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01.
arXiv (CS.LG) 2026-06-16

HRIR-Former: Grid-Free Time-Domain Reconstruction of Head-Related Impulse Responses with a Spatially Encoded Transformer

arXiv:2603.27998v2 Announce Type: replace-cross Abstract: Individualized head-related impulse responses (HRIRs) enable binaural rendering, but dense per-listener measurements are costly. We address HRIR spatial up-sampling from sparse per-listener measurements: given a few measured HRIRs for a listener, predict HRIRs at unmeasured target directions. Prior learning methods often work in the frequency domain, rely on minimum-phase assumptions or separate timing models, and use a fixed direction grid, which can degrade temporal fidelity and spatial continuity. We propose HRIR-Former, a time-domain, grid-free binaural Transformer for reconstructing HRIRs at arbitrary directions from sparse inputs. It uses sinusoidal spatial features, a Conv1D refinement module, and auxiliary interaural time difference (ITD) and interaural level difference (ILD) heads. On SONICOM, it improves normalized mean squared error (NMSE), cosine distance, and ITD/ILD errors over prior methods; ablations validate modules and show minimum-phase preprocessing is unnecessary.

02.
arXiv (CS.LG) 2026-06-16

Fast Non-Episodic Finite-Horizon RL with K-Step Lookahead Thresholding

arXiv:2602.00781v2 Announce Type: replace Abstract: Online reinforcement learning in non-episodic, finite-horizon MDPs remains underexplored and is challenged by the need to estimate returns to a fixed terminal time. Existing infinite-horizon methods, which often rely on discounted contraction, do not naturally account for this fixed-horizon structure. We introduce a modified Q-function: rather than targeting the full-horizon, we learn a K-step lookahead Q-function that truncates planning to the next K steps. To further improve sample efficiency, we introduce a thresholding mechanism: actions are selected only when their estimated K-step lookahead value exceeds a time-varying threshold. We provide an efficient tabular learning algorithm for this novel objective, proving it achieves fast finite-sample convergence: it achieves minimax optimal constant regret for $K=1$ and $\mathcal{O}(\max((K-1),C_{K-1})\sqrt{SAT\log(T)})$ regret for any $K \geq 2$. We numerically evaluate the performance of our algorithm under the objective of maximizing reward. Our implementation adaptively increases K over time, balancing lookahead depth against estimation variance. Empirical results demonstrate superior cumulative rewards over state-of-the-art tabular RL methods across synthetic MDPs and RL environments: JumpRiverswim, FrozenLake and AnyTrading. Code is provided on \href{https://github.com/jamie01713/K-Step-Lookahead}{github}.

03.
arXiv (CS.CV) 2026-06-18

Generalized Kullback-Leibler Divergence Loss

In this paper, we delve deeper into the Kullback-Leibler (KL) Divergence loss and mathematically prove that it is equivalent to the Decoupled Kullback-Leibler (DKL) Divergence loss that consists of (1) a weighted Mean Square Error (wMSE) loss and (2) a Cross-Entropy loss incorporating soft labels. Thanks to the decoupled structure of DKL loss, we have identified two areas for improvement. Firstly, we address the limitation of KL loss in scenarios like knowledge distillation by breaking its asymmetric optimization property along with a smoother weight function. This modification effectively alleviates convergence challenges in optimization, particularly for classes with high predicted scores in soft labels. Secondly, we introduce class-wise global information into KL/DKL to reduce bias arising from individual samples. With these two enhancements, we derive the Generalized Kullback-Leibler (GKL) Divergence loss and evaluate its effectiveness by conducting experiments on CIFAR-10/100, ImageNet, and vision-language datasets, focusing on adversarial training, and knowledge distillation tasks. Specifically, we achieve new state-of-the-art adversarial robustness on the public leaderboard – RobustBench and competitive knowledge distillation performance across CIFAR/ImageNet models and CLIP models, demonstrating the substantial practical merits. Our code is available at https://github.com/jiequancui/DKL.

04.
bioRxiv (Bioinfo) 2026-06-17

DesignMaster: A Multi-Conditional Diffusion Framework for Rational PROTAC Design

Motivation: Proteolysis-targeting chimeras (PROTACs) enable targeted protein degradation through ternary complex formation with E3 ubiquitin ligase. However, the rational design of PROTACs remains highly challenging due to limited structure-activity relationship data and the vast conformational diversity of linkers. Existing computational approaches can be broadly divided into structure-based ternary modelling methods and fragment-based linker generation models. Although these approaches have advanced PROTAC design, they typically neglect key physicochemical constraints and linker-length control during the generation process, causing the generated PROTACs to lack balanced structural properties required for effective ternary complex formation with drug-like characteristics. Results: To address these limitations, we propose DesignMaster, a diffusion-based generative framework that explicitly incorporates linker length and physicochemical properties as controllable conditioning signals. DesignMaster employs an E(3)-equivariant graph Transformer with a gated multi-condition fusion module to inject linker length and physicochemical constraints throughout the diffusion process, enabling fine-grained and constraint-aware molecular generation. Experiments on PROTAC-DB 2.0 and 3.0 demonstrate that DesignMaster outperforms state-of-the-art baselines, with a 3.2% improvement in validity and a 34.4% improvement in recovery. The Case study shows DesignMaster achieves a 51.78% reduction in RMSD when predicting the linker of PROTAC BCPyr targeting 6W7O, highlighting its potential for practical structure-guided PROTAC design. Availability: The source code and datasets are available at https://github.com/ABILiLab/DesignMaster.

05.
arXiv (CS.CV) 2026-06-11

Finding Sparse Subnetworks in One Training Cycle via Progressive Magnitude-Based Pruning

Neural network pruning reduces model size by removing less important parameters while aiming to preserve predictive performance. Although the Lottery Ticket Hypothesis (LTH) shows that sparse subnetworks can match dense networks when trained from suitable initializations, its iterative pruning procedure requires multiple complete training cycles. This work evaluates progressive magnitude-based pruning as a single-cycle alternative. The method gradually increases sparsity during training using a linear schedule and updates pruning masks based on active weight magnitudes. We conduct systematic experiments on CIFAR-10 and MNIST across ResNet, VGG-style, and LeNet architectures, comparing the proposed method with representative iterative and initialization-based pruning baselines, including LTH, SNIP, and GraSP. On CIFAR-10, the method achieves 95.12\% accuracy on ResNet-18 at 72.9\% sparsity, compared with 90.5\% reported for LTH. At extreme sparsity, it achieves 93.13\% accuracy on a VGG-like architecture at 97\% sparsity, compared with approximately 92.0\% for SNIP, and 93.44\% accuracy on VGG-19 at 97.97\% sparsity, compared with 92.19\% for GraSP at 98\% sparsity. A sparsity-accuracy analysis on ResNet-18 further shows that accuracy remains within 0.1 percentage points of the dense baseline across 70–85\% sparsity. These results indicate that progressive magnitude-based pruning provides an effective single-cycle approach for neural network sparsification under the evaluated settings.

06.
bioRxiv (Bioinfo) 2026-06-18

novelBGC: An interactive dual-score framework for biosynthetic gene cluster novelty assessment and candidate prioritisation

Genome mining now yields tens of thousands of putative biosynthetic gene clusters (BGCs) per project, yet, separating genuinely novel candidates from rediscoveries of known compounds remains the rate-limiting step before experimental validation. Single-axis prioritisation tools, antiSMASH similarity, BiG-FAM GCF distance, and self-resistance-enzyme (SRE) filters such as ARTS, each surface a different facet of evidence, yet their isolated use systematically over-ranks rediscovery-prone BGCs and overlooks genuinely orphan clusters. We present novelBGC, a web-hosted framework that converts these disparate outputs into two deliberately non-inverse continuous metrics per BGC, a Novelty (N) and a Reference Similarity (RS) score which together define a 2D decision plane that resolves rediscoveries, divergent family members, contig-edge artefacts, and uncharted chemistry with interactive visualisations, with all component weights user-tuneable at submission. Retrospective validation across three independent experimental datasets demonstrates the utility of the framework for candidate prioritization. Within the first 186-BGC SRE-guided cloning study, every confirmed bioactive product fell within the low-to-mid N band whereas 55 high-N (N [≥] 0.50) BGCs were never selected. Moreover, in the other two studies, it correctly prioritised the fully orphan lariocidin BGC of Paenibacillus sp. M2 and the divergent within-family indanopyrrole-A idp BGC of Streptomyces sp. CNX-425. Together, these case studies demonstrate that the joint (N, RS) space facilitates prioritization decisions that are difficult to achieve using any single criterion alone. from identical input data. novelBGC requires no command-line expertise, no local tool installation, and no manual integration of intermediate output formats, addressing a well-documented accessibility barrier for wet-laboratory researchers engaging with genome-mining workflows. novelBGC is freely available at https://project.iith.ac.in/sharmaglab/novelbgc/.

07.
bioRxiv (Bioinfo) 2026-06-20

SAbDab2: The structural antibody database in the age of machine learning

The Structural Antibody Database (SAbDab) is a publicly available repository of experimentally determined antibody structures, first released in 2013. Explicit support for single-domain antibodies was added in 2021, with SAbDab-nano. Recently, increasing interest in antibodies has led to a proliferation of novel antibody formats, while simultaneous advances in machine learning have increased demand for standardised, high-quality structure data. Here, we present SAbDab2, re-engineered for the machine-learning age. It introduces support for a variety of new formats, and makes it easy to retrieve and compare all known structures of a given antibody. In addition, SAbDab2 provides ready access to ML-grade structures of antibody and antibody–antigen-complexes, with standardised, versioned train/test splits. These will be updated every six months going forward, and are available at https://zenodo.org/records/20083995. SAbDab2 itself is updated weekly and is freely available at https://sabdab2.opig.stats.ox.ac.uk.

08.
arXiv (CS.LG) 2026-06-18

Data-driven sparse identification of governing PDEs via knockoff filters and multi-criteria trade-offs

arXiv:2605.26631v2 Announce Type: replace-cross Abstract: We propose KO-PDE-IDENT, a data-driven framework for identifying parsimonious partial differential equations (PDEs) with false discovery rate (FDR) control. PDE discovery from noisy observations is often hindered by extreme multicollinearity among candidate terms, which causes typical sparse-regression methods to select spurious terms. To address this problem, KO-PDE-IDENT initially mines a support set of potential candidate terms via model-X knockoff filters with finite-sample FDR control, then refines and ranks the surviving PDE alternatives. The framework integrates three components. First, knockoff feature statistics are constructed by coupling $\ell_{0}$-constrained adaptive best-subset selection with SHapley Additive exPlanations (SHAP), yielding an effective and computationally efficient difference statistic. Second, a recursive feature elimination (RFE) procedure removes terms whose marginal contributions are dispensable and assesses statistical necessity through knockoff-perturbed hypothesis testing. Third, the final model selection is formulated as a multi-criteria decision-making (MCDM) problem, where the optimal governing equation is the alternative that best balances a wide range of criteria such as predictive accuracy, model complexity and coefficient uncertainty. We evaluate KO-PDE-IDENT on five canonical PDEs under severe noise corruption. Empirical results show that our framework can exactly recover the true PDE structure, eliminating false discoveries while retaining all true underlying terms, with low coefficient estimation error.

09.
arXiv (CS.AI) 2026-06-17

A Unified Framework for Context-Aware and Relation-Aware Graph Retrieval-Augmented Generation

arXiv:2606.18075v1 Announce Type: new Abstract: Retrieval-Augmented Generation (RAG) has emerged as a paradigm for enhancing large language models (LLMs) with external knowledge, yet existing graph-based methods face a fundamental limitation: entity-centric and chunk-centric approaches operate on representations anchored to original text without true knowledge fusion. While entity-centric methods connect logically related content and chunk-centric methods preserve context, both retrieve information separately through similarity search, missing emergent understanding from their synthesis. In this paper, we propose HyGRAG, a hierarchical graph RAG framework that transcends source documents by addressing three core challenges: constructing summaries that genuinely integrate contextual and relational information, leveraging these synthesized representations to access emergent knowledge during retrieval, and efficiently updating hierarchical structures for dynamic corpora. Specifically, we design hierarchical index structures over hybrid graphs with both chunk and entity nodes, then iteratively cluster them and generate LLM-based summaries. Then, we design context and relation-aware retrieval that searches across all abstraction levels while expanding through community membership. Moreover, we enable dynamic knowledge update through attachment-based algorithms with only local re-summarization. Experimental results show that HyGRAG improves the average accuracy of multi-hop reasoning tasks by 9.7%, while maintaining reasonable efficiency.

10.
arXiv (CS.CV) 2026-06-18

Motion-Focused Latent Action Enables Cross-Embodiment VLA Training from Human EgoVideos

Training generalist Vision-Language-Action(VLA) models typically requires massive, diverse robotic datasets with high-fidelity action annotations. While egocentric human manipulation videos are abundant and capture significant environmental diversity, the absence of action labels makes them difficult to use in conventional training paradigms. To address this, we propose a latent-action-based framework designed to extract general action priors from unlabeled human videos. The architecture features a Hybrid Disentangled VQ-VAE that decouples motion dynamics from environmental backgrounds through physical masks, enabling the construction of a cross-embodiment action codebook. By pre-training on human videos with the codebook, the VLM backbone learns deep representations of action intent. For adaptation to specific embodiments, we introduce an intent-perception decoupling strategy where the VLM predicts the action intent while a separate frozen visual encoder provides state-specific features to the action expert, thereby reducing action hallucinations. Results in simulation and real-world environments show that our method, pre-trained exclusively on unlabeled human videos, performs competitively with state-of-the-art VLA models trained on massive annotated datasets, requiring only 50 trajectories for downstream adaptation.

11.
arXiv (CS.CV) 2026-06-17

MagicSim: A Unified Infrastructure for Executable Embodied Interaction

Robot learning and embodied agents now require simulation to serve as a shared execution substrate linking control, skills, and planning, not only as a renderer, controller testbed, or fixed task environment. Existing pipelines split these layers with "magic" actions, disconnected training environments, or forward-only renders that cannot reproduce, evaluate, and annotate the same episode. We present MagicSim, an embodied interaction infrastructure built around one deterministic batched runtime and a shared Markov decision process (MDP). From YAML-first specifications that decouple contents, placement, behavior, and agent exposure, MagicSim constructs diverse executable worlds spanning task families, interaction regimes, physics, layouts, sensors, avatars, and robot embodiments in one reset-and-step loop. A common execution interface grounds high-level commands through controllers, atomicskills, planner primitives, and asynchronous planning, realizing them as robot actions rather than simulator-side state edits. One task definition supports three capabilities: benchmark and RL evaluation, an autocollect interface that automatically turns commands into grounded trajectories, and agent/VLM-facing interaction. For automatic execution, commands flow through a Command->Skill->Planner->Robot->Record pipeline, while per-environment command, skill, planning, retry, annotation, and episode states advance independently above the shared physics tick. Successful rollouts are saved as structured multimodal trajectories aligning language supervision, action representations, visual/geometric representations, and task-level status with the executed episode. MagicSim thus unifies diverse world construction, embodied execution, task evaluation, automatic rollout generation, and interactive agent interfaces in one planner-in-the-loop runtime.

12.
arXiv (CS.CL) 2026-06-16

SAMark: A Self-Anchored Text Watermarking with Paragraph-Level Paraphrase Robustness

Semantic-level watermarking (SWM) improves robustness against text modifications by treating sentences as the basic unit. However, robustness to paragraph-level paraphrasing remains difficult because such attacks globally disrupt watermark signals by changing sentence order. In this work, we propose SAMark, a self-anchored watermarking framework that removes the dependency on sentence order by establishing a step-independent green region in semantic space. To improve detectability, we introduce a multi-channel hyperbolic scoring mechanism that amplifies watermark signals while suppressing noise from weakly aligned candidates. We further propose a diversity-aware filtering strategy that combines hard filtering with soft regularization, extending beyond simple n-gram repetition filters to address semantic redundancy. Experimental results show that SAMark achieves up to 90.2% TP@FP1% under typical paragraph-level paraphrasing attacks, outperforming the strongest prior baseline by more than 30% on average, while maintaining generation quality competitive with unwatermarked text and breaking the robustness-quality trade-off that limits prior methods.

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

CredibleDFGO: Differentiable Factor Graph Optimization with Credibility Supervision

arXiv:2605.06100v2 Announce Type: replace-cross Abstract: Global navigation satellite system (GNSS) positioning is widely used for urban navigation, but the covariance reported by the GNSS solver is often unreliable in urban canyons. Existing differentiable factor graph optimization (DFGO) methods learn measurement weighting through the solver, but they still use position-only objectives. As a result, the position estimate may improve while the reported covariance remains too small, too large, or incorrectly oriented. We propose CredibleDFGO (CDFGO), a differentiable GNSS factor graph framework that makes covariance credibility an explicit training target. A Weighting Generation Network (WGN) predicts per-satellite reliability weights, and a differentiable Gauss-Newton solver maps these weights to a position estimate and a Hessian-derived posterior covariance. We use proper scoring rules to supervise the East-North predictive distribution end to end. We study negative log-likelihood (NLL), the energy score (ES), and their combination. Results on three UrbanNav test scenes show consistent gains in covariance credibility. Positioning accuracy also improves on the medium-urban and harsh-urban scenes; on the deep-urban scene, both the mean horizontal error and the 95th-percentile error improve. On the harsh-urban Mong Kok (MK) scene, CDFGO-Combined reduces the mean horizontal error from 13.77 m to 11.68 m, reduces NLL from 40.63 to 6.59, and reduces ES from 12.31 to 9.05 relative to DFGO (MAE). Case studies link the MK improvement to better axis-wise consistency, more credible local covariance ellipses, and satellite-level reweighting.

14.
medRxiv (Medicine) 2026-06-16

Infections and suicide and self-harm: a population-based matched cohort study

Background Infections have been associated with adverse mental health outcomes, including suicide, but evidence beyond severe or central nervous system infections is limited. We investigated associations between a range of acute infections and subsequent suicide/self-harm outcomes. Methods We conducted six infection-specific matched cohort studies using English primary care records from the Clinical Practice Research Datalink Aurum (2007-2024), linked to hospital admissions and mortality data. Adults ([≥]18 years) with a primary care record of infection (gastroenteritis, lower respiratory tract [LRTI], skin/soft-tissue [SSTI], urinary tract [UTI], sepsis, meningitis/encephalitis [positive control]) were matched (age, sex, practice, calendar period) to up to five comparators without infection. We estimated hazard ratios (HRs) for suicide/self-harm outcomes using Cox regression, stratified by matched set and implicitly adjusting for matching factors, with additional adjustment for deprivation, lifestyle factors, and comorbidities. We examined whether associations varied over time, by infection severity, antimicrobial treatment, sex, and prior mental health conditions. Findings Cohorts ranged from 18,192 individuals with meningitis/encephalitis (matched to 90,915 without) to 398,099 with SSTI (matched to 1,743,747). After adjustment, individuals with infection had a higher hazard of suicide/self-harm outcomes than comparators across all cohorts: sepsis (HR 1.79, 95% CI 1.65-1.93), gastroenteritis (1.62, 1.55-1.70), meningitis/encephalitis (1.56, 1.32-1.84), UTI (1.41, 1.33-1.50), SSTI (1.37, 1.31-1.43), and LRTI (1.37, 1.31-1.44). Risk was highest in the year post-infection, attenuating over time, and was higher among severe infections and those without prior mental health conditions. Interpretation Common acute infections recorded in primary care are associated with increased risk of suicide and self-harm, particularly following severe infections and in the year post-infection. Findings support suicide risk monitoring following acute infection, particularly among individuals without prior mental health conditions, and highlight infection prevention as a potentially modifiable strategy in vulnerable populations. Funding Wellcome and La Caixa. Copyright This work is licensed under a Creative Commons Attribution (CC BY) licence.

15.
medRxiv (Medicine) 2026-06-10

Resolving Diagnostic Discordance in Group 2 Pulmonary Hypertension Through Staged Physiologic Testing: Insights From PVDOMICS

Background World Symposium on Pulmonary Hypertension (WSPH) Group 2 pulmonary hypertension (PH) is a clinically integrated phenotype attributed to left heart disease, whereas pre- versus post-capillary classification is operationalized primarily by pulmonary capillary wedge pressure (PCWP). Although current recommendations emphasize contextual interpretation and provocative testing for intermediate PCWP values, the relationship between PCWP-based classification and underlying phenotype has not been systematically evaluated. We aim to quantify phenotype-hemodynamic discordance across the PCWP spectrum and evaluate a staged physiology-guided framework incorporating inhaled nitric oxide (iNO), ventricular geometry, and provocative testing. Methods We studied 1,032 participants from the NHLBI-sponsored PVDOMICS cohort with multidisciplinary adjudicated phenotypes integrating clinical, imaging, physiologic, and hemodynamic data. Stage-specific PCWP thresholds classified pre- versus post-capillary physiology at rest, during iNO, and during provocation (fluid challenge or invasive cardiopulmonary exercise testing [iCPET]). Echocardiographic right ventricular-to-left ventricular (RV/LV) ratio was evaluated as a marker of ventricular interdependence. Restricted cubic spline and staged concordance analyses defined certainty-based PCWP ranges and incremental diagnostic yield. Results Adjudicated Group 2 phenotype was present in 37.0% of participants. Resting PCWP demonstrated good discrimination (AUC 0.86), but substantial bidirectional phenotype-hemodynamic discordance persisted across intermediate PCWP ranges. At a resting PCWP of 12 mmHg, 25% of participants classified as pre-capillary had adjudicated Group 2 PH, whereas at 18 mmHg, 35% classified as post-capillary remained discordant non-Group 2. Concordance did not approach 90% until PCWP values were 24 mmHg. Dynamic testing incrementally improved concordance within these overlap zones. Nearly half of adjudicated Group 2 PH participants (46.5%) were not identified by resting PCWP alone; incorporation of iNO and provocative testing increased cumulative Group 2 identification by 63.4% and improved sensitivity from 79.9% to 83.7%. Model discrimination improved from an AUC of 0.863 to 0.908 (likelihood-ratio P

16.
arXiv (quant-ph) 2026-06-19

Faking entanglement with imperceptible measurement deviations

arXiv:2606.20396v1 Announce Type: new Abstract: Quantum entanglement is a central resource underpinning emerging quantum technologies, enabling capabilities beyond those of classical systems. Accurate verification of entanglement is therefore crucial. However, experimental schemes usually rely on the assumption that quantum measurements can be realized exactly. As the complexity of a quantum system grows, this assumption typically becomes increasingly unrealistic, therefore leading to a widening mismatch between theoretical models and experimental implementations. Here we demonstrate that arbitrarily small measurement errors, when adversarially encoded in the measurement apparatus, can lead to the false certification of high-dimensional entanglement in systems that are, in fact, separable. This is achieved by introducing explicit hacking attacks to measurement devices in well-established entanglement verification tests. We further experimentally demonstrate this effect using classical photonic states encoded in the spatial degree of freedom, spanning up to 61 dimensions with measurement fidelity errors as low as 0.23%. Our results uncover a fundamental vulnerability in current methods for high-dimensional entanglement detection, highlighting the susceptibility of complex quantum devices to small adversarial perturbations. The findings underscore the need for developing secure verification of quantum information that is robust to bounded discrepancies between theory and experiment.

17.
arXiv (CS.CV) 2026-06-16

Seeing Roads Through Words: A Language-Guided Framework for RGB-T Driving Scene Segmentation

Robust semantic segmentation of road scenes under adverse illumination, lighting, and shadow conditions remain a core challenge for autonomous driving applications. RGB-Thermal fusion is a standard approach, yet existing methods apply static fusion strategies uniformly across all conditions, allowing modality-specific noise to propagate throughout the network. Hence, we propose CLARITY that dynamically adapts its fusion strategy to the detected scene condition. Guided by vision-language model (VLM) priors, the network learns to modulate each modality's contribution based on the illumination state while leveraging object embeddings for segmentation, rather than applying a fixed fusion policy. We further introduce two mechanisms - one which preserves valid dark-object semantics that prior noise-suppression methods incorrectly discard, and a hierarchical decoder that enforces structural consistency across scales to sharpen boundaries on thin objects. Experiments on the MFNet dataset demonstrate that CLARITY establishes a new state-of-the-art (SOTA), achieving 62.3% mIoU and 77.5% mAcc.

18.
bioRxiv (Bioinfo) 2026-06-21

Machine learning evaluation of gene expression-based ALS subtypes across brain and blood tissues

The clinical and molecular heterogeneity observed in amyotrophic lateral sclerosis (ALS) presents a challenge for diagnosis, prognosis, and treatment. RNA sequencing of post-mortem brain samples from ALS patients has identified several subtypes with distinct molecular signatures. We sought to evaluate these subtypes across diverse tissues and datasets and assess the feasibility of supervised machine learning models for sample classification. Unsupervised clustering and pathway analysis were performed to confirm the presence of ALS subtypes in motor cortex samples. Three machine learning strategies were then used to create models based on post-mortem motor cortex expression data of 112 people with ALS from the London Neurodegenerative Diseases Brain Bank. These models were subsequently improved through feature selection and evaluated in independent cohorts from motor cortex (n = 257, NYGC ALS Consortium) and blood (n = 96, Macquarie University Neurodegenerative Disease Biobank) samples. Multi-class linear discriminant analysis (LDA) models were then used for subtype classification. Clustering of ALS post-mortem motor cortex samples confirmed the presence of three subtypes: neuroinflammation (ALS-Neu), extracellular matrix organisation and muscle contraction (ALS-OxA), and synaptic and neuropeptide signalling (ALS-SNs). Among all machine learning strategies, random forests produced the most accurate and stable models for binary classification (~93% accuracy across the three subtypes). After feature selection, random forest models were able to classify samples from an independent post-mortem motor cortex cohort in their respective subtypes (AUC of ~0.98 across the three subtypes). When these models were evaluated in blood using LDA, we found consistent clustering patterns, with samples aligning in the same subtype regions of the post-mortem motor cortex samples, with ALS-SNs being the subtype in which samples were classified with the highest confidence (LDA class probability ~86%). Moreover, classification for this subtype improved when blood samples were collected closer to death. Our findings support the presence of three gene expression-based ALS subtypes in motor cortex samples and the utility of machine learning strategies for subtype classification. We also observed that the subtypes identified in the brain partially match those in the blood, with samples from the late stages of the disease more likely to be correctly predicted into the ALS-SNs cluster. This suggests a longitudinal effect in subtype identification that requires further investigation.

19.
arXiv (CS.AI) 2026-06-12

(Human) Attention Is (Still) All You Need: Human oversight makes AI-assisted social science reliable

arXiv:2606.12848v1 Announce Type: new Abstract: Large language models (LLMs) are increasingly used for tasks once reserved for trained researchers, including hypothesis generation, specification choice, and drafting conclusions. We argue that the reliability of AI-assisted research depends not only on model capability, but also on how cognitive labour is structured between humans and machines. We study this problem through Human-in-the-Loop Economic Research (HLER), a decision architecture based on pre-commitment, decision sequencing, accountability, and attention allocation. In a pre-specified 2*4 factorial experiment with 280 complete research runs across four datasets, an unconstrained multi-agent baseline produced critical failures in 72% of runs. Using the same underlying model, the same agent decomposition, and identical prompts for the shared reasoning agents, HLER reduced the failure rate to 16% by imposing three architectural commitments: LLMs reason but do not execute data work, data and estimation are handled deterministically, and three human decision gates bind the workflow. Fisher's exact test rejects equality of failure rates at p

20.
arXiv (CS.AI) 2026-06-16

MedAI: Evaluating TxAgent's Therapeutic Agentic Reasoning in the NeurIPS CURE-Bench Competition

arXiv:2512.11682v2 Announce Type: replace Abstract: Therapeutic decision-making in clinical medicine constitutes a high-stakes domain in which AI guidance interacts with complex interactions among patient characteristics, disease processes, and pharmacological agents. Tasks such as drug recommendation, treatment planning, and adverse-effect prediction demand robust, multi-step reasoning grounded in reliable biomedical knowledge. Agentic AI methods, exemplified by TxAgent, address these challenges through iterative retrieval-augmented generation (RAG). TxAgent employs a fine-tuned Llama-3.1-8B model that dynamically generates and executes function calls to a unified biomedical tool suite (ToolUniverse), integrating FDA Drug API, OpenTargets, and Monarch resources to ensure access to current therapeutic information. In contrast to general-purpose RAG systems, medical applications impose stringent safety constraints, rendering the accuracy of both the reasoning trace and the sequence of tool invocations critical. These considerations motivate evaluation protocols treating token-level reasoning and tool-usage behaviors as explicit supervision signals. This work presents insights derived from our participation in the CURE-Bench NeurIPS 2025 Challenge, which benchmarks therapeutic-reasoning systems using metrics that assess correctness, tool utilization, and reasoning quality. We analyze how retrieval quality for function (tool) calls influences overall model performance and demonstrate performance gains achieved through improved tool-retrieval strategies. Our work was awarded the Excellence Award in Open Science. Complete information can be found at https://curebench.ai/.

22.
bioRxiv (Bioinfo) 2026-06-18

A Two-Stage Interpretable Framework for Predicting Plant-Derived Small RNA Targets on Human 3'UTRs

Authors:

Can plant-derived small RNAs target human mRNA 3'UTRs via complementary base pairing and produce experimentally detectable regulatory effects? This question concerns not only the fundamental feasibility of cross-kingdom RNA regulation but also the technological pathway for screening plant-derived active small nucleic acids. Existing miRNA target prediction tools are predominantly designed for endogenous miRNA-mRNA systems, exhibiting notable limitations when applied to cross-species small RNA inputs and small-sample wet-lab experimental adaptation. In this study, we developed a two-layer prediction framework, MetaLulu-AI. The first layer builds upon publicly available human miRNA-mRNA 3'UTR interaction data, utilizing XGBoost to learn foundational binding rules on human 3'UTRs based on 41 interpretable computational features, including seed region pairing types, local context sequence composition, site positioning, and RNA secondary structures. The second layer is tailored to the experimental system of plant-derived small RNAs and human target genes. It introduces 40 experimental samples using significant changes in endogenous protein expression as the regulatory standard (determined by Western blot or ELISA 48 hours post-transfection of small RNAs via Lipo3000). Using 52-dimensional computational features and the optimal transcript scores from the first layer as inputs, this layer employs TabPFN for experimental label adaptation. The first-layer dataset consists of 38,752 training samples, 5,536 validation samples, and 11,073 testing samples (totaling 55,361), with a positive-to-negative sample ratio of approximately 1:5.4. On the randomly split test set, the model achieved an AUC of 0.9686, a recall of 0.8523, a precision of 0.8080, and an accuracy of 0.9452 (at a decision threshold of 0.4797). Group-based splitting revealed that the model maintains high discriminative power for unseen genes (AUC = 0.9541), though its generalization ability for completely unseen miRNAs decreases (AUC = 0.7390). For the 40 experimental samples in the second layer, the TabPFN model achieved an average AUC of 0.7406 {+/-} 0.092 across ten repeated 70/30 random splits, outperforming the baseline of directly using the first-layer scores (0.3563 {+/-} 0.149); the average AUC in a 5-fold cross-validation was 0.770 {+/-} 0.177. SHAP analysis demonstrated a clear divergence in the discriminative basis of the two models: the first layer relies more heavily on the thermodynamics of the small RNA itself and the quality of canonical seed sites, whereas the second layer focuses more on the local UTR environment and statistical site features. Although the current second-layer results are constrained by sample size and gene coverage, this framework serves as a preliminary observation of the adaptation mechanism for cross-kingdom regulation experiments, and motivating future large-scale validation. Under stricter leave-one-gene-out and leave-one-small-RNA-out evaluation, the adapter exceeded the first-layer score baseline but only matched the majority-class baseline, underscoring that entity-level generalization is not yet established.

23.
arXiv (CS.LG) 2026-06-15

A Statistical and Machine Learning Framework for Operational Threshold Detection and Deployable Dispatch Controller Development in Hydrogen Multi-Energy Systems

arXiv:2606.14601v1 Announce Type: new Abstract: This study presents a statistical and machine learning framework for characterizing a hydrogen-based multi-energy system (H-MES) using one year of high-resolution operational data. Statistical analysis revealed a binary operation driven by renewable surplus, with solar irradiance explaining 45.7% of rank-based variance in hydrogen production, a large effect by conventional standards. Only high-irradiance periods triggered meaningful electrolyzer engagement, while electricity demand exerted a weaker inverse suppression effect ($\epsilon^2 = 0.126$). Multiple regression confirmed electrolyzer power as the dominant linear predictor, with a synergistic solar-wind interaction. Notably, Random Forest analysis ranked wind output first in predictive importance despite its weak bivariate correlation (r = 0.167), revealing non-linear dynamics invisible to parametric methods. A sequence model exploited strong 24-hour autocorrelation (r = 0.845) for operational forecasting, while a reinforcement learning agent optimized hydrogen revenue dispatch. The core contribution is demonstrating that statistical and machine learning approaches are complementary for H-MES modeling and control.

24.
medRxiv (Medicine) 2026-06-15

The clinical utility of functional testing in fibroblasts to diagnose primary mitochondrial disease

Genome sequencing of the heterogeneous primary mitochondrial disorders (PMD) frequently reveals variants of uncertain significance that require functional tests for diagnosis, and does not identify variants in all patients. We analyzed mitochondrial enzyme assays, blue native polyacrylamide gel electrophoresis (BN-PAGE) with in-gel activity staining, complex I assembly blot, and select protein abundances in fibroblasts of a case series of 204 PMD patients divided into functional classes, in comparison to 51 controls and 53 differential diagnostic conditions. Overall, sensitivity and specificity for respiratory chain enzyme assays were 46% and 93% respectively, for BN-PAGE 40% and 98%, for complex I assembly assay 49% and 99%. The overall sensitivity of all tests was 76%, specificity 93%, with positive predictive value 96% and negative predictive value 67%. Categories with high sensitivity were isolated complex deficiencies, nuclear DNA-encoded mitochondrial protein synthesis defects, co-factor defects, and mitochondrial amino-acyl-tRNA synthetase conditions when aided by protein abundance. Mitochondrial DNA mutations and maintenance disorders showed poor sensitivities. Secondary dysfunctions were rare. A complete battery of functional tests showed strong diagnostic clinical utility in fibroblasts.

25.
arXiv (CS.LG) 2026-06-12

Understanding Truncated Positional Encodings for Graph Neural Networks

arXiv:2606.13671v1 Announce Type: new Abstract: Positional encodings (PEs) enhance the power of graph neural networks (GNNs), both theoretically and empirically. Two of the most popular families of PEs - spectral (e.g., Laplacian eigenspaces, effective resistance) and walk-based (polynomials of the adjacency matrix) - are theoretically equivalent in expressive power, with expressivity between the 1-WL and 3-WL tests. However, this equivalence assumes the GNN uses the "complete" version of these PEs, which requires $O(n^3)$ time and space complexity. Instead, practitioners commonly use truncated variants of these encodings, such as the first $k$ eigenspaces or powers of the adjacency matrix. However, the theoretical properties of these truncated PEs are unknown. In this work, we initiate the study of these truncated PEs. Theoretically, we show that, under truncation, several families of PEs are fundamentally different in expressive power. As a corollary, we show that truncated spectral PEs are no longer stronger than the 1-WL test. We also study a family of spectral PEs, the $k$-harmonic distances, to highlight the differences in expressive power of even closely related truncated PEs. Finally, we experimentally show that a mix of truncated PEs is preferable to any single family on real-world datasets.