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

A Layered Security Framework Against Prompt Injection in RAG-Based Chatbots

Prompt injection is ranked as the most critical vulnerability in large language model (LLM) deployments by the OWASP Top 10 for LLM Applications, yet existing defenses operate at isolated pipeline stages and remain incomplete. Input filters cannot inspect retrieved documents, while output monitors cannot prevent malicious payloads from reaching the model. Consequently, retrieval-augmented generation (RAG) chatbots remain vulnerable to indirect injection, where a poisoned knowledge-base document compromises every user whose query retrieves it. We present a three-layer framework that intercepts both direct and indirect prompt injection throughout the inference pipeline. Layer 1 screens user input using a rule-based pattern library and a fine-tuned semantic anomaly classifier. Layer 2 enforces a provenance-based instruction hierarchy during context assembly, preventing retrieved content from overriding operator policy. Layer 3 audits model output using a policy rule engine and semantic drift detector before delivery. A continuous audit loop aggregates structured logs and supports retraining to adapt the classifier to emerging attack patterns. The framework is model-agnostic and deploys as middleware without modifying the underlying LLM. Evaluation on 5,080 samples across GPT-4o, Llama 3, and Mistral 7B shows that the framework reduces Attack Success Rate (ASR) from 71.4\% to 11.3\%, outperforming the best single-layer baseline by 27.3 percentage points and a published guardrail system by 23.8 percentage points, while maintaining a 4.8\% false positive rate and a median latency overhead of 61.2 ms. Ablation studies confirm that all three layers provide complementary protection and that their combined effect exceeds the sum of individual contributions.

02.
medRxiv (Medicine) 2026-06-22

Impact of Antidiabetic Medications on IgG and Plasma Protein N-Glycosylation in Type 2 Diabetes Patients

Introduction. Diabetes is a growing global health challenge, necessitating effective management strategies. Glycosylation, a highly regulated post-translational protein modification, has emerged as a pivotal factor in diabetes pathophysiology. However, the modulation of protein glycosylation by antidiabetic treatment is still largely unknown. This study explored the longitudinal effects of four distinct antidiabetic therapies - metformin, insulin, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and glucagon-like peptide-1 receptor agonists (GLP-1RA) - on plasma protein and immunoglobulin G (IgG) glycosylation in patients with type 2 diabetes (T2D). Research Design and Methods. Plasma protein and IgG N-glycans were enzymatically released, purified and chromatographically profiled in a cohort of 124 patients, examined at four time points, to assess therapy-induced glycan alterations. Linear mixed models adjusting for covariates and multiple testing (FDR

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

Unsupervised Diffusion Solver for Combinatorial Optimization via Combinatorial Adjoint Matching

arXiv:2605.30920v2 Announce Type: replace Abstract: Diffusion-based neural solvers have shown strong promise for combinatorial optimization (CO), but existing methods typically rely on supervised training with large collections of near-optimal solutions. In this work, we extend adjoint-based trajectory optimization methods to discrete combinatorial domains. We formulate diffusion-based CO as a stochastic control problem over Continuous-Time Markov Chains and introduce discrete adjoint dynamics for propagating optimization signals through discrete generative trajectories. Building on this formulation, we propose Combinatorial Adjoint Matching (CAM), an unsupervised training framework for discrete diffusion solvers with structured and low-variance trajectory-level optimization signals. Empirically, CAM consistently outperforms existing unsupervised diffusion baselines and achieves performance competitive with strong supervised diffusion solvers and even traditional solvers across diverse combinatorial optimization problems. Our code is available at https://github.com/Shengyu-Feng/CAM.

04.
arXiv (CS.LG) 2026-06-18

DIPHINE: Diffusion-based $\Phi$-ID Neural Estimator

arXiv:2606.18997v1 Announce Type: new Abstract: Uncovering the true informational architecture of real-world complex systems requires disentangling how their components uniquely store, redundantly share, and synergistically integrate information over time. Integrated Information Decomposition ($\Phi$ID) is a framework for decomposing the information dynamics of multivariate systems into sixteen non-overlapping atoms that characterize redundant, unique, and synergistic modes of information storage, transfer, and integration. Existing methods to compute $\Phi$ID are restricted to Gaussian or discrete systems, preventing its application to continuous non-Gaussian dynamical systems. We address this limitation by proposing DIPHINE (Diffusion-based $\Phi$-ID Neural Estimator), the first neural estimator that leverages score-based diffusion models to jointly estimate all the mutual information terms required by $\Phi$ID from a single amortized network, recovering the sixteen atoms through Möbius inversion. We provide a theoretical analysis of error propagation through the inversion, showing that the Jacobian of the mapping from mutual informations to atoms is integer-valued and that the synergy-to-synergy atom is provably the hardest to estimate. We demonstrate accurate recovery of ground-truth atoms on synthetic benchmarks, superior performance compared to established mutual information estimators, and the ability to extract physiologically interpretable information-dynamic structure on an application involving real data without any distributional assumptions.

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

Closing the Social-Semantic Gap: SPSD for Edge-Based Prompt Compression in Cloud LLM Inference

arXiv:2606.19364v1 Announce Type: new Abstract: The prefill stage of Large Language Model (LLM) inference is a growing contributor to cloud-scale energy cost. Many consumer-support and conversational prompts contain social scaffolding: politeness markers, apologetic preamble, repetition, and rapport-building language that is important for human communication but carries low marginal information for machine reasoning. We call this discrepancy the Social-Semantic Gap. We present SPSD (Sentiment Preserving Semantic Distillation), an edge-based pipeline that compresses user prompts using a 4-bit quantised Small Language Model before transmission to a cloud-deployed LLM. Evaluation on a 248-prompt corpus using Gemma-2-2B-Instruct (Q4_K_M) as the SLM and Llama-3.1-8B-Instruct as the cloud evaluation model yields a mean input token saving of 99.9 tokens per distilled call, with all 146 distilled calls yielding positive savings. Response quality, assessed by blind LLM-as-judge scoring across 121 pairs, is non-inferior to the raw path within a pre-specified 1-point margin on a 15-point rubric; the judge awarded 43 percent ties, 28 percent distilled wins, and 29 percent raw wins. Cosine similarity is mixed: mean 0.682, median 0.712, with 54.1 percent of pairs above the 0.70 reference threshold. Safety-critical domains are conservatively routed to passthrough via rule-based gates. Per-call net energy saving is estimated at 70-270 uWh under stated assumptions. SPSD shows that on-device prompt distillation can reduce cloud LLM input-token cost while preserving response quality within a practical non-inferiority margin.

06.
bioRxiv (Bioinfo) 2026-06-18

Identification of environmental factors and growth stages in the prediction of fibre yield and fibre quality traits in rain-grown cotton

Context Understanding how and when environmental conditions influence overall crop performance is crucial for optimising the development of genotypes to a specific breeding target environment. We focused on economically important traits of Australian rain-grown cotton including fibre yield and quality traits, which have not been investigated comprehensively. The aim of the study was to identify relevant environmental factors, and the timing and extent of their impact on rain-grown cotton production. Methods We used a data driven approach to analyse the relationship between ten climate related environmental factors across various plant growth stages and eight fibre yield and quality traits, using a large-scale field dataset of 9,283 records collected over 23 years at 4 locations, with 53 unique year-location combinations. We applied eight complementary statistical models including stepwise, penalised and Bayesian linear regression, regression-tree based ensemble methods and deep learning frameworks to (1) select the most essential environmental covariates affecting rain-grown cotton production, and (2) evaluate the predictive performance of these models. Results The environmental impacts on rain-grown cotton production were trait and growth-stage specific. Number of rainy days and solar radiation were identified as the most influential environmental factors for fibre yield traits, vapour pressure deficit at maximum daily temperature was the most influential factor for majority of fibre quality traits. However, each analysed trait was influenced by multiple environmental factors across multiple growth stages (rather than a single factor or a single growth stage). These influential covariates explained a wide range of variation in the traits, accounting for 5.8% to 68.2%. Using the best-fit random forest model, our findings revealed non-linear relationships between key environmental covariates and the traits. Conclusions Environmental factors at different rain-grown cotton growth stages are key determinants for the performance of end-of-season fibre yield and fibre quality parameters. These findings highlight the need to account for environment conditions when developing cotton varieties optimised for rain-grown production systems. Potential strategies are proposed whereby these key environmental factors can be used to increase the rate of genetic gain in rain-grown cotton production systems. Implications The results of this study will be crucial for future genetic evaluations and analyses of genotype-by-environment interaction effects in rain-grown cotton, which must account for the influence of the environment on plant performance. Furthermore, these methods can be applied to other species to identify critical growth stages and environmental factors which most influence crop performance.

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

CoRA: Confidence-Rationale Alignment for Reliable Chain-of-Thought Reasoning

Chain-of-thought (CoT) reasoning can improve LLM performance, but high answer confidence may be misleading when the accompanying CoT rationale is plausible yet incomplete or poorly supported. We study confidence–rationale alignment: whether a model's confidence in its committed answer is justified by its generated rationale. We introduce a GRPO-based reinforcement learning framework that jointly rewards answer correctness, committed-answer probability, and rubric-based rationale support, where the rubric assesses grounding, coherence, task match, and connection to the selected answer without revealing the gold answer to the judge. Across MedQA, MathQA, and OpenBookQA using three open-weight LLMs, our method reduces the confidence–rationale alignment error by up to 26.51% compared with untuned checkpoints, SFT, and correctness-only GRPO, while maintaining competitive accuracy and often improving calibration. These results show that reliable CoT reasoning requires not only confident answers, but rationales that substantively support them.

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

DRA-GRPO: Your GRPO Needs to Know Diverse Reasoning Paths for Mathematical Reasoning

Post-training LLMs with Reinforcement Learning, specifically Group Relative Policy Optimization (GRPO), has emerged as a paradigm for enhancing mathematical reasoning. However, standard GRPO relies on scalar correctness rewards that are often non-injective with respect to semantic content: distinct reasoning paths receive identical rewards. This leads to a Diversity-Quality Inconsistency, where the policy collapses into a narrow set of dominant modes while ignoring equally valid but structurally novel strategies. To bridge this gap, we propose Diversity-aware Reward Adjustment (DRA), a theoretically grounded framework that calibrates the reward signal using the semantic density of sampled groups. By leveraging Submodular Mutual Information (SMI), DRA implements an Inverse Propensity Scoring (IPS) mechanism that effectively de-biases the gradient estimation. This creates a repulsive force against redundancy, driving the policy to achieve better coverage of the high-reward landscape. Our method is plug-and-play and integrates seamlessly with GRPO variants. Empirical evaluations on five math benchmarks demonstrate that DRA-GRPO consistently outperforms strong baselines, achieving an average accuracy of 58.2% on DeepSeek-R1-Distill-Qwen-1.5B with only 7,000 training samples and $55 cost, highlighting the critical role of diversity calibration in data-efficient alignment. The code is available at https://github.com/xiwenc1/DRA-GRPO.

09.
arXiv (CS.CL) 2026-06-19

Characterizing Narrative Content in Web-scale LLM Pretraining Data

The narrative composition of web-scale LLM pretraining corpora remains largely unexplored even though narrative is a fundamental mode of human communication. We present the first fine-grained study of narrative features in Dolma, a 3-trillion-token open pretraining corpus. Drawing on narrative theory, we design a framework spanning three core narrative elements (agency, setting, and events) operationalized as 11 interpretable dimensions. After sampling and annotating a diverse set of 400 passages, we finetune and validate NarraBERT, a RoBERTa-based model for fine-grained narrative prediction. We apply NarraBERT to 3M passages, resulting in a new dataset, NarraDolma. We find (i) narrative structure is measurable at scale across extremely heterogeneous data, (ii) we uncover a continuous, multidimensional narrative structure underlying web text, and (iii) narrative qualities are unequally distributed across pretraining sources and topics in ways that current curation practices neither measure nor account for. Our framework, dataset, and analyses provide a foundation for understanding how narrative qualities are distributed in LLM pretraining data and for studying how data composition affects narrative reasoning tasks. We publicly release NarraDolma and NarraBERT.

10.
arXiv (CS.LG) 2026-06-16

Hidden Degradation Costs in Energy-Cost-Only HEMS Optimisation: Study on Battery and PV Sensitivity

arXiv:2606.16051v1 Announce Type: cross Abstract: Residential battery energy storage systems (BESS) are increasingly deployed alongside photovoltaic (PV) generation to reduce household energy costs under volatile time-of-use (TOU) tariffs. Model predictive control (MPC) is a widely adopted optimisation strategy for home energy management systems (HEMS), typically formulated to minimise net energy cost, subject to physical and operational constraints. However, battery degradation is rarely embedded in the optimisation objective, meaning its cost is unquantified and aggressive; high-cycle-count strategies could incur significant losses once deployed to physical systems. This paper presents a receding-horizon mixed-integer linear programming (MILP) baseline for a UK residential HEMS, using demand data from the REFIT dataset. A 3 by 3 sensitivity study is conducted across three battery sizes and three PV array sizes, with post-hoc degradation cost estimated using the Naumann stress model and rainflow cycle counting. Results show that degradation remains constant for each battery size and can exceed energy cost savings by up to 1,060 %. These results demonstrate that energy-cost-only optimisation systematically underestimates the true system cost, motivating a degradation-aware control formulation.

11.
arXiv (CS.CL) 2026-06-19

Trustworthy Multi-Agent Systems: Mitigating Semantic Drift with the Argent Signaling Protocol

When multi-agent LLM systems produce bad answers, not all failures are equal: some answers are grounded in the right material but incomplete, while others are simply ungrounded and should be stopped. Current retry strategies treat both cases identically (try again and hope for the best), leaving human supervisors unable to tell whether a retry was warranted or whether the system should have halted instead. We introduce the Argent Signaling Protocol (ASP), a compact machine-readable header that accompanies every AI-generated response with structured quality signals: certainty (@C), grounding (@G), stochasticity (@S), and an assumption index that classifies the evidentiary basis of each claim. These signals enable a controller to distinguish repairable failures from containment failures and route each case differently. We evaluate ASP in two modes. In standalone mode, a 27-question document-grounded QA benchmark over the Array BioPharma/Ono license agreement compares baseline prompts against ASP-instrumented controller actions across three local GGUF models. On Qwen~(0.8B), ASP improves pass rate from 11.1% to 33.3% and mean term coverage from 36.7% to 65.4%; on Dobby~(8B), ASP produces 4 fail-to-pass recoveries, raising pass rate from 33.3% to 44.4%; on SmolLM3~(3B), ASP alternates between repair and containment per question. Aggregate improvement is meaningful (12/81 to 21/81 passes). In multi-agent mode, an ASP sidecar sits between a retrieval agent and a downstream decision agent; the sidecar blocks 100% of ungrounded upstream outputs from reaching the downstream agent (24/27 blocked, 0 ungrounded propagations).

12.
arXiv (math.PR) 2026-06-24

A parameterized family of balance indices for phylogenetic networks

arXiv:2606.24562v1 Announce Type: cross Abstract: We introduce a new family of balance indices for phylogenetic networks: the $H_\alpha$ indices, where $\alpha$ is a positive real number. This family includes the $B_2$ index as a special case ($\alpha = 1$) and provides a natural extension of the Sackin index to phylogenetic networks. We show that the $H_\alpha$ indices share many structural properties with the $B_2$ index, most notably a "grafting property" that makes it possible to express the $H_\alpha$ index of a network in terms of the $H_\alpha$ indices of its biconnected components. These properties allow us to identify networks that minimize / maximize $H_\alpha$ for various classes of phylogenetic networks, and to study its distribution for several models of random trees and networks (in particular, Galton-Watson trees and binary Markov branching trees, with a focus on the Yule and PDA models). Finally, we show how local limits can be used to analyze the asymptotic behavior of $H_\alpha$ for large trees and networks, and we obtain general results for the moments of $H_\alpha$ for a broad class of random phylogenetic networks known as blowups of Galton-Watson trees.

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

Tight $L_\infty$ Sample Complexity for Low-Degree and Sparse Boolean Polynomials

arXiv:2606.17319v1 Announce Type: cross Abstract: Motivated by the optimization of bounded binary black-box functions, we study the problem of learning polynomial surrogates over the Boolean hypercube. To ensure that optimizing the surrogate yields good solutions for the underlying objective, we require uniform $L_\infty$-error guarantees rather than the usual $L_2$-type guarantees. We characterize the minimax sample complexity of uniform estimation under subgaussian noise for two classes of bounded polynomials. First, for polynomials of degree at most $d$ on $n$ variables, the sample complexity scales as $n^{d+1}$. Second, for $s$-sparse Fourier-Walsh polynomials with $s \leq n$, it scales as $ns^2$. These rates differ structurally from the noiseless setting, where uniform exact recovery scales as $n^d$ and $ns$, respectively. Our lower bounds hold even for arbitrary adaptive learners, showing that the additional factors are intrinsic to the noisy cases. Standard Fourier-analysis tools for the $L_2$-norm do not naturally extend to the $L_\infty$-setting in a way that yields uniform guarantees. Our proofs overcome this difficulty by relying on suitably chosen auxiliary norms that serve as proxies for controlling the $L_\infty$-error. Together, our results provide a tight characterization of the sample complexity of learning optimization-safe polynomial surrogates.

14.
medRxiv (Medicine) 2026-06-15

Instrumental Activities of Daily Living in Older Adults with Epilepsy: A Cross-Sectional and Longitudinal Multicenter Study

Objective: Instrumental activities of daily living (IADLs) represent a critical but understudied measure of day-to-day function in persons with epilepsy(PWE). In the multicenter Brain Aging and Cognition in Epilepsy (BrACE) study of PWE aged greater than or equal to 55 years, we examined the proportion, clinical correlates, epilepsy-related predictors, and longitudinal trajectory of IADL impairment. Methods: IADLs were assessed using the Functional Activities Questionnaire (FAQ; range=0 to 30; higher=more impaired); a FAQ greater than or equal to 2 defines MCI-level impairment, and a FAQ greater than or equal to 5 defines dementia-level functional impairment. Multivariable logistic regression identified predictors of baseline function. Global cognition (Montreal Cognitive Assessment [MoCA]), individual cognitive measures, and quality of life (QOL) were compared between the impaired and unimpaired groups. Linear regression evaluated predictors of longitudinal functional decline. Results: Of 57 participants (mean age=66.6 years; female=52.6%), 38.6% (n=22) had MCI-level functional impairment and 17.5% (n=10) had dementia-level functional impairment. In univariate analyses, worse FAQ scores were associated with lower education, higher area deprivation index, early-onset epilepsy (EOE less than 60 years), antiseizure medication polytherapy, and epilepsy localization. In multivariable analysis, temporal lobe epilepsy (OR=4.46, 95% CI=1.09, 21.83,p=0.047), EOE(OR=7.14, 95% CI=1.16, 59.97, p=0.046), and lower education(OR=0.70,95% CI=0.49, 0.93, p=0.025) remained independently associated with baseline MCI-level functional-impairment. Lower education (OR=0.55,95% CI=0.29, 0.84, p=0.021) was the only factor associated with dementia-level IADL-impairment. IADL-impaired participants demonstrated lower verbal memory scores (adjusted p=0.041) and MoCA scores (adjusted p

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

Evaluating Second-Order Bias of LLMs Through Epistemic Entitlement

Evaluations of social bias in LLMs largely focus on whether models generate or imply biased content. However, as LLMs are increasingly used as judges of bias, they may exhibit social biases in subtler ways in how they evaluate biased content, which current methods do not systematically capture. We call this second-order bias: social bias in an LLM's judgment about social bias, which we evaluate through a novel, philosophically grounded reasoning task. Drawing on entitlement epistemology, we conceptualize bias as misplaced foundational knowledge that shapes an agent's rational inquiry, and derive a logical reasoning task for LLMs to judge to whom a biased text is acceptable or non-acceptable. We develop two simple metrics to measure how biased LLM judges are in inferring demographics for acceptability without sufficient support, and how these inferences vary across groups targeted by biased texts. Evaluating open and closed models, we find that our task evades safety guardrails by surfacing bias in model judgment. It varies systematically across target groups, reflects implicit social maps, and shows how models are still triggered by demographic labels. Our work points to the need for LLM bias evaluation in judgment tasks and broadly, for more theoretically grounded approaches to bias evaluation in NLP. We release our code and model responses at https://github.com/uofthcdslab/second-order-bias.

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

Quantum optical photoelectron interferometry

arXiv:2606.13447v1 Announce Type: new Abstract: We present a general theoretical framework for multiphoton processes driven by quantum light fields, establishing a direct link between photon statistics and photoelectron observables. Our results show that the autocorrelation and cross-correlation functions, which quantify the underlying photon statistics, are directly mapped onto the resulting photoelectron spectra. Although our framework is broadly applicable, we demonstrate specifically in the example of reconstruction of attosecond beating by interference of two-photon transitions (RABBIT) the influence of the light statistical properties. In this approach, the amplitude, contrast and phase of the oscillations of the sideband signal as a function of pump-probe delay reveal the quantum nature of light. We analyze these observables across several quantum configurations, including correlated infrared and harmonic modes, as well as the uncorrelated case with non-classical harmonic statistics, thereby establishing a general framework for quantum-light RABBIT spectroscopy. We compare the analytical theory with numerical simulations for the case of classical harmonics and an infrared field in a squeezed coherent state, obtaining excellent agreement. Our results reveal how the interplay between classical and quantum correlations dictates the coherence of the photoemission process, providing a new window into the quantum-optical foundations of attosecond science.

17.
PLOS Computational Biology 2026-06-17

Deciphering cell type-specific causal genetic effects on brain imaging-derived phenotypes and disorders with single-cell Mendelian randomization

作者:

by Anyi Yang, Xingzhong Zhao, Xing-Ming Zhao, Yucheng T. Yang Reconstructing causality routes from genetic effects to complex phenotypes in particular cell types is crucial for understanding biological mechanisms underlying the brain-associated phenotypes including imaging-derived phenotypes (IDPs), and brain disorders and behaviors (DBs). Here, we develop a single-cell Mendelian randomization framework to infer cell type-specific causal relationships between gene expression and diverse brain-associated complex phenotypes by integrating single-cell expression quantitative trait loci (cis-eQTLs) and genome-wide association study findings. We identifiy a set of 254 and 217 cis-eQTL target genes (eGenes) that may have causal effects on 112 IDPs and 26 DBs in eight cell types, respectively. These causal eGenes exhibit strong cell type specificity and varied pleiotropy among different types of brain-associated phenotypes. Further integrative analysis reveals putative causality routes among cell type-specific causal eGenes and brain-associated complex phenotypes. Finally, we characterize the spatiotemporal expression patterns of these causal eGenes, and highlight the coordinated associations of the brain-associated phenotypes based on the expression of their causal eGenes. Overall, our study presents a large-scale analysis of the genetic effects of brain structures, disorders and behaviors, providing a catalog of cell type-specific causal eGenes.

18.
arXiv (quant-ph) 2026-06-24

Quantum turbulence in the many-body regime

arXiv:2606.23822v1 Announce Type: cross Abstract: We discuss phenomenology associated with turbulent hydrodynamics in quantum fluids from a condensed-matter perspective. We begin with weakly-interacting superfluids, often modeled by a mean-field theory governed by the Gross-Pitaevskii equation. Considering the effect of quantum fluctuations beyond the mean-field approximation, we propose a study of many-body quantum effects in turbulent hydrodynamics, especially near zero temperature. We motivate examples of quantum many-body systems where such effects may be uncovered. These include bosons confined in a periodic potential in low spatial dimensions (one and two), and the associated quantum critical point of the superfluid-insulator transition, realized in present-day ultracold-atom and quantum computing platforms. We conclude by listing a set of (open) questions that may be answered using modern quantum many-body techniques. This article is part of the theme issue 'Frontiers of turbulence and statistical physics'.

19.
bioRxiv (Bioinfo) 2026-06-16

scIsoAgent enables autonomous isoform-resolved characterization and sequence-informed interpretation of long-read single-cell transcriptomes

Alternative isoform usage can alter gene function independently of total gene expression, creating a need to resolve transcript isoforms at single-cell resolution. Long-read single-cell RNA sequencing meets this need by linking cellular identity to transcript isoforms and sequence-level features. Realizing its full biological value requires reproducible workflows that connect specialized long-read analysis with biological interpretation. Existing large language model (LLM)-based biomedical agents support general omics analysis, but are not designed for isoform-resolved long-read single-cell workflows. Here, we present scIsoAgent, an autonomous LLM-powered scientific agent for long-read single-cell RNA-seq analysis. scIsoAgent turns heterogeneous long-read single-cell inputs into traceable isoform-resolved workflows, using stage-aware planning and persistent computational context to support both execution and interpretation. Across complementary evaluations, this design improved the continuity from analysis planning to executable, interactive workflows compared with general-purpose LLM baselines. In real-data reanalysis, scIsoAgent recovered major findings from published long-read single-cell resources and extended a representative differential transcript usage event into a sequence-informed functional hypothesis. By linking full-length isoform sequences with model-inferred transcript properties, scIsoAgent connects observed isoform usage with potential sequence-level functional consequences. These results demonstrate that autonomous scientific agents can transform fragmented long-read single-cell analysis into coherent, reproducible workflows for isoform-resolved discovery and biological interpretation.

20.
arXiv (CS.AI) 2026-06-24

Reentrant value fields as delayed coupled reaction-diffusion systems on finite graphs

arXiv:2605.03940v4 Announce Type: cross Abstract: We describe a dynamical system in which a symbolic field is coupled to a geometric field via a bipartite Hilbert-Schmidt kernel. The system is fully described by a retarded functional differential equation (RFDE) on the history space, subject to Lipschitz and small gain conditions. We show that the RFDE is well-posed under constant input and that it admits a compact global attractor. The principal subsystem $(H_L, X_R, P)$, which is comprised of the two primary fields as well as an executive field, is shown to be globally stable independent of delay, provided that the interfield coupling satisfies $C_{\mathcal{K}}^2

21.
medRxiv (Medicine) 2026-06-15

Scalable estimation of temporal clustering in accelerometry: a kernel-independent dispersion index grounded in the Hawkes process

Background. Self-exciting (Hawkes) point processes are a natural model for the temporal clustering of human physical activity (PA) recorded by accelerometers, yet they have seldom been used in this setting—in part because the usual maximum-likelihood fitting is challenging due to potential estimation bias and convergence failures on these data. A moment-based alternative—estimating the Hawkes branching ratio from the dispersion index, the variance-to-mean ratio of event counts—is kernel-independent and computationally trivial, but it has not been evaluated for accelerometry or adapted to the intensity-marked recordings accelerometers provide. Methods. Treating each minute above a sedentary threshold as an event, we estimated the Hawkes branching ratio $n$ by maximum likelihood and, as a kernel-independent and far cheaper alternative, from the dispersion index. We compared four dispersion-based estimators—event-count-based, intensity-mark-weighted using the mark-moment ratio, and time-of-day (TOD) adjusted variants of each—against the marked and unmarked maximum-likelihood estimates. Estimators were evaluated for mutual agreement, goodness of fit, and finite-window results in two National Health and Nutrition Examination Survey (NHANES) accelerometry cohorts (hip-worn, $n=2{,}560$; wrist-worn, $n=3{,}132$). We related the resulting temporal clustering measures to all-cause mortality using survey-weighted Cox models, adjusting for PA frequency, Peak30 (the average of the 30 highest PA values), and demographic covariates. Results. Event-count-based dispersion estimates agreed strongly with maximum-likelihood branching ratios ($rapprox0.74$ in both cohorts); the intensity-marked variant incorporating PA intensity variability agreed less well. Marked and unmarked Hawkes models yielded similar excitation and decay parameters, suggesting PA intensity added little clustering information beyond event timing. In the survival analysis, temporal clustering was associated with all-cause mortality independently of PA frequency and Peak30; the direction of association differed between the hip- and wrist-worn cohorts. Conclusions. A scalable dispersion-index estimator recovers the Hawkes branching ratio and matches maximum-likelihood estimates without requiring kernel specification or iterative optimization. It offers a practical tool for quantifying temporal clustering in accelerometry, enabling decomposition of temporal PA patterns into its exogenous initiation and endogenous persistence. Such temporal patterns carry health-relevant information beyond PA intensity and volume. Keywords: dispersion index; Hawkes process; branching ratio; temporal clustering; point process estimation; accelerometry; mortality

22.
medRxiv (Medicine) 2026-06-15

SPIRIT-CONSORT-ELM: Element-Level Assessment of Randomized Controlled Trial Reporting Using Large Language Models

Randomized controlled trials (RCTs) play a central role in assessing the benefits and harms of interventions. Incomplete reporting in RCT publications can compromise the verifiability and usefulness of RCTs. SPIRIT and CONSORT reporting guidelines aim to improve the completeness of RCT protocols and results publications, respectively. However, many RCTs are not reported completely. Checking manuscripts automatically could help authors improve the completeness of reports prior to publication. We previously annotated SPIRIT-CONSORT-TM, a corpus of 200 articles (comprising 100 protocol-results publication pairs) using 83 checklist items drawn from SPIRIT 2013 and CONSORT 2010. We also trained machine learning models to automatically assess reporting at the item level. Each checklist item can include multiple constituent elements (i.e., specific details required for that item), and an item might be considered fully reported when all of its elements are present. However, prior work does not explicitly capture or evaluate reporting at the element level. To address this gap, we extended SPIRIT-CONSORT-TM by incorporating element-level annotations and using them to assess reporting completeness (SPIRIT-CONSORT-ELM). We formulated element-level assessment as a machine reading comprehension task, operationalized through 119 questions, where each question targets a specific reporting element within a checklist item. Using the 200 articles included in SPIRIT-CONSORT-TM, two annotators independently answered 119 questions for 50 articles (25 protocol-results pairs) and resolved any discrepancies through discussion; the remaining 150 articles (75 protocol-results pairs) were assessed by a single annotator. We then developed an automated pipeline for element-level assessment using SPIRIT-CONSORT-ELM. The pipeline first applies a PubMedBERT-based model to identify sentences containing item-level reporting information, then it uses a generative large language model (LLM; GPT-5) with chain-of-thought reasoning to answer element-level questions based on the retrieved evidence. Agreement between the two annotators was high (Gwet's AC1: 0.782) and our pipeline achieved high accuracy in identifying element-level reporting evidence (F1: 0.822, Gwet's AC1: 0.796). Ablation studies indicate that chain-of-thought reasoning and the inclusion of illustrative in-context examples modestly improve LLM performance on the machine reading comprehension task. SPIRIT-CONSORT-ELM provides a benchmark for evaluating reporting guideline completeness at the element level, enabling assessment of RCT transparency beyond the simple presence or absence of checklist items and is publicly available at https://osf.io/kznx4/. The automated pipeline establishes a robust baseline for assessing RCT reporting and demonstrates potential as a practical aid for authors, reviewers, and editors to identify and address gaps in completeness and transparency of RCT reports.

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

FOSC-X: An Extended Framework for Optimal Local Cuts and Non-Horizontal Cluster Selection from Clustering Hierarchies

arXiv:2606.18972v1 Announce Type: cross Abstract: Extracting a flat clustering solution from a hierarchy is a common task in practical cluster analysis and can be formulated as an optimisation problem. Existing approaches focus on finding a single optimal solution. We introduce FOSC-X, a framework for extracting the top-M globally optimal flat clusterings from local, non-horizontal cuts of a hierarchical cluster tree, while optionally enforcing constraints on the number of clusters. This enables automatic identification of multiple high-quality alternative clusterings that capture different aspects of the hierarchical structure. Without constraints, the top-M problem can be solved in polynomial time using dynamic programming, exploiting the property that locally optimal partial candidates within subtrees can be combined to form globally optimal solutions while automatically determining the number of clusters. However, this can lead to solutions with numbers of clusters that are ultimately undesirable – e.g., too large to be meaningful or practically analysed within a particular application domain. Imposing cluster-count constraints breaks the optimality property underlying the unconstrained dynamic programming approach, since locally optimal partial candidates may no longer combine into feasible globally optimal solutions. FOSC-X addresses this challenge through a dynamic programming strategy that maintains compact sets of feasible candidates using lower and upper feasibility bounds while pruning infeasible or dominated combinations. The resulting method guarantees optimal rankings of the top-M solutions with linear-time complexity in the number of cluster nodes and dataset size, both with and without cluster-count constraints. Experiments show that FOSC-X efficiently reveals alternative clustering structures overlooked by single-solution extraction methods.

24.
medRxiv (Medicine) 2026-06-16

Development and reliability and validity test of the Questionnaire on Knowledge, Attitude and Practice of ICU Nurses on Blood Oxygen Saturation Management in Mechanically Ventilated Patients

Objective: A questionnaire on the knowledge, attitude and practice of ICU nurses regarding the management of blood oxygen saturation in patients with mechanical ventilation was compiled, and its reliability and validity were tested. Method: Drawing upon the knowledge-attitude-practice theory, the initial questionnaire draft was developed through literature review and consultation with Delphi experts. Employing convenience sampling, 32 nurses from the General ICU of Wuxi Second People's Hospital were surveyed between 1 August 2025 and 27 September 2025, enabling item screening and assessment of reliability and validity.The full version of the developed questionnaire is provided as Supporting Information (S1 File). All items are published under a CC BY 4.0 license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Result: A questionnaire on the knowledge, attitude and practice of ICU nurses regarding the management of blood oxygen saturation in mechanically ventilated patients was finalised, comprising 26 items: 11 in the knowledge dimension, 6 in the attitude dimension and 9 in the behaviour dimension. The overall Cronbach's coefficient for the questionnaire was 0.88, with dimension-specific coefficients of 0.787, 0.722, and 0.781 respectively. The Spearman-Brown coefficient for the entire questionnaire was 0.967, while dimension-specific coefficients were 0.796, 0.666, and 0.728 respectively. The content validity index at the questionnaire level (S-CVI) was 0.886, and the item-level content validity index (I-CVI) ranged from 0.913 to 0.967. 0.728. The questionnaire's level content validity index (S-CVI) was 0.886, and the item level content validity index (I-CVI) ranged from 0.913 to 1.00. Conclusion: The questionnaire on knowledge, attitude and practice of blood oxygen saturation management in mechanically ventilated patients demonstrates good reliability and validity. It may serve as an assessment tool for intensive care unit nurses regarding their knowledge, attitude, and practices concerning blood oxygen saturation management in mechanically ventilated patients, thereby establishing a foundation for developing targeted intervention strategies in future practice.

25.
medRxiv (Medicine) 2026-06-16

Daily Healthy Eating Index (HEI-2020) scoring reveals diet quality patterns masked by aggregation

The Healthy Eating Index (HEI-2020) is conventionally computed by aggregating intake across days before scoring. Digital food logging enables an alternative: scoring each day and averaging daily scores. These methods are not equivalent. The HEI's density-based structure and component caps cause aggregation to inflate adequacy scores when intake is irregular. Using Food & You data, we show daily HEI correlates more strongly with microbiome diversity, and recommend co-reporting both metrics.