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01.
arXiv (CS.LG) 2026-06-19

CAGE: Curvature-Aware Gradient Estimation For Accurate Quantization-Aware Training

arXiv:2510.18784v3 Announce Type: replace Abstract: Despite significant work on low-bit quantization-aware training (QAT), there is still an accuracy gap between such techniques and native training. To address this, we introduce CAGE (Curvature-Aware Gradient Estimation), a new QAT method that augments the straight-through estimator (STE) gradient with a curvature-aware correction designed to counteract the loss increase induced by quantization. CAGE is derived from a multi-objective view of QAT that balances loss minimization with the quantization constraints, yielding a principled correction term that depends on local curvature information. On the theoretical side, we introduce the notion of Pareto-optimal solutions for quantized optimization, and establish that CAGE yields strong convergence guarantees in the smooth non-convex setting. In terms of implementation, our approach is optimizer-agnostic, but we provide a highly-efficient implementation that leverages Adam statistics. CAGE significantly improves upon the prior state-of-the-art methods in terms of accuracy, for similar computational cost: for QAT fine-tuning, it halves the compression accuracy loss relative to the prior best method, while for QAT pre-training of Llama models, its accuracy for 3-bit weights-and-activations (W3A3) matches the accuracy achieved at 4-bits (W4A4) with the prior best method. The official implementation can be found over https://github.com/IST-DASLab/CAGE .

02.
arXiv (CS.AI) 2026-06-19

AAPA: Adversarially Anchored Preference Alignment for Post-Training of Large Language Models

arXiv:2509.25148v2 Announce Type: replace Abstract: Post-training alignment of large language models often combines supervised fine-tuning (SFT) on expert demonstrations with reinforcement learning (RL) from preference or verifiable feedback. SFT provides a useful behavioral anchor but can overfit to static demonstrations, whereas RL encourages exploration but may drift from expert behavior or exploit imperfect rewards. We propose AAPA (Adversarially Anchored Preference Alignment), a plug-in framework that augments existing post-training objectives with a sentence-level adversarial anchoring signal. AAPA compares policy rollouts with offline, pre-collected expert responses using a fixed lightweight discriminator, and therefore requires neither online teacher inference nor discriminator co-training during policy optimization. The same anchoring term can be added to SFT, GRPO, and CHORD while preserving their original training pipelines. Experiments on instruction-following benchmarks show that AAPA consistently improves the corresponding base objectives across model scales. In particular, the staged AAPA configuration improves over a strong GRPO baseline by 5.77\% on \texttt{Qwen3-0.6B} and 3.75\% on \texttt{Qwen3-4B}. Further analyses on response length, log-probability distributions, and discriminator variants suggest that adversarial anchoring provides a stable semantic grounding signal for preference optimization. Code is available at \url{https://github.com/IsFaqq/AAPA}.

03.
arXiv (CS.LG) 2026-06-17

Toward Controllable Catalyst Inverse Design via Large-Scale Autoregressive Pretraining

arXiv:2606.17445v1 Announce Type: new Abstract: Inverse design of heterogeneous catalysts remains challenging because catalyst surfaces exhibit substantial structural complexity with coupled surface-adsorbate interactions across a vast chemical space that is difficult to explore efficiently through conventional screening alone. Although machine learning-based high-throughput screening has accelerated catalyst discovery, its efficiency inevitably declines as the search space grows, motivating the development of generative models that can directly construct catalysts with target properties. Here, we present a conditional catalyst generative model based on the Generative Pretrained Transformer architecture with a numerical embedding layer that enables the generation of catalyst structures conditioned on both categorical and continuous properties within a single autoregressive framework. The model was pretrained on 133 million catalyst structures and subsequently fine-tuned on approximately 460,000 optimized structures with associated categorical properties and binding energies for conditional generation. The resulting model achieved 98% structural validity, 95% optimization validity, and high categorical condition fidelity, with a 93 % joint match rate for adsorbate type and composition. For binding energy conditioning, the match rate of approximately 20% represents a four-fold improvement over the baseline training distribution, and the generated distributions shift systematically toward the target values, enabling a 1.5 to 4-fold improvement in screening efficiency for reaction-targeted catalyst discovery without additional fine-tuning. These results show that large-scale autoregressive pre-training, combined with explicit property conditioning, provides a practical route toward controllable catalyst generation and accelerated catalysts discovery.

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

Residual Context Diffusion Language Models

Diffusion Large Language Models (dLLMs) have emerged as a promising alternative to purely autoregressive language models because they can decode multiple tokens in parallel. However, state-of-the-art block-wise dLLMs rely on a "remasking" mechanism that decodes only the most confident tokens and discards the rest, effectively wasting computation. We demonstrate that recycling computation from the discarded tokens is beneficial, as these tokens retain contextual information useful for subsequent decoding iterations. In light of this, we propose Residual Context Diffusion (RCD), a module that converts these discarded token representations into contextual residuals and injects them back for the next denoising step. RCD uses a decoupled two-stage training pipeline to bypass the memory bottlenecks associated with backpropagation. We validate our method on both long CoT reasoning (SDAR) and short CoT instruction following (LLaDA) models. We demonstrate that a standard dLLM can be efficiently converted to the RCD paradigm with merely ~300 million tokens. RCD consistently improves frontier dLLMs by 4-11 percentage points in accuracy with minimal extra computation overhead across a wide range of benchmarks. Notably, on the most challenging AIME tasks, RCD nearly doubles baseline accuracy and attains up to 4-5x fewer denoising steps at baseline's peak accuracy.

05.
arXiv (CS.AI) 2026-06-16

Tensor-Coord: Algebraic Decomposition of Joint Plan Tensors for Conflict-Free Multi-Agent LLM Planning

Authors:

arXiv:2606.16478v1 Announce Type: new Abstract: Large language models (LLMs) remain limited in multi-agent planning because independently generated plans can create coordination failures such as spatial collisions, resource contention, and temporal deadlocks. We introduce Tensor-Coord, a multilinear algebra framework that represents the joint plan of N agents as a third-order tensor \(T \in R^{N \times H \times A}\) over agents, timesteps, and actions. Canonical Polyadic (CP) and Tucker decompositions are used to identify latent coordination structure. The minimal epsilon-approximate CP rank R* defines a computable coordination complexity measure, with \(CC(Pi)=(R*-N)/N\). We prove that R*=N is necessary and sufficient for plan independence. The residual \(E=T-T_{R*}\) defines a conflict score over agent pairs, timesteps, and actions, localizing failures without domain-specific rules. Tucker factors provide interpretable agent roles, temporal phases, and action clusters that are converted into natural language constraints for iterative LLM replanning. Experiments on multi-robot delivery tasks across Easy (2 agents, 5x5 grid), Medium (3 agents, 5x5 grid), and Hard (4 agents, 5x5 grid) settings show convergence to conflict-free plans in 100% of 2-agent cases within 1.4 iterations on average, 80% of 3-agent cases within 3.2 iterations, and 60% of 4-agent cases within 4.0 iterations. CP rank scaled approximately linearly as \(R*(N) = 3.9N + 0.5\), supporting its use as a predictor of coordination complexity.

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

Multilevel Stochastic Plug-and-Play for Sparse-View CT Reconstruction

Sparse-view computed tomography (SVCT) reduces radiation exposure and acquisition time, but the limited number of projection views makes the reconstruction problem severely ill-posed and leads to streak artifacts when analytical methods are used. Plug-and-Play (PnP) methods provide an effective way to combine data fidelity with learned image priors, while stochastic PnP methods further improve robustness by matching the denoiser input distribution through re-noising. However, these methods often require many iterations to converge, which limits their practical efficiency. In this work, we propose a multilevel (ML) stochastic PnP method for SVCT that accelerates stochastic PnP reconstruction. We highlight that, in the stochastic setting, directly enforcing prior coherence across levels would require accurately estimating fine-level prior gradients through multiple denoiser function evaluations, which substantially increases the computational cost. Motivated by this observation, we perform the multilevel steps in multiresolution analysis (MRA) approximation spaces. This choice is supported by the structure of the wavelet decomposition, which causes the prior-coherence correction to vanish in expectation, thereby avoiding costly estimation of fine-level stochastic prior gradients for the coarse-level corrections. Experiments on SVCT reconstruction show that our method, called Multilevel Stochastic Plug-and-Play (ML-SPnP), achieves reconstruction quality comparable to state-of-the-art methods while substantially reducing runtime.

07.
arXiv (CS.AI) 2026-06-24

Bitwise Systolic Array Architecture for Runtime-Reconfigurable Multi-precision Quantized Multiplication on Hardware Accelerators

arXiv:2602.23334v2 Announce Type: replace-cross Abstract: Neural network accelerators have been widely applied to edge devices for complex tasks like object tracking, image recognition, etc. Previous works have explored the quantization technologies in related lightweight accelerator designs to reduce hardware resource consumption. However, low precision leads to high accuracy loss in inference. Therefore, mixed-precision quantization becomes an alternative solution by applying different precision in different layers to trade off resource consumption and accuracy. Because regular designs for multiplication on hardware cannot support the precision reconfiguration for a multi-precision Quantized Neural Network (QNN) model in runtime, we propose a runtime reconfigurable multi-precision multi-channel bitwise systolic array design for QNN accelerators. We have implemented and evaluated our work on the Ultra96 FPGA platform. Results show that our work can achieve 1.3185 to 3.5671 times speedup in inferring mixed-precision models and has less critical path delay, supporting a higher clock frequency (250MHz).

08.
arXiv (CS.AI) 2026-06-17

FinAcumen: Financial Multimodal Reasoning via Self-Evolving Experience Memory Harness

arXiv:2606.17642v1 Announce Type: new Abstract: Financial multimodal reasoning requires agents to coordinate numerical computation, retrieval, visual interpretation, and temporal grounding across heterogeneous evidence sources. Existing tool-augmented agents improve execution fidelity, yet remain largely stateless across episodes, repeatedly rediscovering reasoning strategies and failure patterns. In high-stakes financial settings, this leads to unreliable tool routing, noisy retrieval, and hallucination-prone reasoning. We present FinAcumen, a financial reasoning agent framework centered on selective experience memory for tool-augmented multimodal reasoning. FinAcumen accumulates financially grounded reasoning experience from prior trajectories, distilling successful strategies and failure-derived cautionary rules into a persistent memory bank. During inference, retrieved experiences condition reasoning only when semantic relevance exceeds a calibrated threshold, while irrelevant memory is explicitly suppressed through a fallback mechanism. A deterministic financial tool environment further grounds numerical computation, retrieval, visual decoding, and answer verification.Across four financial multimodal reasoning benchmarks, FinAcumen consistently improves a frozen 8B vision-language model over finance-specialized models and approaches leading proprietary general-purpose models. Further analysis shows that selective experience activation improves reasoning reliability under retrieval uncertainty. Our code is anonymously available at https://anonymous.4open.science/r/FinAcumen

09.
arXiv (CS.CV) 2026-06-11

Mitigating Content Shift and Hallucination in GenAI Image Editing via Structural Refinement

Generative AI (GenAI) image editors, such as Nano Banana, produce visually compelling results for retouching tasks, enabling non-experts to edit images through text prompts alone. However, the generative nature of these models often introduces spatial misalignment, texture distortion, and content hallucination, all of which are detrimental to downstream workflows that require pixel-level fidelity. We identify a problem setting we call "structure-preserving GenAI fusion" for black-box GenAI image retouching: retain the perceptual enhancements of a GenAI output while enforcing structural faithfulness to the original input image. To address this problem, we propose a post-processing framework that fuses an input image with its GenAI-enhanced counterpart by first establishing coarse spatial and photometric correspondences, then performing a fusion stage that transfers desired enhancements while suppressing hallucinated content. In the absence of direct prior work in this setting, we evaluate our framework against representative methods from photorealistic style transfer and image fusion. Our experiments demonstrate that our method better preserves aesthetic quality while maintaining pixel-level structural consistency and the input resolution.

10.
arXiv (CS.CL) 2026-06-24

A Training-Free Mixture-of-Agents Framework for Multi-Document Summarization using LLMs and Knowledge Graphs

Multi-Document Summarization (MDS) plays a critical role in distilling essential information from collections of textual data. Existing approaches often struggle to capture complex inter-document relationships, rely heavily on large amounts of labeled data for supervised training, or exhibit limited generalization across domains and languages. To address these limitations, we present a training-free mixture-of-agents framework for MDS that leverages the complementary strengths of large language models (LLMs) and knowledge graphs. Our approach decomposes summarization into specialized agent tasks: extractive selection, knowledge-aware abstraction, and iterative refinement, each operating without task-specific fine-tuning. We unify their outputs using a multi-perspective consistency mechanism guided by LLMs. Experiments across four datasets in English and Vietnamese demonstrate state-of-the-art or competitive performance, validating the effectiveness and adaptability of our modular design.

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

Towards Responsibly Non-Compliant Machines

arXiv:2606.12147v1 Announce Type: new Abstract: We consider the problem of engineering autonomous intelligent agents that are capable to responsibly not comply with user requests. We argue that machine non-compliance comes in many different forms, and sketch the issues we should pursue on the road of accomplishing responsibly non-compliant intelligent machines. We anchor responsible non-compliance in justifications for task refusal, pathways to override the non-compliance, as well as careful tracking of security risks and liability transfers.

12.
arXiv (CS.CV) 2026-06-15

HumP-KD: A Hybrid Uncertainty-Aware Multi-Stage Progressive Knowledge Distillation Framework for Efficient Fire Classification

Real-time fire classification systems require models that are simultaneously accurate, computationally efficient, and deployable on resource-constrained hardware. This work proposes HumP-KD, a Hybrid Uncertainty-aware Multi-stage Progressive Knowledge Distillation framework for efficient fire classification. Two datasets, FlameVision and Dataset-II, containing 8,600 and 31,309 images, are used. Various CNN and transformer baselines are applied under standard preprocessing, online augmentation, Gaussian noise and motion blur robustness conditions. The proposed HumP-KD model distills knowledge from two frozen heterogeneous transformer teachers, Swin-Tiny and ViT-Base, along with their Meta-MLP ensemble, into a lightweight MobileViT-S student via three tightly integrated components. Hierarchical Progressive Knowledge Distillation employs a Hierarchical Feature Builder. It generates a fused spatial attention mask to guide distillation toward discriminative regions selectively. Multi-Stage Knowledge Distillation progressively activates three distillation stages across training. On Dataset-II, HumP-KD achieves a mean F1 score of $0.9876 \pm 0.0063$ across 10 independent trials, significantly outperforming the MobileViT-S baseline trained without distillation ($0.9537 \pm 0.0351$), with statistical significance confirmed by both independent t-test ($p = 0.0195$) and Wilcoxon signed-rank test ($W = 1$, $p = 0.0039$). The proposed method also demonstrates strong generalization across datasets and robustness under degraded visual conditions. The student model retains only 4.94M parameters and 19.01Mb model size, representing a $5.7\times$ parameter reduction over Swin-Tiny and a $17.5\times$ reduction over ViT-Base, while achieving 37.72 CPU FPS, making it suitable for real-time deployment.

13.
medRxiv (Medicine) 2026-06-17

Clinician knowledge and self-efficacy in snakebite management: A cross-sectional assessment in Northern Uganda

Background: Snakebite envenomation (SBE) is a major public health crisis in rural Uganda, yet it remains a neglected tropical disease. Effective management is often compromised by systemic barriers and a lack of clinician training. This study assessed clinician self-efficacy and objective knowledge regarding SBE management in Northern Uganda. Methods: A descriptive, cross-sectional study was conducted between February and July 2025 among 379 healthcare workers in Gulu, Omoro, and Pader districts. A validated questionnaire was used to collect data on socio-demographics, self-reported efficacy (scale 1-10), and objective knowledge. Knowledge scores [&ge;]70% were categorized as adequate. Multivariable logistic regression identified independent predictors of adequate knowledge, and Spearmans correlation ({rho}) assessed the relationship between knowledge and self-efficacy. Results: The participants had a mean age of 35.6 years (SD {+/-}7.3), were predominantly female (56.5%, 214/379), and most (83.6%, 317/379) practiced at Health Centre III level facilities. While 53.8% (204/379) reported prior training, 48.3% (183/379) of these had not received an update in over 10 years. Adequate knowledge was demonstrated by 51.5% (195/379) of participants. In the multivariable analysis, practicing in Omoro (adjusted odds ratio [aOR]: 0.3, 95% CI: 0.1-0.6, p < 0.001) or Pader (aOR: 0.2, 95% CI: 0.1-0.4, p < 0.001) was associated with lower odds of adequate knowledge compared to Gulu district. Prior training significantly increased the odds of adequate knowledge (aOR: 2.3, 95% CI: 1.3-4.2, p = 0.006). A moderate positive correlation was observed between self-efficacy and objective knowledge (Spearmans {rho} = 0.33, p < 0.0001). Conclusion: Approximately half of the frontline healthcare workers in Northern Uganda lack adequate knowledge on SBE management, with significant geographic differences and outdated training. The gap between clinician self-efficacy and objective knowledge poses a risk to patient safety. Regular, mandatory refresher training and targeted educational outreach to remote districts are required to reduce SBE-related morbidity and mortality.

14.
arXiv (quant-ph) 2026-06-24

Concatenating Algebraic Codes over High-Rate Quantum LDPC Codes

arXiv:2605.21898v2 Announce Type: replace Abstract: Different quantum error correction schemes trade off overhead, error suppression, and hardware connectivity. Code concatenation can relax these tradeoffs by using an outer code whose non-local connectivity is supplied by logical operations of an inner code rather than directly by hardware. Prior works showed that this can reduce memory overhead for local low-rate inner codes such as the surface code. Here, we study concatenation over non-local, high-rate inner codes. Such inner codes experience correlated errors among the many logical qubits in a single codeblock. We handle this by treating each block as a single logical Galois qudit, enabling concatenation with algebraic outer codes with excellent parameters and, crucially, list decoders. In particular, we consider a memory system formed by concatenating quantum Reed-Solomon outer codes over the gross code. For fault-tolerant syndrome extraction, we develop a Galois qudit Shor scheme using "time-like" Reed-Solomon protection against measurement errors. Interestingly, a lightweight fault tolerance scheme, that would fail for qubits, works well for large-alphabet qudits, suggesting a very different theory of fault tolerance for such qudits. The whole protocol is optimised via improved bicycle instruction logical error rates, novel compilation strategies, and recent decoder post-selection rules. At uniform $10^{-3}$ physical noise, the concatenated gross code reaches the teraquop regime, which it previously could not access, with a lower space overhead than the $288$-qubit two-gross code, while offering several advantages from the engineering standpoint. Beyond our main case study, we believe the core ideas of Galois qudits, quantum Reed-Solomon outer codes, and list decoding, will prove generically powerful and highly transferable ideas across high-rate quantum architectures.

15.
arXiv (CS.CL) 2026-06-24

Aspect-Based Sentiment Evolution and its Correlation with Review Rounds in Multi-Round Peer Reviews: A Deep Learning Approach

Mining sentiment information from the textual content of peer review comments offers valuable insights into the scientific evaluation process. However, previous studies are often constrained by coarse-grained analysis and the lack of differentiation across review rounds. Notably, the dynamic shifts in reviewers' focus and sentiment tendencies throughout multiple review stages remain underexplored. To address this gap, the present study investigates the distribution and evolution of aspect-level sentiments and examines their correlation with the number of review rounds. We begin by segmenting the multi-round review comments of 11,063 accepted papers from Nature Communications and identifying fine-grained review aspect clusters. A manually annotated corpus of approximately 5,000 review sentences is then constructed. Using this dataset, we train a series of deep learning-based aspect sentiment classification models. Among them, the LCF-BERT-CDM model achieves the best performance, with a Macro-F1 score of 82.65%. Subsequent statistical analysis reveals a consistent trend: as the number of review rounds increases, the proportion of positive sentiments rises, while negative sentiments decline. Correlation analysis further indicates that aspect sentiment scores are negatively associated with the total number of review rounds. Key aspects exhibiting stronger correlations include "experiments", "research significance" and "result analysis".

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

LLMs+Graphs: Toward Graph-Native, Synergistic AI Systems

arXiv:2606.11560v1 Announce Type: cross Abstract: Large Language Models (LLMs) have advanced rapidly, but their limitations in structured and multi-hop reasoning underscore the need for graph-native, synergistic artificial intelligence (AI) systems. Graph-structured data underpins critical applications across social, biological, financial, transportation, web, and knowledge domains, making it essential to understand how LLMs can leverage graph computation for grounded, context-rich inference. Three complementary synergies are emerging: LLMs augmented with graph computation for retrieval and reasoning; bidirectional integration between LLMs and knowledge graphs (KGs), where LLMs support KG construction and curation while KGs enforce semantic constraints and factual consistency; and AI agents strengthened by graph algorithms for planning, decision making, and multi-step reasoning. In parallel, LLMs introduce new capabilities for graph data management and graph machine learning (ML) through natural language interfaces and hybrid LLM-graph neural network (GNN) pipelines. This tutorial synthesizes the algorithms, systems, and design principles driving these converging directions, offering data science and data mining researchers a unified perspective on integrating LLMs, graph data management, graph mining, graph ML, and agentic computation into next-generation graph-native AI systems.

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

Tacit Coordination of Large Language Models

arXiv:2601.22184v2 Announce Type: replace-cross Abstract: Large Language Models (LLMs) are increasingly deployed in multi-agent settings that require coordination without communication, from human-AI interaction to safety-critical scenarios. Humans often overcome the absence of communication through focal points: salient solutions that naturally stand out to all participants. We present the first large-scale evaluation of how, when, and why focal points emerge in LLMs, comparing their behaviour with humans across cooperative and competitive games, including realistic search and rescue scenarios, demonstrating when focal points enable effective coordination. Across more than 20 open- and closed-source models, we find that LLMs exhibit a remarkable ability to coordinate without communication, often matching or outperforming humans. However, the same models consistently fail in tasks requiring numerical common sense or culturally nuanced notions of salience. We additionally evaluate simple learning-free strategies that substantially improve coordination both among LLMs and between humans and LLMs. Our results reveal striking coordination capabilities, as well as social limitations in modern LLMs, and offer new insight into the latent notions of salience encoded within them. Our findings caution against assuming that LLMs share humans' cultural and perceptual substrate when deployed in coordination settings.

18.
arXiv (CS.LG) 2026-06-17

From Drift to Coherence: Stabilizing Beliefs in LLMs

arXiv:2606.17832v1 Announce Type: new Abstract: Large language models (LLMs) are often hypothesized to perform implicit Bayesian inference, yet a key coherence condition, the martingale property of predictive beliefs, has been shown to fail in controlled synthetic in-context learning settings. We revisit this question in a more typical usage regime: generic multiple-choice question answering. Exploiting the discrete answer space, we compute exact predictive distributions and study belief dynamics induced by autoregressive answer resampling. We introduce prompted predictive resampling (PPR), where an LLM generates a sequence of answers to the same question. Empirically, PPR reveals early-stage belief drift, indicating martingale violations. However, after sufficient resampling steps, the belief process self-stabilizes and converges to a coherent predictive distribution. Based on this observation, we further propose (i) a seed-answer prompting strategy to accelerate stabilization, and (ii) a self-consistency loss that amortizes early-stage drift into the model via fine-tuning. Experiments on multiple-choice QA benchmarks show that our methods substantially reduce belief drift and improve predictive coherence without sacrificing accuracy.

19.
bioRxiv (Bioinfo) 2026-06-23

biomeStat: Using Agentic AI for Scalable Genomic Epidemiology Demonstrated Through End-to-End Analysis of 1,000 Asian Dengue Virus Genomes

Genomic epidemiology workflows typically require expert curation of multiple specialized tools, extensive manual parameter tuning, and access to heterogeneous compute infrastructure. While standard generative AI models often hallucinate in complex biological domains, we introduce biomeStat: an autonomous AI agent that functions as a strict deterministic orchestrator. By automatically writing code to execute established bioinformatics tools in sandboxed environments, biomeStat dynamically provisions compute resources (CPU and GPU) and guarantees reproducibility, making it immediately useful for scientists without requiring command-line expertise. To demonstrate the platform, we performed a fully autonomous genomic epidemiology and structural analysis of 1,000 Dengue virus (DENV) genomes sampled from 16 Asian countries between 2000 and 2025. The agent seamlessly orchestrated phylogenetic reconstruction (IQ-TREE, TreeTime), Bayesian phylodynamics (BEAST2 via NVIDIA H200 GPU), selection pressure analysis (HyPhy), and structural mapping (PyMOL). The analysis was completed in under 24 hours of wall-clock time, revealing endemic stability (R_e ~1.0) and identifying 1,869 candidate immune escape sites structurally colocalized with B-cell and T-cell epitopes. Furthermore, the agent validated 176 highly conserved drug target residues across the viral replication complex, confirming that resistance-associated positions for emerging antivirals JNJ-1802 and NITD-688 remain absolutely conserved across all four serotypes. By bridging the gap between natural language intent and deterministic computational execution, biomeStat reduces weeks of expert effort into a single-session analysis with full methodological transparency.

20.
Nature (Science) 2026-06-24

Zero-shot design of drug-binding proteins via neural iterative selection−expansion

Authors:

The design of proteins that bind to small molecules has been challenging because it requires simultaneous optimization of the protein sequence, protein structure and ligand conformation1–7. Current deep-learning algorithms have struggled to navigate this landscape, precluding the zero-shot design of binders. Here we show that by combining two neural networks in an iterative design algorithm, small-molecule binding proteins can be created from scratch with high accuracy. We trained a graph neural network—ligand-aware sequence engineering message-passing neural network (LASErMPNN)—to design&nbsp;compatible protein sequences for an input&nbsp;protein backbone and docked ligand. We paired &nbsp;LASErMPNN with a structure predictor that models a three-dimensional protein–ligand complex for an input protein sequence and ligand identity. The closed-loop iteration of these reciprocal networks optimized sequence–structure–ligand compatibility, and outperformed a comparable design loop using a physics-based energy function. We used our strategy, termed neural iterative selection–expansion (NISE),&nbsp;to design proteins that, using different folds, specifically bind to two chemically distinct small-molecule drugs, exatecan and apixaban, with success rates of 100% and 83%, respectively. The tightest NISE binders had nanomolar-to-picomolar affinities, surpassing those of the next-leading method by 70-fold for exatecan and nearly 10,000-fold for apixaban. LASErMPNN then suggested two amino-acid substitutions that improved the affinity of the&nbsp;tightest&nbsp;exatecan binder by 100-fold without any experimental input. The optimized binder protected the labile lactone ring of exatecan from hydrolysis for days. Our work describes a general recipe for using neural networks to automate the design of small-molecule binding proteins for applications in drug delivery, sensing and catalysis. &nbsp;By pairing two neural networks in an iterative optimization algorithm, small-molecule binding proteins can be designed from scratch with high accuracy, affinity&nbsp;and success rates, showing promise for applications in&nbsp;drug delivery and sequestration.

21.
medRxiv (Medicine) 2026-06-11

A Global Health Quality Improvement Project: Enhancing Cervical Cancer Awareness and screening in Nigeria

Background Cervical cancer remains a significant global public health challenge, ranking as the fourth most common cancer among women worldwide. According to The World Health Organization (WHO) 604,000 women were diagnosed with cervical cancer globally in 2020, with over 342,000 deaths amongst this group [1]. Despite its high mortality, cervical cancer is largely preventable through early detection and vaccination against human papillomavirus (HPV), which causes nearly all cases of cervical cancer [1,2] In Nigeria, it is the second most common cancer among women in Nigeria and a leading cause of cancer-related deaths, with low screening rates exacerbating late diagnoses and poor outcomes [1]. Despite global commitments to elimination with Pap smear screening and HPV vaccination, less than 10% of women in Nigeria have undergone screening due to misconceptions, stigma, and limited awareness. Educational interventions may improve awareness and promote screening behaviors. This global health quality improvement (QI) project aimed to enhance cervical cancer awareness and increase Pap smear uptake at the Central Bank of Nigeria (CBN) Clinic in Abuja, Nigeria. Methods In November 2024, we conducted a health education intervention at the Central Bank of Nigeria (CBN) through a structured educational session for male and female CBN staff members. The session focused on cervical cancer prevention, risk factors, and screening guidelines. Additionally, cervical cancer awareness was raised via email, social media, and electronic bulletin board. Participants completed pre and post-interventions surveys assessing cervical cancer knowledge across 10 key items and demographic characteristics. Pap smear uptake was assessed using the CBN clinic records for three months before and after the intervention. Institutional approval was obtained from CBN and external institutional review board approval was not required. Results 188 participants attended the health education session with 124 survey responses (70 pre-event, 54 post-event). Participants were mostly women aged 30-39. Post-intervention, eight of ten survey questions showed improved knowledge, with five demonstrating statistically significant gains: understanding Pap smear frequency (p

22.
arXiv (CS.LG) 2026-06-18

Effects of sparsity and superposition on loss in simple autoencoders

arXiv:2606.18538v1 Announce Type: new Abstract: One of the major difficulties in the mechanistic interpretability of neural networks is the occurrence of polysemanticity, which suggests that each neuron is typically responsible for multiple different tasks, impeding a clean interpretation of their function. The seminal paper of Elhage et al. (2022) argues that this occurs due to superposition, a phenomenon where the neural network represents distinct features as non-orthogonal directions in a lower-dimensional space, a strategy that allows much greater compression of the data without sacrificing fidelity due to the feature sparsity of input vectors. Elhage et al. (2022) empirically validates these hypotheses in a rather natural and simple autoencoder with sparse inputs. The contribution of the present work is to analyze the mathematical basis for the occurrence and optimality of superposition, while rigorously corroborating some of their findings. In particular, we provide upper and lower bounds for the L2 reconstruction loss, tight in the very sparse regime, for power activation functions. A short list of interesting open problems are also included at the end.

23.
PLOS Computational Biology 2026-06-22

pyhgf: A neural network library for predictive coding

by Nicolas Legrand, Lilian Weber, Peter Thestrup Waade, Anna Hedvig Møller Daugaard, Mojtaba Khodadadi, Nace Mikuš, Christoph Mathys 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 algorithms as belief propagation. Moreover, 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 main functions of the library are differentiable and seamlessly integrate into sampling or optimization workflows. Additionally, we offer generalized Bayesian filtering and the hierarchical Gaussian filter as key examples of dynamic networks implemented in our library. The source code, tutorials, and documentation are hosted under the main repository at https://github.com/ComputationalPsychiatry/pyhgf.

24.
arXiv (CS.CL) 2026-06-24

MEMPROBE: Probing Long-Term Agent Memory via Hidden User-State Recovery

Long-term memory promises LLM agents that grow more capable across sessions, maintaining an accurate, evolving understanding of the user that interaction forms. In practice, however, this memory is evaluated mostly through downstream behavior, such as later answers, personalization quality, or task success, which tests that understanding only indirectly and leaves the memory artifact itself largely unaudited. We argue that long-term memory should instead be evaluated as an auditable post-interaction artifact: after ordinary assistance, what structured user state can be reconstructed from the memory the agent leaves behind? We instantiate this view in MEMPROBE, a benchmark in which a memory-equipped agent assists simulated users, each carrying a hidden, taxonomy-anchored user-state bank, across a trajectory of leak-controlled tasks, after which that bank is reconstructed from the agent's resulting memory under both full-store and top-k access. Built on synthetic ground truth for efficient, scalable measurement, MEMPROBE spans 50 simulated users with 31 hidden dimensions each (1,550 recovery targets) and tests 5 representative memory systems. Testing state-of-the-art memory agents, we find that successful assistance and recoverable memory behave as distinct capabilities. Task completion nearly saturates, even for a memoryless baseline, while category-balanced recovery stays moderate (about 0.6) and drops further under top-k retrieval. MEMPROBE is the first benchmark to study memory recovery directly, reconstructing the user state a system retains and scoring it against ground truth. We see recovery as a concrete objective for future memory agents to optimize, and MEMPROBE as a step toward an environment where agents are trained to remember their users, growing more faithful the longer they know them.

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medRxiv (Medicine) 2026-06-22

Evidence-guided AI regularization for suicidal ideation prediction in pediatric bipolar disorder

Background: Suicide prediction models in psychiatry often rely on purely data-driven feature selection, which can produce unstable and clinically opaque predictor sets in modest-sized samples. We developed Evidence-Based AI LASSO (EBAL), an evidence-guided regularization framework that incorporates curated clinical evidence into feature-specific penalty factors for interpretable prediction. Methods: Baseline data from 136 youth with confirmed bipolar spectrum disorder in the Greater Houston Area Bipolar Registry were analyzed using 20 candidate clinical predictors. Forty higher-level evidence documents on suicidality and related predictor domains were curated through a structured evidence synthesis workflow and indexed as an auditable evidence corpus. An open-weight large language model assigned feature-specific penalty factors using a prespecified scoring rubric, and these penalties were used to fit a weighted LASSO model. EBAL was compared with a standard evidence-agnostic LASSO using nested leave-one-out cross-validation. Results: For suicidal ideation, EBAL achieved an AUROC of 0.768, balanced accuracy of 0.757, sensitivity of 0.758, and specificity of 0.757. The standard LASSO achieved an AUROC of 0.760 and balanced accuracy of 0.715. EBAL improved balanced accuracy (+0.042, p=0.010) and Matthews correlation coefficient (+0.079, p=0.010), while retaining fewer stable predictors than standard LASSO (11/20 vs 18/20). The strongest positive predictors were current depressed mood, duration of mood disorder illness, and comorbid generalized anxiety disorder. For suicidal behavior, both models performed near chance and retained all candidate predictors. Limitations: The study was cross-sectional, single-site, and modest in sample size, with no external validation cohort. Conclusions: EBAL produced a sparser and more clinically coherent model for suicidal ideation in pediatric bipolar disorder, but did not improve prediction of suicidal behavior. These findings support evidence-guided regularization as a transparent strategy for aligning psychiatric prediction models with prior clinical knowledge while preserving interpretability.