies and incompatibilities with biology, but important limitations still remain. Moreover, the approximations significantly decrease accuracy in benchmarks, suggesting that an entirely different approach may be more fruitful. Here, grounded on recent theory for Hebbian learning in soft winner-take-all networks, we present multilayer SoftHebb, i.e. an algorithm that trains deep neural networks, without any feedback, target, or error signals. As a result, it achieves efficiency by avoiding weight transport, non-local plasticity, time-locking of layer updates, iterative equilibria, and (self-) supervisory or other feedback signals -- which were necessary in other approaches. Its increased efficiency and biological compatibility do not trade off accuracy compared to state-of-the-art bio-plausible learning, but rather improve it. With up to five hidden layers and an added linear classifier, accuracies on MNIST, CIFAR-10, STL-10, and ImageNet, respectively reach 99.4%, 80.3%, 76.2%, and 27.3%. In conclusion, SoftHebb shows with a radically different approach from BP that Deep Learning over few layers may be plausible in the brain and increases the accuracy of bio-plausible machine learning. Code is available at https://github.com/NeuromorphicComputing/SoftHebb.

Pre-trained language models like ChatGPT have significantly improved code generation. As these models scale up, there is an increasing need for the output to handle more intricate tasks. Moreover, in bioinformatics, generating functional programs poses additional notable challenges due to the amount of domain knowledge, the need for complicated data operations, and intricate functional dependencies between the operations. Here, we present BioCoder, a benchmark developed to evaluate existing pre-trained models in generating bioinformatics code. In relation to function-code generation, BioCoder covers potential package dependencies, class declarations, and global variables. It incorporates 1026 functions and 1243 methods in Python and Java from GitHub and 253 examples from the Rosalind Project. BioCoder incorporates a fuzz-testing framework for evaluation, and we have applied it to evaluate many models including InCoder, CodeGen, CodeGen2, SantaCoder, StarCoder, StarCoder+, InstructCodeT5+, and ChatGPT. Our detailed analysis of these models emphasizes the importance of domain knowledge, pragmatic code generation, and contextual understanding. Our dataset, benchmark, Docker images, and scripts required for testing are all available at https://github.com/gersteinlab/biocoder.

The application of deep learning methods, particularly foundation models, in biological research has surged in recent years. These models can be text-based or trained on underlying biological data, especially omics data of various types. However, comparing the performance of these models consistently has proven to be a challenge due to differences in training data and downstream tasks. To tackle this problem, we developed an architecture-agnostic benchmarking approach that, instead of evaluating the models directly, leverages entity representation vectors from each model and trains simple predictive models for each benchmarking task. This ensures that all types of models are evaluated using the same input and output types. Here we focus on gene properties collected from professionally curated bioinformatics databases. These gene properties are categorized into five major groups: genomic properties, regulatory functions, localization, biological processes, and protein properties. Overall, we define hundreds of tasks based on these databases, which include binary, multi-label, and multi-class classification tasks. We apply these benchmark tasks to evaluate expression-based models, large language models, protein language models, DNA-based models, and traditional baselines. Our findings suggest that text-based models and protein language models generally outperform expression-based models in genomic properties and regulatory functions tasks, whereas expression-based models demonstrate superior performance in localization tasks. These results should aid in the development of more informed artificial intelligence strategies for biological understanding and therapeutic discovery. To ensure the reproducibility and transparency of our findings, we have made the source code and benchmark data publicly accessible for further investigation and expansion at github.com/BiomedSciAI/gene-benchmark.

Deep research -- producing comprehensive, citation-grounded reports by searching and synthesizing information from hundreds of live web sources -- marks an important frontier for agentic systems. To rigorously evaluate this ability, four principles are essential: tasks should be (1) user-centric, reflecting realistic information needs, (2) dynamic, requiring up-to-date information beyond parametric knowledge, (3) unambiguous, ensuring consistent interpretation across users, and (4) multi-faceted and search-intensive, requiring search over numerous web sources and in-depth analysis. Existing benchmarks fall short of these principles, often focusing on narrow domains or posing ambiguous questions that hinder fair comparison. Guided by these principles, we introduce LiveResearchBench, a benchmark of 100 expert-curated tasks spanning daily life, enterprise, and academia, each requiring extensive, dynamic, real-time web search and synthesis. Built with over 1,500 hours of human labor, LiveResearchBench provides a rigorous basis for systematic evaluation. To evaluate citation-grounded long-form reports, we introduce DeepEval, a comprehensive suite covering both content- and report-level quality, including coverage, presentation, citation accuracy and association, consistency and depth of analysis. DeepEval integrates four complementary evaluation protocols, each designed to ensure stable assessment and high agreement with human judgments. Using LiveResearchBench and DeepEval, we conduct a comprehensive evaluation of 17 frontier deep research systems, including single-agent web search, single-agent deep research, and multi-agent systems. Our analysis reveals current strengths, recurring failure modes, and key system components needed to advance reliable, insightful deep research.

Human medical data can be challenging to obtain due to data privacy concerns, difficulties conducting certain types of experiments, or prohibitive associated costs. In many settings, data from animal models or in-vitro cell lines are available to help augment our understanding of human data. However, this data is known for having low etiological validity in comparison to human data. In this work, we augment small human medical datasets with in-vitro data and animal models. We use Invariant Risk Minimisation (IRM) to elucidate invariant features by considering cross-organism data as belonging to different data-generating environments. Our models identify genes of relevance to human cancer development. We observe a degree of consistency between varying the amounts of human and mouse data used, however, further work is required to obtain conclusive insights. As a secondary contribution, we enhance existing open source datasets and provide two uniformly processed, cross-organism, homologue gene-matched datasets to the community.

Despite the ecological significance of invertebrates, global trait databases remain heavily biased toward vertebrates and plants, limiting comprehensive ecological analyses of high-diversity groups like ground beetles. Ground beetles (Coleoptera: Carabidae) serve as critical bioindicators of ecosystem health, providing valuable insights into biodiversity shifts driven by environmental changes. While the National Ecological Observatory Network (NEON) maintains an extensive collection of carabid specimens from across the United States, these primarily exist as physical collections, restricting widespread research access and large-scale analysis. To address these gaps, we present a multimodal dataset digitizing over 13,200 NEON carabids from 30 sites spanning the continental US and Hawaii through high-resolution imaging, enabling broader access and computational analysis. The dataset includes digitally measured elytra length and width of each specimen, establishing a foundation for automated trait extraction using AI. Validated against manual measurements, our digital trait extraction achieves sub-millimeter precision, ensuring reliability for ecological and computational studies. By addressing invertebrate under-representation in trait databases, this work supports AI-driven tools for automated species identification and trait-based research, fostering advancements in biodiversity monitoring and conservation.

Verifying scientific claims presents a significantly greater challenge than verifying political or news-related claims. Unlike the relatively broad audience for political claims, the users of scientific claim verification systems can vary widely, ranging from researchers testing specific hypotheses to everyday users seeking information on a medication. Additionally, the evidence for scientific claims is often highly complex, involving technical terminology and intricate domain-specific concepts that require specialized models for accurate verification. Despite considerable interest from the research community, there is a noticeable lack of large-scale scientific claim verification datasets to benchmark and train effective models. To bridge this gap, we introduce two large-scale datasets, SciClaimHunt and SciClaimHunt_Num, derived from scientific research papers. We propose several baseline models tailored for scientific claim verification to assess the effectiveness of these datasets. Additionally, we evaluate models trained on SciClaimHunt and SciClaimHunt_Num against existing scientific claim verification datasets to gauge their quality and reliability. Furthermore, we conduct human evaluations of the claims in proposed datasets and perform error analysis to assess the effectiveness of the proposed baseline models. Our findings indicate that SciClaimHunt and SciClaimHunt_Num serve as highly reliable resources for training models in scientific claim verification.

In response to the pressing need for advanced clinical problem-solving tools in healthcare, we introduce BooksMed, a novel framework based on a Large Language Model (LLM). BooksMed uniquely emulates human cognitive processes to deliver evidence-based and reliable responses, utilizing the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework to effectively quantify evidence strength. For clinical decision-making to be appropriately assessed, an evaluation metric that is clinically aligned and validated is required. As a solution, we present ExpertMedQA, a multispecialty clinical benchmark comprised of open-ended, expert-level clinical questions, and validated by a diverse group of medical professionals. By demanding an in-depth understanding and critical appraisal of up-to-date clinical literature, ExpertMedQA rigorously evaluates LLM performance. BooksMed outperforms existing state-of-the-art models Med-PaLM 2, Almanac, and ChatGPT in a variety of medical scenarios. Therefore, a framework that mimics human cognitive stages could be a useful tool for providing reliable and evidence-based responses to clinical inquiries.

Medical systematic reviews can be very costly and resource intensive. We explore how Large Language Models (LLMs) can support and be trained to perform literature screening when provided with a detailed set of selection criteria. Specifically, we instruction tune LLaMA and Guanaco models to perform abstract screening for medical systematic reviews. Our best model, Bio-SIEVE, outperforms both ChatGPT and trained traditional approaches, and generalises better across medical domains. However, there remains the challenge of adapting the model to safety-first scenarios. We also explore the impact of multi-task training with Bio-SIEVE-Multi, including tasks such as PICO extraction and exclusion reasoning, but find that it is unable to match single-task Bio-SIEVE's performance. We see Bio-SIEVE as an important step towards specialising LLMs for the biomedical systematic review process and explore its future developmental opportunities. We release our models, code and a list of DOIs to reconstruct our dataset for reproducibility.

The sciences of biological and artificial intelligence are ever more intertwined. Neural computational principles inspire new intelligent machines, which are in turn used to advance theoretical understanding of the brain. To promote further exchange of ideas and collaboration between biological and artificial intelligence researchers, we introduce the 2023 installment of the Algonauts Project challenge: How the Human Brain Makes Sense of Natural Scenes (http://algonauts.csail.mit.edu). This installment prompts the fields of artificial and biological intelligence to come together towards building computational models of the visual brain using the largest and richest dataset of fMRI responses to visual scenes, the Natural Scenes Dataset (NSD). NSD provides high-quality fMRI responses to ~73,000 different naturalistic colored scenes, making it the ideal candidate for data-driven model building approaches promoted by the 2023 challenge. The challenge is open to all and makes results directly comparable and transparent through a public leaderboard automatically updated after each submission, thus allowing for rapid model development. We believe that the 2023 installment will spark symbiotic collaborations between biological and artificial intelligence scientists, leading to a deeper understanding of the brain through cutting-edge computational models and to novel ways of engineering artificial intelligent agents through inductive biases from biological systems.

Misinformation in healthcare, from vaccine hesitancy to unproven treatments, poses risks to public health and trust in medical systems. While machine learning and natural language processing have advanced automated fact-checking, validating biomedical claims remains uniquely challenging due to complex terminology, the need for domain expertise, and the critical importance of grounding in scientific evidence. We introduce CER (Combining Evidence and Reasoning), a novel framework for biomedical fact-checking that integrates scientific evidence retrieval, reasoning via large language models, and supervised veracity prediction. By integrating the text-generation capabilities of large language models with advanced retrieval techniques for high-quality biomedical scientific evidence, CER effectively mitigates the risk of hallucinations, ensuring that generated outputs are grounded in verifiable, evidence-based sources. Evaluations on expert-annotated datasets (HealthFC, BioASQ-7b, SciFact) demonstrate state-of-the-art performance and promising cross-dataset generalization. Code and data are released for transparency and reproducibility: https://github.com/PRAISELab-PicusLab/CER

The potential of Multimodal Large Language Models (MLLMs) in domain of medical imaging raise the demands of systematic and rigorous evaluation frameworks that are aligned with the real-world medical imaging practice. Existing practices that report single or coarse-grained metrics are lack the granularity required for specialized clinical support and fail to assess the reliability of reasoning mechanisms. To address this, we propose a paradigm shift toward multidimensional, fine-grained and in-depth evaluation. Based on a two-stage systematic construction pipeline designed for this paradigm, we instantiate it with MedRCube. We benchmark 33 MLLMs, Lingshu-32B achieve top-tier performance. Crucially, MedRCube exposes a series of pronounced insights inaccessible under prior evaluation settings. Furthermore, we introduce a credibility evaluation subset to quantify reasoning credibility, uncover a highly significant positive association between shortcut behavior and diagnostic task performance, raising concerns for clinically trustworthy deployment. The resources of this work can be found at https://github.com/F1mc/MedRCube.

A growing body of research examines personality traits in Large Language Models (LLMs), particularly in human-agent collaboration. Prior work has frequently applied the Big Five inventory to assess LLM behavior analogous to human personality, without questioning the underlying assumptions. This paper critically evaluates whether LLM responses to personality tests satisfy six defining characteristics of personality. We find that none are fully met, indicating that such assessments do not measure a construct equivalent to human personality. We propose a research agenda for shifting from anthropomorphic trait attribution toward functional evaluations, clarifying what personality tests actually capture in LLMs and developing LLM-specific frameworks for characterizing stable, intrinsic behavior.

Biological neural networks define the brain function and intelligence of humans and other mammals, and form ultra-large, spatial, structured graphs. Their neuronal organization is closely interconnected with the spatial organization of the brain's microvasculature, which supplies oxygen to the neurons and builds a complementary spatial graph. This vasculature (or the vessel structure) plays an important role in neuroscience; for example, the organization of (and changes to) vessel structure can represent early signs of various pathologies, e.g. Alzheimer's disease or stroke. Recently, advances in tissue clearing have enabled whole brain imaging and segmentation of the entirety of the mouse brain's vasculature. Building on these advances in imaging, we are presenting an extendable dataset of whole-brain vessel graphs based on specific imaging protocols. Specifically, we extract vascular graphs using a refined graph extraction scheme leveraging the volume rendering engine Voreen and provide them in an accessible and adaptable form through the OGB and PyTorch Geometric dataloaders. Moreover, we benchmark numerous state-of-the-art graph learning algorithms on the biologically relevant tasks of vessel prediction and vessel classification using the introduced vessel graph dataset. Our work paves a path towards advancing graph learning research into the field of neuroscience. Complementarily, the presented dataset raises challenging graph learning research questions for the machine learning community, in terms of incorporating biological priors into learning algorithms, or in scaling these algorithms to handle sparse,spatial graphs with millions of nodes and edges. All datasets and code are available for download at https://github.com/jocpae/VesselGraph .

Hypertension, defined as blood pressure (BP) that is above normal, holds paramount significance in the realm of public health, as it serves as a critical precursor to various cardiovascular diseases (CVDs) and significantly contributes to elevated mortality rates worldwide. However, many existing BP measurement technologies and standards might be biased because they do not consider clinical outcomes, comorbidities, or demographic factors, making them inconclusive for diagnostic purposes. There is limited data-driven research focused on studying the variance in BP measurements across these variables. In this work, we employed GPT-35-turbo, a large language model (LLM), to automatically extract the mean and standard deviation values of BP for both males and females from a dataset comprising 25 million abstracts sourced from PubMed. 993 article abstracts met our predefined inclusion criteria (i.e., presence of references to blood pressure, units of blood pressure such as mmHg, and mention of biological sex). Based on the automatically-extracted information from these articles, we conducted an analysis of the variations of BP values across biological sex. Our results showed the viability of utilizing LLMs to study the BP variations across different demographic factors.

Understanding how individuals with Parkinson's disease (PD) describe cognitive experiences in their daily lives can offer valuable insights into disease-related cognitive and emotional changes. However, extracting such information from unstructured patient narratives is challenging due to the subtle, overlapping nature of cognitive constructs. This study developed and evaluated natural language processing (NLP) models to automatically identify categories that reflect various cognitive processes from de-identified first-person narratives. Three model families, a Bio_ClinicalBERT-based span categorization model for nested entity recognition, a fine-tuned Meta-Llama-3-8B-Instruct model using QLoRA for instruction following, and GPT-4o mini evaluated under zero- and few-shot settings, were compared on their performance on extracting seven categories. Our findings indicated that model performance varied substantially across categories and model families. The fine-tuned Meta-Llama-3-8B-Instruct achieved the highest overall F1-scores (0.74 micro-average and 0.59 macro-average), particularly excelling in context-dependent categories such as thought and social interaction. Bio_ClinicalBERT exhibited high precision but low recall and performed comparable to Llama for some category types such as location and time but failed on other categories such as thought, emotion and social interaction. Compared to conventional information extraction tasks, this task presents a greater challenge due to the abstract and overlapping nature of narrative accounts of complex cognitive processes. Nonetheless, with continued refinement, these NLP systems hold promise for enabling low-burden, longitudinal monitoring of cognitive function and serving as a valuable complement to formal neuropsychological assessments in PD.

Global comparisons of wellbeing increasingly rely on survey questions that ask respondents to evaluate their lives, most commonly in the form of "life satisfaction" and "Cantril ladder" items. These measures underpin international rankings such as the World Happiness Report and inform policy initiatives worldwide, yet their comparability has not been established with contemporary global data. Using the Gallup World Poll, Global Flourishing Study, and World Values Survey, I show that the two question formats yield divergent distributions, rankings, and response patterns that vary across countries and surveys, defying simple explanations. To explore differences in respondents' cognitive interpretations, I compare regression coefficients from the Global Flourishing Study, analyzing how each question wording relates to life circumstances. While international rankings of wellbeing are unstable, the scientific study of the determinants of life evaluations appears more robust. Together, the findings underscore the need for a renewed research agenda on critical limitations to cross-country comparability of wellbeing.

The challenge of replicating research results has posed a significant impediment to the field of molecular biology. The advent of modern intelligent systems has led to notable progress in various domains. Consequently, we embarked on an investigation of intelligent monitoring systems as a means of tackling the issue of the reproducibility crisis. Specifically, we first curate a comprehensive multimodal dataset, named ProBio, as an initial step towards this objective. This dataset comprises fine-grained hierarchical annotations intended for the purpose of studying activity understanding in BioLab. Next, we devise two challenging benchmarks, transparent solution tracking and multimodal action recognition, to emphasize the unique characteristics and difficulties associated with activity understanding in BioLab settings. Finally, we provide a thorough experimental evaluation of contemporary video understanding models and highlight their limitations in this specialized domain to identify potential avenues for future research. We hope ProBio with associated benchmarks may garner increased focus on modern AI techniques in the realm of molecular biology.

Today's large language models (LLMs) routinely generate coherent, grammatical and seemingly meaningful paragraphs of text. This achievement has led to speculation that these networks are -- or will soon become -- "thinking machines", capable of performing tasks that require abstract knowledge and reasoning. Here, we review the capabilities of LLMs by considering their performance on two different aspects of language use: 'formal linguistic competence', which includes knowledge of rules and patterns of a given language, and 'functional linguistic competence', a host of cognitive abilities required for language understanding and use in the real world. Drawing on evidence from cognitive neuroscience, we show that formal competence in humans relies on specialized language processing mechanisms, whereas functional competence recruits multiple extralinguistic capacities that comprise human thought, such as formal reasoning, world knowledge, situation modeling, and social cognition. In line with this distinction, LLMs show impressive (although imperfect) performance on tasks requiring formal linguistic competence, but fail on many tests requiring functional competence. Based on this evidence, we argue that (1) contemporary LLMs should be taken seriously as models of formal linguistic skills; (2) models that master real-life language use would need to incorporate or develop not only a core language module, but also multiple non-language-specific cognitive capacities required for modeling thought. Overall, a distinction between formal and functional linguistic competence helps clarify the discourse surrounding LLMs' potential and provides a path toward building models that understand and use language in human-like ways.

Knowledge graphs (KGs) are increasingly used to support large lan guage model (LLM) reasoning, but standard triplet-based KGs treat each relation as globally valid. In many settings, whether a relation should count as evidence depends on the context. We therefore formulate triplet validity as a triplet-specific function of context and refer to this formulation as a Quantum Knowledge Graph (QKG). We instantiate QKG in medicine using a diabetes-centered PrimeKG subgraph, whose 68,651 context-sensitive relations are further annotated with patient-group-specific constraints. We evaluate it in a reasoner--validator pipeline for medical question answering on a KG-grounded subset of MedReason containing 2,788 questions. With Haiku-4.5 as both the Reasoner and the Validator, KG-backed validation significantly improves over a no-validator baseline (+0.61 pp), and QKG with context matching yields the largest gain, outperforming both KG validation without context matching (+0.79 pp) and the no-validator baseline (+1.40 pp; paired McNemar, all p<0.05). Under a stronger validator (Qwen-3.6-Plus), the raw QKG gain over the no-validator baseline grows from +1.40 pp to +5.96 pp; the context-matching gap is non-significant (p=0.73) on the raw set but becomes borderline significant (p=0.05) after adjustment for knowledge leakage and suspicious questions, consistent with a benchmark-gold ceiling rather than a QKG limitation. Taken together, the results support the view that the value of a KG in LLM-based clinical reasoning lies not merely in storing medically related facts, but in representing whether those facts are applicable to the specific patient context. For reproducibility and further research, we release the curated QKG datasets and source code.https://github.com/HKAI-Sci/QKG

Despite their widespread success, the application of deep neural networks to functional data remains scarce today. The infinite dimensionality of functional data means standard learning algorithms can be applied only after appropriate dimension reduction, typically achieved via basis expansions. Currently, these bases are chosen a priori without the information for the task at hand and thus may not be effective for the designated task. We instead propose to adaptively learn these bases in an end-to-end fashion. We introduce neural networks that employ a new Basis Layer whose hidden units are each basis functions themselves implemented as a micro neural network. Our architecture learns to apply parsimonious dimension reduction to functional inputs that focuses only on information relevant to the target rather than irrelevant variation in the input function. Across numerous classification/regression tasks with functional data, our method empirically outperforms other types of neural networks, and we prove that our approach is statistically consistent with low generalization error. Code is available at: https://github.com/jwyyy/AdaFNN.

Large language models (LLMs) trained on text demonstrated remarkable results on natural language processing (NLP) tasks. These models have been adapted to decipher the language of DNA, where sequences of nucleotides act as "words" that encode genomic functions. However, the genome differs fundamentally from natural language, as it lacks clearly defined words or a consistent grammar. Although DNA language models (DNALMs) such as DNABERT, GENA-LM have achieved high level of performance on genome-related biological tasks, these models do not encode biological functions in the presence of sequence variations. To address this problem, we pre-train foundation models that effectively integrate sequence variations, in particular Single Nucleotide Polymorphisms (SNPs), as they underlie important biological functions. Specifically, we use ModernBERT to pre-train two different Biomedical Foundation Models (BMFM), namely, BMFM-DNA-REF in which the model is trained with sequences of varying lengths along with their reverse complements derived from the reference genome and BMFM-DNA-SNP in which the model is trained with sequences created using a novel representation scheme that encodes sequence variations. Our findings indicate that integrating sequence variations into DNALMs helps capture the biological functions as seen in improvements on all fine-tuning tasks. To explore the model's practical utility, we experimented with various strategies for SNP imputation on promoter detection task introduced in DNABERT-2. However, we acknowledge that the current benchmarks are limited in their ability to fully evaluate these models. To enable more comprehensive assessment in the future and encourage community contributions, we release our models through HuggingFace and the code to reproduce the results at https://github.com/BiomedSciAI/biomed-multi-omic

With the continuous advancement of reasoning abilities in Large Language Models (LLMs), their application to scientific reasoning tasks has gained significant research attention. Current research primarily emphasizes boosting LLMs' performance on scientific QA benchmarks by training on larger, more comprehensive datasets with extended reasoning chains. However, these approaches neglect the essence of the scientific reasoning process -- logicality, which is the rational foundation to ensure the validity of reasoning steps leading to reliable conclusions. In this work, we make the first systematic investigation into the internal logicality underlying LLM scientific reasoning, and develop a scientific logicality-enriched methodology, including a set of assessment criteria and data sampling methods for logicality-guided training, to improve the logical faithfulness as well as task performance. Further, we take physics, characterized by its diverse logical structures and formalisms, as an exemplar discipline to practise the above methodology. For data construction, we extract scientific problems from academic literature and sample a high-quality dataset exhibiting strong logicality. Experiments based on three different backbone LLMs reveal that: 1) the training data we constructed can effectively improve the scientific logicality in LLM reasoning; and 2) the enriched scientific logicality plays a critical role in solving scientific problems. Code is available at https://github.com/ScienceOne-AI/PhysLogic{https://github.com/ScienceOne-AI/PhysLogic}.

Biomedical text mining and question-answering are essential yet highly demanding tasks, particularly in the face of the exponential growth of biomedical literature. In this work, we present our participation in the 13th edition of the BioASQ challenge, which involves biomedical semantic question-answering for Task 13b and biomedical question-answering for developing topics for the Synergy task. We deploy a selection of open-source large language models (LLMs) as retrieval-augmented generators to answer biomedical questions. Various models are used to process the questions. A majority voting system combines their output to determine the final answer for Yes/No questions, while for list and factoid type questions, the union of their answers in used. We evaluated 13 state-of-the-art open source LLMs, exploring all possible model combinations to contribute to the final answer, resulting in tailored LLM pipelines for each question type. Our findings provide valuable insight into which combinations of LLMs consistently produce superior results for specific question types. In the four rounds of the 2025 BioASQ challenge, our system achieved notable results: in the Synergy task, we secured 1st place for ideal answers and 2nd place for exact answers in round 2, as well as two shared 1st places for exact answers in round 3 and 4.

In this position paper, we argue that human baselines in foundation model evaluations must be more rigorous and more transparent to enable meaningful comparisons of human vs. AI performance, and we provide recommendations and a reporting checklist towards this end. Human performance baselines are vital for the machine learning community, downstream users, and policymakers to interpret AI evaluations. Models are often claimed to achieve "super-human" performance, but existing baselining methods are neither sufficiently rigorous nor sufficiently well-documented to robustly measure and assess performance differences. Based on a meta-review of the measurement theory and AI evaluation literatures, we derive a framework with recommendations for designing, executing, and reporting human baselines. We synthesize our recommendations into a checklist that we use to systematically review 115 human baselines (studies) in foundation model evaluations and thus identify shortcomings in existing baselining methods; our checklist can also assist researchers in conducting human baselines and reporting results. We hope our work can advance more rigorous AI evaluation practices that can better serve both the research community and policymakers. Data is available at: https://github.com/kevinlwei/human-baselines

Despite its widespread use in neural networks, error backpropagation has faced criticism for its lack of biological plausibility, suffering from issues such as the backward locking problem and the weight transport problem. These limitations have motivated researchers to explore more biologically plausible learning algorithms that could potentially shed light on how biological neural systems adapt and learn. Inspired by the counter-current exchange mechanisms observed in biological systems, we propose counter-current learning (CCL), a biologically plausible framework for credit assignment in neural networks. This framework employs a feedforward network to process input data and a feedback network to process targets, with each network enhancing the other through anti-parallel signal propagation. By leveraging the more informative signals from the bottom layer of the feedback network to guide the updates of the top layer of the feedforward network and vice versa, CCL enables the simultaneous transformation of source inputs to target outputs and the dynamic mutual influence of these transformations. Experimental results on MNIST, FashionMNIST, CIFAR10, and CIFAR100 datasets using multi-layer perceptrons and convolutional neural networks demonstrate that CCL achieves comparable performance to other biologically plausible algorithms while offering a more biologically realistic learning mechanism. Furthermore, we showcase the applicability of our approach to an autoencoder task, underscoring its potential for unsupervised representation learning. Our work presents a direction for biologically inspired and plausible learning algorithms, offering an alternative mechanism of learning and adaptation in neural networks.

Human language is one of the most expressive tools for conveying intent, yet most artificial or biological systems lack mechanisms to interpret or respond meaningfully to it. Bridging this gap could enable more natural forms of control over complex, decentralized systems. In AI and artificial life, recent work explores how language can specify high-level goals, but most systems still depend on engineered rewards, task-specific supervision, or rigid command sets, limiting generalization to novel instructions. Similar constraints apply in synthetic biology and bioengineering, where the locus of control is often genomic rather than environmental perturbation. A key open question is whether artificial or biological collectives can be guided by free-form natural language alone, without task-specific tuning or carefully designed evaluation metrics. We provide one possible answer here by showing, for the first time, that simple agents' collective behavior can be guided by free-form language prompts: one AI model transforms an imperative prompt into an intervention that is applied to simulated cells; a second AI model scores how well the prompt describes the resulting cellular dynamics; and the former AI model is evolved to improve the scores generated by the latter. Unlike previous work, our method does not require engineered fitness functions or domain-specific prompt design. We show that the evolved system generalizes to unseen prompts without retraining. By treating natural language as a control layer, the system suggests a future in which spoken or written prompts could direct computational, robotic, or biological systems to desired behaviors. This work provides a concrete step toward this vision of AI-biology partnerships, in which language replaces mathematical objective functions, fixed rules, and domain-specific programming.

The accelerating loss of biodiversity presents critical challenges for ecological research and conservation strategies. The preservation of biodiversity is paramount for maintaining ecological balance and ensuring the sustainability of ecosystems. However, biodiversity faces numerous threats, including habitat loss, climate change, and the proliferation of invasive species. Addressing these and other ecology-related challenges, both at local and global scales, requires comprehensive monitoring, predictive and conservation planning capabilities. Artificial Intelligence (AI) Foundation Models (FMs) have gained significant momentum in numerous scientific domains by leveraging vast datasets to learn general-purpose representations adaptable to various downstream tasks. This paradigm holds immense promise for biodiversity conservation. In response, we introduce BioAnalyst, the first Foundation Model tailored for biodiversity analysis and conservation planning. BioAnalyst employs a transformer-based architecture, pre-trained on extensive multi-modal datasets encompassing species occurrence records, remote sensing indicators, climate and environmental variables. BioAnalyst is designed for adaptability, allowing for fine-tuning of a range of downstream tasks, such as species distribution modelling, habitat suitability assessments, invasive species detection, and population trend forecasting. We evaluate the model's performance on two downstream use cases, demonstrating its generalisability compared to existing methods, particularly in data-scarce scenarios for two distinct use-cases, establishing a new accuracy baseline for ecological forecasting. By openly releasing BioAnalyst and its fine-tuning workflows to the scientific community, we aim to foster collaborative efforts in biodiversity modelling and advance AI-driven solutions to pressing ecological challenges.

As Large Language Models (LLMs) exhibit plateauing performance on conventional benchmarks, a pivotal challenge persists: evaluating their proficiency in complex, open-ended tasks characterizing genuine expert-level cognition. Existing frameworks suffer from narrow domain coverage, reliance on generalist tasks, or self-evaluation biases. To bridge this gap, we present XpertBench, a high-fidelity benchmark engineered to assess LLMs across authentic professional domains. XpertBench consists of 1,346 meticulously curated tasks across 80 categories, spanning finance, healthcare, legal services, education, and dual-track research (STEM and Humanities). These tasks are derived from over 1,000 submissions by domain experts--including researchers from elite institutions and practitioners with extensive clinical or industrial experience--ensuring superior ecological validity. Each task uses detailed rubrics with mostly 15-40 weighted checkpoints to assess professional rigor. To facilitate scalable yet human-aligned assessment, we introduce ShotJudge, a novel evaluation paradigm that employs LLM judges calibrated with expert few-shot exemplars to mitigate self-rewarding biases. Our empirical evaluation of state-of-the-art LLMs reveals a pronounced performance ceiling: even leading models achieve a peak success rate of only ~66%, with a mean score around 55%. Models also exhibit domain-specific divergence, showing non-overlapping strengths in quantitative reasoning versus linguistic synthesis.. These findings underscore a significant "expert-gap" in current AI systems and establish XpertBench as a critical instrument for navigating the transition from general-purpose assistants to specialized professional collaborators.

This paper describes the results of SemEval 2023 task 7 -- Multi-Evidence Natural Language Inference for Clinical Trial Data (NLI4CT) -- consisting of 2 tasks, a Natural Language Inference (NLI) task, and an evidence selection task on clinical trial data. The proposed challenges require multi-hop biomedical and numerical reasoning, which are of significant importance to the development of systems capable of large-scale interpretation and retrieval of medical evidence, to provide personalized evidence-based care. Task 1, the entailment task, received 643 submissions from 40 participants, and Task 2, the evidence selection task, received 364 submissions from 23 participants. The tasks are challenging, with the majority of submitted systems failing to significantly outperform the majority class baseline on the entailment task, and we observe significantly better performance on the evidence selection task than on the entailment task. Increasing the number of model parameters leads to a direct increase in performance, far more significant than the effect of biomedical pre-training. Future works could explore the limitations of large models for generalization and numerical inference, and investigate methods to augment clinical datasets to allow for more rigorous testing and to facilitate fine-tuning. We envisage that the dataset, models, and results of this task will be useful to the biomedical NLI and evidence retrieval communities. The dataset, competition leaderboard, and website are publicly available.

In contrast to their remarkable performance on general knowledge QA, the true abilities of Large Language Models (LLMs) in tasks demanding deep, specialized reasoning, such as in protein biology, have yet to be thoroughly investigated. Current benchmarks suffer from critical deficiencies, such as data contamination due to outdated test sets, insufficient focus on essential protein-specific tasks, and a neglect of multimodal assessments. To resolve these issues, we introduce LiveProteinBench, a contamination-free, multimodal benchmark of 12 tasks for evaluating LLM performance on protein property and function prediction. Its central innovation lies in a test set composed exclusively of proteins validated after the start of 2025, guaranteeing that the data is novel to all tested models. We benchmarked a suite of prominent general-purpose LLMs and specialized biological LLMs using both unimodal and multimodal input schemes. Our results show that: 1) General-purpose proprietary large models demonstrate superior zero-shot performance when encountering new protein data, outperforming their open-source and domain-specific counterparts by over 20\% accuracy. 2) The effective use of multi-view structural information remains a significant challenge, as the inclusion of structural images often fails to provide a consistent benefit and can even degrade performance. This highlights the limitations of current models in effectively fusing information across different modalities. 3) Models' performance scales more directly with the computational cost during inference than with its parameter count, underscoring the critical role of Chain-of-Thought reasoning capabilities for protein-specific tasks. LiveProteinBench delineates the current performance frontiers for LLMs in bioinformatics and presents new challenges for the development of future multimodal foundation models for biology

Bayesian models of cognition have gained considerable traction in computational neuroscience and psychiatry. Their scopes are now expected to expand rapidly to artificial intelligence, providing general inference frameworks to support embodied, adaptable, and energy-efficient autonomous agents. A central theory in this domain is predictive coding, which posits that learning and behaviour are driven by hierarchical probabilistic inferences about the causes of sensory inputs. Biological realism constrains these networks to rely on simple local computations in the form of precision-weighted predictions and prediction errors. This can make this framework highly efficient, but its implementation comes with unique challenges on the software development side. Embedding such models in standard neural network libraries often becomes limiting, as these libraries' compilation and differentiation backends can force a conceptual separation between optimization algorithms and the systems being optimized. This critically departs from other biological principles such as self-monitoring, self-organisation, cellular growth and functional plasticity. In this paper, we introduce pyhgf: a Python package backed by JAX and Rust for creating, manipulating and sampling dynamic networks for predictive coding. We improve over other frameworks by enclosing the network components as transparent, modular and malleable variables in the message-passing steps. The resulting graphs can implement arbitrary computational complexities as beliefs propagation. But the transparency of core variables can also translate into inference processes that leverage self-organisation principles, and express structure learning, meta-learning or causal discovery as the consequence of network structural adaptation to surprising inputs. The code, tutorials and documentation are hosted at: https://github.com/ilabcode/pyhgf.

Existing regulatory frameworks for biomedical AI include robustness as a key component but lack detailed implementational guidance. The recent rise of biomedical foundation models creates new hurdles in testing and certification given their broad capabilities and susceptibility to complex distribution shifts. To balance test feasibility and effectiveness, we suggest a priority-based, task-oriented approach to tailor robustness evaluation objectives to a predefined specification. We urge concrete policies to adopt a granular categorization of robustness concepts in the specification. Our approach promotes the standardization of risk assessment and monitoring, which guides technical developments and mitigation efforts.

Hepato-pancreato-biliary (HPB) disorders represent a global public health challenge due to their high morbidity and mortality. Although large language models (LLMs) have shown promising performance in general medical question-answering tasks, the current evaluation benchmarks are mostly derived from standardized examinations or manually designed questions, lacking HPB coverage and clinical cases. To address these issues, we systematically eatablish an HPB disease evaluation benchmark comprising 3,535 closed-ended multiple-choice questions and 337 open-ended real diagnosis cases, which encompasses all the 33 main categories and 465 subcategories of HPB diseases defined in the International Statistical Classification of Diseases, 10th Revision (ICD-10). The multiple-choice questions are curated from public datasets and synthesized data, and the clinical cases are collected from prestigious medical journals, case-sharing platforms, and collaborating hospitals. By evalauting commercial and open-source general and medical LLMs on our established benchmark, namely ClinBench-HBP, we find that while commercial LLMs perform competently on medical exam questions, they exhibit substantial performance degradation on HPB diagnosis tasks, especially on complex, inpatient clinical cases. Those medical LLMs also show limited generalizability to HPB diseases. Our results reveal the critical limitations of current LLMs in the domain of HPB diseases, underscoring the imperative need for future medical LLMs to handle real, complex clinical diagnostics rather than simple medical exam questions. The benchmark will be released at https://clinbench-hpb.github.io.

Real-world phenomena do not generate arbitrary variability: their signals concentrate on compact, low-variability subsets of functional space, enabling rapid generalization from few examples. A small child can recognize a dog after extremely limited exposure because the perceptual manifold of "dog" is compact, structured, and low-dimensional. We formalize this principle through a deterministic functional-topological framework in which the set of valid realizations produced by a physical process forms a compact subset of a Banach space, endowed with stable invariants, a finite Hausdorff radius, and an induced continuous perceptual functional. This geometry provides explicit limits on knowledge, conditions for identifiability, and guarantees for generalization from sparse evidence -- properties fundamental to both natural and artificial intelligence. Across electromechanical, electrochemical, and physiological domains, we show that real-world processes consistently generate compact perceptual manifolds with the same geometric characteristics. Their boundaries can be discovered in a fully self-supervised manner as the empirical radius saturates with increasing sampling, even when the governing equations are unknown. These results demonstrate that deterministic functional topology offers a unified mathematical foundation for perception, representation, and world-model construction. It provides a geometric explanation for why biological learners and self-supervised AI systems can generalize from few observations, and establishes compact perceptual manifolds as a fundamental building block for future AI architectures. Finally, this work unifies biological perception and modern self-supervised models under a single geometric principle: both derive their generalization ability from the compactness and invariants of real-world perceptual manifolds.

Space biology research aims to understand fundamental effects of spaceflight on organisms, develop foundational knowledge to support deep space exploration, and ultimately bioengineer spacecraft and habitats to stabilize the ecosystem of plants, crops, microbes, animals, and humans for sustained multi-planetary life. To advance these aims, the field leverages experiments, platforms, data, and model organisms from both spaceborne and ground-analog studies. As research is extended beyond low Earth orbit, experiments and platforms must be maximally autonomous, light, agile, and intelligent to expedite knowledge discovery. Here we present a summary of recommendations from a workshop organized by the National Aeronautics and Space Administration on artificial intelligence, machine learning, and modeling applications which offer key solutions toward these space biology challenges. In the next decade, the synthesis of artificial intelligence into the field of space biology will deepen the biological understanding of spaceflight effects, facilitate predictive modeling and analytics, support maximally autonomous and reproducible experiments, and efficiently manage spaceborne data and metadata, all with the goal to enable life to thrive in deep space.

We present the findings of "The Alzheimer's Disease Prediction Of Longitudinal Evolution" (TADPOLE) Challenge, which compared the performance of 92 algorithms from 33 international teams at predicting the future trajectory of 219 individuals at risk of Alzheimer's disease. Challenge participants were required to make a prediction, for each month of a 5-year future time period, of three key outcomes: clinical diagnosis, Alzheimer's Disease Assessment Scale Cognitive Subdomain (ADAS-Cog13), and total volume of the ventricles. The methods used by challenge participants included multivariate linear regression, machine learning methods such as support vector machines and deep neural networks, as well as disease progression models. No single submission was best at predicting all three outcomes. For clinical diagnosis and ventricle volume prediction, the best algorithms strongly outperform simple baselines in predictive ability. However, for ADAS-Cog13 no single submitted prediction method was significantly better than random guesswork. Two ensemble methods based on taking the mean and median over all predictions, obtained top scores on almost all tasks. Better than average performance at diagnosis prediction was generally associated with the additional inclusion of features from cerebrospinal fluid (CSF) samples and diffusion tensor imaging (DTI). On the other hand, better performance at ventricle volume prediction was associated with inclusion of summary statistics, such as the slope or maxima/minima of biomarkers. TADPOLE's unique results suggest that current prediction algorithms provide sufficient accuracy to exploit biomarkers related to clinical diagnosis and ventricle volume, for cohort refinement in clinical trials for Alzheimer's disease. However, results call into question the usage of cognitive test scores for patient selection and as a primary endpoint in clinical trials.

With the increasing awareness of health and the growing desire for aesthetic physique, fitness has become a prevailing trend. However, the potential risks associated with fitness training, especially with weight-loaded fitness actions, cannot be overlooked. Action Quality Assessment (AQA), a technology that quantifies the quality of human action and provides feedback, holds the potential to assist fitness enthusiasts of varying skill levels in achieving better training outcomes. Nevertheless, current AQA methodologies and datasets are limited to single-view competitive sports scenarios and RGB modality and lack professional assessment and guidance of fitness actions. To address this gap, we propose the FLEX dataset, the first multi-modal, multi-action, large-scale dataset that incorporates surface electromyography (sEMG) signals into AQA. FLEX utilizes high-precision MoCap to collect 20 different weight-loaded actions performed by 38 subjects across 3 different skill levels for 10 repetitions each, containing 5 different views of the RGB video, 3D pose, sEMG, and physiological information. Additionally, FLEX incorporates knowledge graphs into AQA, constructing annotation rules in the form of penalty functions that map weight-loaded actions, action keysteps, error types, and feedback. We conducted various baseline methodologies on FLEX, demonstrating that multimodal data, multiview data, and fine-grained annotations significantly enhance model performance. FLEX not only advances AQA methodologies and datasets towards multi-modal and multi-action scenarios but also fosters the integration of artificial intelligence within the fitness domain. Dataset and code are available at https://haoyin116.github.io/FLEX_Dataset.

We introduce Functional Diffusion Processes (FDPs), which generalize score-based diffusion models to infinite-dimensional function spaces. FDPs require a new mathematical framework to describe the forward and backward dynamics, and several extensions to derive practical training objectives. These include infinite-dimensional versions of Girsanov theorem, in order to be able to compute an ELBO, and of the sampling theorem, in order to guarantee that functional evaluations in a countable set of points are equivalent to infinite-dimensional functions. We use FDPs to build a new breed of generative models in function spaces, which do not require specialized network architectures, and that can work with any kind of continuous data. Our results on real data show that FDPs achieve high-quality image generation, using a simple MLP architecture with orders of magnitude fewer parameters than existing diffusion models.

Cell-type-specific marker genes are fundamental to plant biology, yet existing resources primarily rely on curated databases or high-throughput studies without explicitly modeling the supporting evidence found in scientific literature. We introduce PlantMarkerBench, a multi-species benchmark for evaluating literature-grounded plant marker evidence interpretation from full-text biological papers. PlantMarkerBench is constructed using a modular curation pipeline integrating large-scale literature retrieval, hybrid search, species-aware biological grounding, structured evidence extraction, and targeted human review. The benchmark spans four plant species -- Arabidopsis, maize, rice, and tomato -- and contains 5,550 sentence-level evidence instances annotated for marker-evidence validity, evidence type, and support strength. We define two benchmark tasks: determining whether a candidate sentence provides valid marker evidence for a gene-cell-type pair, and classifying the evidence into expression, localization, function, indirect, or negative categories. We benchmark diverse open-weight and closed-source language models across species and prompting strategies. Although frontier models achieve relatively strong performance on direct expression evidence, performance drops substantially on functional, indirect, and weak-support evidence, with evidence-type confusion emerging as a dominant failure mode. Open-weight models additionally exhibit elevated false-positive rates under ambiguous biological contexts. PlantMarkerBench provides a challenging and reproducible evaluation framework for literature-grounded biological evidence attribution and supports future research on trustworthy scientific information extraction and AI-assisted plant biology.

Computational measurement of human behavior from video has recently become feasible due to major advances in AI. These advances now enable granular and precise quantification of facial expression, head movement, body action, and other behavioral modalities and are increasingly used in psychology, psychiatry, neuroscience, and mental health research. However, mainstream adoption remains slow. Most existing methods and software are developed for engineering audiences, require specialized software stacks, and fail to provide behavioral measurements at a level directly useful for hypothesis-driven research. As a result, there is a large barrier to entry for researchers who wish to use modern, AI-based tools in their work. We introduce Bitbox, an open-source toolkit designed to remove this barrier and make advanced computational analysis directly usable by behavioral scientists and clinical researchers. Bitbox is guided by principles of reproducibility, modularity, and interpretability. It provides a standardized interface for extracting high-level behavioral measurements from video, leveraging multiple face, head, and body processors. The core modules have been tested and validated on clinical samples and are designed so that new measures can be added with minimal effort. Bitbox is intended to serve both sides of the translational gap. It gives behavioral researchers access to robust, high-level behavioral metrics without requiring engineering expertise, and it provides computer scientists a practical mechanism for disseminating methods to domains where their impact is most needed. We expect that Bitbox will accelerate integration of computational behavioral measurement into behavioral, clinical, and mental health research. Bitbox has been designed from the beginning as a community-driven effort that will evolve through contributions from both method developers and domain scientists.

Verbal confidence elicitation is widely used to extract uncertainty estimates from LLMs. We tested whether seven instruction-tuned open-weight models (3-9B parameters, four families) produce verbalised confidence that meets minimal validity criteria for item-level Type-2 discrimination under minimal numeric elicitation with greedy decoding. In a pre-registered study (OSF: osf.io/azbvx), 524 TriviaQA items were administered under numeric (0-100) and categorical (10-class) elicitation to eight models at Q5_K_M quantisation on consumer hardware, yielding 8,384 deterministic trials. A psychometric validity screen was applied to each model-format cell. All seven instruct models were classified Invalid on numeric confidence (H2 confirmed, 7/7 vs. predicted >=4/7), with a mean ceiling rate of 91.7% (H1 confirmed). Categorical elicitation did not rescue validity. Instead, it disrupted task performance in six of seven models, producing accuracy below 5% (H4 not confirmed). Token-level logprobability did not usefully predict verbalised confidence under the observed variance regime (H5 confirmed, mean cross-validated R^2 < 0.01). Within the reasoning-distilled model, reasoning-trace length showed a strong negative partial correlation with confidence (rho = -0.36, p < .001), consistent with the Reasoning Contamination Effect. These results do not imply that internal uncertainty representations are absent. They show that minimal verbal elicitation fails to preserve internal signals at the output interface in this model-size regime. Psychometric screening should precede any downstream use of such signals.

The idea of personality in descriptive psychology, traditionally defined through observable behavior, has now been extended to Large Language Models (LLMs) to better understand their behavior. This raises a question: do LLMs exhibit distinct and consistent personality traits, similar to humans? Existing self-assessment personality tests, while applicable, lack the necessary validity and reliability for precise personality measurements. To address this, we introduce TRAIT, a new tool consisting of 8K multi-choice questions designed to assess the personality of LLMs with validity and reliability. TRAIT is built on the psychometrically validated human questionnaire, Big Five Inventory (BFI) and Short Dark Triad (SD-3), enhanced with the ATOMIC10X knowledge graph for testing personality in a variety of real scenarios. TRAIT overcomes the reliability and validity issues when measuring personality of LLM with self-assessment, showing the highest scores across three metrics: refusal rate, prompt sensitivity, and option order sensitivity. It reveals notable insights into personality of LLM: 1) LLMs exhibit distinct and consistent personality, which is highly influenced by their training data (i.e., data used for alignment tuning), and 2) current prompting techniques have limited effectiveness in eliciting certain traits, such as high psychopathy or low conscientiousness, suggesting the need for further research in this direction.

Noise is a ubiquitous feature of the physical world. As a result, the first prerequisite of life is fault tolerance: maintaining integrity of state despite external bombardment. Recent experimental advances have revealed that biological systems achieve fault tolerance by implementing mathematically intricate error-correcting codes and by organizing in a modular fashion that physically separates functionally distinct subsystems. These elaborate structures represent a vanishing volume in the massive genetic configuration space. How is it possible that the primitive process of evolution, by which all biological systems evolved, achieved such unusual results? In this work, through experiments in Boolean networks, we show that the simultaneous presence of error correction and modularity in biological systems is no coincidence. Rather, it is a typical co-occurrence in noisy dynamic systems undergoing evolution. From this, we deduce the principle of error correction enhanced evolvability: systems possessing error-correcting codes are more effectively improved by evolution than those without.

Foundation models trained at scale exhibit remarkable emergent behaviors, learning new capabilities beyond their initial training objectives. We find such emergent behaviors in biological vision models via large-scale contrastive vision-language training. To achieve this, we first curate TreeOfLife-200M, comprising 214 million images of living organisms, the largest and most diverse biological organism image dataset to date. We then train BioCLIP 2 on TreeOfLife-200M to distinguish different species. Despite the narrow training objective, BioCLIP 2 yields extraordinary accuracy when applied to various biological visual tasks such as habitat classification and trait prediction. We identify emergent properties in the learned embedding space of BioCLIP 2. At the inter-species level, the embedding distribution of different species aligns closely with functional and ecological meanings (e.g., beak sizes and habitats). At the intra-species level, instead of being diminished, the intra-species variations (e.g., life stages and sexes) are preserved and better separated in subspaces orthogonal to inter-species distinctions. We provide formal proof and analyses to explain why hierarchical supervision and contrastive objectives encourage these emergent properties. Crucially, our results reveal that these properties become increasingly significant with larger-scale training data, leading to a biologically meaningful embedding space.

Despite the success of large language models (LLMs) on general-purpose tasks, their performance in highly specialized domains such as biomedicine remains unsatisfactory. A key limitation is the inability of LLMs to effectively leverage biomedical tools, which clinical experts and biomedical researchers rely on extensively in daily workflows. While recent general-domain tool-calling datasets have substantially improved the capabilities of LLM agents, existing efforts in the biomedical domain largely rely on in-context learning and restrict models to a small set of tools. To address this gap, we introduce BioTool, a comprehensive biomedical tool-calling dataset designed for fine-tuning LLMs. BioTool comprises 34 frequently used tools collected from the NCBI, Ensembl, and UniProt databases, along with 7,040 high-quality, human-verified query-API call pairs spanning variation, genomics, proteomics, evolution, and general biology. Fine-tuning a 4-billion-parameter LLM on BioTool yields substantial improvements in biomedical tool-calling performance, outperforming cutting-edge commercial LLMs such as GPT-5.1. Furthermore, human expert evaluations demonstrate that integrating a BioTool-fine-tuned tool caller significantly improves downstream answer quality compared to the same LLM without tool usage, highlighting the effectiveness of BioTool in enhancing the biomedical capabilities of LLMs. The full dataset and evaluation code are available at https://github.com/gxx27/BioTool

Previous work has shown correlations between the hidden states of large language models and fMRI brain responses, on language tasks. These correlations have been taken as evidence of the representational similarity of these models and brain states. This study tests whether these previous results are robust to several possible concerns. Specifically this study shows: (i) that the previous results are still found after dimensionality reduction, and thus are not attributable to the curse of dimensionality; (ii) that previous results are confirmed when using new measures of similarity; (iii) that correlations between brain representations and those from models are specific to models trained on human language; and (iv) that the results are dependent on the presence of positional encoding in the models. These results confirm and strengthen the results of previous research and contribute to the debate on the biological plausibility and interpretability of state-of-the-art large language models.

Multimodal learning enhances the perceptual capabilities of cognitive systems by integrating information from different sensory modalities. However, existing multimodal fusion research typically assumes static integration, not fully incorporating key dynamic mechanisms found in the brain. Specifically, the brain exhibits an inverse effectiveness phenomenon, wherein weaker unimodal cues yield stronger multisensory integration benefits; conversely, when individual modal cues are stronger, the effect of fusion is diminished. This mechanism enables biological systems to achieve robust cognition even with scarce or noisy perceptual cues. Inspired by this biological mechanism, we explore the relationship between multimodal output and information from individual modalities, proposing an inverse effectiveness driven multimodal fusion (IEMF) strategy. By incorporating this strategy into neural networks, we achieve more efficient integration with improved model performance and computational efficiency, demonstrating up to 50% reduction in computational cost across diverse fusion methods. We conduct experiments on audio-visual classification, continual learning, and question answering tasks to validate our method. Results consistently demonstrate that our method performs excellently in these tasks. To verify universality and generalization, we also conduct experiments on Artificial Neural Networks (ANN) and Spiking Neural Networks (SNN), with results showing good adaptability to both network types. Our research emphasizes the potential of incorporating biologically inspired mechanisms into multimodal networks and provides promising directions for the future development of multimodal artificial intelligence. The code is available at https://github.com/Brain-Cog-Lab/IEMF.

As opposed to evaluating computation and logic-based reasoning, current benchmarks for evaluating large language models (LLMs) in medicine are primarily focused on question-answering involving domain knowledge and descriptive reasoning. While such qualitative capabilities are vital to medical diagnosis, in real-world scenarios, doctors frequently use clinical calculators that follow quantitative equations and rule-based reasoning paradigms for evidence-based decision support. To this end, we propose MedCalc-Bench, a first-of-its-kind dataset focused on evaluating the medical calculation capability of LLMs. MedCalc-Bench contains an evaluation set of over 1000 manually reviewed instances from 55 different medical calculation tasks. Each instance in MedCalc-Bench consists of a patient note, a question requesting to compute a specific medical value, a ground truth answer, and a step-by-step explanation showing how the answer is obtained. While our evaluation results show the potential of LLMs in this area, none of them are effective enough for clinical settings. Common issues include extracting the incorrect entities, not using the correct equation or rules for a calculation task, or incorrectly performing the arithmetic for the computation. We hope our study highlights the quantitative knowledge and reasoning gaps in LLMs within medical settings, encouraging future improvements of LLMs for various clinical calculation tasks.

Biometric capture devices have been utilised to estimate a person's alertness through near-infrared iris images, expanding their use beyond just biometric recognition. However, capturing a substantial number of corresponding images related to alcohol consumption, drug use, and sleep deprivation to create a dataset for training an AI model presents a significant challenge. Typically, a large quantity of images is required to effectively implement a deep learning approach. Currently, training downstream models with a huge number of images based on foundational models provides a real opportunity to enhance this area, thanks to the generalisation capabilities of self-supervised models. This work examines the application of deep learning and foundational models in predicting fitness for duty, which is defined as the subject condition related to determining the alertness for work.

The study of biological materials and bio-inspired materials science is well established; however, surprisingly little knowledge has been systematically translated to engineering solutions. To accelerate discovery and guide insights, an open-source autoregressive transformer large language model (LLM), BioinspiredLLM, is reported. The model was finetuned with a corpus of over a thousand peer-reviewed articles in the field of structural biological and bio-inspired materials and can be prompted to recall information, assist with research tasks, and function as an engine for creativity. The model has proven that it is able to accurately recall information about biological materials and is further enhanced with enhanced reasoning ability, as well as with retrieval-augmented generation to incorporate new data during generation that can also help to traceback sources, update the knowledge base, and connect knowledge domains. BioinspiredLLM also has been shown to develop sound hypotheses regarding biological materials design and remarkably so for materials that have never been explicitly studied before. Lastly, the model showed impressive promise in collaborating with other generative artificial intelligence models in a workflow that can reshape the traditional materials design process. This collaborative generative artificial intelligence method can stimulate and enhance bio-inspired materials design workflows. Biological materials are at a critical intersection of multiple scientific fields and models like BioinspiredLLM help to connect knowledge domains.

In October 2007, a Research Proposal for the University of Sydney, Australia, the author suggested that biovie-physical phenomenon as `electrodynamic dependant biological vision', is governed by relativistic quantum laws and biovision. The phenomenon on the basis of `biovielectroluminescence', satisfies man/microbio/megabio/computer vision (MMMCV), as a robust candidate for physical and visual sciences. The general aim of this addendum is to present a refined text of Sections 1-3 of that proposal and highlighting the contents of its Appendix in form of a `Mechanisms' Section. We then briefly remind in an article aimed for December 2007, by appending two more equations into Section 3, a theoretical II-time scenario as a time model well-proposed for the phenomenon. The time model within the core of the proposal, plays a significant role in emphasizing the principle points on Objectives no. 1-8, Sub-hypothesis 3.1.2, mentioned in Article [arXiv:0710.0410]. It also expresses the time concept in terms of causing quantized energy f(|E|) of time |t|, emit in regard to shortening the probability of particle loci as predictable patterns of particle's un-occurred motion, a solution to Heisenberg's uncertainty principle (HUP) into a simplistic manner. We conclude that, practical frames via a time algorithm to this model, fixates such predictable patterns of motion of scenery bodies onto recordable observation points of a MMMCV system. It even suppresses/predicts superposition phenomena coming from a human subject and/or other bio-subjects for any decision making event, e.g., brainwave quantum patterns based on vision. Maintaining the existential probability of Riemann surfaces of II-time scenarios in the context of biovielectroluminescence, makes motion-prediction a possibility.

Analysis of learned representations has a blind spot: it focuses on similarity, measuring how closely embeddings align with external references, but similarity reveals only what is represented, not whether that structure is robust. We introduce geometric stability, a distinct dimension that quantifies how reliably representational geometry holds under perturbation, and present Shesha, a framework for measuring it. Across 2,463 configurations in seven domains, we show that stability and similarity are empirically uncorrelated (ρapprox 0.01) and mechanistically distinct: similarity metrics collapse after removing the top principal components, while stability retains sensitivity to fine-grained manifold structure. This distinction yields actionable insights: for safety monitoring, stability acts as a functional geometric canary, detecting structural drift nearly 2times more sensitively than CKA while filtering out the non-functional noise that triggers false alarms in rigid distance metrics; for controllability, supervised stability predicts linear steerability (ρ= 0.89-0.96); for model selection, stability dissociates from transferability, revealing a geometric tax that transfer optimization incurs. Beyond machine learning, stability predicts CRISPR perturbation coherence and neural-behavioral coupling. By quantifying how reliably systems maintain structure, geometric stability provides a necessary complement to similarity for auditing representations across biological and computational systems.

We introduce AbGen, the first benchmark designed to evaluate the capabilities of LLMs in designing ablation studies for scientific research. AbGen consists of 1,500 expert-annotated examples derived from 807 NLP papers. In this benchmark, LLMs are tasked with generating detailed ablation study designs for a specified module or process based on the given research context. Our evaluation of leading LLMs, such as DeepSeek-R1-0528 and o4-mini, highlights a significant performance gap between these models and human experts in terms of the importance, faithfulness, and soundness of the ablation study designs. Moreover, we demonstrate that current automated evaluation methods are not reliable for our task, as they show a significant discrepancy when compared to human assessment. To better investigate this, we develop AbGen-Eval, a meta-evaluation benchmark designed to assess the reliability of commonly used automated evaluation systems in measuring LLM performance on our task. We investigate various LLM-as-Judge systems on AbGen-Eval, providing insights for future research on developing more effective and reliable LLM-based evaluation systems for complex scientific tasks.

The discourse around toxicity and LLMs in NLP largely revolves around detection tasks. This work shifts the focus to evaluating LLMs' reasoning about toxicity -- from their explanations that justify a stance -- to enhance their trustworthiness in downstream tasks. Despite extensive research on explainability, it is not straightforward to adopt existing methods to evaluate free-form toxicity explanation due to their over-reliance on input text perturbations, among other challenges. To account for these, we propose a novel, theoretically-grounded multi-dimensional criterion, Human-Aligned Faithfulness (HAF), that measures the extent to which LLMs' free-form toxicity explanations align with those of a rational human under ideal conditions. We develop six metrics, based on uncertainty quantification, to comprehensively evaluate \haf of LLMs' toxicity explanations with no human involvement, and highlight how "non-ideal" the explanations are. We conduct several experiments on three Llama models (of size up to 70B) and an 8B Ministral model on five diverse toxicity datasets. Our results show that while LLMs generate plausible explanations to simple prompts, their reasoning about toxicity breaks down when prompted about the nuanced relations between the complete set of reasons, the individual reasons, and their toxicity stances, resulting in inconsistent and nonsensical responses. We open-source our code and LLM-generated explanations at https://github.com/uofthcdslab/HAF.

Several studies showed that Large Language Models (LLMs) can answer medical questions correctly, even outperforming the average human score in some medical exams. However, to our knowledge, no study has been conducted to assess the ability of language models to validate existing or generated medical text for correctness and consistency. In this paper, we introduce MEDEC (https://github.com/abachaa/MEDEC), the first publicly available benchmark for medical error detection and correction in clinical notes, covering five types of errors (Diagnosis, Management, Treatment, Pharmacotherapy, and Causal Organism). MEDEC consists of 3,848 clinical texts, including 488 clinical notes from three US hospital systems that were not previously seen by any LLM. The dataset has been used for the MEDIQA-CORR shared task to evaluate seventeen participating systems [Ben Abacha et al., 2024]. In this paper, we describe the data creation methods and we evaluate recent LLMs (e.g., o1-preview, GPT-4, Claude 3.5 Sonnet, and Gemini 2.0 Flash) for the tasks of detecting and correcting medical errors requiring both medical knowledge and reasoning capabilities. We also conducted a comparative study where two medical doctors performed the same task on the MEDEC test set. The results showed that MEDEC is a sufficiently challenging benchmark to assess the ability of models to validate existing or generated notes and to correct medical errors. We also found that although recent LLMs have a good performance in error detection and correction, they are still outperformed by medical doctors in these tasks. We discuss the potential factors behind this gap, the insights from our experiments, the limitations of current evaluation metrics, and share potential pointers for future research.

Human space exploration beyond low Earth orbit will involve missions of significant distance and duration. To effectively mitigate myriad space health hazards, paradigm shifts in data and space health systems are necessary to enable Earth-independence, rather than Earth-reliance. Promising developments in the fields of artificial intelligence and machine learning for biology and health can address these needs. We propose an appropriately autonomous and intelligent Precision Space Health system that will monitor, aggregate, and assess biomedical statuses; analyze and predict personalized adverse health outcomes; adapt and respond to newly accumulated data; and provide preventive, actionable, and timely insights to individual deep space crew members and iterative decision support to their crew medical officer. Here we present a summary of recommendations from a workshop organized by the National Aeronautics and Space Administration, on future applications of artificial intelligence in space biology and health. In the next decade, biomonitoring technology, biomarker science, spacecraft hardware, intelligent software, and streamlined data management must mature and be woven together into a Precision Space Health system to enable humanity to thrive in deep space.

Bionic vision uses neuroprostheses to restore useful vision to people living with incurable blindness. However, a major outstanding challenge is predicting what people 'see' when they use their devices. The limited field of view of current devices necessitates head movements to scan the scene, which is difficult to simulate on a computer screen. In addition, many computational models of bionic vision lack biological realism. To address these challenges, we present VR-SPV, an open-source virtual reality toolbox for simulated prosthetic vision that uses a psychophysically validated computational model to allow sighted participants to 'see through the eyes' of a bionic eye user. To demonstrate its utility, we systematically evaluated how clinically reported visual distortions affect performance in a letter recognition and an immersive obstacle avoidance task. Our results highlight the importance of using an appropriate phosphene model when predicting visual outcomes for bionic vision.

Functional brain network (FBN) modeling often relies on local pairwise interactions, whose limitation in capturing high-order dependencies is theoretically analyzed in this paper. Meanwhile, the computational burden and heuristic nature of current hypergraph modeling approaches hinder end-to-end learning of FBN structures directly from data distributions. To address this, we propose to extract high-order FBN structures under global constraints, and implement this as a Global Constraints oriented Multi-resolution (GCM) FBN structure learning framework. It incorporates 4 types of global constraint (signal synchronization, subject identity, expected edge numbers, and data labels) to enable learning FBN structures for 4 distinct levels (sample/subject/group/project) of modeling resolution. Experimental results demonstrate that GCM achieves up to a 30.6% improvement in relative accuracy and a 96.3% reduction in computational time across 5 datasets and 2 task settings, compared to 9 baselines and 10 state-of-the-art methods. Extensive experiments validate the contributions of individual components and highlight the interpretability of GCM. This work offers a novel perspective on FBN structure learning and provides a foundation for interdisciplinary applications in cognitive neuroscience. Code is publicly available on https://github.com/lzhan94swu/GCM.

Medicine is inherently multimodal, with rich data modalities spanning text, imaging, genomics, and more. Generalist biomedical artificial intelligence (AI) systems that flexibly encode, integrate, and interpret this data at scale can potentially enable impactful applications ranging from scientific discovery to care delivery. To enable the development of these models, we first curate MultiMedBench, a new multimodal biomedical benchmark. MultiMedBench encompasses 14 diverse tasks such as medical question answering, mammography and dermatology image interpretation, radiology report generation and summarization, and genomic variant calling. We then introduce Med-PaLM Multimodal (Med-PaLM M), our proof of concept for a generalist biomedical AI system. Med-PaLM M is a large multimodal generative model that flexibly encodes and interprets biomedical data including clinical language, imaging, and genomics with the same set of model weights. Med-PaLM M reaches performance competitive with or exceeding the state of the art on all MultiMedBench tasks, often surpassing specialist models by a wide margin. We also report examples of zero-shot generalization to novel medical concepts and tasks, positive transfer learning across tasks, and emergent zero-shot medical reasoning. To further probe the capabilities and limitations of Med-PaLM M, we conduct a radiologist evaluation of model-generated (and human) chest X-ray reports and observe encouraging performance across model scales. In a side-by-side ranking on 246 retrospective chest X-rays, clinicians express a pairwise preference for Med-PaLM M reports over those produced by radiologists in up to 40.50% of cases, suggesting potential clinical utility. While considerable work is needed to validate these models in real-world use cases, our results represent a milestone towards the development of generalist biomedical AI systems.

Several recent works seek to develop foundation models specifically for medical applications, adapting general-purpose large language models (LLMs) and vision-language models (VLMs) via continued pretraining on publicly available biomedical corpora. These works typically claim that such domain-adaptive pretraining (DAPT) improves performance on downstream medical tasks, such as answering medical licensing exam questions. In this paper, we compare seven public "medical" LLMs and two VLMs against their corresponding base models, arriving at a different conclusion: all medical VLMs and nearly all medical LLMs fail to consistently improve over their base models in the zero-/few-shot prompting regime for medical question-answering (QA) tasks. For instance, across the tasks and model pairs we consider in the 3-shot setting, medical LLMs only outperform their base models in 12.1% of cases, reach a (statistical) tie in 49.8% of cases, and are significantly worse than their base models in the remaining 38.2% of cases. Our conclusions are based on (i) comparing each medical model head-to-head, directly against the corresponding base model; (ii) optimizing the prompts for each model separately; and (iii) accounting for statistical uncertainty in comparisons. While these basic practices are not consistently adopted in the literature, our ablations show that they substantially impact conclusions. Our findings suggest that state-of-the-art general-domain models may already exhibit strong medical knowledge and reasoning capabilities, and offer recommendations to strengthen the conclusions of future studies.

We introduce a cross-domain behavioural assay of monitoring-control coupling in LLMs, grounded in the Nelson and Narens (1990) metacognitive framework and applying human psychometric methodology to LLM evaluation. The battery comprises 524 items across six cognitive domains (learning, metacognitive calibration, social cognition, attention, executive function, prospective regulation), each grounded in an established experimental paradigm. Tasks T1-T5 were pre-registered on OSF prior to data collection; T6 was added as an exploratory extension. After every forced-choice response, dual probes adapted from Koriat and Goldsmith (1996) ask the model to KEEP or WITHDRAW its answer and to BET or decline. The critical metric is the withdraw delta: the difference in withdrawal rate between incorrect and correct items. Applied to 20 frontier LLMs (10,480 evaluations), the battery discriminates three profiles consistent with the Nelson-Narens architecture: blanket confidence, blanket withdrawal, and selective sensitivity. Accuracy rank and metacognitive sensitivity rank are largely inverted. Retrospective monitoring and prospective regulation appear dissociable (r = .17, 95% CI wide given n=20; exemplar-based evidence is the primary support). Scaling on metacognitive calibration is architecture-dependent: monotonically decreasing (Qwen), monotonically increasing (GPT-5.4), or flat (Gemma). Behavioural findings converge structurally with an independent Type-2 SDT approach, providing preliminary cross-method construct validity. All items, data, and code: https://github.com/synthiumjp/metacognitive-monitoring-battery.

Objective: Question answering (QA) systems have the potential to improve the quality of clinical care by providing health professionals with the latest and most relevant evidence. However, QA systems have not been widely adopted. This systematic review aims to characterize current medical QA systems, assess their suitability for healthcare, and identify areas of improvement. Materials and methods: We searched PubMed, IEEE Xplore, ACM Digital Library, ACL Anthology and forward and backward citations on 7th February 2023. We included peer-reviewed journal and conference papers describing the design and evaluation of biomedical QA systems. Two reviewers screened titles, abstracts, and full-text articles. We conducted a narrative synthesis and risk of bias assessment for each study. We assessed the utility of biomedical QA systems. Results: We included 79 studies and identified themes, including question realism, answer reliability, answer utility, clinical specialism, systems, usability, and evaluation methods. Clinicians' questions used to train and evaluate QA systems were restricted to certain sources, types and complexity levels. No system communicated confidence levels in the answers or sources. Many studies suffered from high risks of bias and applicability concerns. Only 8 studies completely satisfied any criterion for clinical utility, and only 7 reported user evaluations. Most systems were built with limited input from clinicians. Discussion: While machine learning methods have led to increased accuracy, most studies imperfectly reflected real-world healthcare information needs. Key research priorities include developing more realistic healthcare QA datasets and considering the reliability of answer sources, rather than merely focusing on accuracy.

Scientific research proceeds through iterative cycles of hypothesis generation, experiment design, execution, and revision. AI agents can automate parts of this process, but existing approaches typically follow a single research trajectory or coordinate through a central planner with fixed objectives. As a result, they struggle to sustain parallel exploration, adapt as experimental evidence changes, or preserve knowledge of failed directions over long-running experiments. We introduce AutoScientists, a decentralized team of AI agents for long-running computational scientific experimentation. Agents interpret a shared experimental state, self-organize into teams around promising hypotheses, critique proposals before using experimental compute, and share successes and failures to reduce redundant exploration. Under matched experimental budgets, AutoScientists improves over prior AI agents across biomedical machine learning, language-model training optimization, and protein fitness prediction. On BioML-Bench, spanning biomedical imaging, protein engineering, single-cell omics, and drug discovery, AutoScientists achieves a mean leaderboard percentile of 74.4% across 24 tasks, improving over the strongest AI agent by +8.33%. On GPT training optimization, AutoScientists reaches a target validation bits-per-byte 1.9x faster than Autoresearch and continues discovering improvements from a starting champion where the single-agent approach finds none (7 vs. 0 accepted improvements). On ProteinGym fitness prediction, AutoScientists discovers a method for ACE2-Spike binding that improves over the current state-of-the-art model by +12.5% in Spearman correlation. Applied without modification across all 217 ProteinGym assays, the same method improves over the prior state of the art by +6.5% (Spearman correlation).

Recurrent Neural Networks (RNNs) are popular models of brain function. The typical training strategy is to adjust their input-output behavior so that it matches that of the biological circuit of interest. Even though this strategy ensures that the biological and artificial networks perform the same computational task, it does not guarantee that their internal activity dynamics match. This suggests that the trained RNNs might end up performing the task employing a different internal computational mechanism, which would make them a suboptimal model of the biological circuit. In this work, we introduce a novel training strategy that allows learning not only the input-output behavior of an RNN but also its internal network dynamics, based on sparse neural recordings. We test the proposed method by training an RNN to simultaneously reproduce internal dynamics and output signals of a physiologically-inspired neural model. Specifically, this model generates the multiphasic muscle-like activity patterns typically observed during the execution of reaching movements, based on the oscillatory activation patterns concurrently observed in the motor cortex. Remarkably, we show that the reproduction of the internal dynamics is successful even when the training algorithm relies on the activities of a small subset of neurons sampled from the biological network. Furthermore, we show that training the RNNs with this method significantly improves their generalization performance. Overall, our results suggest that the proposed method is suitable for building powerful functional RNN models, which automatically capture important computational properties of the biological circuit of interest from sparse neural recordings.

Large Language Models (LLMs) are increasingly capable of generating complete applications from natural language instructions, creating new opportunities in science and education. In these domains, interactive scientific demonstrations are particularly valuable for explaining concepts, supporting new teaching methods, and presenting research findings. Generating such demonstrations requires models to combine accurate scientific knowledge with the ability to implement interactive front-end code that behaves correctly and responds to user actions. This capability goes beyond the scope of existing benchmarks, which typically evaluate either knowledge question answering without grounding in code or static web code generation without scientific interactivity. To evaluate this integrated ability, we design a hybrid framework that combines programmatic functional testing to rigorously verify interaction logic with visually-grounded qualitative testing to assess rendered outputs against reference snapshots. Building on this framework, we present InteractScience, a benchmark consisting of a substantial set of carefully designed questions across five scientific domains, each paired with unit tests, reference snapshots, and checklists. We evaluate 30 leading open- and closed-source LLMs and report results that highlight ongoing weaknesses in integrating domain knowledge with interactive front-end coding. Our work positions InteractScience as the first benchmark to automatically measure this combined capability with realistic interactive operations, providing a foundation for advancing reliable and educationally useful scientific demonstration code generation. All code and data are publicly available at https://github.com/open-compass/InteractScience.

Artificial intelligence systems are increasingly deployed in biomedical research. However, current evaluation frameworks may inadequately assess their effectiveness as research collaborators. This rapid review examines benchmarking practices for AI systems in preclinical biomedical research. Three major databases and two preprint servers were searched from January 1, 2018 to October 31, 2025, identifying 14 benchmarks that assess AI capabilities in literature understanding, experimental design, and hypothesis generation. The results revealed that all current benchmarks assess isolated component capabilities, including data analysis quality, hypothesis validity, and experimental protocol design. However, authentic research collaboration requires integrated workflows spanning multiple sessions, with contextual memory, adaptive dialogue, and constraint propagation. This gap implies that systems excelling on component benchmarks may fail as practical research co-pilots. A process-oriented evaluation framework is proposed that addresses four critical dimensions absent from current benchmarks: dialogue quality, workflow orchestration, session continuity, and researcher experience. These dimensions are essential for evaluating AI systems as research co-pilots rather than as isolated task executors.

A database of images of approximately 960 unique plants belonging to 12 species at several growth stages is made publicly available. It comprises annotated RGB images with a physical resolution of roughly 10 pixels per mm. To standardise the evaluation of classification results obtained with the database, a benchmark based on f_{1} scores is proposed. The dataset is available at https://vision.eng.au.dk/plant-seedlings-dataset