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01.
medRxiv (Medicine) 2026-06-15

Non-invasive intracranial pressure waveform reconstruction with deep learning

Purpose: Continuous intracranial pressure (ICP) monitoring requires invasive instrumentation, reaching only a narrow subset of critically ill patients. We tested whether deep learning models trained on routinely acquired extracranial signals can reconstruct continuous ICP waveforms at clinically relevant accuracy in an independent external cohort. Methods: In adults admitted to the ICU at a single quaternary health system, five deep learning architectures were trained on high-frequency arterial blood pressure (ABP), photoplethysmography (PPG), and electrocardiography (ECG) waveforms, using invasive (intraparenchymal) ICP as ground truth. Two fusion strategies (early and late) and three training objectives (waveform-morphology, baseline robust regression, and weighted robust regression) were evaluated. Models were externally validated on the held-out MIMIC-III Waveform Database. Performance was assessed by mean absolute error (MAE) and waveform similarity by Pearson correlation (r). Results: We analyzed data from 158 critically ill adults (~5,322 hours) across two quaternary health systems (Johns Hopkins Hospital, Baltimore; Beth Israel Deaconess Medical Center, Boston). Validation MAE ranged from 4.276 mmHg [95% CI 4.269, 4.283] (gated recurrent, late fusion) to 4.946 mmHg [95% CI 4.938, 4.956] (attention-based, early fusion), with Pearson r ranging from 0.599 [95% CI 0.599, 0.600] to 0.722 [95% CI 0.722, 0.723]. The multiscale encoder-decoder model demonstrated the most favorable MAE-correlation tradeoff. Conclusion: This is the first demonstration that continuous ICP waveform reconstruction from bedside signals generalizes across institutions at clinically relevant accuracy, establishing a foundation for non-invasive ICP monitoring and motivating validation across broader populations and ICP ranges.

02.
arXiv (CS.CV) 2026-06-18

Clinically Aligned Geometry Constraints for Robust IVUS Vessel Boundary Segmentation

Intravascular ultrasound (IVUS) lumen and external elastic membrane (EEM) segmentation is important for quantitative coronary plaque burden assessment. Errors in lumen or EEM delineation directly propagate to plaque area, plaque burden and geometric measurements. However, standard methods prioritising overlap scores often suffer from boundary drift and topology errors, leading to inaccurate clinical measurements. We present GeoCat, a geometry-consistent network that processes 5-frame IVUS clips using dual Cartesian-polar encoders with cross-domain attention and temporal fusion. A differentiable geometry consistency loss directly supervises clinically relevant descriptors including diameters, orientations, and cross-sectional areas. The model is trained on 12,242 annotated frames from 146 patients acquired with two commercial IVUS systems. We evaluate performance using both segmentation accuracy and plaque-relevant clinical metrics, including Dice/IoU, boundary measures(95HD (mm), ASSD), topology violation rate, and clinical geometry errors (dmax/dmin, angles, and areas). On our dataset, GeoCat achieves a Dice of 0.93, reduces 95HD to 0.14 mm, and lowers topology violations to 1.0%. Importantly, it significantly improves geometric fidelity, yielding diameter errors of 0.13-0.16 mm and angular errors of ~8 degrees, supporting reliable plaque burden quantification.

03.
Nature Biotechnology 2026-06-05

Structural motif search across the protein universe with Folddisco

作者:

Detecting similar protein structural motifs in large structure collections is computationally expensive. We developed Folddisco, a fast structural motif search tool that uses an index of position-independent geometric features, including side-chain orientation, combined with a rarity-based scoring system. Folddisco is 20-fold faster in querying and fourfold more storage-efficient than existing methods while improving accuracy. Folddisco is freely available online ( https://folddisco.foldseek.com ), along with a webserver ( https://search.foldseek.com/folddisco ). Folddisco enables protein structural motif search in million scale databases.

04.
arXiv (CS.CL) 2026-06-15

Achieving Precise Text-To-Cypher Via Grounded Knowledge Graph Data Generation

Property Graphs are rapidly being adopted as database frameworks for representing heterogeneous data sources. To enable precise access to the information contained in them we need conversational interfaces based on Text-To-Cypher (Text2Cypher) parsers. This paper presents an automatic synthetic data generation method that can be leveraged to fine-tune small LLMs for this task. We conduct experiments on all the major Text-To-Cypher benchmarks, demonstrating that with our synthetic data generation approach we can significantly increase the performance of small LLMs, allowing them to compete with much larger proprietary models. This means that in settings in which models must be locally deployed we can ensure data-sovereignty without sacrificing accuracy and without costly annotation campaigns.

05.
arXiv (CS.CL) 2026-06-18

Continuous Audio Thinking for Large Audio Language Models

Large audio language models (LALMs) have shown impressive capabilities on diverse audio understanding tasks, ranging from speech transcription to music analysis. However, because LALMs are typically trained to produce text-aligned responses, their hidden states are progressively shaped for text generation rather than for preserving acoustic information. As a result, the diverse acoustic content that audio carries, such as phonetic detail, prosody, sound events, affect, and pitch, is lost along the way and difficult to leverage in the response. We introduce Continuous Audio Thinking (CoAT), a framework that equips audio language models with a continuous latent workspace for organizing acoustic information prior to response generation, grounded by distillation from audio experts. Within the thinking space, the model can utilize the rich acoustic information provided by expert distillation when generating its response. Furthermore, the proposed continuous thinking block can be processed in a single prefill, so CoAT does not require additional autoregressive decoding cost over the baseline. Across three LALMs, Qwen2-Audio, Qwen2.5-Omni-7B, and Audio Flamingo~3, performance gains on a broad benchmark suite spanning audio reasoning, audio understanding, music classification, speech emotion, and speech transcription demonstrate the effectiveness of CoAT. Further analysis confirms that the auxiliary supervision propagates from the thinking positions to the model's textual responses.

06.
arXiv (CS.AI) 2026-06-16

Co-Scraper: query-aware DOM Pruning and Reusable Scraper Synthesis for Lightweight Web Data Extraction

arXiv:2606.14821v1 Announce Type: cross Abstract: The abundant and heterogeneous nature of web content necessitates automated information extraction, and generating scrapers that can be reused across similar web pages offers an effective solution for scalable data extraction. In this work, we propose Co-Scraper, a two-stage framework capable of handling the hierarchical complexity of long HTML documents. By integrating a query-aware DOM pruning mechanism with stable extraction strategy induction, Co-Scraper can effectively transforms web content into executable programmatic wrappers using a fine-tuned Qwen3-8B model. On the test set of SWDE, Co-Scraper achieves state-of-the-art performance with an F1 score of 94.78% and a reuse success rate of 90.39%. This framework significantly enhances the accuracy and resilience of data extraction, providing a highly efficient approach for web data acquisition tasks.

07.
bioRxiv (Bioinfo) 2026-06-08

DipSkmer: Reference-free population genomics with diploid genome skims

Ecologists and conservation biologists rely on genetic diversity as a key essential biodiversity variable (EBV) used to track population health and dynamics, and utilize the population parameter {theta} (estimated by the average pairwise genomic distance) as a key metric of diversity. While whole-genome-sequencing (wgs) is increasingly affordable, it will be considerable time before the full diversity of life is represented by high-quality assembled genomes; even then, constant monitoring will still require repeated sampling of populations. In contrast, genome skimming (low-coverage, short-read wgs) is highly cost-effective but challenging to analyze because the coverage is too low for assembly and reliable error correction. Mature methods, such as Mash, exist for estimating pairwise genomic distances based on the Jaccard similarity of k-mer sets computed using sketching techniques. Some, such as Skmer, additionally model the impacts of low coverage. These methods have been successfully applied to assembly-free species identification and phylogenetics; however, their use in population genetics has been limited. This is because these methods implicitly treat genomes as haploid and heterozygosity confounds true estimates of genomic distance for diploid organisms. In this paper, we address this problem through a number of technical advances. First, we use coalescent theory to mathematically derive how the Jaccard index between two diploid samples changes with the scaled population size parameter ({theta}). Next, we derive an estimator that computes {theta} from the Jaccard index, in addition to several auxiliary variables, which we also estimate from the genome skims. The resulting method, DipSkmer, enables more accurate estimates of coverage, sequencing error, and pairwise nucleotide distance for diploid samples. Analyses of both simulated and empirical datasets show that for diploids and low distances (e.g.,

08.
arXiv (CS.AI) 2026-06-11

Information bottleneck for learning the phase space of dynamics from high-dimensional experimental data

arXiv:2604.24662v2 Announce Type: replace-cross Abstract: Identifying the dynamical state variables of a system from high-dimensional observations is a central problem across physical sciences. The challenge is that the state variables are not directly observable and must be inferred from raw high-dimensional data without supervision. Here we introduce DySIB (Dynamical Symmetric Information Bottleneck) as a method to learn low-dimensional representations of time-series data by maximizing predictive mutual information between past and future observation windows while penalizing representation complexity. This objective operates entirely in latent space and avoids reconstruction of the observations. We apply DySIB to an experimental video dataset of a physical pendulum, where the underlying state space is known. The method, with hyperparameters of the learning architecture set self-consistently by the data, recovers a two-dimensional representation that matches the dimensionality, topology, and geometry of the pendulum phase space, with the learned coordinates aligning smoothly with the canonical angle and angular velocity. These results demonstrate, on a well-characterized experimental system, that predictive information in latent space can be used to recover interpretable dynamical coordinates directly from high-dimensional data.

09.
arXiv (CS.CV) 2026-06-15

C-MambaPose: A Physics-Informed Complex Mamba Framework for Cross-Environment WiFi Human Pose Estimation

Human pose estimation (HPE) utilizing wireless WiFi signals has emerged as a promising technology owing to its device-free nature, privacy preservation, and robustness against occlusion and poor lighting. However, existing methods often overlook the physical complex phase information of WiFi signals and fail to generalize across diverse environments due to severe domain shifts. In this paper, we present C-MambaPose, a physics-informed complex-valued Mamba-GraFormer hybrid framework for robust cross-environment WiFi-based 3D HPE. Our framework first sanitizes raw WiFi Channel State Information (CSI) phase errors and constructs a phase-preserving complex-valued representation. We then employ a Spatiotemporal Complex Mamba encoder with a dynamic selective receptive field to capture fine-grained phase dynamics. A cross-attention joint-query mapper maps the unstructured sequence tokens to human joints, which are decoded by a Graph Convolutional Network (GCN) to predict anatomically coherent 3D coordinates. Extensive evaluations on the MM-Fi dataset show that C-MambaPose achieves competitive or superior performance to state-of-the-art baselines across all settings, setting a new state-of-the-art specifically on the challenging cross-environment split, requiring only 3.78 M parameters-an 83.1\% reduction compared to GraphPose-Fi[chen2026graph] and an 85.7\% reduction compared to MetaFi++[zhou2023metafi++], while maintaining a comparable size to DT-Pose[chen2025towards] (which is only 18\% smaller) but achieving significantly superior performance without requiring any pretraining. Our code is publicly available at https://github.com/phucngvinuni/cmampose.git.

10.
arXiv (CS.CV) 2026-06-16

Fusion-E2Pulse: A Multimodal Event-RGB Fusion Network for Non-contact Pulse Wave Reconstruction

Non-contact pulse wave reconstruction hinges on the precise recovery of waveform morphology, including the dicrotic notch. Conventional Red-Green-Blue (RGB)-based methods, which extract physiological signals from recorded facial videos, are constrained by the integral imaging mechanism of standard cameras, where the exposure process induces a smoothing effect that attenuates subtle vascular pulsation details. Conversely, neuromorphic event cameras, while offering exceptional sensitivity to intensity fluctuations, are inherently susceptible to noise and artifacts induced by minor motion. To exploit the synergy between frame-based integration and event-based differential sensing, we propose a novel multimodal network named Fusion-E2Pulse. This framework utilizes filtered RGB signals as structural priors to suppress motion artifacts, while leveraging the high-sensitivity of event streams to recover fine-grained morphological details. Experimental results demonstrate that Fusion-E2Pulse achieves state-of-the-art performance, effectively balancing noise suppression and morphological fidelity, achieving a mean absolute error of 0.78 bpm for heart rate estimation, a waveform correlation of 0.89, and a systolic phase duration error of 16.74 ms, validating its efficacy in reconstructing fine-grained pathological features.

11.
Nature (Science) 2026-06-17

A 98-qubit trapped-ion quantum computer with all-to-all connectivity

Quantum computers require both high-fidelity operations and large qubit numbers to surpass classical capabilities1. Trapped-ion platforms have demonstrated the highest gate fidelities of any modality2–6 but scaling to larger qubit numbers while preserving performance has remained a central challenge. We report on Quantinuum Helios, a 98-qubit trapped-ion quantum processor based on the quantum charge-coupled device (QCCD) architecture7. Helios features 137Ba+ hyperfine qubits8,9, all-to-all connectivity enabled by a rotatable ion storage ring connecting two quantum operation regions by a junction10,11, speed improvements from parallelized operations12 and a new software stack with real-time compilation of dynamic programs13. Averaged over all operational zones in the system, we achieve average infidelities of 2.5(1) × 10−5 for single-qubit (1Q) gates, 7.9(2) × 10−4 for two-qubit (2Q) gates and 3.3(5) × 10−4 for state preparation and measurement (SPAM), none of which are fundamentally limited and probably able to be improved. These component infidelities are predictive of system-level performance in both random Clifford circuits and random circuit sampling (RCS), the latter demonstrating that Helios operates well beyond the reach of classical simulation and establishes a new frontier of fidelity and complexity for quantum computers14. A new quantum computer, Quantinuum Helios, which is a 98-qubit trapped-ion quantum processor built on the QCCD architecture, demonstrates performance well beyond classical capabilities and provides a path for scaling up quantum computing.

12.
arXiv (CS.LG) 2026-06-17

Recursive Scaling in Masked Diffusion Models

arXiv:2606.18022v1 Announce Type: new Abstract: Masked diffusion models (MDMs) have recently emerged as a promising paradigm for sequence generation. Scaling MDMs is conventionally achieved by increasing the parameter count or the number of denoising steps. We introduce Recursive Masked Diffusion Models (R-MDMs), which add recursive depth as a third scaling axis by repeatedly applying the same denoising transformer within each diffusion step. Recursion enables iterative refinement of the output through parameter reuse, increasing effective model depth without increasing parameter count. Across structured generation tasks, including Sudoku and Countdown, we show that R-MDMs achieve substantially improved parameter efficiency: a model with $L$ recursive iterations often matches the performance of non-recursive baselines with roughly $L\times$ more parameters. Moreover, recursive refinement can partially substitute for additional denoising steps, allowing recursive models to reach the same generation quality with fewer forward passes at inference time. These results suggest that recursive depth is a practically useful scaling mechanism for MDMs, improving both parameter efficiency and the allocation of test-time compute.

13.
arXiv (CS.AI) 2026-06-11

Are Frontier LLMs Ready for Cybersecurity? Evidence for Vertical Foundation Models from Dual-Mode Vulnerability Benchmarks

arXiv:2605.23243v2 Announce Type: replace-cross Abstract: We evaluate whether frontier LLMs are ready for cybersecurity through a dual-mode benchmark: white-box function-level vulnerability detection (VulnLLM-R, across C/Java/Python) and black-box web application security testing (five production-style applications with 118 ground-truth vulnerabilities across 20+ CWE families, which we will open-source). We test six frontier models (GPT-5.4, Codex~5.3, Claude Opus~4.6, Sonnet~4.6, Gemini~3.1~Pro and Gemini~3~Flash) and two domain-specialized models across four testing paradigms. Our findings are sobering: (1)~every frontier model produces 10-50% false positive rates in white-box detection, systematically over-predicting vulnerabilities; (2)~in black-box testing, frontier models achieve only 4-8% ground-truth coverage, improving to just 10-19% even with external security tools (Playwright MCP, Burp Suite MCP); (3)~structured penetration-testing methodology encoded in domain-specialized agents raises per-family detection above 50%, demonstrating that methodology, not scale, is the primary lever; and (4)~a domain-specialized defense model achieves the highest precision (0.904) and lowest false positive rate (9.7%) among all models, on a single GPU. We identify the absence of structured security testing traces end-to-end request/response sequences, failure-heavy data, and multi-step attack chains as the fundamental training data bottleneck, and propose self-play security testing as a data generation strategy. Our results make the case for vertical foundation models purpose-built for cybersecurity.

14.
medRxiv (Medicine) 2026-06-16

Reporting patterns of adverse drug withdrawal events using individual case safety reports in United States and European databases

Introduction: Adverse drug withdrawal events (ADWEs) are a key safety concern with deprescribing but are infrequently reported in trials. Although pharmacovigilance systems have advanced our understanding of medication-related harms, it is unclear how extensively these systems have been used for ADWEs. Objectives: To examine the reporting patterns of ADWEs for all drugs recorded in United States and European pharmacovigilance databases between 2004 and 2023. Methods: A retrospective study was conducted using two pharmacovigilance databases, the publicly available FDA-FAERS dataset and EMA-EV Level 2A (individual-level) dataset. ADWE cases were identified using relevant MedDRA preferred terms. Data on patient characteristics, reporter type, drugs, indication, ADWE outcomes, dechallenge/rechallenge, seriousness criteria, time to onset, duration, and causality were summarised. Results: A total of 158,505 ADWE reports were analysed (FDA-FAERS: 145,514; EMA-EV: 12,987), with mean ages of 46.1 (FDA; 55.3% female) and 45.5 years (EMA; 57.1% female). The frequently reported drug classes were opioids (FDA: oxycodone, 29.8%; EMA: buprenorphine, 19%), antidepressants (FDA: duloxetine, 32%; EMA: venlafaxine, 25.9%) and gabapentinoids (FDA: pregabalin, 6.7%; EMA: pregabalin, 6.0%). The most common adverse outcomes were other serious medical conditions (FDA=63.9%; EMA=46.0%), hospitalisation (FDA=15.9%; EMA=28.3%), and disability (FDA=13.3%; EMA=6.2%) and these outcomes varied significantly based on sex and age group (p

15.
arXiv (CS.AI) 2026-06-16

Visual-Seeker: Towards Visual-Native Multimodal Agentic Search via Active Visual Reasoning

arXiv:2606.15231v1 Announce Type: new Abstract: Multimodal large language models (MLLMs) have demonstrated impressive capabilities in many visual tasks, but they often struggle with factual grounding when confronted with complex, open-world scenarios. While recent multimodal deep search agents attempt to address this issue by utilizing external tools, the visual-native search paradigm remains underexplored. Existing methods primarily rely on simple images with explicit semantics and text-only evidence trajectories, limiting the agent's ability to perform multi-hop, cross-modal reasoning and search. To address these limitations, we propose Visual-Seeker, a visual-native multimodal deep search agent via active visual reasoning. Rather than treating vision as a static input, our agent actively attends to fine-grained visual details, dynamically harvests visual evidence throughout the search process. To unlock its visual-native potential, we design an active visual reasoning data pipeline and synthesize 5K high-quality multimodal trajectories for model training. Extensive experiments demonstrate the state-of-the-art performance across five challenging multimodal search benchmarks, even surpassing several proprietary models, validating robust visual-native reasoning and search in real-world web environments. The code and data can be accessed at: https://github.com/ZhengboZhang/Visual-Seeker.

16.
arXiv (CS.AI) 2026-06-11

Lung-SRAD: Spectral-Aware Regularized Audio DASS with Dual-Axis Patch-Mix Contrastive Learning for Respiratory Sound Classification

arXiv:2606.11922v1 Announce Type: cross Abstract: Recent respiratory sound classification (RSC) studies largely rely on CLS-token driven self-attention architectures such as the Audio Spectrogram Transformer (AST). While effective at modeling global context, recent analyses suggest a low-pass filtering behavior that may reduce sensitivity to localized abnormal patterns. In this work, we investigate State Space Models (SSMs) as an alternative backbone for RSC. Using the Distilled Audio State Space model, we analyze intermediate representations through spectral response curves and observe stronger preservation of mid-to-high spatial-frequency components. Based on these observations, we introduce spectral-aware layer regularization using Gaussian convolution applied to selected layers. We further propose Dual-Axis Patch-Mix contrastive learning tailored to SSM-based audio models for robust representation learning. Experiments on the ICBHI benchmark show that our approach achieves 64.48% score, outperforming the AST baseline by 5%. Code is available at https://github.com/RSC-Toolkit/Lung-SRAD.

17.
arXiv (CS.CV) 2026-06-12

ReFoCUS: Reinforcement-guided Frame Optimization for Contextual Understanding

Recent progress in Large Multi-modal Models (LMMs) has enabled effective vision-language reasoning, yet the ability to video understanding remains constrained by suboptimal frame selection strategies, albeit with the rapid development of video-specialized LMMs. Prior works attempted to solve this with static heuristics or external retrieval modules to feed frame-level information, but these approaches often fail to capture visual cues grounded to the given user queries conflating raw visual dynamics with true semantic relevance. In this paper, we introduce ReFoCUS (Reinforcement-guided Frame Optimization for Contextual UnderStanding), the first framework to integrate online policy-gradient reinforcement learning into frame-level optimization for video-LLMs. ReFoCUS aims to learn a frame selection policy, leveraging reward signals derived from reference models to capture their underlying scoring behavior over frame combinations that best support temporally grounded responses. To efficiently explore the large combinatorial frame space, we employ an autoregressive and query-conditional selection architecture that ensures contextual consistency while reducing complexity. Our policy learning removes the need for explicit frame-level supervision, as it implicitly discovers optimal and semantically consistent frame compositions. ReFoCUS consistently improves reasoning accuracy across multiple video QA benchmarks, demonstrating the advantage of aligning frame selection with model-internal utility.

18.
arXiv (CS.CL) 2026-06-15

Optimizing the Cost-Quality Tradeoff of Agentic Theorem Provers in Lean

Large language models (LLMs) are increasingly used in workflows for generating formal proofs in Lean. These workflows often decompose problems into smaller lemmas, sample many proof attempts, and use compiler feedback to guide search. However, they can be prohibitively expensive, often spending substantial compute on attempts that ultimately fail. In this work, we address this problem with an action routing agent that consists of a data plane and a control plane. The data plane generates natural-language lemma decompositions, formalizes them in Lean, and samples proof attempts for the resulting theorem and lemma targets. The control plane observes previous failed Lean attempts, estimates both the likelihood of success and cost of another attempt, and decides whether to continue proving the current target or restart from a new breakdown. On a subset of PutnamBench, our agent decreases the cost by $28.9\%$ over a fixed-step baseline on average, preserving performance while using substantially less compute. These results suggest that failed Lean trajectories provide actionable signals for cost-aware resource allocation in agentic theorem proving.

19.
arXiv (CS.CL) 2026-06-17

ProvenanceGuard: Source-Aware Factuality Verification for MCP-Based LLM Agents

Tool-using LLM agents increasingly use the Model Context Protocol (MCP) to answer from heterogeneous evidence sources, including search, APIs, databases, clinical records, and formulary tools. Standard factuality metrics usually test whether an answer is supported by pooled evidence, missing a provenance-sensitive failure mode: a claim may be supported somewhere while being attributed to the wrong source. We call this cross-source conflation. We introduce ProvenanceGuard, a source-aware verifier for MCP-grounded answers. It consumes captured MCP traces with stable tool IDs, source IDs, and raw outputs; decomposes answers into atomic claims; routes claims to source-specific evidence; checks support with NLI and a token-alignment proxy; compares stated attribution with the routed source; and returns per-claim verdicts plus an answer-level allow/block decision. Blocked answers can be repaired with retrieval-augmented answer revision and re-verified. We evaluate on 281 medical-domain MCP-agent traces. A 266-trace adjudicated subset yields 2,325 LLM-assisted claim labels split by trace; 361 held-out labels are human-verified. On the 40-trace held-out split, ProvenanceGuard achieves block F1 0.802 and source accuracy 0.858 over 260 source-eligible claims, outperforming source-blind baselines that do not emit claim-to-source IDs. On a harder multi-source benchmark it reaches block F1 0.846, while source-plus-relation accuracy drops to 0.229, showing that exact source ownership remains difficult with semantically close sources. Repair-and-reverify resolves all blocked answers in the full trace set, often via conservative fallback. In 50 controlled clinical conflation probes, ProvenanceGuard detects all injected attribution swaps with no retained wrong attribution. These results show that source attribution is an independent axis for factuality verification in MCP-based agents.

20.
medRxiv (Medicine) 2026-06-17

Clinical Study Protocol of the 'Biomarkers of Severity of COVID-19 Patients' (BIOMARCOVID) Project

Introduction The coronavirus disease 2019 (COVID-19) pandemic has challenged health care systems worldwide, in certain areas exceeding hospital capacities and human resources. This has underscored the importance of having better tools to predict the outcome of potentially severe respiratory infections such as SARS-CoV-2. Predicting COVID-19 severity may allow physicians to better manage ICU beds and increase the chances of patient survival through appropriate management. During the toughest months of the pandemic, most physicians tried to identify patients that might develop severe forms based primarily on clinical features on admission (e.g., BMI, age). In this context, significant research has focused on identifying comorbidities, clinical manifestations, and routine blood biomarkers to predict disease severity. However, despite the demonstrated value of untargeted metabolomics in assessing severity, limited data exist on its use for identifying novel metabolite biomarkers that could improve both the sensitivity and specificity of outcome prediction. Our goal is to identify metabolite biomarkers that could enhance the predictive accuracy of standard medical biology data and clinical parameters. Methods and analysis This is a retrospective, observational, monocentric cohort study conducted at the Centre Hospitalier Universitaire Grenoble Alpes (CHUGA). The maximum number of eligible patients admitted for PCR-confirmed COVID-19 between March and December 2020 will be included. Severity outcome is defined using the WHO 10-category ordinal scale (mild: categories 4-5; severe: >5). Blood samples were collected within 48 hours of admission and analyzed for 62 routine blood tests and untargeted multiplatform LC-MS/MS metabolomics across four national platforms. Statistical analysis will include logistic regression with variable selection for the primary aim, and multi-block chemometric integration of clinical, biological, and metabolomics data as a secondary aim. Ethics and dissemination A study steering committee has been formed to ensure the accuracy of the collected data by thoroughly reviewing it prior to the data lock. All aspects of the study comply with ethical standards, including approval by the CHUGA institutional review board and adherence to CNIL Reference Methodology MR004 for the protection of participants' rights, privacy, and confidentiality. This study is registered on the French Health Data Hub (number F20210218154851). Results will be disseminated through peer-reviewed publications, presentations at national and international scientific and clinical conferences, and reports shared with key healthcare system stakeholders.

21.
arXiv (CS.LG) 2026-06-16

Learning Hybrid Biophysical Neuron Models with Neural ODEs

arXiv:2606.16693v1 Announce Type: cross Abstract: Biophysical neuron models link measurements of neural activity to underlying cellular mechanisms. Yet, a central challenge is that the kinetics of many ion channels are poorly characterized, and practical simplifications – omitting channels or reducing morphological detail – introduce systematic gaps between model and biology. Bridging these gaps requires approaches that can flexibly discover unmodeled dynamics while preserving mechanistic interpretability. Here, we introduce a hybrid modeling framework that embeds neural ordinary differential equations into conductance-based biophysical models to capture unknown currents or mis-specified channel kinetics. By parameterizing the neural ODE in terms of voltage-dependent steady-state and time-constant functions, we recover interpretable gating dynamics directly from voltage recordings without assuming a functional form. We show that the hybrid model fits the gating kinetics of 2400 ion channel models and recovers unknown gating dynamics from single current-clamp recordings, generalizing to out-of-distribution stimulus regimes under realistic inputs and parameter misspecification. We also use our method to reduce a multicompartment model of a cortical neuron into a single-compartment hybrid model with a learned axial current, yielding up to an order of magnitude lower computational cost. Together, our results establish a plug-and-play framework for selectively replacing unknown components of conductance-based models with neural ODEs while preserving their mechanistic structure.

22.
arXiv (CS.LG) 2026-06-11

Kalman Linear Attention: Parallel Bayesian Filtering For Efficient Language Modelling and State Tracking

arXiv:2602.10743v2 Announce Type: replace Abstract: State-space language models such as Mamba and gated linear attention (GLA) offer linear-complexity, parallelisable alternatives to transformers, but their linear state updates limit expressivity and robust state tracking. We close this gap from a probabilistic angle, casting sequence mixing as exact Bayesian filtering with the Kalman filter as the core primitive. Classical Kalman filters give principled state and uncertainty estimates but are viewed as inherently sequential; we show that reparameterising them in information form turns their updates into an associative scan - so the per-token recurrent update is non-linear (a Möbius/precision recursion) yet remains temporally parallel. The resulting Kalman Linear Attention (KLA) layer is a drop-in sequence mixer that performs time-parallel probabilistic inference, carries an explicit belief-state uncertainty, and is strictly more expressive than GLA-style linear updates at the same computational cost. This expressivity translates directly into stronger state tracking: KLA solves permutation-composition ($A_5$) tasks that linear SSMs and attention cannot, while staying scan-parallel. As a drop-in primitive it also matches or improves on modern SSMs and GLAs across synthetic token-manipulation and zero-shot commonsense benchmarks, and is among the first stacked Bayesian-filtering primitives trained at the billion-token scale.

23.
arXiv (CS.AI) 2026-06-17

MODE: Modality-Decomposed Expert-Level Mixed-Precision Quantization for MoE Multimodal LLMs

arXiv:2606.17118v1 Announce Type: cross Abstract: Mixture-of-Experts Multimodal Large Language Models (MoE-MLLMs) offer remarkable performance but incur prohibitive GPU memory costs, making compression essential. Among PTQ methods, expert-level mixed-precision quantization has proven effective for MoE-LLMs, yet suffers notable degradation on MoE-MLLMs due to two overlooked biases in expert importance estimation. (1) At the cross-modal level, the numerical dominance of vision tokens causes expert selection frequency to be dominated by vision tokens, masking experts that are critical to the text modality; (2) at the intra-vision level, the large proportion of redundant vision tokens further skew frequency statistics, obscuring experts critical for informative visual content. To bridge gaps, we propose MODE, a modality-decomposed expert-level mixed-precision quantization framework for MoE-MLLMs that decomposes expert selection frequency by modality, filters redundant vision tokens to obtain denoised visual frequency, and further evaluates quantization sensitivity per modality as a complementary signal to frequency-based estimation. These signals are integrated into an Integer Linear Programming formulation to assign per-expert bit-widths under a given budget. Extensive experiments show that MODE is particularly well-suited for MoE-MLLMs, limiting average performance loss to within 2.9% at W3A16, with larger gains at the extreme 2-bit setting.

24.
arXiv (CS.CV) 2026-06-16

BioAutoML-NAS: An End-to-End AutoML Framework for Multimodal Insect Classification via Neural Architecture Search on Large-Scale Biodiversity Data

Insect classification is important for agricultural management and ecological research, as it directly affects crop health and production. However, this task remains challenging due to the complex characteristics of insects, class imbalance, and large-scale datasets. To address these issues, we propose BioAutoML-NAS, the first BioAutoML model using multimodal data, including images, and metadata, which applies neural architecture search (NAS) for images to automatically learn the best operations for each connection within each cell. Multiple cells are stacked to form the full network, each extracting detailed image feature representations. A multimodal fusion module combines image embeddings with metadata, allowing the model to use both visual and categorical biological information to classify insects. An alternating bi-level optimization training strategy jointly updates network weights and architecture parameters, while zero operations remove less important connections, producing sparse, efficient, and high-performing architectures. Extensive evaluation on the BIOSCAN-5M dataset demonstrates that BioAutoML-NAS achieves 96.81% accuracy, 97.46% precision, 96.81% recall, and a 97.05% F1 score, outperforming state-of-the-art transfer learning, transformer, AutoML, and NAS methods by approximately 16%, 10%, and 8% respectively. Further validation on the Insects-1M dataset obtains 93.25% accuracy, 93.71% precision, 92.74% recall, and a 93.22% F1 score. These results demonstrate that BioAutoML-NAS provides accurate, confident insect classification that supports modern sustainable farming.

25.
arXiv (CS.AI) 2026-06-16

Protein Design with Agent Rosetta: A Case Study for Specialized Scientific Agents

arXiv:2603.15952v2 Announce Type: replace Abstract: Large language models (LLMs) are capable of emulating reasoning and using tools, creating opportunities for autonomous agents that execute complex scientific tasks. Protein design provides a natural testbed: although machine learning (ML) methods achieve strong results, these are largely restricted to canonical amino acids and narrow objectives, leaving unfilled need for a generalist tool for broad design pipelines. We introduce Agent Rosetta, an LLM agent paired with a structured environment for operating Rosetta, the leading physics-based heteropolymer design software, capable of modeling non-canonical building blocks and geometries. Agent Rosetta iteratively refines designs to achieve user-defined objectives, combining LLM reasoning with Rosetta's generality. We evaluate Agent Rosetta on design with canonical amino acids, matching specialized models and expert baselines, and with non-canonical residues – where ML approaches fail – achieving comparable performance. Critically, prompt engineering alone often fails to generate Rosetta actions, demonstrating that environment design is essential for integrating LLM agents with specialized software. Our results show that properly designed environments enable LLM agents to make scientific software accessible while matching specialized tools and human experts.