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01.
arXiv (math.PR) 2026-06-12

Conditional means, vector pricings, amenability and fixed points in cones

arXiv:2512.13829v4 Announce Type: replace Abstract: We develop a generalization of conditional probability for arbitrary ordered vector spaces. A related problem is that of assigning a numerical value to one vector relative to another. We characterize the groups for which these generalized probabilities can be stationary, respectively invariant. Our results deviate from the setting of classical probability and lead to a new criterion for amenability and for fixed points in cones.

02.
arXiv (CS.CL) 2026-06-11

Self-Attention as Transport: Limits of Symmetric Spectral Diagnostics

When a language model processes a hallucinated response, its attention routing tends to fail in one of two shapes: over-concentrating on a narrow set of positions, or spreading so diffusely that relevance is diluted, and the shape of the failure carries diagnostic signal. We study these shapes as a diagnostic characterization, computed from attention matrices under forced scoring of benchmark-labeled responses rather than during live generation. A widely used family of spectral methods analyzes the symmetric component of the degree-normalized attention operator, which governs transport capacity; we prove that every transpose-invariant spectral diagnostic of this operator is structurally orientation-blind (it cannot distinguish an operator from its transpose, and therefore cannot detect information-flow direction), with a converse to the blindness theorem bounding any Lipschitz diagnostic's transpose sensitivity by the asymmetry coefficient $G$. Pairing this with a closed-form bipartite-Cheeger landscape for canonical causal architectures, we show that uniform causal attention satisfies an $n$-independent floor $\phi \ge 1/5$, while window attention pierces the floor as $O(w/n)$; failure modes are shape-different, not just value-different. This floor is an idealized-architecture benchmark, not an empirical attractor: the fraction of real attention heads that pierce it is itself an architectural signature. The resulting two-axis diagnostic ($\phi$ for capacity, $G$ for direction) yields a falsifiable polarity prediction: bottleneck- and diffuse-dominated benchmarks should exhibit opposite polarity. Under length-controlled evaluation, transport features retain interpretable signal (0.62-0.84 LC-AUROC) across the tested decoder-only, encoder-only, and encoder-decoder models, with polarity reversing as predicted between HaluEval and MedHallu.

03.
arXiv (CS.CL) 2026-06-12

HKVM-RAG: Key-Value-Separated Hypergraph Evidence Organization for Multi-Hop RAG

Multi-hop RAG poses a data-engineering problem beyond passage matching: under fixed retrieval budgets, a system must organize retrieved text into evidence units that expose answer chains. Dense retrievers score passages independently, while graph-based memories make associations explicit but often rely on pairwise or entity-centered keys that fragment multi-hop evidence. We present HKVM-RAG, a key-value-separated evidence-organization layer. It assembles answer-path hyperedges from cached passage-level LLM evidence tuples and uses them as retrieval keys, while retaining passage text as answer values. To isolate key-space design, our fixed-substrate protocol holds the tuple cache, candidate passages, reader, and evaluation budget constant across pairwise graph and hypergraph variants. Weighted hypergraph key-value retrieval improves over KG-PPR by +3.426 F1 on 2WikiMultiHopQA and +3.592 F1 on MuSiQue; HotpotQA shows that higher structured support coverage need not yield standalone answer-F1 gains. We therefore study WHG-KV as an evidence-control signal rather than a dense-retrieval replacement. Oracle and train-to-dev analyses identify support selection as repairable, and a dense-aware controller combines frozen ColBERTv2 and HKVM rank/score features using out-of-fold HKVM predictions. It reaches 88.846, 65.073, and 85.810 F1 on the three benchmarks, improving over ColBERTv2 by +11.084, +6.763, and +5.966 F1. Source-level ablations show that matched non-WHG structured signals do not match the WHG-KV gains. These results provide bounded evidence that key-value-separated hypergraph organization can serve as a reusable evidence-control mechanism for multi-hop RAG.

04.
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.

05.
arXiv (CS.LG) 2026-06-18

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

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

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

Self-CTRL: Self-Consistency Training with Reinforcement Learning

arXiv:2606.18327v1 Announce Type: cross Abstract: Language models (LMs) that faithfully describe their own behavior can more easily be audited, understood, and trusted by users. This paper describes Self-Consistency Training with Reinforcement Learning (Self-CTRL), a method that optimizes for consistency between a LM's self-explanations and behavior on related inputs by updating explanations to better predict behavior or updating behavior to better match explanations. We apply our method in two domains. First, we study a formal probabilistic reasoning task in which LMs must learn to imitate a family of biased samplers and evaluated on their ability to report the associated biases. We find that consistency training improves the correlation between self-reported and behaviorally-measured latent biases from $R^2=0.24$ to $R^2=0.64$ on a set of held-out distributions, matching the generalization of direct ground-truth supervision. Second, we study a constitutional AI domain in which LMs must describe when they will refuse or comply with user requests. Here, Self-CTRL produces rules that faithfully describe the model's behavior on held-out requests, improving the refusal predictions of a third-party auditor model from $36\%$ to $92\%$. In the other direction, behavior updates improve alignment, reducing HarmBench failure rate from $15.0\%$ to $0.5\%$ without substantially increasing refusal on harmless prompts. By aligning explanations and behavior, our work provides a general recipe for training AI models to be safer, more transparent, and more controllable.

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

Why Tree-Style Branching Matters for Thought Advantage Estimation in GRPO

Group Relative Policy Optimization (GRPO) trains Chain-of-Thought reasoning with verifiable rewards, but estimating thought-level advantages without value functions often suffers from high variance. Although tree-style branching is used in practice to reduce variance, it lacks a theoretical explanation of why it works and whether it is important or potentially necessary. We study thought-level advantage estimation in GRPO from a variance perspective under a minimal tree-style setting where multiple continuations are sampled for each thought. Using the multivariate delta method, we reveal a sampling-dimension asymmetry. Increasing sampled thoughts ($K$) leaves a strictly positive estimation-variance floor, whereas increasing continuations per thought ($M$) drives the leading-order estimation variance to zero at rate $1/M$. This implies that, within the fixed-temperature GRPO-style estimator without value models studied here, accurate thought-level advantage estimation cannot be achieved by scaling thought sampling alone, making continuation-level branching a principled and potentially necessary mechanism rather than a heuristic. Experiments further provide empirical evidence for its effectiveness and potential necessity, demonstrating improved optimization stability, training efficiency, and final performance not only in math but also across vision domains and under different model architectures and sizes.

08.
arXiv (CS.CL) 2026-06-16

ESBMC-PLC: Formal Verification of IEC 61131-3 Ladder Diagram Programs Using SMT-Based Model Checking

PLCs execute safety-critical programs across industrial sectors. The dominant PLC notation, ladder diagram (LD) per IEC 61131-3, remains absent from formal verification: SMT-based model checkers cannot process LD's rung-and-coil graphics. This paper presents ESBMC-PLC, the first open-source formal verifier with native LD support (PLCopen XML format), implemented as a new ESBMC frontend. ESBMC-PLC translates LD rungs to GOTO IR, models the PLC scan cycle as a while(true) loop with nondeterministic inputs, and checks safety properties via SMT-based bounded model checking or k-induction. A five-property YAML language (mutual_exclusion, invariant, absence, response, reachability) avoids temporal logic. A survey of 22 studies (2020-2026) identifies four research gaps; ESBMC-PLC closes two of them. Evaluation on 13 benchmarks (6 domains, 3 sources - including deployed CONTROLLINO PLCs and MathWorks Simulink PLC Coder) shows correct classification across 61 properties: all 9 author-constructed programs (Categories A/B) as expected, all 4 vendor programs (Category C) correctly unlabeled, with 8 bugs found (actionable counterexamples), 7 unbounded k-induction proofs, all runs under 60ms on Apple Silicon. Feature comparison with PLCverif shows that ESBMC-PLC is the only open-source tool that combines native LD, k-induction, and SMT bit-vector semantics.

09.
arXiv (CS.CL) 2026-06-12

RAGPPI: RAG Benchmark for Protein-Protein Interactions in Drug Discovery

Retrieving the biological impacts of protein-protein interactions (PPIs) is essential for target identification (Target ID) in drug development. Given the vast number of proteins involved, this process remains time-consuming and challenging. Large Language Models (LLMs) and Retrieval-Augmented Generation (RAG) frameworks have supported Target ID; however, no benchmark currently exists for identifying the biological impacts of PPIs. To bridge this gap, we introduce the RAG Benchmark for PPIs (RAGPPI), a factual question-answer benchmark of 4,420 question-answer pairs that focus on the potential biological impacts of PPIs. Through interviews with experts, we identified criteria for a benchmark dataset, such as a type of QA and source. We built a gold-standard dataset (500 QA pairs) through expert-driven data annotation. We developed an ensemble auto-evaluation LLM that incorporates expert labeling characteristics, average fact-abstract similarity (F1), and low-similarity fact counts (F2), enabling the construction of a silver-standard dataset (3,720 QA pairs). We are committed to maintaining RAGPPI as a resource to support the research community in advancing RAG systems for drug discovery QA solutions.

10.
arXiv (quant-ph) 2026-06-17

Creating squeezed and non-classical collective motional many-body states through stroboscopic Rydberg dressing

arXiv:2606.17849v1 Announce Type: cross Abstract: Realizing conditional quantum operations, e.g., quantum gates, for quantum computing and simulation requires controlled interactions between particles. Often, these interactions depend on the interparticle distance, and accordingly, an uncertainty of the relative particle position may translate into gate infidelities. We consider here a quantum computing platform based on an array of neutral atoms and present a method that allows to reduce the uncertainty of all interatomic distances. Our approach exploits the coupling between atomic motion and stroboscopically excited atomic Rydberg states. It allows to collectively squeeze the modes corresponding to interatomic displacements, thereby reducing distance fluctuations down to a fraction of the motional vacuum state. Furthermore, the method permits the creation of non-classical states with substantial Wigner negativity. These correlated states may allow reducing motional decoherence, increasing gate fidelity, and potentially yield a resource for quantum-enhanced metrology.

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

RetailBench: Benchmarking long horizon reasoning and coherent decision making of LLM agents in realistic retail environments

arXiv:2606.15862v1 Announce Type: new Abstract: Large language model (LLM) agents have made rapid progress on short-horizon, well-scoped tasks, yet their ability to sustain coherent decisions in dynamic long-horizon environments remains uncertain. We introduce RetailBench, a data-grounded simulation benchmark for evaluating tool-using LLM agents in single-store supermarket operation. RetailBench models retail management as a partially observable decision process and is designed to support thousand-day-scale simulations. In this environment, agents must manage pricing, replenishment, supplier selection, shelf assortment, inventory aging, customer feedback, external events, and cash-flow constraints. We evaluate seven contemporary LLMs under representative agent frameworks over a 180-day evaluation horizon and compare them with a privileged oracle policy. Results show substantial variation across models: only a small subset survives the full evaluation horizon, and even the strongest LLM runs remain substantially behind the oracle policy in final net worth and sales outcomes. Behavioral analysis attributes these gaps to incomplete evidence acquisition, surface-level decision making, and the lack of a consistent long-horizon policy. RetailBench provides a controlled testbed for studying reliable autonomy in economically grounded long-horizon decision-making.

12.
bioRxiv (Bioinfo) 2026-06-17

An Integrated Framework for Transcriptomic Characterization and Lorentzian Hyperbolic Visualization of a High-Risk Topological Branch in Alzheimer's Disease

Alzheimer's disease (AD) is a highly heterogeneous brain disorder in which molecular alterations vary across brain regions, disease stages, and patient subgroups. This study introduces an integrated analytical framework for characterizing transcriptomic variation associated with a high-risk topological branch, which was identified based on Lorentz distance in postmortem Brodmann area 36 samples from the Mount Sinai Brain Bank cohort, where over 70% of samples were in Braak stages V-VI. The framework integrates weighted gene co-expression network analysis, repeated stability-based differential expression analysis, network-level gene filtering, Gene Ontology enrichment, and nested stratified cross-validation to evaluate whether topological branch-associated genes capture biologically meaningful signals and carry predictive information for high-Braak group status. The identified gene sets were functionally enriched for neuronal development, neuron projection organization, synaptic signaling, vesicle fusion, and regulated synaptic release, suggesting that the high-risk topological branch reflects biologically relevant transcriptomic programs linked to neurodegenerative progression. Nested cross-validation further showed that the selected genes achieved measurable internal predictive performance for distinguishing high-Braak samples. As a second methodological contribution, we introduced a Lorentzian hyperbolic variant of t-distributed stochastic neighbor embedding (Lorentz t-SNE) to explore latent non-Euclidean structure in transcriptomic data. This method embeds samples in hyperbolic space, providing an alternative to Euclidean embeddings for representing hierarchical or nonlinear structures. Compared with conventional Euclidean embeddings, the proposed Lorentz t-SNE revealed a more localized organization of high-Braak samples. Together, these results demonstrate the utility of the proposed analytical framework and Lorentz t-SNE for investigating heterogeneous, potentially non-Euclidean organization in AD transcriptomes.

13.
medRxiv (Medicine) 2026-06-18

Can Vision-Language Models See the Vital Signs? Benchmarking and Fine-Tuning for Intraoperative Monitor Reading

Background Vital-sign deterioration is a leading contributor to preventable perioperative death, yet manual monitor reading is intermittent, error-prone, and subject to alarm fatigue. Automating this perceptual step could enable continuous surveillance, but existing solutions depend on device-specific hardware integration or cloud-hosted vision-language models (VLMs), which raise privacy, cost, and connectivity barriers in resource-limited healthcare facilities. Methods We constructed a benchmark of 200 in-the-wild intraoperative monitor photographs (spanning multiple vendors, angles, and illumination conditions) annotated for eight vital-sign parameters: heart rate, SpO2, ETCO2, respiratory rate, systolic/diastolic/mean blood pressure, and temperature. We evaluated an optical character recognition (OCR)-based pipeline, nine instruction-tuned VLMs (four commercial, five open-weight ranging from [≤]4B to 31B parameters) under two prompting regimes, and a compact open model (Qwen3.5-9B) adapted via low-rank fine-tuning (LoRA, 0.46% of parameters updated). Results Under a domain-aware prompt, frontier VLMs reached 0.98-0.997 exact-match accuracy zero-shot, whereas the OCR pipeline and [≤]4B model scored approximately 0.20 lower, defining a 9B-class usable floor. LoRA fine-tuning Qwen3.5-9B on 80-120 images raised accuracy from 0.953 to 0.994 (statistically indistinguishable from the best commercial model) and reduced the critical-error rate fivefold (0.0313 [->] 0.0063). Ablations showed that performance saturated at 80 training images and rank-8 adapters. Conclusion Monitor reading is a solved perception problem for VLMs above the 9B scale. A lightweight fine-tuned open model achieves frontier accuracy while running entirely on local hardware, preserving data privacy, offline capability, and near-zero marginal cost. Residual errors stem from blood-pressure source ambiguity and are addressable with explicit disambiguation logic.

14.
arXiv (CS.AI) 2026-06-19

IHBench: Evaluating Post-Interruption Recovery in Voice Agents with Structured Workflows

arXiv:2606.19595v1 Announce Type: cross Abstract: Voice agents deployed in structured workflows (customer service, healthcare scheduling, account management) must handle frequent user interruptions while maintaining progress through multi-step procedures. Existing benchmarks for speech-capable models focus on the timing of interruptions: barge-in detection, endpointing, and turn-taking dynamics. They leave unmeasured what happens after the interruption: does the agent resume the workflow at the correct step? Does it address the user's interjection? Does it avoid re-delivering content the user already heard? We introduce IHBench (Interruption Handling Benchmark), a benchmark that evaluates post-interruption recovery in voice agents executing state-machine-driven workflows across 10 enterprise domains. Six interruption types are injected at controlled points mid-utterance, with per-interruption evaluation rubrics generated alongside the data. Each interruption is scored on two axes: task fulfillment and recovery quality. We evaluate 27 audio-language model configurations from OpenAI, Google, and the open-weight community. Models vary widely, and recovery quality depends strongly on the interruption type. Across our experiments, closed-weight models are consistently more robust to interruptions than open-weight ones: they win far more often on task fulfillment, degrade roughly 3.3x more slowly as conversations grow longer, and show no audio-versus-text modality gap, whereas the open-weight models lose ground on all three. A human study validates the LLM judge against human annotators, and a cross-benchmark analysis against AudioMultiChallenge indicates that recovery quality is a largely distinct capability axis.

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

From Chatbot to Digital Colleague: The Paradigm Shift Toward Persistent Autonomous AI

arXiv:2606.14502v1 Announce Type: new Abstract: Large Language Models (LLMs) are undergoing a fundamental transformation from conversational generators into integrated AI systems capable of reasoning, action, memory, and self-improvement. We conceptualize this transition as a shift from Chatbot to Digital Colleague: from conversational answers to persistent work. We organize this transition along two tightly coupled dimensions. First, at the cognitive core level, LLMs are advancing from Chatbot-era "fast thinking" systems driven by next-token prediction toward Thinking LLMs that leverage inference-time computation, Chain-of-Thought reasoning, reflection, process supervision, and reinforcement learning to support more deliberate and reliable cognition. Second, at the tool-augmented task execution level, LLMs are progressing from tool-calling Agents that invoke external resources in an ad hoc manner toward OpenClaw-style workstation systems (OpenClaw) equipped with persistent Workspaces, skills, verification loops, and governance. The "Workspace + Skill" paradigm makes episodic tool use colleague-like via state persistence, reusable procedures, task closure, and experience reuse. We examine data construction shifts from instruction-response pairs to State-Action-Observation trajectories and evaluation from static benchmarks to sandboxed, auditable, self-evolving AI ecosystems.

16.
PLOS Computational Biology 2026-06-18

Mechanisms underlying spontaneous and evoked calcium responses in oligodendrocyte precursor cells: A modeling investigation

作者:

by Martin Lardy, Leqi Wang, Claire Guerrier, Veronica T. Cheli, Pablo M. Paez, Anmar Khadra Calcium (Ca2+) signaling has emerged as a central regulator of activity-dependent myelination in oligodendrocytes. These Ca2+ signals encompass both the stimulus-independent spontaneous Ca2+ local transients (SCaLTs) generated intrinsically in a voltage-independent manner or facilitated by the membrane voltage, as well as evoked responses triggered by ATP and glutamate release. To investigate the regulatory mechanisms underlying this combined spiking activity, we developed a stochastic spatiotemporal flux-balance model of Ca2+ transients in oligodendrocyte precursor cells (OPCs). The model incorporates all the relevant fluxes in these cells and integrates membrane voltage dynamics with a Ca2+-induced Ca2+-release (CICR) mechanism using parameters fitted to Ca2+ fluorescence recordings. The model reproduced the intrinsic and voltage-facilitated SCaLTs in OPCs in the absence of purinergic and glutamatergic receptors, and captured the three distinct patterns of evoked Ca2+ responses induced by prolonged ATP and glutamate stimulations identified using machine classifier. The model highlighted the role of ATP and glutamate in generating these clusters, and showed that the fast dynamics of CICR is key to producing these evoked responses. Further analysis of the model also revealed that voltage-gated L- and T-type Ca2+ channels slightly increase the frequency of SCaLTs, while stimulation with ATP and glutamate, using randomly distributed pulses mimicking in vivo conditions, leads to an increase in both the amplitudes of Ca2+ spikes (i.e., the combination of SCaLTs and evoked responses) and the prevalence of wide spikes, especially upon glutamate stimulation. Bifurcation analysis of the deterministic version of the model, in the absence of diffusion, demonstrated that ATP and glutamate stimulation can shift the system into an oscillatory regime, thereby increasing the deterministic component of SCaLT dynamics. This study thus offers a comprehensive representation of OPC Ca2+ transients linking recorded in vitro behaviors to in vivo dynamics.

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

PointDiffusion: Diffusion-Based Scene Completion in the Point Cloud Domain

Reconstructing dense 3D scenes from sparse LiDAR point clouds is a fundamental challenge in autonomous driving, where latent diffusion models offer a promising solution. However, existing approaches rely on object-level autoencoders that collapse into unstable global representations at outdoor scale and suffer from ground truth data corrupted by odometry drift that systematically degrades supervision quality. Furthermore, multi-step diffusion inference incurs prohibitive latency for real-time deployment. We propose a novel multi-token Gaussian VAE with cross-attention pooling for stable scene-scale LiDAR compression, combined with an anchor-based ICP ground truth refinement pipeline that eliminates drift-induced noise from training supervision. Together, these components enable a scaffold-free single-step diffusion completion model that achieves an approximately 16x reduction in squared Chamfer distance on SemanticKITTI seq. 08 (0.396 m^2 to 0.024 m^2), surpasses LiDiff and ScoreLiDAR by 17-19% and 10-11%, respectively, and operates at 25-143x lower inference latency. Our results demonstrate that data quality dominates model design in this regime and that multi-token latent spaces provide a stable first stage for latent diffusion-based scene completion.

18.
arXiv (CS.AI) 2026-06-16

Multiple Descents in Deep Learning as a Sequence of Order-Chaos Transitions in LSTM Networks

arXiv:2505.20030v2 Announce Type: replace-cross Abstract: We observe a novel `multiple-descent' phenomenon during the learning process of a recurrent neural network called long-short-term memory (LSTM) networks during its training on real-world task, in which the performance goes through long cycles of up and down trends multiple times after the model is overtrained. By carrying out asymptotic stability analysis of the models, we found that the cycles in performance – indicated by loss function in test data – are closely associated with the phase transition process between order and chaos of the model, and the local optimal training step are consistently at the critical transition point between the two phases. More importantly, the most optimal point of the model usually occurs at the first transition from order to chaos, where the `width' of the `edge of chaos' is often the widest, allowing the best exploration of weight configurations for learning.

19.
medRxiv (Medicine) 2026-06-15

ICD-10 Code Ambiguity Obscures Treatment-Eligible Adults with Spinal Muscular Atrophy: A Single-Center Chart Review and Patient Outreach Study

Background. Three disease-modifying therapies (DMTs) for spinal muscular atrophy (SMA) have been approved since 2016, yet many adults remain untreated. Identifying them depends on ICD-10 codes that capture SMA but do not reliably distinguish it from other related conditions. We examined, in one U.S. health system, both patients' engagement with therapy and the accuracy of the codes used to find them. Methods. We conducted a retrospective chart review of adults in an academic health system identified by SMA-associated ICD-10 codes, with manual adjudication of diagnosis and DMT status. Confirmed SMA-positive, DMT-naive patients were invited to a structured telephone interview on treatment awareness and barriers. Results. Of 60 charts, 22 (36.7%; 95% CI 25.6-49.3%) were appropriately coded for SMA or a related disorder; only 16 (26.7%) had molecularly confirmed SMA. The other 38 (63.3%) were miscoded, spanning spinal and bulbar muscular atrophy, asymptomatic carriers, prenatal screening, and conditions unrelated to SMA. Ten of the 16 confirmed patients (62.5%) were DMT-naive; one was interviewed, one declined, and eight could not be reached. The non-response is itself a finding: the patients least visible to administrative data are the hardest to reach. Conclusions. ICD-10 ambiguity is a barrier to treatment access in adult SMA, as is loss to follow-up. We make two recommendations: continuous documentation-coding alignment that uses natural language processing to verify the genetic precondition, and type-specific SMA codes (subcodes for Types 0-4) anchored on molecular SMN1 confirmation. Together these would support cohort identification, outreach, and evidence generation without adding to clinician burden.

20.
medRxiv (Medicine) 2026-06-20

EpiLink: a simulation-based compatibility model for genomic transmission clustering in infectious disease surveillance

Identifying recently linked infections from pathogen genome sequences is central to infectious disease surveillance, yet many clustering approaches rely on fixed genetic distance thresholds whose relationship to transmission is often unclear. This limitation is especially important in rapidly growing outbreaks and superspreading events, where many cases may be sampled close together in time and share little genetic variation, making true transmission links difficult to distinguish from other closely related infections. Supervised models can improve discrimination, but they require labelled transmission data that are rarely available during outbreak response. We developed EpiLink, a threshold-free method that estimates whether two cases are compatible with recent transmission. Here, compatibility means how well the observed genetic distance and sampling-time difference between two cases fit what would be expected if they were linked by defined recent transmission scenarios. EpiLink simulates plausible recent transmission histories while accounting for uncertainty in infection timing, testing delay, and mutation accumulation, then assigns higher scores to pairs whose observed differences are typical of those simulations. EpiLink was evaluated using both synthetic and empirical SARS-CoV-2 outbreak data from the 2020 Boston epidemic. Two EpiLink variants were compared to a logistic regression model trained on labelled transmission data. One EpiLink variant assumed deterministic mutation accumulation, with genetic differences proportional to elapsed evolutionary time; the other accounted for stochasticity by sampling mutation counts from a Poisson distribution. The logistic regression model performed better at distinguishing linked from unlinked pairs, but EpiLink achieved comparable clustering accuracy. In the Boston data, EpiLink recovered clusters enriched for documented conference and skilled nursing facility outbreaks. EpiLink thus provides an interpretable, simulation-based approach for identifying recent transmission clusters when fixed thresholds are difficult to justify and labelled transmission data are unavailable.

21.
arXiv (CS.AI) 2026-06-11

MetaPlate: Counterfactual-Guided RAG-LLM Tool for Personalized Food Recommendation and Hyperglycemia Prevention

arXiv:2606.10120v2 Announce Type: replace-cross Abstract: Postprandial hyperglycemia is a key risk factor for metabolic disorders; however, existing dietary guidance is often static, impractical, and insufficiently personalized, providing recommendations that are difficult to follow or not impactful. While recent advances leverage continuous glucose monitoring (CGM) and machine learning to predict glycemic responses, these approaches are largely predictive and lack actionable guidance. Moreover, recommendation systems are often misaligned with user goals and require extensive input. We present MetaPlate, a counterfactual explanation (CF) guided, context-aware decision-support framework that generates personalized meal recommendations to mitigate postprandial glucose excursions in healthy adults. MetaPlate integrates multimodal data, including CGM readings, wearable-derived physiological signals, and user-provided meal inputs from $25$ individuals to model pre-meal context. A machine learning model predicts glucose response, while a CF optimization module adjusts meal composition modifying macronutrient amounts to maintain glucose levels within a target range ($\leq 140$ mg/dL). An LLM-based retrieval-augmented generation (RAG) layer enhances interpretability by producing human-readable recommendations using constrained search of the USDA food database. We evaluate MetaPlate via a structured expert-in-the-loop assessment with registered dietitians (RDs), comparing performance before and after prompt refinement. Results show improvements in meal realism, portion suitability, and recommendation likelihood, with expert feedback indicating a shift from clinically implausible outputs to actionable, contextually appropriate recommendations. Our findings emphasize the importance of domain knowledge and structured constraints in LLM-driven systems and highlight the potential of MetaPlate as a real-time personalized dietary decision-support tool.

22.
arXiv (CS.AI) 2026-06-16

Quantifying the Impact of Lossy Compression on Neural Generative Surrogate Modeling

arXiv:2606.15959v1 Announce Type: cross Abstract: Neural networks are used as generative surrogate models for scientific discovery, which are trainable approximations of scientific simulations. These models enable users to replace time-consuming numerical simulations with learned alternatives, providing quick solutions. However, high-fidelity generative surrogate models require massive training datasets, which can create storage and I/O challenges. Lossy compression is a promising way to reduce this burden, but compression errors may affect the model quality in subtle ways, making it challenging to quantify their impact. In this work, we examine how lossy compression of training data impacts the quality of generative surrogate models. We begin by characterizing the uncertainty inherent in training neural networks, showing that identical training configurations can produce different models. By exploiting this variability, we propose a method to estimate how much compression-induced error a surrogate model can tolerate without affecting its accuracy. Evaluation of two application simulations demonstrates that our approach significantly reduces memory/storage requirements and speeds up training while producing high-quality surrogate models. These results show that lossy compression saves data storage up to 23.7x and 39x with negligible impact on the quality of the surrogate model. Meanwhile, reducing the size of the training data set also enhances the data loading speed and reduces the training time by up to 3x.

23.
arXiv (CS.LG) 2026-06-16

Identification and Inference for Algorithmic Frontiers with Selective Labels

arXiv:2606.14977v1 Announce Type: cross Abstract: This paper provides identification results to characterize a fairness-accuracy (FA) frontier, and statistical inference tools to test hypotheses and build a confidence set for the FA-frontier, when outcomes are observed only for selected individuals. When the selection process is unrestricted but loss is measured in specific ways, we provide a characterization of the sharp identification region of the FA-frontier. Under an assumption of unconfoundedness conditional on observables (and unrestricted loss functions), we obtain point identification and propose a debiased machine learning estimator, derive its asymptotic distribution, and show how this can be used to carry out inference for the FA-frontier. In work in progress, we extend the partial identification results to a broader class of loss functions.

24.
bioRxiv (Bioinfo) 2026-06-11

Amylo-Pipe: an integrated web server for mechanistic and kinetic prediction of protein and peptide aggregation

Protein aggregation is central to amyloid-related disorders and remains a major developability challenge for protein therapeutics. Over the past two decades, significant advances have been made to predict aggregation-prone regions (APRs) and estimate aggregation propensity in proteins and peptides. In contrast, the prediction of aggregation kinetics has received relatively less attention due to the limited availability and heterogeneity of experimental data. Consequently, aggregation propensities from APR prediction algorithms were widely accepted as a means to predict relative changes in the aggregation kinetics of proteins and mutants. Previous studies have demonstrated, using large-scale datasets, that aggregation propensity shows a weak or inconsistent correlation with aggregation kinetics. In the present study, we have integrated complementary state-of-the-art mechanistic and kinetic prediction tools for protein aggregation into a unified, user-friendly web framework entitled "Amylo-Pipe". Amylo-Pipe also implements practical features that are especially useful for protein engineering, such as gatekeeper-residue mutational scanning to support the design of aggregation-resistant variants. By consolidating multiple prediction tasks in a single interface, Amylo-Pipe enables a more comprehensive assessment of aggregation behavior than APR-only workflows. The web server is freely accessible at: https://web.iitm.ac.in/bioinfo2/amylopipe/.

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

Wasserstein Convergence of ODE-Based Samplers in Decentralized Diffusion Model via Velocity Field Decomposition

arXiv:2606.15835v1 Announce Type: cross Abstract: Diffusion models have achieved impressive empirical success in generative tasks, and their convergence theory is now relatively well understood. Motivated by privacy and scalability, recent decentralized diffusion architectures replace a single global velocity field with multiple local experts and a routing mechanism, yielding a sampling dynamics with stochastic expert switching that falls outside standard diffusion convergence analyses. In this work, We study a decentralized diffusion framework with stochastic velocity fields and ODE-based sampling. We establish a convergence guarantee in Wasserstein-2 distance, showing that the distribution of the $N$-step discretization converges to the analytical solution at rate $\mathcal{O}(N^{-1/2}+\varepsilon)$ in $W_2$, where $\varepsilon$ captures the neural approximation errors. To our knowledge, this is the first $W_2$ convergence result for decentralized diffusion models with an ODE-based sampling scheme.