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

Not All Retrievals are Useful: Cross-Attention for Input-Aware RAG in Time Series Forecasting

arXiv:2603.14709v2 Announce Type: replace Abstract: Retrieval-augmented generation (RAG) enhances zero-shot time series (TS) forecasting by leveraging external knowledge bases, yet existing approaches overlook input-level relevance when fusing retrieved samples with the query. We argue that not all retrievals are equally useful, and irrelevant ones can degrade performance. To this end, we propose Cross-RAG, a zero-shot RAG-based forecasting framework that selectively attends to query-relevant retrieved samples via query–retrieval cross-attention. By modeling input-level relevance between the query and retrieved samples, Cross-RAG jointly incorporates three sources of information: 1) the query itself, 2) the retrieved samples, and 3) their relational interactions. In particular, this input-aware design enables Cross-RAG to remain stable as the number of retrieved samples $k$ grows, whereas prior methods without cross-attention require careful $k$ tuning to avoid degradation from irrelevant retrievals. Extensive experiments demonstrate that Cross-RAG consistently improves zero-shot forecasting performance across multiple TSFM backbones and various RAG methods, with additional analyses confirming its effectiveness across various retrieval scenarios. Code is available at https://github.com/seunghan96/cross-rag/.

02.
arXiv (quant-ph) 2026-06-17

Cavity-enhanced superconducting response in an underdoped cuprate

arXiv:2606.18084v1 Announce Type: cross Abstract: Superconductors carry electrical current without resistance when paired electrons condense into a coherent macroscopic quantum state. In underdoped cuprates, evidence suggests that pairing-related correlations and superconducting fluctuations can survive above the temperature at which global coherence is lost, pointing to phase fluctuations as a key limitation on superconductivity in this regime. Motivated by recent demonstrations of cavity-modified collective states in quantum materials, we investigate whether superconducting coherence can be stabilized by engineering the electromagnetic environment of the superconductor. We study an underdoped YBa$_2$Cu$_3$O$_{7-\delta}$ thin film in a tunable terahertz cavity formed with a semi-transparent gold mirror. From temperature-dependent terahertz transmission measurements, we find that the cavity enhances the superconducting response below the critical temperature, with an increase of the inferred superfluid weight. The effect becomes more pronounced at smaller cavity lengths and is accompanied by an upward shift of the superconducting onset temperature. Calculations based on a cavity-coupled model for phase-fluctuating superconductors capture these trends and support an interpretation in terms of cavity-enhanced phase stiffness. These results showcase the potential of cavity engineering for designing emergent functionalities in correlated systems.

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

Low-Cost Neuromorphic Fall Detection Using Synthetic Event Data and Hybrid SNNs

This work presents the development of hybrid models that integrate spiking neural networks (SNNs) with components of convolutional neural networks (CNNs) to learn from simulated event-based camera data (Dynamic Vision Sensor, DVS) generated from conventional smartphone videos. Aimed primarily at human fall detection, the approach leverages the energy efficiency and spatio-temporal processing capabilities of SNNs by converting video frames into event-based data. The proposed models are evaluated through simulations on multiple datasets, comparing their performance to that of traditional machine learning models. Results demonstrate significant gains in efficiency without sacrificing accuracy, underscoring the potential of combining SNNs and DVS technology for complex tasks in real-world environments.

04.
arXiv (CS.CV) 2026-06-11

Time-Conditioned and Multi-Time Survival Prediction from 2D PET/CT Projections in Lung Cancer

Accurate prediction of overall survival (OS) from positron emission tomography/computed tomography (PET/CT) can support personalized treatment and follow-up strategies in oncology. However, the impact of temporal modeling on imaging-based survival prediction remains insufficiently explored. We investigate how different temporal formulations influence survival prediction by developing two complementary approaches: Attention-guided Time-Conditioned Survival (ATCS) and Multi-Time Survival (MTS). We retrospectively analyzed pre-treatment PET/CT images from 848 patients with non-small cell lung cancer (NSCLC), including 556 for model development and 292 for held-out testing. A previously proposed Time-Conditioned Survival (TCS) model was used as a baseline. Models were trained using 5-fold cross-validation and evaluated on the test set using time-dependent area under the curve (AUC) at 6-month intervals from 0.5 to 5 years. Both ATCS and MTS outperformed the baseline TCS model, achieving mean AUCs of 0.794 and 0.793, respectively, compared to 0.767. ATCS performed better at earlier time points (0.5-3 years), whereas MTS performed better at later intervals (3.5-5 years). Combining tumor-specific and tissue-wise PET/CT features improved performance over either input alone. Finer temporal discretization improved short-term prediction, while coarser intervals provided more stable long-term estimates. These findings demonstrate that temporal modeling and input design influence PET/CT-based survival prediction. The proposed approaches enable time-specific survival estimation from pre-treatment imaging and may support improved risk stratification and clinical decision-making.

05.
arXiv (CS.AI) 2026-06-17

Model Validation of Agentic AI Systems: A POMDP-Based Framework for Belief-State, Forecast, and Policy Validation

arXiv:2606.17383v1 Announce Type: cross Abstract: Agentic artificial intelligence systems introduce a new class of model risk. Unlike traditional predictive models, autonomous agents continuously acquire information, form beliefs regarding latent states of the environment, generate forecasts, select actions, and adapt their behavior over time. Existing validation methodologies focus primarily on predictive accuracy and therefore provide limited insight into the quality of the underlying decision process. This paper proposes a model validation framework for agentic AI based on Partially Observable Markov Decision Processes (POMDPs). The framework decomposes autonomous decision making into information, beliefs, forecasts, actions, and utility, allowing each component to be validated independently. Large language models (LLMs) are formalized as approximate Bayesian filtering operators, and a model-risk taxonomy is developed encompassing state-space, filtering, forecast, policy, utility-specification, and parameter risks. The model risk validation methodology is demonstrated through a portfolio-management case study in which an agent infers latent market regimes from market and macroeconomic information, generates belief-conditioned forecasts, and constructs portfolios using a Black–Litterman framework. Empirical validation combines performance analysis, belief calibration diagnostics, coverage tests, ablation studies, and parameter-sensitivity analysis. The results indicate that latent-state inference contributes independently to decision quality and that the principal conclusions remain robust across a broad range of parameter values. The principal contribution of the paper is a practical framework for extending established model risk management concepts to autonomous AI systems and providing a rigorous foundation for their validation, governance, and monitoring.

06.
medRxiv (Medicine) 2026-06-15

Therapeutic efficacy study on shoulder impingement syndrome in swimmers: a network meta-analysis

Shoulder impingement syndrome (SIS), including subacromial impingement and rotator cuff tendinitis, is commonly caused by repetitive swimming movements and associated shoulder joint dysfunction. Despite numerous available treatment options, no consensus exists on the most effective treatment option. Therefore, this systematic review and network meta-analysis aimed to investigate treatment methods for SIS in swimmers. Using a frequentist framework and Cochrane PICOS principles, we compared SIS treatments, constructed network evidence diagrams, and assessed heterogeneity. A total of 45 studies were included in the qualitative synthesis, and 42 contributed to the network meta-analysis, comprising 1752 participants, 9 treatment categories, and outcome measures. For pain outcomes, some adjunctive interventions combined with exercise showed favorable ranking probabilities, although several estimates were accompanied by wide confidence intervals. For shoulder range-of-motion outcomes, taping, acupuncture, manual therapy, and sport-specific training showed favorable effects in selected comparisons, particularly for external and internal rotation. According to surface under the cumulative ranking curve (SUCRA) rankings, exercise combined with medium-frequency therapy ranked highly for pain reduction, whereas exercise combined with acupuncture or extracorporeal shock wave therapy ranked highly for shoulder flexion. Exercise combined with taping ranked highly for external rotation, and exercise combined with manual therapy ranked highly for internal rotation. However, the interpretation of ranking results should remain cautious because uncertainty and inconsistency were present in some comparisons. Exercise-based rehabilitation appears to remain central to the management of SIS in swimmers. Several adjunctive interventions showed favorable findings for selected outcomes, especially pain relief and shoulder rotational function. However, the available evidence was affected by heterogeneity, inconsistency, and imprecision across some treatment comparisons. More rigorously designed swimmer-specific randomized controlled trials are needed before firm treatment hierarchies can be established. Trial registration: The protocol for this systematic review is registered with PROSPERO (www.crd.york.ac.uk/PROSPERO; registration number: CRD42024498851). The first submission of PROSPERO was on January 15, 2024, and it was revised and updated on March 25, 2026.

07.
arXiv (CS.CV) 2026-06-16

Spatial Priors via Space Filling Curves for Small and Limited Data Vision Transformers

Though Vision Transformers (ViTs) have become the dominant backbone in many computer vision tasks, due to permutation equivariance, their attention mechanism lacks explicit spatial inductive biases. This become particularly important in two settings: when model capacity is small or training data is limited. Inspired by the attention masking strategies in Linear Transformers and the scanning patterns of Vision SSMs, we introduce VIOLIN, a lightweight masked attention mechanism that encodes spatial structure within attention via Space Filling Curves (SFCs) with less than 0.0015% extra parameters and negligible computational overhead. VIOLIN scans the image using multiple SFCs to construct curve-specific decay masks, which are then combined and multiplied with the attention matrix. Across a wide range of evaluations, VIOLIN consistently improves performance. In limited data regimes such as fine-tuning on VTAB-1K, it boosts accuracy across all task groups and by up to 8.7% on the tasks where spatial information is essential. It can be combined with parameter-efficient fine-tuning methods such as LoRA to further increase the performance. Beyond fine-tuning, VIOLIN improves various small scale ViT architectures (e.g., DeiT, DINO) during pretraining on ImageNet-1K. Additionally, on pixel-level CIFAR-100 training, a task that is highly dependent on location information, VIOLIN increases accuracy by up to 7.2%. Overall, VIOLIN provides a computationally efficient yet effective way to inject spatial inductive bias into ViTs, especially benefiting small models and limited data settings.

08.
arXiv (CS.CV) 2026-06-12

JSCGC: Joint Source-Channel-Generation Coding for Wireless Generative Communications

Conventional communication systems, including both separation-based coding and learning-based joint source-channel coding (JSCC), are typically designed under Shannon's rate-distortion theory. However, relying on generic distortion metrics fails to capture complex human visual perception, often resulting in blurred or unrealistic reconstructions. In this paper, we propose Joint Source-Channel-Generation Coding (JSCGC), a generative communication paradigm that replaces the conventional decoder with a generative model at the receiver. The received signal is treated as a condition that controls the sampling process into the learned conditional distribution, reformulating communication from deterministic reconstruction for distortion minimization to controlled generation for mutual information maximization under perceptual constraints. Based on this formulation, we develop a unified joint training and efficient stochastic sampling framework, and provide theoretical analysis of its effectiveness in both learning and inference stages. Extensive experiments on latent-space image transmission demonstrate that the JSCGC consistently improves feature-based, semantic-level, and distributional quality across diverse channel conditions, while exhibiting a distinct error behavior characterized by semantic inconsistency rather than distortion.

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

Improving Cross-Format Robustness in Language Models with Multi-Format Training

Large language models often remain sensitive to answer format: a question solved correctly in one form may fail in another semantically equivalent form. To study this gap, we define cross-format robustness as the extent to which a model answers the same underlying question consistently across formats. We then compare full-format training with FormatMix, which expands only a subset of training items into multiple equivalent formats using either random or targeted selection. Across GLM4 and Llama-3.1, multi-format supervision consistently improves both task performance and cross-format robustness, whereas Multiple-choice question (MCQ)-only supervision alone brings little benefit and can even reduce robustness. We further find that expanding only about 30% of the training set into multiple formats often recovers most of the gain from full-format training, and this effect appears across the model families and sizes we study. These results suggest that format diversity, rather than additional supervision alone, is the key driver of robustness. That lightweight multi-format augmentation is a practical way to make LLMs less sensitive to answer format without changing the base model.

10.
arXiv (CS.AI) 2026-06-15

Communication Policy Evolution for Proactive LLM Agents

arXiv:2606.14314v1 Announce Type: new Abstract: LLM agents have rapidly evolved into autonomous systems, yet a persistent information gap remains between users and agents: communication is costly, while users' identical preferences further limit information exchange. To investigate how agents should communicate across modalities, this paper formalizes Communication Policy, establishes textual and UI-based policies, and then evaluates communication policies across diverse environments, personas, and model combinations. Building information asymmetry for proactive agents, we set up two complementary settings, User-Agent and Planner-Executor. Experimental results reveal complementary strengths between interaction channels: text-based interaction often facilitates task performance, while structured UI improves agents' response quality and persona compliance. Motivated by that, a hybrid method combines these advantages. We further propose Communication Policy Evolution (CPE), a self-evolution framework for refining communication policies through rollout and prompt-level evolving. Without model modification, CPE achieves the best task success across multiple settings using prompt refinement alone. Our findings identify communication behavior as a critical yet underexplored design dimension for LLM agents.

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

Do We Still Need Humans in the Loop? Comparing Human and LLM Annotation in Active Learning for Hostility Detection

Instruction-tuned LLMs can annotate thousands of instances at low cost. This raises two questions for active learning (AL): can LLM labels replace human labels within the AL loop, and does AL remain necessary when entire corpora can be cheaply labeled? We investigate both on a new dataset of 277,902 German political TikTok comments (25,974 LLM-labeled, 5,000 human-annotated), comparing LLM and human annotation across seven conditions, four encoders, and 10 random seeds. Under a two-question interface that mirrors the human annotation task, LLM annotation at scale outperforms human-supervised classifiers at roughly one-tenth the cost (\$28 for GPT-5.2 Batch API vs. \$316 for Prolific). The advantage holds for both a closed-source (GPT-5.2) and an open-weight (Qwen3.5-122B-10B) LLM, is robust under soft-label evaluation, and is unlocked specifically by the two-question decomposition; a holistic single-prompt baseline only ties with human supervision. AL provides no reliable advantage over random sampling under either LLM annotator. However, error structure varies sharply: only GPT-5.2 under the two-question interface produces classifiers with near-human FP/FN balance, while other LLM variants over-flag border-control and economic competition discourse. We release the dataset and code.

12.
arXiv (quant-ph) 2026-06-16

Readout-Induced Leakage in Superconducting Circuits with Nonlinear Couplings

arXiv:2606.16055v1 Announce Type: new Abstract: In superconducting circuits, drive-induced unwanted transitions limit the readout power, thereby constraining readout speed and fidelity. When such transitions excite the qubit into leakage states, they produce correlated errors that are particularly harmful for quantum error correction. Native nonlinear qubit-readout resonator coupling is a promising alternative to conventional linear hybridization because it provides intrinsic Purcell protection and stricter selection rules for multiphoton processes. In realistic devices, however, we show that such a coupling alone neither eliminates nor necessarily suppresses drive-induced transitions. Instead, if not appropriately engineered, these couplings often worsen the situation by introducing additional parasitic processes. Moreover, the rates of these unwanted transitions remain sensitive to the choice of readout frequency, regardless of the coupling mechanism. We demonstrate that readout-induced leakage can thus vary by orders of magnitude even when readout frequencies differ by less than ~7%. Our results establish that the benefits of native nonlinear couplings are realized only through informed device design, including the spectral placement of relevant auxiliary modes and elimination of parasitic ones.

13.
arXiv (CS.CV) 2026-06-19

SketchKeyAnime: Reference-anchored Sparse Key-Sketch Animation Synthesis

Traditional animation production relies heavily on manual drawing and iterative refinement, particularly for key-pose design, in-betweening, and character coloring. While existing animation and video generation methods have made notable progress, they typically depend on RGB boundary frames, dense frame-wise conditions, or complete sketch sequences, limiting their applicability under low-cost input conditions. We present SketchKeyAnime, a video diffusion framework for generating structurally controllable, appearance-consistent, and temporally coherent animations from sparse key-sketch inputs. Given a single reference RGB image and a few temporally indexed key sketches, SketchKeyAnime introduces a dual-branch conditioning mechanism to encode local geometric constraints alongside semantic-temporal context. It leverages Sketch Cross Attention to fuse reference image and sketch conditions with learnable gating, and incorporates an Adaptive Weighted Loss to strengthen supervision on key-sketch frames and line-art regions. Experimental results on the Aesthetic subset of Sakuga-42M show that our approach consistently outperforms representative animation interpolation and sketch-guided generation baselines. Compared to the best-performing baseline, SketchKeyAnime reduces EDMD by 31.9\% and FVD by 9.5\%, demonstrating superior sketch fidelity and temporal coherence, while achieving the best overall performance across most quantitative metrics. These results validate the proposed framework and highlight its potential for low-cost, highly controllable animation creation.

14.
arXiv (CS.CL) 2026-06-16

Uncertainty Is Not a Safety Net for Clinical VQA, but Can It Anticipate Model Failure?

Safe deployment of clinical vision-language models (VLMs) requires reliable uncertainty estimation (UE): a signal indicating when predictions should be trusted or escalated to a clinician. We test whether current UE methods actually deliver this signal. Benchmarking 8 methods across 12 VLMs on clinical visual question-answering (VQA), we find that UE quality is not an intrinsic property of the UE method: it tracks model accuracy, degrading precisely where the model performance is weakest, and therefore where reliability is most needed. When we stress-test models by hiding the correct option among the multiple-choice answers (NOTA perturbations), accuracy collapses while uncertainty barely changes, leaving models systematically miscalibrated. Yet, we find that uncertainty on the unperturbed input reliably anticipates which predictions will collapse under NOTA, indicating that UE in current VLMs carries diagnostic information about model fragility. Our results position UE as a diagnostic tool for identifying fragile predictions and motivate perturbation-based evaluation as a path toward safe clinical deployment.

15.
arXiv (CS.AI) 2026-06-17

CogGen: Cognitive-Load-Inspired Fully Unsupervised Deep Generative Modeling for Compressively Sampled MRI Reconstruction

arXiv:2603.04438v3 Announce Type: replace-cross Abstract: Fully unsupervised deep generative modeling (FU-DGM) offers significant potential for compressively sampled magnetic resonance imaging (CS-MRI) reconstruction. Representative FU-DGM formulations, such as deep image prior (DIP) and implicit neural representation (INR), employ architectural bias to induce a low-dimensional manifold in the image space that aligns with the forward observation. However, as the underlying inverse system is highly ill-posed, prolonged iterative fitting in FU-DGM typically leads to poor efficiency and noise amplification. In this paper, guided by the cognitive principle of easy-to-hard learning, we propose CogGen, an FU-DGM framework that reformulates CS-MRI reconstruction as a staged inversion problem. Specifically, CogGen implements an self-paced curriculum learning (SPCL)-driven progressive scheduling strategy through an MRI-aware dual-threshold weighting criterion, which adaptively regulates k-space measurement participation. The data-consistency residual thresholding evaluates the fitting reliability of the current generator, while the k-space radius thresholding controls stage-wise measurement exposure, thereby avoiding uniform fitting throughout optimization. Theoretically, our analysis shows that, when early stages favor easy-to-fit measurements, CogGen yields a reduced local sufficient-iteration bound and a smaller cumulative noise-amplification bound, explaining the improved convergence behavior and reconstruction fidelity of CogGen within a finite iteration budget. Numerical experiments demonstrate that both CogGen instantiations, CogGen-DIP and CogGen-INR, achieve superior performance over prevailing CS-MRI reconstruction techniques, including unsupervised and supervised pipelines.

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

Neuron Level Analysis of Large Language Model in Legal Domain Reasoning

We presented a neuron-level analysis of legal-domain reasoning in LLMs, comparing it with other applied domain tasks across seven open-weight models. Using neuron attribution scores to rank and suppress influential neurons, we confirmed that suppressing the identified neurons collapses accuracy on the target task, whereas suppressing the same number of random neurons does not. We further found a small subset of neurons influential across all seven tasks; once these are removed, suppressing the remaining neurons degrades only the task they were identified from, revealing genuinely task-specific neurons in every model studied. Within the legal domain, the three benchmarks exhibit relatively high neuron overlap and tend to be affected jointly, suggesting of legal components neurons that span jurisdictions. The distribution of identified neurons in our experiments suggests that the hypothesis that influential neurons are concentrated in middle MLP layers may depend on the input format and content, rather than being a universal phenomenon.

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

Let LLMs Judge Each Other: Multi-Agent Peer-Reviewed Reasoning for Medical Question Answering

Objective: To enhance the accuracy, interpretability, and robustness of large language models (LLMs) in medical question answering (MedQA). Method: We designed a multi-agent peer-reviewed reasoning method in which multiple LLM agents independently generate chain-of-thought reasoning with candidate answers, then act as peer reviewers to evaluate each other's reasoning for factual correctness and logical soundness. The highest-rated reasoning chain is selected to produce the final answer. Experiments were conducted with five state-of-the-art LLMs (Llama-3.1-8B, Qwen2.5-7B, Phi-4, DeepSeek-LLM-7B, GPT-oss-20B) on three benchmark datasets: HeadQA, MedQA-USMLE, and PubMedQA. Performance was compared against single-model chain-of-thought reasoning and chain-of-thought-based majority voting. Results: Peer-reviewed reasoning consistently outperformed both baselines. The best model combination achieved an average accuracy of 0.820 across datasets, exceeding the strongest single model (0.777) and majority voting ensembles (up to 0.789). The method also scaled effectively with more participating models, while peer assessments reliably distinguished high- from low-quality reasoning chains. Conclusion: The proposed multi-agent peer-reviewed reasoning method enables LLMs to act as both solvers and evaluators, yielding superior performance in MedQA. By emphasizing reasoning quality rather than answer agreement alone, this approach improves accuracy, interpretability, and robustness, offering a promising direction for trustworthy biomedical AI systems.

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

More Context, Larger Models, or Moral Knowledge? A Systematic Study of Schwartz Value Detection in Political Texts

Detecting Schwartz values in political text is difficult because implicit cues often depend on surrounding arguments and fine-grained distinctions between neighboring values. We study when context and explicit moral knowledge help sentence-level value detection. Using the ValuesML/Touché ValueEval format, we compare sentence, window, and full-document inputs; no-RAG and retrieval-augmented settings with a curated moral knowledge base; supervised DeBERTa-v3-base/large encoders; and zero-shot LLMs from 12B to 123B parameters. The results show that more context is not uniformly better: full-document context improves supervised DeBERTa encoders by 3.8-4.8 macro-F1 points over sentence-only input, but does not consistently help zero-shot LLMs. Retrieved moral knowledge is more consistently useful in matched comparisons, improving each tested model family and context condition under early fusion. However, scaling from DeBERTa-v3-base to large and from 12B to larger LLMs does not guarantee gains, and simple early fusion outperforms the tested late-fusion and cross-attention RAG variants for encoders. Per-value analyses show that context and retrieval help most for socially situated or conceptually confusable values. These findings suggest that value-sensitive NLP should evaluate context, knowledge, and model family jointly rather than treating longer inputs or larger models as universal improvements.

20.
arXiv (CS.CL) 2026-06-11

Fast Speech Foundation Model Distillation Using Interleaved Stacking

Distilling a large speech foundation model (SFM) into an efficient student model has been successfully applied to low-resource environments. Although distillation reduces inference latency, it requires an additional student model training. However, the training efficiency of SFM distillation remains underexplored. In this work, we explore training acceleration of SFM distillation to speed up model deployment. We examine the potential of stacking, in which the model depth is progressively increased through training until the target model depth is reached. While existing stacking methods improve training speed, they suffer from performance degradation. To handle this limitation, we propose interleaved stacking, a novel stacking method that consistently preserves layer position throughout the stacking process. This property is particularly critical in SFMs, in which each layer encodes distinct layer-specific knowledge. We validate the effectiveness of the proposed method on SUPERB.

21.
PLOS Computational Biology 2026-06-11

A zero-parameter first-principles gate framework for full-length TP53 missense variant interpretation

by Masamichi Iizumi Missense variant interpretation often achieves useful predictive performance but remains mechanistically opaque, particularly in proteins that combine structured domains with intrinsically disordered regions (IDRs). We developed Gate & Channel, a zero-parameter, first-principles framework for full-length TP53 missense variant analysis in which each prediction is generated by explicit IF-THEN gates derived from physicochemistry, geometry, structural constraints, and polymer physics rather than fitted weights. Variants are evaluated across independent channels representing distinct physical failure modes; a variant is predicted disruptive if any gate closes. A second hierarchical layer (“Geta”) encodes physically grounded post-closure exceptions, allowing sensitivity and specificity to be improved on disjoint variant populations. The v18 framework consists of 12 channels and 2 Getas spanning structured domains and IDRs, capturing DNA-contact disruption, Zn coordination, burial-dependent packing, secondary-structure compatibility, post-translational modification chemistry, short linear motif disruption (including a multi-partner coupled-folding face), proline-directed kinase recognition, and IDR-specific proline and glycine backbone constraints. Across 1,369 TP53 missense variants, the framework achieved 84.5% sensitivity and 89.1% positive predictive value, with 90.9% sensitivity preserved in the DNA-binding core and all 9/9 hotspot mutations captured. A post hoc audit of discordant IDR calls indicated that many apparent false positives had plausible molecular rationales, consistent with a distinction between molecular mechanism disruption and clinical penetrance. Applied to KRAS, TDP-43, and BRCA1, the same channels capture the dominant pathogenic mechanisms in each protein as a proof of principle, while residual missed variants name specific gates yet to be written. The framework is distributed as the open-source Python package pathogenicity-gates (v0.5.1, MIT). These results show that a substantial fraction of full-length TP53 missense variation can be resolved through explicit, auditable physical gates that carry meaning beyond TP53, with each remaining failure naming the next rule to be written.

22.
medRxiv (Medicine) 2026-06-17

Multi-strain Probiotics Alter Gut Microbiota and Estrobolome Pathways in Primary Dysmenorrhea

Background: Exact cause of primary dysmenorrhoea is unknown but recent evidence uncovers a potential link between gut dysbiosis and benign gynaecological disorder via disruption of estrobolome. Methods: A randomized controlled trial to investigate the effects of multi-strain oral probiotics on primary dysmenorrhoea has been conducted. This is a secondary analysis comparing the stool microbiome in women with primary dysmenorrhoea and those without (control), and the effects of treatment with probiotics versus placebo. Results: Although microbial richness and evenness were comparable between groups (alpha diversity, p > 0.05), gut microbial community composition differed significantly (Bray Curtis PERMANOVA, p = 0.015), characterised by reduced Bifidobacterium adolescentis and Blautia and enrichment of Faecalibacterium in dysmenorrhoea, alongside condition-specific core taxa. Post-intervention analysis revealed significant shifts in microbial community structure between pre- and post-treatment groups (PERMANOVA, F = 2.11, p = 0.005), with probiotic supplementation inducing more consistent and directed microbiome changes than placebo, without altering alpha diversity (p > 0.05). Functional prediction showed no significant difference in overall beta glucuronidase pathway abundance (p > 0.05); however, dysmenorrhoea was associated with higher abundance of beta glucuronidase producing taxa (MaAsLin2, q < 0.05) that were differentially modulated by probiotic treatment. Conclusion: This discovery provides evidence on the microbial disruption in primary dysmenorrhoea as well as the benefit of probiotics to modulate the intestinal microbiota to improve the condition.

23.
arXiv (CS.LG) 2026-06-18

Fair Online Resource Allocation

arXiv:2606.18679v1 Announce Type: cross Abstract: We study the problem of fair online resource allocation, motivated by applications such as refugee resettlement and airline scheduling, where agents arrive sequentially and must be assigned to facilities with limited capacities. We introduce a model that maximizes the overall welfare subject to resource constraints and a Lipschitz fairness requirement, which ensures that similar agents arriving in the same batch receive similar expected outcomes. We first analyze the offline problem, proving that the value of the optimal fair allocation is at least an $\Omega(1/\gamma)$ fraction of the optimal unfair allocation, where $\gamma$ is the fairness coefficient, thereby bounding the price of fairness. For the online setting, we propose an algorithm based on dual mirror descent that enforces fairness constraints within batches while estimating optimal dual variables. We prove that this algorithm achieves sublinear regret relative to the optimal offline fluid benchmark. Finally, we validate our theoretical results using real-world data from the Refugee Economies Programme, demonstrating the algorithm's performance and examining the trade-offs between welfare maximization and fairness enforcement.

24.
medRxiv (Medicine) 2026-06-16

Exercise Training Improves Skeletal Muscle Insulin Sensitivity and Reprograms the Adipose Transcriptome in Heavier Monozygotic Twins

Exercise training improves skeletal muscle insulin sensitivity, yet its effects on white adipose tissue remain incompletely understood. We investigated how adiposity and exercise training influence insulin-stimulated glucose uptake in skeletal muscle and abdominal subcutaneous adipose tissue (ASAT), alongside adaptations in gene expression and DNA-methylation. Ten monozygotic twin pairs discordant for BMI underwent [18F]FDG-PET/CT imaging of skeletal muscle (vastus lateralis, VL) and ASAT during a euglycemic-hyperinsulinaemic clamp before and after six months of exercise training. VL and ASAT biopsies were analyzed using mRNA-sequencing and reduced representation bisulfite sequencing. Exercise training improved whole-body and VL insulin sensitivity in leaner and heavier co-twins (p

25.
arXiv (CS.LG) 2026-06-18

Measurement noise limits the advantage of nonlinear models over linear models in biomedical prediction

arXiv:2606.18420v1 Announce Type: new Abstract: On biomedical tabular data, flexible models such as deep networks, gradient-boosted trees, and kernel methods are repeatedly matched or beaten by linear and logistic regression given the same features. The usual reaction is to treat this as a model-side shortfall, to be fixed with more data, a better architecture, or tuning, on the assumption that the nonlinear structure is there and the model has failed to capture it. We argue that these fixes cannot help when the binding limit is the measurement rather than the model, as it frequently is in biomedicine. Additive noise blurs the population-optimal predictor, and because blurring removes a function's fine, rapidly varying detail before its broad shape, it erases nonlinear structure faster than linear structure. A degree-$k$ interaction is attenuated by the $k$-th power of feature reliability, while the linear part is attenuated only once. At the reliabilities typical of biomedical measurement, the nonlinear advantage can vanish even when the underlying biology is strongly nonlinear, and what the noise removes cannot be recovered by a larger cohort or a more flexible model, only by better measurement. The nonlinearity is hidden, not absent, and a tie between linear and flexible models is not by itself a verdict on the biology. These pieces are classical, drawn from measurement-error statistics, psychometrics, and Gaussian analysis, and we assemble them into an exact excess-risk identity. Measurement reliability is one of three conditions, alongside sample size and feature representation, that must align for a flexible model to help, and together they leave only a narrow window that most biomedical tasks fall outside. Across 140 UK Biobank tasks, the gap between flexible and linear models, where it exists, carries the predicted noise signature, and the three conditions can be separated by intervention but not by a benchmark alone.