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01.
medRxiv (Medicine) 2026-06-17

Determinants of non-utilization of insecticide-treated nets among children under five in Rwanda: analyses of the 2024 Rwanda malaria indicator survey

作者:
Eduah↗K. N↗A. O↗

Background Insecticide-treated nets (ITNs) are effective for preventing malaria among children under five years, who bear a disproportionate burden of malaria. This study assessed the prevalence and determinants of ITN non-utilization among children under five in Rwanda using data from the 2024 Rwanda Malaria Indicator Survey (RMIS).Methodology This cross-sectional study utilized nationally representative data from the 2024 RMIS. Analyses were restricted to children under five residing in households that owned at least one ITN. The outcome was non-utilization of ITN, defined as not sleeping under an ITN the night preceding the survey. Survey-weighted descriptive statistics were used to estimate the prevalence of ITN non-utilization. Factors associated with non-utilization were identified using a survey-weighted Poisson regression model. Adjusted prevalence ratios (aPRs), 95% confidence intervals and p-values were reported.Results A total of 1,979 children were included in the study. The weighted prevalence of ITN non-utilization among children under five years was 20.11% (95% CI: 17.81 - 22.63). After adjusting for other factors, children aged 2 - 3 years were associated with an 83% higher prevalence of ITN non-utilization compared with those aged [&le;]1 year (aPR = 1.83, 95% CI: 1.423 - 2.352, p < 0.001). Compared with households that owned only one ITN, children in households with three or more ITNs were associated with a 76% lower prevalence of ITN non-utilization (aPR = 0.24, 95% CI: 0.171 - 0.332, p < 0.001). Children living in households with 5 - 7 members were associated with an 87% higher prevalence of ITN non-utilization compared with those in households with 1 - 4 members (aPR = 1.87, 95% CI: 1.476 - 2.358, p < 0.001).Conclusion The findings suggest that ITN utilization among children is influenced not only by household access to nets but also by household composition and dynamics that shape the allocation and use of available preventive resources.

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

Forged Calamity: Benchmark for Cross-Domain Synthetic Disaster Detection in the Age of Diffusion

作者:
Duc-Manh Phan↗Quoc-Duy Tran↗Duy-Khang Do↗Anh-Tuan Vo↗Hai-Dang Nguyen↗Trong Le Do↗Mai-Khiem Tran↗Vinh-Tiep Nguyen↗Tam V. Nguyen↗Isao Echizen↗Minh-Triet Tran↗Trung-Nghia Le↗…

The rapid advancement of text-to-image diffusion models has enabled the creation of highly photorealistic synthetic images that closely resemble real photographs, making it increasingly difficult to distinguish authentic content from AI-generated fabrications. This poses challenges for cybersecurity, digital forensics, and disaster response, where fake imagery of floods, fires, or earthquakes can spread misinformation or disrupt emergency operations. To address this, we introduce Forged Calamity, a benchmark dataset for synthetic disaster detection containing 30,000 images, including 6,000 real and 24,000 synthetic samples generated by four diffusion models. Comprehensive experiments across fine-tuned and zero-shot settings reveal consistent weaknesses in current forensic approaches. Fine-tuned detectors perform well in-distribution but lose up to 50\% accuracy on unseen generators or disaster types, showing overfitting to model-specific artifacts. Zero-shot generalized detectors also struggle to maintain stable accuracy, with only limited resilience in a few representation-robust models. These findings highlight persistent generalization gaps and the urgent need for domain- and model-agnostic detection methods to ensure visual authenticity in the diffusion era.

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

SuCo: Sufficiency-guided Continuous Adaptive Reasoning

作者:
Jiahao Wang↗Bingyu Liang↗Chenhao Hu↗Longhui Zhang↗Xuebo Liu↗Min zhang↗Jing Li↗Xuelong Li↗

Despite remarkable performance on complex tasks, Large Reasoning Models (LRMs) often generate excessively long Chain-of-Thoughts (CoT), inflating computational costs even for simple queries. Existing efforts to mitigate this inefficiency typically rely on discrete reasoning modes or fixed budget tiers, lacking a principled criterion of when reasoning is sufficient. In this work, we introduce Minimal Sufficient CoT (MSC), defined as the shortest prefix of a CoT trajectory which is adequate for producing the correct answer. We empirically show that MSC not only reduces reasoning tokens, but also improves accuracy across difficulty levels. Building on MSC, we propose Sufficiency-guided Continuous Adaptive Reasoning (SuCo), a two-stage training framework for autonomous reasoning control along a continuous spectrum. In stage 1, MSC-Aligned Fine-Tuning (MFT) constructs MSC data using problem-adaptive sufficiency thresholds that naturally scale with question difficulty, then fine-tunes the model to internalize concise yet sufficient reasoning patterns. In stage 2, Sufficiency-Aware Policy Optimization (SAPO) further optimizes the model through reinforcement learning with dynamic complexity tracking and sufficiency-aware rewards that penalize both over- and under-thinking. Extensive experiments across mathematics, code, and science benchmarks show that SuCo consistently achieves improvements in both accuracy and reasoning efficiency.

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04.
arXiv (CS.AI) 2026-06-16

RAID: Semantic Graph Diffusion for True Cold-Start and Cross-Lingual Forecasting

作者:
Arunkumar V↗Manoranjan Gandhudi↗Gangadharan G. R↗Arun Prakash↗S. Senthilkumar↗

arXiv:2606.16925v1 Announce Type: new Abstract: Time-series foundation models show strong transfer performance when given a non-empty history window. However, true cold-start scenarios, where a new item has no prior observations, violate this assumption. We propose RAID (Retrieval-Augmented Iterative Diffusion) a framework, which replaces history-based correlation learning with metadata-driven semantic retrieval and graph-conditioned diffusion. RAID maps textual metadata into a shared semantic space using a frozen multilingual embedding model and constructs an inductive retrieval graph that extends naturally to unseen items. It first forms a base forecast by aggregating information from semantically related neighbors, then refines this forecast with a gated diffusion module to model residual uncertainty. Under a strict true cold-start protocol, RAID outperforms strong foundation models and competitive baselines on both forecasting accuracy and prediction interval coverage, while reducing inference latency by an order of magnitude through non-autoregressive decoding. The shared semantic space also enables zero-shot cross-lingual transfer, allowing a model trained on English descriptions to generalize to items described in other languages without direct supervision.

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05.
arXiv (CS.CL) 2026-06-19

LedgerAgent: Structured State for Policy-Adherent Tool-Calling Agents

作者:
Md Nayem Uddin↗Amir Saeidi↗Eduardo Blanco↗Chitta Baral↗

Policy-adherent tool-calling agents in customer-service domains must maintain task states across turns while calling tools and obeying domain policies. Task states consist of relevant facts, identifiers, constraints, and conditions observed through user interaction and tool calls. In standard agents, task states are not represented separately. Observations, tool returns, and policy instructions are placed in the prompt, leaving agents to reconstruct the relevant states from the prompt each time they decide what to do next. This design makes state management implicit, creating two common failure modes. An agent may retrieve the right facts but later ground its decision in stale, missing, or incorrect information; and a syntactically valid tool call may still violate a domain policy that depends on the current task state. We introduce \textsc{LedgerAgent}, an inference-time method for tool-calling agents that maintains observed task states in a separate ledger and renders the states into the prompt. The ledger is also used to check state-dependent policy constraints before environment-changing tool calls are executed, blocking policy violations. Across four customer-service domains and a mixed panel of open- and closed-weight models, \textsc{LedgerAgent} improves average pass\textasciicircum{}k over a standard prompt-based tool-calling approach, with the largest gains under stricter multi-trial consistency metrics.

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

Conformalized Quantum DeepONet Ensembles for Scalable Operator Learning with Distribution-Free Uncertainty

作者:
Purav Matlia↗Christian Moya↗Guang Lin↗

arXiv:2605.00330v2 Announce Type: replace Abstract: Operator learning enables fast surrogate modeling of high-dimensional dynamical systems, but existing approaches face two fundamental limitations: quadratic inference complexity and unreliable uncertainty quantification in safety-critical settings. We propose Conformalized Quantum DeepONet Ensembles, a framework that addresses both challenges simultaneously. By leveraging Quantum Orthogonal Neural Networks (QOrthoNNs), we reduce operator inference complexity from O(n^2) to O(n), enabling scalable evaluation over fine discretizations. To provide rigorous uncertainty quantification, we combine ensemble-based epistemic modeling with adaptive conformal prediction, yielding distribution-free coverage guarantees. A key challenge in ensembling is that naive parallelism scales hardware resources linearly with the number of models. We resolve this by using Superposed Parameterized Quantum Circuits (SPQCs), which compress multiple ensemble members into a single circuit and enable simultaneous multi-model execution. Experiments on synthetic partial differential equations and real-world power system dynamics demonstrate that our approach achieves accurate predictions while maintaining calibrated uncertainty under realistic quantum noise. These results establish a practical pathway toward scalable, uncertainty-aware operator learning in quantum machine learning.

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07.
bioRxiv (Bioinfo) 2026-06-11

TifBERT: a self-supervised foundation model for normalization-robust bulk RNA-seq representation learning

作者:
Hosseini↗Sharma↗

Bulk RNA sequencing remains central to translational genomics, yet foundation-model development has largely focused on single-cell data. Existing transformer approaches for bulk RNA-seq often rely on expression discretization, numerical reconstruction, external gene embeddings, or restricted gene sets, limiting robustness across normalization schemes and cohorts. Here, we introduce TifBERT, a self-supervised framework for full-transcriptome bulk RNA-seq representation learning. TifBERT converts each unordered expression profile into a sample-specific gene sequence using term frequency-inverse document frequency (TF-IDF) ordering, prioritizing genes that are both highly expressed within a sample and selectively expressed across the cohort. It is then pretrained using masked gene modeling, predicting gene identities from transcriptomic context rather than reconstructing expression values. Pretrained on harmonized TCGA Pan-Cancer data spanning five RNA-seq normalization schemes, TifBERT learns contextual representations across approximately 10,000 genes without expression binning, landmark-gene restriction, or external biological embeddings. Across 33 TCGA cancer types, TifBERT achieved 90.83% accuracy, 0.996 macro AUC-ROC, and 0.903 MCC. It also captured pathway-level biology, achieving mean sample-wise and pathway-wise Pearson correlations of 0.754 and 0.762 across 1,387 PARADIGM pathway activities. Independent evaluation on GTEx healthy tissues showed preservation of tissue-level transcriptomic structure without retraining. In comparison with existing models, TifBERT achieves competitive subtype discrimination with substantially greater stability and produces markedly richer embedding geometry (effective rank 95.6 versus 6.3), without requiring expression discretization or in-distribution pretraining exposure. Together, TifBERT provides a scalable, normalization-independent foundation model for reusable bulk transcriptomic representation learning

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08.
bioRxiv (Bioinfo) 2026-06-12

Systematic functional annotation of thousands of BAHD acyltransferases in plant genomes using Protein Language Model and phylogenomic tools

作者:
Smith↗Yuan↗Melissinos↗Satani↗Grissom↗Moghe↗G. D↗

The functional annotation of plant genes lags significantly behind their genomic annotation. Closing this gap requires thorough cataloging of reported protein activities alongside predictive methods that scale beyond sequence-similarity inference. Focusing on the BAHD acyltransferase enzyme family as a model, we assembled FuncZymeDB-BAHD, a large database of 2,705 LLM-retrieved and curated enzyme-acceptor-donor activities covering 336 BAHDs from 156 plant species, a 2-to-6-fold expansion over Swiss-Prot and prior compilations. We further developed FuncPred-OG, which maps queries to orthologous groups and previously characterized enzymes in FuncZymeDB-BAHD, returning hits with high evidence provenance. FuncPred-OG enabled functional prediction of over half of BAHDs across 85 plant proteomes, of which five novel predictions were validated via in vitro assays and recent studies. For the remaining BAHDs without FuncPred-OG annotation, we developed FuncPred-AI, where logistic-regression classifiers trained on protein language model embeddings achieved high Area-Under-the-Precision-Recall-curve (AUPR) scores and correct-hit rates up to 93%. FuncPred-AI yielded >1 probable donor/acceptor annotation for 99.9% (8894/8897) of BAHDs in our pan-plant dataset. Finally, the FuncPred workflow and datasets were deployed on a web portal for broader utilization, potentially reducing experimentalist efforts for selecting candidates from days to minutes. Overall, this framework provides a generalizable template for functional annotation of entire enzyme families.

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

CASR: A Robust Cyclic Framework for Arbitrary Large-Scale Super-Resolution with Distribution Alignment and Self-Similarity Awareness

作者:
Wenhao Guo↗Zhaoran Zhao↗Peng Lu↗Sheng Li↗Qian Qiao↗DeRui Li↗

Arbitrary-Scale SR (ASISR) remains fundamentally limited by cross-scale distribution shift: once the inference scale leaves the training range, noise, blur, and artifacts accumulate sharply. We revisit this challenge from a cross-scale distribution transition perspective and propose CASR, a simple yet highly efficient cyclic SR framework that reformulates ultra-magnification as a sequence of in-distribution scale transitions. This design ensures stable inference at arbitrary scales while requiring only a single model. CASR tackles two major bottlenecks: distribution drift across iterations and patch-wise diffusion inconsistencies. The proposed SSAM module aligns structural distributions via superpixel aggregation, preventing error accumulation, while SARM module restores high-frequency textures by enforcing correlation-guided consistency and preserving self-similarity structure through correlation alignment. Despite using only a single model, our approach significantly reduces distribution drift, preserves long-range texture consistency, and achieves superior generalization even at extreme magnification.

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10.
bioRxiv (Bioinfo) 2026-06-11

Tumour evolution as ground truth for cancer whole-genome sequencing

作者:
Valeriani↗Gandolfi↗Buscaroli↗Davydzenka↗Santacatterina↗Antonello↗Sadr↗A. H↗Gazziero↗V. A↗Milite↗Rivaroli↗…

Cancer genomes are shaped by evolutionary processes that couple mutagenesis, clonal selection, chromosomal instability, spatial growth and treatment response into structured genomic patterns, yet current benchmarking strategies largely ignore this evolutionary dependency. Here, we present SCOUT, a large-scale synthetic whole-genome sequencing resource of over 200 samples, designed for systematic benchmarking of tumour genomic analysis and evolutionary inference under controlled evolutionary ground truth. Unlike conventional task-specific simulations, SCOUT models tumour evolution as a latent generative process that simultaneously shapes mutations, copy-number alterations, variant allele frequencies, mutational signatures and clonal architectures. SCOUT recapitulates key features of solid and haematological malignancies, including driver mutations, chromosomal instability, intratumour heterogeneity, spatial sampling and treatment-associated evolutionary dynamics in tumour and matched-normal longitudinal and multi-region sequencing designs. Using SCOUT, we benchmarked widely used methods for somatic variant detection, copy-number analysis, mutational signature inference and tumour evolutionary reconstruction. Across analytical tasks, performance deteriorated in low-purity, highly subclonal and structurally complex tumours, while spatial sampling bias and hypermutation generated spurious evolutionary signals that confounded tumour interpretation across multiple inference layers. Evolutionary simulations further distinguished lineage-restricted genetic bottlenecks from multi-lineage resistance dynamics associated with tumour plasticity. Tumour purity consistently exerted a stronger effect on inference accuracy than sequencing depth. Together, our results establish evolutionary ground truth as a prerequisite for reproducible benchmarking and biologically interpretable analysis of cancer whole-genome sequencing data.

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

High-Fidelity 4D Hand-Object Capture via Multi-View Spatiotemporal Tracking and Physics-Aware Gaussians

作者:
Bo Peng↗Xu Chen↗Yi Gu↗Hidenobu Matsuki↗Mingsong Dou↗Jingjing Shen↗Deying Kong↗Juyong Zhang↗Zhengyang Shen↗

The growing demand for high-fidelity 4D hand-object interaction (HOI) data in embodied AI and spatial computing is currently bottlenecked by the reliance on pre-scanned object templates and physical markers. While recent methods have demonstrated promising results in reconstructing 4D hand-object interaction from videos, they are highly sensitive to initial estimates of hand and object poses. Yet, estimating these poses from images is challenging, in particular under severe occlusion which is inherent in hand-object interaction scenarios. We propose a novel system for the robust and accurate reconstruction of hands and objects from synchronized and calibrated multi-view videos without requiring any templates or markers. Our system consists of two main components with key innovations: (1) a multi-view feed-forward transformer model that aggregates cross-view geometry and temporal cues to provide a reliable, metric-consistent initialization for both poses and dense object geometry, and (2) a hand-object physics-aware Gaussian-based optimization framework to refine the initial estimates, integrating tetrahedral constraints, collision refinement, and appearance decomposition to produce physically plausible and visually accurate reconstruction. Validated on public benchmarks and an extensive internal dataset, our pipeline achieves highly robust, artifact-free reconstruction, providing an efficient foundation for automated 4D asset generation. Our project page are available at https://zyshen021.github.io/HOSTPG/.

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12.
arXiv (CS.LG) 2026-06-11

Mechanisms of Introspective Awareness

作者:
Uzay Macar↗Li Yang↗Atticus Wang↗Peter Wallich↗Emmanuel Ameisen↗Jack Lindsey↗

arXiv:2603.21396v5 Announce Type: replace Abstract: Recent work has shown that LLMs can sometimes detect when steering vectors are injected into their residual stream and identify the injected concept – a phenomenon termed "introspective awareness." We investigate the mechanisms underlying this capability in open-weights models. First, we find that it is behaviorally robust: models detect injected steering vectors at moderate rates with 0% false positives across diverse prompts and dialogue formats. Notably, this capability emerges specifically from post-training; we show that preference optimization algorithms like DPO can elicit it, but standard supervised finetuning does not. We provide evidence that detection cannot be explained by simple linear association between certain steering vectors and directions promoting affirmative responses. We trace the detection mechanism to a two-stage circuit in which "evidence carrier" features in early post-injection layers detect perturbations monotonically along diverse directions, suppressing downstream "gate" features that implement a default negative response. This circuit is absent in base models and robust to refusal ablation. Identification of injected concepts relies on largely distinct later-layer mechanisms that only weakly overlap with those involved in detection. Finally, we show that introspective capability is substantially underelicited: ablating refusal directions improves detection by +53%, and a trained bias vector improves it by +75% on held-out concepts, both without meaningfully increasing false positives. Our results suggest that this introspective awareness of injected concepts is robust and mechanistically nontrivial, and could be substantially amplified in future models. Code: https://github.com/safety-research/introspection-mechanisms.

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13.
arXiv (CS.AI) 2026-06-17

Small Initialization Matters for Large Language Models

作者:
Liangkai Hang↗Junjie Yao↗Zhiyu Li↗Feiyu Xiong↗Hongkang Yang↗Zhi-Qin John Xu↗

arXiv:2606.17945v1 Announce Type: new Abstract: Large language models provide a tractable system for asking how intelligence itself emerges, rather than only how LLMs can be engineered. Although progress is usually attributed to scale, data and architecture, we show that parameter initialization is a gene-like determinant of training and, in particular, of model capacity. Reducing the initialization scale consistently improves pretraining, with the largest gains on reasoning-demanding tasks. We identify two widely used empirical settings that restrain the advantage of small initialization, and show how relaxing them restores favorable scaling. We further uncover a critical initialization that balances the reasoning and training. Mechanistically, small initialization drives a distinct developmental trajectory: parameters first condense into low-complexity structures and later expand into richer representations, giving concrete form to the idea that compression is intelligence. Token-level analyses show that the gains concentrate on non-trivial, context-constrained predictions rather than all tokens uniformly. These results motivate a simple $\gamma$-initialization rule: expose initialization rage as an explicit knob and use small initialization by default, an almost cost-free intervention that improves pretraining and strengthens reasoning across model scales.

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14.
arXiv (CS.LG) 2026-06-18

Enhanced Graph Neural Networks using K-Hop Gaussian Diffusion

作者:
Xuling Zhang↗Peng Wang↗Daiyan Li↗Aoran Huang↗Zeiwei Chen↗Yongkui Yang↗

arXiv:2606.18317v1 Announce Type: new Abstract: Most graph neural network (GNN) cores rely on graph convolutions, typically implemented as message passing between direct (single-hop) neighbors. In many real-world graphs, edges can be noisy or poorly defined, limiting information propagation to local neighborhoods. Existing diffusion kernels, such as Personalized PageRank (PPR) and Heat Kernel, alleviate this issue through global propagation, but still struggle with complex local structures and distant node noise. To address these limitations, we propose a K-Hop Gaussian (KHG) diffusion kernel as a preprocessing module for graph data. KHG introduces multi-hop diffusion with Gaussian weighting for remote nodes, balancing local and global information propagation before applying standard GNNs. Experiments on multiple benchmark datasets demonstrate that KHG significantly outperforms traditional message-passing GNNs, as well as PPR and Heat Kernel diffusion, particularly in noisy or structurally complex graphs.

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15.
arXiv (math.PR) 2026-06-16

The optimal sub-Gaussian normalisation for randomised monotone functions

作者:
Thomas Anton↗Rabee Tourky↗

arXiv:2312.01265v5 Announce Type: replace Abstract: Let $\mathcal{M}$ denote the class of randomised monotone functions on $\mathbb{R}$ with values in $[0,1]$, and let $U_{\mathcal{M}}\colon \mathbb{R}_+\to \mathbb{R}_+$ be the minimal function for which $$ \mathbb{P}\left\{ \sqrt{\eta_f}\, \sup_{t\in\mathbb{R}} \left| f_Z(t) - \Exf{f_Z(t)} \right| \ge \varepsilon\sqrt{U_{\mathcal{M}}(\eta_f)} \right\} \le 2\e^{-2\varepsilon^2} $$ holds for every member $f_Z$ of $\mathcal{M}$ with finite effective sample size $\eta_f$ and every positive $\varepsilon$. We prove that for every $x> 1$, $$ \left| \sqrt{U_{\mathcal{M}}(x)} - \sqrt{\log_4 x} \right| \le 2 \min\!\left\{ 1,\, \frac{2 \ln(\e + \ln x)}{\sqrt{\ln x}} \right\}\,. $$ The optimal adjustment $\sqrt{U_{\mathcal{M}}(x)}$ matches $\frac{1}{\sqrt{2\ln 2}}\sqrt{\ln x}$ for all $x>1$, with residuals bounded as above.

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16.
arXiv (CS.CL) 2026-06-19

Your Mouse and Eyes Secretly Leak Your Preference: LLM Alignment using Implicit Feedback from Users

作者:
Haw-Shiuan Chang↗Jeffrey Gomez↗Mehul Patwari↗Aryan Sajith↗Hamed Zamani↗

To align a Large Language Model (LLM), most existing methods collect explicit human feedback and train a reward model to predict the human preference based on the response text. These existing methods have two key limitations. First, the users rarely provide explicit feedback for LLM responses, which makes the high-quality preference annotation expensive to collect. Second, the methods do not leverage implicit human feedback, which has proven vital to the economic moats of Internet giants. To quantify the value of implicit feedback, we build a new dataset called IFLLM, which collects 1336 multi-turn questions from the 59 Mechanical Turk workers, their mouse trajectories, and eye gazing points to the LLMs' responses from their webcams. IFLLM shows that the users have very diverse types of gazing behavior and mouse trajectories. Our reward model based on the implicit user feedback boosts the accuracy of the text-based reward model from 55% to 64% and nearly triples the relative response quality improvements after applying the DPO to eight LLMs, demonstrating the value of implicit feedback in the wild. Our data collection website, dataset, and codes can be found at https://github.com/themehulpatwari/llm-implicit-feedback/.

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17.
PLOS Computational Biology 2026-06-05

Heuristic multi-site optimization for protein sequence design using Masked Protein Language Models

作者:
Lijuan Wang↗

by Lijuan Wang, Yuze Wang, Chen Qiu, Liwei Xiao, Xianliang Liu, Junjie Chen Protein sequence design for tailored functional properties is a fundamental task in protein engineering, with critical applications in drug discovery and therapeutic development. Efficient navigation of the combinatorial vastness of protein sequence space to identify functional variants remains a formidable challenge. Conventional approaches, which predominantly rely on template-based local search or single-residue mutagenesis, are constrained by their susceptibility to local optima and their potential risk of destabilizing native structural stability. In this study, we introduce ProtHMSO, a heuristic multi-site optimization framework leveraging masked protein language models (ProtLMs) for context-aware sequence exploration. ProtHMSO mimics natural evolutionary mechanisms by employing ProtLM-derived substitution probabilities to guide heuristic searches for synergistic mutations, thereby constraining combinatorial search spaces through evolutionary and biophysical priors. ProtHMSO is further applied to replace the exploration strategies in genetic algorithms (GAs) and Monte Carlo tree search (MCTS) for improving their convergence efficiency. Benchmark experiments demonstrate that protein sequences generated by ProtHMSO exhibit superior functional performance and closer alignment with natural sequence distribution, compared with state-of-the-art methods. These advancements highlight that ProtHMSO has strong potential and compatibility to accelerate functional protein discovery, offering a robust framework for efficient and context-aware exploration of protein sequence space.

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18.
bioRxiv (Bioinfo) 2026-06-12

CAREPath: Semantic Context-Aware Reasoning Paths with Mechanism-Augmented Embeddings for Drug Repurposing

作者:
song↗bang↗koo↗Kim↗lee↗

Biomedical knowledge graphs (BKGs) that include drugs, genes, and diseases support drug repurposing by connecting drugs to diseases through gene-mediated multi-hop paths, thereby enabling mechanism-of-action reasoning. However, deeper traversal does not necessarily improve mechanistic reasoning: long paths grow combinatorially and frequently pass through hub genes, producing irrelevant gene regulatory signals, whereas overly constrained or sparse paths may miss broader biological context. We propose CAREPath, a KG-LLM framework inspired by depth-first search (DFS)-like and breadth-first search (BFS)-like reasoning to balance mechanistic specificity, scalability, and context recovery. The DFS-like module constrains traversal to short disease-gene-drug paths, converts each path into a structured prompt, and encodes it with a biomedical language model to generate semantic path embeddings. Complementarily, the BFS-like module constructs entity-level mechanism-context embeddings from one-hop gene neighborhoods and enriches them through similarity-guided augmentation using pharmacologically related drugs and gene-signature-similar diseases. Across five biomedical KGs, CAREPath achieves the best overall AUPRC among 18 baselines, improving performance by up to 3.8%. Additional analyses show that semantic short-path encoding contributes most to performance, while mechanism-context augmentation improves robustness under sparse evidence and strengthens Gene Ontology functional agreement. Case studies and recently FDAapproved indications further demonstrate its practical relevance, positioning CAREPath as an interpretable framework for scalable and mechanism-aware drug repurposing. Source code is available at https://github.com/hamppy-song/CAREPath.

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19.
arXiv (CS.CV) 2026-06-16

Human Cognition in Machines: A Unified Perspective of World Models

作者:
Timothy Rupprecht↗Pu Zhao↗Amir Taherin↗Arash Akbari↗Arman Akbari↗Yumei He↗Tooba Imtiaz↗Sean Duffy↗Juyi Lin↗Yixiao Chen↗Rahul Chowdhury↗Enfu Nan↗…

This report of world models distinguishes prior works by the cognitive functions they innovate. Many works claim an almost human-like cognitive capability in their world models. To evaluate these claims requires a proper grounding in first principles from human and machine cognition theory. In moving towards human-like world models we present a conceptual unified framework for world models that fully incorporates all the cognitive functions (i.e., memory, perception, language, reasoning, imagining, motivation, and metacognition) and identify gaps in existing research as a guide for future states of the art. In particular, we find that motivation (especially intrinsic motivation) and metacognition remain drastically under-researched, and we propose concrete directions to address these gaps informed by active inference and global workspace theory. We also introduce epistemic world models, a new category encompassing agent frameworks for scientific discovery that operate over structured knowledge. Our taxonomy, applied to video, embodied, and epistemic world models, suggests research directions where prior taxonomies have not.

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20.
medRxiv (Medicine) 2026-06-10

Optimisation of steatotic liver disease screening algorithm for resource-poor settings using machine learning

作者:
Mettananda↗Sivasumithran↗Ranaweera↗Madhubhashini↗Ranawaka↗Pathmeswaran↗Dassanayake↗

Background The European Association for the Study of the Liver (ESAL) - Steatotic Liver Disease (SLD) screening algorithm involves two steps; initial screening with FIB-4 followed by referral for vibration-controlled transient elastography (VCTE) in patients likely to have significant fibrosis (SF). However, VCTE is not widely available in resource-limited settings. Aim To optimise the EASL SLD screening algorithm for resource-poor settings using machine learning (ML). Methods We analysed data from 964 adults aged [&ge;]35 years who underwent VCTE at a tertiary referral centre in Sri Lanka between November 2024 and 2025. Multiple ML models using different methods and variable combinations were trained on 80% of the dataset and tested on the remaining 20%. Best models were selected based on performance and externally validated using data from 430 patients who underwent VCTE before November 2024. Model performance was compared with the FIB-4 using confusion matrices. Results A Random Forest model incorporating age, AST, ALT, and platelet count separately, rather than using FIB-4, outperformed. The all-variable ML model showed the best predictive performance for SF, with accuracy of 77.2%, recall of 0.762, precision of 0.778, and AUC-ROC of 0.818. The variables used in the model, in descending order of feature importance, were AST, platelet count, BMI, ALT, age, diabetes mellitus, hypertension, dyslipidaemia, sex, family history, hypothyroidism, diabetes complication and smoking. External validation demonstrated 75.1% accuracy and an AUC of 0.779. When used as the first step of the SLD screening algorithm, the all-variable ML model identified 37 (17.1%) additional true positives and reduced false-negative diagnoses by 50% compared with FIB-4. Conclusions ML-based models were more effective than the FIB-4 score as the first-line screening tool for VCTE referral, substantially improving the identification of patients with significant fibrosis in this South Asian cohort.

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21.
arXiv (CS.CV) 2026-06-17

Impact of Hand Impairment and Occlusions on Hand Pose Estimation Accuracy in Augmented Reality Applications

作者:
Damian M. Manzone↗Mathew Szymanowski↗Olga Taran↗Shuo Cai↗Melissa Marquez-Chin↗Tammy Zeng↗Hardeep Singh↗Cesar Marquez-Chin↗Jos\'e Zariffa↗

Mixed reality applications can be designed for hand rehabilitation. Augmented reality (AR) head mounted displays (HMDs) specifically allow for ecologically valid tasks because individuals can see their real environment and interact with real objects while receiving additional cues on the HMD. While these applications rely on accurate hand pose estimation, there is a gap in investigating the influence of hand impairment or occlusion from real-object interactions on pose estimation accuracy. Further, comparisons between AR HMD predictions and state-of-the-art pose estimation methods have not been established. The current study assessed pose estimation accuracy of the HoloLens 2 HMD and state-of-the-art pose estimation algorithms (WiLoR, HaMeR, WildHands, and MediaPipe) while individuals with cervical spinal cord injury (cSCI; n = 13, Neurological Level of Injury: C3-C6; American Spinal Injury Association Impairment Scale: A-D) and 15 uninjured controls interacted with clear and opaque objects. Ground truth estimates of 3D joint positions were generated via triangulation from a multi-camera setup. Pose estimation accuracy did not differ between the cSCI and uninjured control groups suggesting that 3D joint predictions from the HoloLens 2 and pose estimation algorithms can generalize to populations with hand impairment. Further, clear objects provided a small accuracy advantage over opaque objects (0.1 mm) and predictions from both WiLoR and HaMeR were slightly more accurate than the HoloLens 2 (2 mm). Overall, these results suggest that the HoloLens 2 may be viable for hand rehabilitation applications and the dataset generated can be used to refine pose estimation methods for hand-impaired populations.

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22.
bioRxiv (Bioinfo) 2026-06-11

A systematic imputation framework for sparse, multimodal space biology datasets: application to retinal imaging and omics from the RR9 mission

作者:
Nagesh↗Sanders↗Costes↗S. V↗Avci↗Sigit↗Agarwal↗Haghighi↗Batool↗Karouia↗Chander↗A. M↗…

Space biology experiments are expensive, logistically complex, and inherently limited in sample size, resulting in datasets that are frequently incomplete and highly heterogeneous (2). Missing data is a fundamental barrier to building reliable computational models of how the human body responds to spaceflight. This work introduces a systematic framework for addressing missing data through imputation. We developed a validated four-stage framework for imputation specifically designed to preserve biological signal needed for digital twin development, while quantifying trade-offs in downstream analyses. Using retinal imaging and omics data from the NASA RR9 mission as a case study (9), we demonstrate how to diagnose why data is missing(10), select and optimize appropriate imputation strategies (5,10), and rigorously evaluate whether imputed data remains biologically meaningful. A key finding of this work is that while imputation substantially improves the performance of predictive models, it can simultaneously obscure subtle biological patterns; a critical trade-off that researchers must understand before applying these methods (11). This framework provides practical, actionable guidance for space biologists and data scientists working with sparse, multimodal datasets in space biology, and represents a foundational step toward more complete and reliable data-driven models of human physiology in extreme environments.

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23.
arXiv (CS.CL) 2026-06-12

Multi-Bitwidth Quantization for LLMs Using Additive Codebooks

作者:
Liza Babaoglu↗Shuangyi Chen↗Ashish Khisti↗

As large language models (LLMs) are increasingly deployed across heterogeneous hardware with varying resource constraints, the ability to adaptively manage the trade-off between performance and efficiency without retraining is critical. We propose Drop-by-Drop, a novel multi-bitwidth post-training quantization framework that enables inference-time precision control over LLM weights from a single trained model. Our method is theoretically grounded in information theory and successive refinement. We establish that LLM weights, which commonly follow a Gaussian distribution, can be optimally reconstructed with increasing fidelity as additional bits are incorporated, under a weighted mean squared error distortion motivated by LLM loss functions. To realize this in practice, Drop-by-Drop incorporates Matryoshka-style supervision into the loss function, exploiting the structure of additive codebooks. Drop-by-Drop produces a single model where ordered subsets of codebooks yield accurate partial reconstructions at each precision level. This approach significantly reduces storage and memory overhead by allowing a single checkpoint to serve multiple bitwidths, while maintaining competitive perplexity and accuracy across major architectures, such as Qwen, LLaMA, Gemma, and Mistral.

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24.
arXiv (CS.LG) 2026-06-19

Multimodal Concept Bottleneck Models

作者:
Tongqing Shi↗Ge Yan↗Tuomas Oikarinen↗Tsui-Wei Weng↗

arXiv:2606.19882v1 Announce Type: cross Abstract: Concept Bottleneck Models (CBMs) enhance the interpretability of deep learning networks by aligning the features extracted from images with natural concepts. However, existing CBMs are constrained in their ability to generalize beyond a fixed set of predefined classes and the risk of non-concept information leakage, where predictive signals outside the intended concepts are inadvertently exploited. In this paper, we propose Multimodal Concept Bottleneck Model (MM-CBM) to address these issues and extend CBMs into CLIP. MM-CBM utilizes dual Concept Bottleneck Layers (CBLs) to align both the image and text embeddings into interpretable features. This allows us to perform new vision tasks like zero-shot classification or image retrieval in an interpretable way. Compared to existing methods, MM-CBM achieves up to 51.26% accuracy improvement on average across four standard benchmarks. Our method maintains high accuracy, staying within ~5% of black-box performance while offering greater interpretability.

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

A Decision-Theoretic View of Test-Time Training: When, How Far, and Which Directions to Adapt

作者:
Tomoya Wakayama↗

arXiv:2606.15569v1 Announce Type: new Abstract: Test-time training (TTT) adapts a pretrained model to each prompt via parameter updates, improving accuracy under pretraining-to-test distribution shifts. Yet, its performance often suffers from instability and sensitivity to hyperparameters such as update steps and subspace. We explain this behavior through a decision-theoretic lens, treating TTT as implicit Bayesian inference in the kernel regime. Under a Gaussian process benchmark, we show that TTT reduces prediction error when updates are spectrally matched to the prompt's signal-to-noise ratio and aligned with query-relevant eigen-directions. This perspective underpins the following results: (1) we show when fixed update steps and subspaces fail under distribution shifts, motivating adaptive strategies; (2) we prove that selecting update steps via prompt evidence admits a PAC-Bayes guarantee against overfitting; and (3) we characterize the Bayes-optimal update subspace under a linear-Gaussian correction model, yielding a scoring rule for selecting Transformer blocks and heads. Our theory helps explain the empirical instability of TTT, taking a step toward principled guidance for when, how far, and which directions to adapt.

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