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

Minimal Filling Architectures of Polynomial Neural Networks: Counterexamples, Frontier Search, and Defects

arXiv:2605.09609v2 Announce Type: replace Abstract: We provide counterexamples to the unimodal minimal filling architecture conjecture for polynomial neural networks (PNNs) with power activation functions. Fixing the input and output widths, the conjecture states that any minimal filling architecture has unimodal widths for the hidden layers. We found counterexamples via a frontier search, recursive dimension bounds on neurovarieties, and symbolic computation. Notably, several subarchitectures of our main example exhibit large defect, in contrast with the predominantly small-defect behavior observed in prior literature.

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

Before the Pull Request: Mining Multi-Agent Coordination

arXiv:2606.19616v1 Announce Type: cross Abstract: Autonomous coding agents now open millions of pull requests, yet large-scale studies find their PRs are produced faster but accepted less often - a coordination and trust gap that pull-request-level telemetry cannot explain. We argue the missing signal lives before the PR, in how concurrent agents claim, divide, and collide over shared work. We study this process through grite, our open-source coordination substrate that needs no central server and stores its records inside git itself, so its append-only, signed event log captures the coordination process directly. We show that (i) this shared substrate reduces duplicate and conflicting work at bounded overhead - the share of work that merely re-does a teammate's task falls from 78% to 0% while useful throughput more than triples; (ii) every agent's copy of the log converges to the same state with no write silently dropped, where a file-based tracker loses concurrent writes; and (iii) the log is a mineable artefact from which concrete failure modes - conflicting edits, lock starvation, redundant rediscovery, race-to-close - are automatically recoverable with provenance, several invisible in pull-request history. We release the dataset, harness, and mining toolkit.

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

CausalT5k: Diagnosing Refusal and Failure Modes in Trustworthy Causal Reasoning Across Causal Rungs

arXiv:2602.08939v2 Announce Type: replace Abstract: Large language models increasingly produce fluent causal explanations, yet they often fail in ways aggregate accuracy cannot diagnose: confusing association with intervention, abandoning correct judgments under pressure, over-refusing valid claims, or answering when evidence is underdetermined. We introduce CTK, a diagnostic benchmark of 5,147 cases and growing, across 10 domains and all three levels of Pearl's Ladder of Causation. Unlike benchmarks that only score correctness, CTK reveals why a model failed by annotating causal rung, trap type, pressure sensitivity, refusal quality, and Utility-Safety tradeoffs. Its Sheep/Wolf taxonomy separates valid causal designs from inferential traps; paired neutral/pressure variants measure sycophantic drift through Bad Flip Rate; and Wise Refusal fields test whether a model identifies the missing information needed before endorsing a claim. CTK exposes failure modes hidden by aggregate accuracy: the Skepticism Trap, Rung Collapse under scaling, pressure-induced drift, Detection-Correction gaps, and counterfactual error modes. Rather than prescribing a correction method, it provides the diagnostic substrate for studying causal-reasoning failure profiles.

04.
arXiv (CS.CL) 2026-06-12

Order Is Not Control

AI alignment, interpretability, steering, and neural perturbation studies identify order-inducing objects. We argue that order is not control. Control requires a receiver-gated response law: a denominator-indexed operator mapping material state, action/drive, bath, and receiver state to response displacement, sinks, effort, and basin projection. We identify it across biological, LLM, adapter, and stochastic-operator panels. The laws are local: an intervention can be admitted, saturated, sign-changing, leaky, or overdriven depending on medium, bath, receiver state, action port, and comparator. Control is assigned when finite effort moves a target or outcome-readout class under the same denominator while damage, null/evasive, invalid format, overdrive, and unnecessary effort stay bounded. Mouse ALM, C. elegans, and zebrafish panels provide physical response-operator evidence while excluding coordinate identity and controller conclusions. LLM panels show generated-output response laws: across four material conditions, response vectors are predictable at 72.8-73.7% component-sign accuracy, rising to 84.3-84.8% on nonzero components; held-out observers predict system-effect and target/oracle families at 93.6% and 91.7% accuracy. Constitution-conditioned adapters reshape susceptibility as prepared media, and stochastic-operator panels separate measured opportunity from deployable action policies. This gives a driven-dissipative response-system account at the mesoscopic control level: drives act through prepared media, baths, and receivers, producing admitted movement, impedance, sinks, or overdrive. The evidence supports local admitted control and measurable stochastic response operators, while leaving deployable pre-generation control, hidden/logit causal sufficiency, biological-to-LLM coordinate identity, and literal thermodynamic quantities outside scope.

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

Streaming Interventions: Can Video Large Language Models Correct Mistakes as They Occur?

arXiv:2606.09547v2 Announce Type: replace-cross Abstract: Learning everyday skills, like cooking a dish, relies increasingly on instructional media such as online videos. This opens the door to the use of video (and multimodal) large language models (LLMs) as task guidance assistants. A crucial capability for the real-world success of a prospective task guidance assistant is it's ability to intervene proactively as soon as a mistake is apparent in order to guide the user. To evaluate this crucial capability, we introduce Ego-MC-Bench (Mistake Corrections), a benchmark for evaluating reactive, step-by-step task guidance in realistic cooking scenarios. Extensive experiments show that Ego-MC-Bench is highly challenging for state-of-the-art video LLMs. We argue that a key reason is the limited availability of training data for fine-tuning models on this task. Although there exists a wide range of cooking video datasets, existing datasets lack examples of mistakes along with appropriately timed interventions. To help address this data limitation, we also introduce Ego-CoMist, a counterfactual synthetic dataset created by transforming non -interactive cooking videos into supervised training examples showing proactive interventions. We show that fine-tuning on Ego-CoMist yields performance gains especially for smaller and more efficient video LLMs that are well suited for delivering assistance on edge devices.

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

Data-Forcing Distillation: Restoring Diversity and Fidelity in Few-Step Video Generation

Recent progress has shown promise in distilling multi-step video diffusion models into efficient few-step students. Among them, Distribution Matching Distillation (DMD) and its successor DMD2 achieved strong generation quality and fast convergence. However, due to the nature of the reverse Kullback–Leibler (KL) objective, these methods exhibit two persistent failure modes: a substantial drop in sample diversity, and visibly over-saturated outputs that deviate from real-video appearance. In this work, we propose Data-Forcing Distillation (DFD), a simple post-training framework that restores diversity and fidelity in DMD with only a single-line of code change. At its core is the teacher score discrepancy to guide the student toward the real-data distribution, pulling it to missing modes (mitigating mode collapse) and away from problematic modes absent in real data (avoiding over-saturation). We provide an in-depth theoretical analysis of our framework and validate our approach on text-to-video, image-to-video, and autoregressive video generation. With only 100–300 steps of finetuning, DFD effectively restores diversity and fidelity on both Wan2.1-1.3B and Cosmos-Predict2.5-2B model, resolving the over-saturation artifacts with significantly better video dynamics and appearance, and even outperforms the teacher model.

07.
arXiv (CS.CV) 2026-06-12

Cascade Classification of Dermoscopic Images of Skin Neoplasms with Controllable Sensitivity and External Clinical Validation

Purpose. To compare deep learning architectures and classification schemes for dermoscopic images of skin neoplasms and assess their generalization on transfer from open international datasets to independent clinical datasets of Russian practice. Methods. Four architectures (ViT-B/16, Swin-S, ConvNeXt-S, EfficientNetV2-S) were compared in three schemes: binary (malignant/benign), single-stage four-class (benign, MEL, SCC, BCC), and a two-stage cascade (binary triage, then three-class differentiation MEL/SCC/BCC). All models used ImageNet-pretrained weights and a single augmentation protocol on aggregated open ISIC Archive data, and were evaluated on an internal held-out sample and two clinical datasets (Melanoscope AI mobile system; Sechenov University). Results. Internally the binary stage attains ROC-AUC 0.952-0.966; on Sechenov University it drops to 0.797-0.893, sensitivity to 0.53-0.67, and ECE rises from 0.02 to 0.27-0.39 with underestimation of malignancy, quantifying a generalization gap in ranking and calibration. Paired tests confirm one inter-architecture result on clinical data: the deficit of ViT-B/16 at the binary stage (p

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

A Framework for Evaluating Agentic Skills at Scale

Agent skills – structured, reusable knowledge artifacts that augment LLM agent capabilities – have been rapidly adopted in industry, yet their cross-domain impact and use across commercial and open-source models remain under-studied, and no reusable methodology exists for evaluating an individual skill. In this work, we present an evaluation framework that lets a skill author construct realistic tasks to rigorously assess the aspects of a skill that matter most to them, and that estimates skill utility by solving those tasks. Further, we apply our evaluation approach at scale to 500 real-world skills, generating 1,000 tasks derived from the skills' content, along with instruction-following and goal-completion scoring rubrics. Using these metrics, we evaluate how 19 agent-model configurations, both proprietary and open-source, perform on the tasks. Our results show that models vary widely in how closely they adhere to the instructions encoded in skills, leading to substantial differences in their performance gains. Furthermore, we show that access to a skill significantly changes model behavior compared to the no-skill setup, providing an essential mechanism for encoding opinionated workflows into LLM agents. We release our evaluation dataset to support future work on agent skills.

09.
medRxiv (Medicine) 2026-06-17

Investigating shared genetic overlap of immune-mediated inflammatory diseases and cardiometabolic diseases

Abstract Background: Immune-mediated inflammatory diseases (IMIDs) are associated with increased risk of cardiometabolic diseases. Investigating genetic overlap among these conditions can provide insights into their clinical management. Methods: Genetic correlation was assessed using linkage disequilibrium score regression (LDSC). Then, a meta-analysis was conducted using Association Analysis Based on SubSETs (ASSET) to pinpoint independent single nucleotide polymorphisms (SNPs) shared across the diseases. Each independent SNP was then used to define a genomic window (+/-500KB) for colocalisation analysis and Local Analysis of [co]Variant Association (LAVA) to offer multiple layers of regional pleiotropic evidence. Over-representation analysis was then run to identify enriched biological pathways, which then were used for drug target analysis. Results: The LDSC analysis showed a significant global genetic correlation for rheumatoid arthritis (RA) and cardiometabolic diseases including hypertension, coronary artery disease (CAD), heart failure (HF), stroke, atrial fibrillation (AF), and type two diabetes mellitus (T2DM) ranging from rg = 0.09 to 0.24. ASSET meta-analysis identified 164 independent SNPs shared across RA and the cardiometabolic diseases with P < 5 x 10- in the overall one-sided meta-analysis P-value, FDR < 0.05 in both individual GWASs, and TRUE phenotype matrix. Colocalisation analysis revealed multiple loci with strong evidence (Posterior probabilities [&ge;] 80) of single causal SNPs between the trait pairs. LAVA analysis was then used as an additional layer of confirmation for the findings generated by ASSET and colocalisation and thus several loci were highlighted. Over-representation analysis showed significant enriched immune-related pathways across RA-hypertension, RA-CAD, RA-AF, and RA-T2DM trait pairs. Drug target analysis highlighted several drugs which could be further tested for their effectiveness in RA and its common comorbidities. Conclusion: The findings revealed a shared genetic architecture and key immune-related biological pathways underlying RA and its associated cardiometabolic comorbidities. The identified genes and drugs provide opportunities for further therapeutic assessment which could improve clinical management strategies.

10.
arXiv (CS.AI) 2026-06-12

Hellinger Multimodal Variational Autoencoders

arXiv:2601.06572v4 Announce Type: replace-cross Abstract: Multimodal variational autoencoders (VAEs) are widely used for weakly supervised generative learning with multiple modalities. Predominant methods aggregate unimodal inference distributions using either a product of experts (PoE), a mixture of experts (MoE), or their combinations to approximate the joint posterior. In this work, we revisit multimodal inference through the lens of probabilistic opinion pooling, an optimization-based approach. We start from Hölder pooling with $\alpha=0.5$, which corresponds to the unique symmetric member of the $\alpha-divergence$ family, and derive a moment-matching approximation, termed Hellinger. We then leverage such an approximation to propose HELVAE, a multimodal VAE that avoids sub-sampling, yielding an efficient yet effective model that: (i) learns more expressive latent representations as additional modalities are observed; and (ii) empirically achieves better trade-offs between generative coherence and quality, outperforming state-of-the-art multimodal VAE models.

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

MemSlides: A Hierarchical Memory Driven Agent Framework for Personalized Slide Generation with Multi-turn Local Revision

Personalized presentation generation requires more than conditioning on a current prompt or template: agents must preserve stable user preferences across tasks, retain newly introduced preferences and constraints during multi-turn revision, and carry out local edits reliably. We propose MemSlides, a hierarchical memory framework for personalized presentation agents that separates long-term memory from working memory and further divides long-term memory into user profile memory and tool memory. User profile memory stores intent-conditioned profiles for round-0 personalization, working memory carries active preferences and session constraints across revision rounds, and tool memory stores reusable execution experience for reliable localized editing. MemSlides pairs this memory design with scoped slide-local revision, so targeted updates act on the smallest affected region instead of repeatedly regenerating the full deck. In controlled experiments, user profile memory improves persona-alignment judgments on a multi-persona, multi-intent profile bank, tool-memory injection improves closed-loop modify behavior in diagnostic matched-pair settings, and qualitative cases illustrate working memory's ability to carryover preferences. Taken together, these results suggest that effective personalization in presentation authoring depends on separating persistent user profiles, session-level working memory, and reusable execution experience across generation and localized revision.

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

Quantum enhancement and Doppler suppression of Kasevich-Chu atom interferometer with motional squeezing states

arXiv:2606.16632v1 Announce Type: new Abstract: Hybridization of internal and external atomic degrees of freedom in a Kasevich-Chu interferometer enables the possibility to enhance the sensitivity significantly even under quantum-standard limit. By introducing motional squeezing state as an input, we systematically derive the computational framework of quantum and classical Fisher information of two measurement protocols for arbitrary strength of Doppler effects. Through maximizing the corresponding classical Fisher information, we obtain the optimal control parameters and the corresponding quantum Fisher information. For population measurement, the largest sensitivity can be as large as four times than the semi-classical limit through enlarging the atom coherence length. For joint measurement of population and position, the competition between quantum enhancement and Doppler suppression induces two three behaviors, in one regime, the quantum enhancement dominates even in presence of strong Doppler broadening effects where the sensitivity is significantly enhanced; while in another regime, an optimal squeezing parameter is observed where the classical Fisher information reaches the maximum. Our results clearly demonstrate the robustness of external quantum enhancement against Doppler suppression. Our proposal can be readily applied to gravimeter of mobile platform where decoherence from noise will damage the many-body entanglement of internal spin squeezing.

13.
arXiv (CS.CV) 2026-06-16

Explainable Flood Segmentation on Sentinel-1 SAR Imagery: A Comparative Study of CNN and Transformer Architectures

Rapid and accurate flood prediction is essential for disaster response and mitigation planning. Synthetic Aperture Radar (SAR) sensors in satellites are well-suited for this purpose because they operate independently of weather and daylight conditions. Although SAR-based data enable all-weather flood monitoring, distinguishing flooded land from permanent water remains a significant challenge, particularly when flooding is defined strictly as inundated land. This study provides a comprehensive comparison of convolutional neural network (CNN) and vision transformer architectures for multi-class flood segmentation using Sentinel-1 SAR imagery, specifically trained to separate flooded land from permanent water bodies and land. Three state-of-the-art (SOTA)CNN-based models, U-Net, U-Net++, and DeepLabV3 with ResNet-34 backbone, and three SegFormer variants (b0,b1,b2) were evaluated in two benchmark datasets, the ETCI NASA dataset and SenFloods11, using scene-based data splits to ensure a realistic assessment of spatial generalization. The results demonstrate that SegFormer-b2 significantly outperforms the U-Net baseline on the ETCI dataset (higher flood IoU across all 7 test scenes in the Wilcoxon signed-rank test), while after fine-tuning on Sen1Floods11, the advantage narrows to within the range of scene variability and is concentrated in spatially fragmented flood events. The study includes both qualitative and quantitative explainability techniques to visually comprehend model decisions and systematically assess prediction reliability. Qualitative analysis reveals that SegFormer-b2 produces more spatially coherent Grad-CAM activations focused on flood-relevant features, while U-Net generates more informative uncertainty estimates along flood boundaries.

14.
arXiv (CS.LG) 2026-06-15

Multidimensional Bayesian Active Machine Learning of Working Memory Task Performance

arXiv:2510.00375v2 Announce Type: replace Abstract: While adaptive experimental design has outgrown one-dimensional, staircase-based adaptations, most cognitive experiments still control a single factor and summarize performance with a scalar. We show a validation of a Bayesian, two-axis, active-classification approach, carried out in an immersive virtual testing environment for a 5-by-5 working-memory reconstruction task. Two variables are controlled: spatial load L (number of occupied tiles) and feature-binding load K (number of distinct colors) of items. Stimulus acquisition is guided by posterior uncertainty of a nonparametric Gaussian Process (GP) probabilistic classifier, which outputs a surface over (L, K) rather than a single threshold or max span value. In a young adult population, we compare GP-driven Adaptive Mode (AM) with a traditional adaptive staircase Classic Mode (CM), which varies L only at K = 3. Parity between the methods is achieved for this cohort, with an intraclass coefficient of 0.755 at K = 3. Additionally, AM reveals individual differences in interactions between spatial load and feature binding. AM estimates converge more quickly than other sampling strategies, demonstrating that only about 30 samples are required for accurate fitting of the full model.

15.
Science (Express) 2026-04-16

Protein-templated synthesis of dinucleotide repeat DNA by an antiphage reverse transcriptase | Science

作者: 未知作者

Defense-associated reverse transcriptases (DRTs) are widespread bacterial anti-phage systems that use unconventional mechanisms of polynucleotide synthesis. We show that DRT3, which comprises two distinct RTs (Drt3a and Drt3b) and a noncoding RNA (ncRNA), synthesizes alternating poly(GT/AC) double-stranded DNA. Cryo–electron microscopy structures at 2.6 Å resolution reveal a D3-symmetric 6:6:6 complex of Drt3a, Drt3b, and ncRNA. Drt3a produces the poly(GT) strand using a conserved ACACAC template within the ncRNA. Notably, Drt3b synthesizes a complementary, protein-primed poly(AC) strand in the complete absence of a nucleic acid template, using conserved active site residues specific to Drt3b to enforce precise base alternation. These findings expand the functional landscape of nucleic acid polymerases, revealing a protein-templated mechanism for sequence-specific DNA synthesis.

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

Variational Polaron Theory for Ground States of Strongly Coupled Light-Matter and Electron-Phonon Systems

arXiv:2606.19748v1 Announce Type: cross Abstract: Strong light-matter and electron-phonon coupling generate ground states dressed by virtual bosonic excitations, making bare-state truncations and perturbative treatments unreliable in the ultrastrong-coupling regime. We introduce a nonperturbative variational ground-state framework based on a state-dependent polaron transformation, combined with a product-state ansatz and a second-order perturbative correction for residual matter-boson entanglement. We show that the optimized transformed frame becomes asymptotically decoupled at infinite coupling, because the leading linear coupling is canceled while off-diagonal matter transitions are suppressed by displaced-oscillator overlaps. The approach is asymptotically correct in both weak- and strong-coupling limits and remains accurate in the intermediate regime, where fixed polaron transformations are least reliable. Dicke-model benchmarks reproduce ground-state energies, fidelities, and the superradiant transition, with second-order energy errors below 0.2%. Holstein-model benchmarks yield errors below 0.5% and clarify how translational symmetry affects wave-function quality. This dressed-basis framework enables nonperturbative modeling of strongly coupled light-matter and electron-phonon systems.

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

"Is This Not Enough?": Asymmetries in Institutional Accountability and Collective Sensemaking in the Case of Canada's Algorithmic Visa Triage System

arXiv:2606.13071v1 Announce Type: cross Abstract: This paper examines how algorithmic accountability in Canada's visa system is articulated institutionally and experienced by applicants across borders. We analyzed Immigration, Refugees and Citizenship Canada (IRCC)'s Algorithmic Impact Assessment (AIA) for the temporary resident visa (TRV) triage system using the algorithmic decision-making adapted for the public sector (ADMAPS) framework and analyzed Reddit discussions among applicants using a mixed-methods approach. We show that while institutional artifacts emphasize transparency, procedural safeguards, and bounded impacts, applicants engage in collective sensemaking to interpret opaque decisions, often relying on peer knowledge amid uncertainty. We identify three asymmetries between how institutional accountability is structured and how people perceive the process: epistemic asymmetry in access to decision logic, jurisdictional asymmetry in exposure shaped by geopolitical positioning, and temporal–relational asymmetry in how waiting and uncertainty are experienced. We emphasize why it is important to shift attention from institutional design to the uneven distribution of experiences with public-sector algorithmic governance. Together, these contributions demonstrate how algorithmic governance systems in the context of transnational migration produce structured asymmetries not captured by institutional disclosure frameworks, and how extending ADMAPS can account for those uneven translations of accountability.

18.
medRxiv (Medicine) 2026-06-15

Quality Improvement Based Implementation and Evaluation of a Decision Aid for Patients with Nephrolithiasis

Introduction Patients with nephrolithiasis face challenges in making a high-quality, preference sensitive decision. Our prior work established feasibility and patient acceptance of a software-based decision aid (DA). The objectives for this study were to identify implementation strategies for the DA in routine care and determine whether DA implementation enhances decisional quality for patients. Methods New nephrolithiasis patients were recruited from the institution Medical Center from June 2018 to April 2024 to receive a software-based pre-visit DA that measured care preferences and used decision analysis to rank treatments. The RE-AIM framework and Plan-Do-Study-Act (PDSA) cycles were used to improve implementation outcomes. Patients completed survey instruments evaluating decisional conflict, shared decision-making, care satisfaction, and treatment choice following their provider visit. These metrics were compared in the DA cohort (n=81) to those in a usual care cohort (n=78) with Wilcoxon rank-sum and Chi-square (or Fishers exact) tests. Results Implementation data revealed sustained reach and progressive improvement in fidelity. The DA cohort reported higher decisional quality relative to controls (p=0.003) and reported greater support/advice to make a choice (p=0.005). The DA cohort more often discussed options with their doctor (87.5% vs 69.2%, p=0.005) and were more likely to be promoters of their provider (p

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

Reinforcement Learning for LLM-based Event Forecasting

arXiv:2606.15917v1 Announce Type: new Abstract: We use Group Relative Policy Optimization (GRPO), a recently devised sample and memory efficient reinforcement learning method, to finetune pretrained LLMs in the range of 1.5B to 14B parameters equipped with the ability to get current information through the use of a Wikipedia revisions tool, or news summaries, to forecast real events beyond the knowledge cutoff of the LLM, as well as problems made to simulate different aspects of the dynamics of that training. We use the results of these experiments to comment on the scaling capability of LLMs for forecasting, as well as classify how judgmental forecasting fits into the verifiable/unverifiable domain taxonomy, considering the impact of the inherent aleatoric uncertainty when forecasting future events (e.g. the roll of a die). As a result of the GRPO training, we manage to bring a 1.5B parameter transformer (Qwen 2.5 1.5B) to forecasting performance superior to Claude Sonnet 3.5 over the same dataset as measured by cross entropy from the market agreed probabilities. We also discuss various dead ends on the path to this result.

20.
arXiv (CS.LG) 2026-06-19

Multi-Modal Contrastive Learning for Implicit Earth Embeddings via Location Tying

arXiv:2606.20167v1 Announce Type: new Abstract: Spatial prediction tasks are often limited by a lack of high-quality labelled ground-truth observations. To overcome this challenge, self-supervised pre-training is a possible solution, with contrastive learning dominant for location encoders. Those approaches usually align geographic coordinates with just one additional modality. We propose two multimodal contrastive learning architectures: Multimodal Embedding via Location Tying (MELT) and Sequential Alternating Location Training (SALT). These architectures expand this framework beyond two modalities by utilising unpaired geospatial data. Both methods are technically viable and match the performance of the strongest two-modality baseline (SATCLIP) across four downstream tasks. However, increasing the number of modalities does not consistently improve performance, suggesting that the chosen location encoder is the main limitation - the contrastive objective reaches its peak early, regardless of modality diversity or pre-training volume. MELT provides more stable training than SALT and presents a stronger foundation for future scaling.

21.
medRxiv (Medicine) 2026-06-22

Panel-level multilocus methylation quantification in native cell-free DNA by PCR-compatible sequential enzymatic processing

DNA methylation is informative for liquid biopsy, but low template abundance, distributed methylation signals and workflow complexity limit implementation. Here we present Delta-HLD, a PCR-compatible methylation assay platform that quantifies methylation directly in native DNA through sequential hybridization, ligation and methylation-sensitive digestion. The assay co-reports methylation-dependent signals from multiple loci through a shared amplification architecture, generating a single panel-level PCR readout. We established the chemistry, optimized panel size and composition through model-guided experiments, and implemented the assay as a triplex qPCR workflow with per-sample internal process controls. Plasma proof-of-concept analyses showed discriminatory signal in CRC and proof-of-concept transferability to hepatocellular carcinoma. Additional platelet-retaining experiments identified a strategy to increase recovery of analyzable circulating templates while reducing genomic DNA recognition. Delta-HLD provides a compact PCR-compatible framework for low-input methylation analysis without base conversion.

22.
medRxiv (Medicine) 2026-06-11

A global cross-sectional survey of health professionals' interest-confidence gaps in value-based health care implementation: a learning needs assessment

Abstract Objectives Value-Based Health Care (VBHC) increasingly guides health system redesign internationally. Despite the increasing availability of VBHC education, gaps remain between health professionals' conceptual understanding of VBHC and their confidence to implement it in practice. This study assessed perceived learning needs and preferences of healthcare professionals across foundational topics essential to VBHC implementation. Design Cross-sectional online survey study Setting and participants The survey was distributed to the global VBHC community and yielded 518 responses. Most respondents were based in the UK and Ireland (51%) and 65% had more than 10 years of experience in the health sector. Participants represented a variety of professional backgrounds, including clinicians (34%), operational or executive managers and leaders (22%), and life sciences or procurement professionals (13%). Primary and secondary outcome measures Primary outcome measures included self-reported interest and confidence across 15 VBHC domains and the magnitude of the gap between them. Secondary outcomes included perceived implementation challenges and preferred VBHC learning approaches, including prior engagement with VBHC-related learning. Results Respondents identified substantial VBHC implementation challenges, including implementing outcome measurement (62.4%), conflicting priorities (57.7%), and resistance to change (56.8%). Interest in all VBHC domains was high (median >= 80/10), while confidence to implement remained substantially lower across most domains (median

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

Informative Missingness to Generate Irregular Clinical Time Series

arXiv:2606.17106v1 Announce Type: new Abstract: Laboratory tests in electronic health records are collected irregularly, and the absence of a test order can be as informative as the measurement itself. Such missingness reflects clinicians' decisions and patient physiology, making it important to model it directly rather than treat it as a preprocessing artifact. Here we present a diffusion-based approach for generating clinical time series that jointly models laboratory values and their observation patterns using the public Data Analytics Challenge on Missing Data Imputation (DACMI) benchmark derived from MIMIC-III. To preserve realistic sampling, we align chart times into 4-hour intervals and segment admissions into 7-day windows, producing trajectories that pair each lab value with a corresponding observation indicator. Standard transformations and normalization are applied to stabilize training. Our method extends the TimeDiff framework to learn continuous lab values and discrete missingness patterns through complementary diffusion objectives. Experiments show that the generated data closely match real patient trajectories across individual lab distributions and joint value-missingness embeddings, demonstrating that diffusion models can capture clinically meaningful dependencies between patient physiology and clinicians' testing behavior under MNAR-like (missing-not-at-random) missingness. These preliminary results indicate that our model can serve as an initial component toward developing clinical foundation models. By producing synthetic priors that preserve key physiology-missingness relationships, this work motivates the subsequent training of Prior-Data Fitted Networks capable of leveraging informative missingness, which we will investigate in the extended work.

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

Skill-to-LoRA: From Using Skills to Learning Behaviors for Token-Efficient LLM Agents

arXiv:2606.16769v1 Announce Type: new Abstract: Agent skills are commonly distributed as SKILL.md files: human-readable procedural documents that describe workflows, tools, resources, and domain conventions. While convenient for inspection and reuse, this design requires the same reusable procedure to be repeatedly injected into the runtime context. We propose Skill-to-LoRA(S2L), a behavior-centric skill representation that replaces runtime skill text with skill-specific LoRA adapters. Rather than compressing the skill document itself, S2L models the behavioral change induced by the skill text: offline, the complete SKILL.md is used to synthesize skill-guided demonstrations; online, the full document is omitted and the corresponding LoRA adapter is dynamically loaded to activate the learned skill behavior. We evaluate S2L with Qwen3.6-27B on a 21-skill subset of SWE-Skills-Bench. Compared with the no-skill and Full Skill Text baselines, S2L improves pass rate by 2.9 and 5.2 percentage points, respectively, while reducing per-step token cost by 6.6% relative to Full Skill Text prompting. S2L matches or improves Full Skill Text on 18/21 skills and the no-skill baseline on 15/21 skills. Control experiments further show that the gains depend on skill-specific adapter alignment: Wrong-LoRA and Shared-LoRA both reduce performance. These results suggest that many procedural agent skills can be converted from runtime instructions into trainable, dynamically loadable behavioral modules. Code will be released upon acceptance.

25.
arXiv (CS.AI) 2026-06-19

Hard or Just Unreached? Diagnosing the Sampling Blind Spot in Math-Reasoning Difficulty Estimation

arXiv:2606.19636v1 Announce Type: cross Abstract: Math and science reasoning benchmarks rely on pass@k, the fraction of sampled chains that reach gold, as the canonical per-example difficulty signal. The same signal drives RL with verifiable rewards, math data curation, synthetic curricula, and verifier training. We show this proxy has a persistent blind spot on its hardest stratum: on the eight free-form math cells we test (GSM8K and MATH across four open-weight models), 10.3-22.9% of the examples that no sampling seed solves in six tries are instead solved at matched compute by a six-chain deterministic regime. These are greedy decoding plus five cheap residual-stream perturbations applied via activation grafting, while greedy alone solves at most 6% on these math cells. Recovery scales with the additional budget, across perturbations whose mechanistic distinctness we verify across all twelve cells (cross-kind fix-set Jaccard