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

Global Ease of Living Index: a machine learning framework for longitudinal analysis of major economies

arXiv:2502.06866v3 Announce Type: replace-cross Abstract: The drastic changes in the global economy, geopolitical conditions, and disruptions such as the COVID-19 pandemic have impacted the cost of living and quality of life. It is essential to comprehend the long-term implications of the cost of living and quality of life in major economies. A transparent and comprehensive living index must include multiple dimensions of living conditions. In this study, we present an approach to quantifying the quality of life through the Global Ease of Living Index that combines various socio-economic and infrastructural factors into a single composite score. Our index utilises economic indicators that define living standards, which could help in targeted interventions to improve specific areas. We present a machine learning framework to address missing data for certain economic indicators in specific countries. We then curate and update the data and use a dimensionality reduction approach (Principal Component Analysis and Factor Analysis) to create the Ease of Living Index for major economies since 1970. Our work significantly adds to the literature by offering a practical tool for policymakers to identify areas needing improvement, such as healthcare systems, employment opportunities, and public safety. Our approach with open data and code can be easily reproduced and applied to various contexts, providing transparency and accessibility for ongoing research and policy development in quality-of-life assessment.

02.
Nature (Science) 2026-06-17

Reimagining machine vision with optical computing

作者: 未知作者

A general-purpose artificial-intelligence vision system for use in image-sensing devices has been developed by embedding fundamentals of core computer-vision operations into a light-manipulating planar material called an optical metasurface. A prototype enables accurate, real-time perception and processing across diverse tasks, suggesting that this could be a solution for rapid, low-energy, on-device vision intelligence. A specialized ‘metasurface’ can preprocess incoming scene information on image-generating devices.

03.
arXiv (math.PR) 2026-06-16

Sharp freezing time estimates for the subcritical Facilitated Exclusion Process

arXiv:2606.15233v1 Announce Type: new Abstract: We investigate the exact transience time of the Facilitated Exclusion Process (FEP) on the one-dimensional torus with $N$ sites. The FEP exhibits an active/inactive phase transition at critical density $1/2$, such that in the subcritical density regime $(0,1/2)$, it becomes frozen after a finite time period – the transience time or freezing time. We first show that for the FEP starting from a Bernoulli product measure of marginal density $\rho \in (0,1/2)$, the transience time has exactly the scale of $\Theta(\log^3 N)$. Secondly, we prove that in the near-critical case $\rho \simeq 1/2 - N^{-\alpha}$ for $\alpha \in (0,1)$, the transience time is polynomial and has a scale of $N^{1 \wedge (2\alpha)}$. The key idea is to estimate the typical size of locally supercritical intervals of the initial distribution, which has order $\log N$ in the subcritical case and $N^{1 \wedge (2\alpha)}$ in the near-critical case. In the subcritical case this is enough, whereas in the near-critical case we need additional dynamical decorrelation inequalities to apply this static result to estimate the freezing time.

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

Slots, Transitions, Loops: Learning Composable World Models for ARC

ARC tests in-context rule induction: given a few input-output demonstrations, a model must infer the hidden rule and apply it to a new query. While many approaches express ARC rules through language, code, or symbolic programs, ARC itself is visual-symbolic: rules appear as grid transitions over objects, colors, shapes, and spatial relations. We introduce Loop-OWM, an object-centric world-modeling architecture that learns these rules as composable transitions over structured states. It combines color-prototype slots, demonstration-conditioned task summaries, and a looped transition model with dense propagation and slot-conditioned correction. On both ARC-1 and ARC-2, Loop-OWM outperforms non-looped and looped baselines with comparable or fewer parameters. These results suggest that ARC rules can be learned not only as language descriptions or searched programs, but also as transitions over visual-symbolic world states.

05.
Nature Biotechnology 2026-06-19

Efficient site-specific gene addition using R2 retrotransposons in tobacco and rice

作者:

Precise integration of multikilobase DNA fragments remains a major technical barrier in plants. Here we introduce non-long terminal repeat (non-LTR) R2 retrotransposons as a versatile system for targeted gene integration in plants. We reconstituted R2 activity in Nicotiana benthamiana and benchmarked insertion efficiency and fidelity using a TMV-based episomal reporter system. We demonstrate site-specific integration of GFP (2.2 kb) and recombinase-compatible landing pads (0.6 kb) into 28S rDNA arrays, with intact cassette insertion frequencies up to 75% and 53%, respectively. To temporally constrain donor availability and avoid DNA intermediates, we combined in planta effector expression with recombinant RNA virus-mediated donor delivery. We apply R2 retrotransposons for targeted insertion of resistance cassettes within the rDNA of rice callus, achieving integration efficiencies up to 17%. These results position R2 retrotransposons as a double-strand break-free system for RNA-templated insertion of multikilobase gene cassettes at rDNA loci, for safe-harbor trait stacking in plants with potential applications in crop improvement and synthetic biology. Retrotransposons are applied in plants for safe-harbor transgene integration.

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

HarnessBridge: Learnable Bidirectional Controller for LLM Agent Harness

arXiv:2606.12882v1 Announce Type: new Abstract: Large language models are increasingly deployed as agents for long-horizon tasks, yet their performance is shaped not only by model capability and environment design, but also by the harness that mediates agent–environment interaction. Existing harnesses are largely manually engineered, making them difficult to scale as trajectories grow longer and interactions become more complex. In this work, we ask whether harness can be generated by a learnable plug-in module that can be trained in an end-to-end fashion. We introduce HarnessBridge, a lightweight learnable harness controller that parameterizes the agent–environment interface as a bidirectional projection. HarnessBridge learns two bidirectional projections: observation projection, which distills raw trajectories into compact, decision-relevant states, and action projection, which converts proposed actions into executable transitions or trajectory-grounded rejections. We train HarnessBridge on a harness supervision dataset via unified instruction tuning. On Terminal-Bench~2.0 and SWE-bench Verified, HarnessBridge matches or surpasses strong specialized harnesses while substantially reducing token usage and trajectory length, and generalizes from smaller generators to larger commercial models.

07.
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.

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

ProvenanceGuard: Source-Aware Factuality Verification for MCP-Based LLM Agents

Tool-using LLM agents increasingly use the Model Context Protocol (MCP) to answer from heterogeneous evidence sources, including search, APIs, databases, clinical records, and formulary tools. Standard factuality metrics usually test whether an answer is supported by pooled evidence, missing a provenance-sensitive failure mode: a claim may be supported somewhere while being attributed to the wrong source. We call this cross-source conflation. We introduce ProvenanceGuard, a source-aware verifier for MCP-grounded answers. It consumes captured MCP traces with stable tool IDs, source IDs, and raw outputs; decomposes answers into atomic claims; routes claims to source-specific evidence; checks support with NLI and a token-alignment proxy; compares stated attribution with the routed source; and returns per-claim verdicts plus an answer-level allow/block decision. Blocked answers can be repaired with retrieval-augmented answer revision and re-verified. We evaluate on 281 medical-domain MCP-agent traces. A 266-trace adjudicated subset yields 2,325 LLM-assisted claim labels split by trace; 361 held-out labels are human-verified. On the 40-trace held-out split, ProvenanceGuard achieves block F1 0.802 and source accuracy 0.858 over 260 source-eligible claims, outperforming source-blind baselines that do not emit claim-to-source IDs. On a harder multi-source benchmark it reaches block F1 0.846, while source-plus-relation accuracy drops to 0.229, showing that exact source ownership remains difficult with semantically close sources. Repair-and-reverify resolves all blocked answers in the full trace set, often via conservative fallback. In 50 controlled clinical conflation probes, ProvenanceGuard detects all injected attribution swaps with no retained wrong attribution. These results show that source attribution is an independent axis for factuality verification in MCP-based agents.

09.
arXiv (quant-ph) 2026-06-15

Quantum geometrical description of hole spin qubits far away from the $\Gamma$-point

arXiv:2606.14683v1 Announce Type: cross Abstract: Hole spin qubits provide one of the leading platforms for spin-based quantum computing due to their large intrinsic spin-orbit interaction (SOI), which enables fast electrical manipulation. The SOI of planar quantum dots has mostly been investigated in theoretical studies by examining the SOI already present in the two-dimensional hole gas (2DHG). Here, we study the SOI created by the in-plane confinement by deriving non-perturbative effective Hamiltonians numerically for hole spin qubits. We find that the quantum geometry of the 2DHG naturally emerges, leading to a meaningful non-perturbative definition of pseudospin valid far away from the $\Gamma$-point. The SOI of the 2DHG and of the in-plane confinement have different forms; therefore, they cannot be turned off simultaneously, ruining the perfect spin-orbit switch functionality of spin qubits. We construct effective Hamiltonians using the symmetry approach for various low-dimensional hole systems: (i) a heavy-hole confined in a SiGe/Ge/SiGe heterostructure, (ii) a light-hole confined in SnGe/Ge, (iii) a gate-defined nanowire in SiGe/Ge/SiGe, and (iv) a hole confined in a Ge/Si core/shell nanowire. The non-perturbative effective Hamiltonians provide results with excellent agreement with the full Hamiltonians.

10.
arXiv (CS.CL) 2026-06-17

Dynamic Rollout Editing for Reducing Overthinking in RL-Trained Reasoning Models

Long-form chain-of-thought reasoning can improve LLM performance on complex tasks, but models often continue generating unnecessary reasoning after a correct answer has emerged. We refer to this behavior as overthinking. We study this phenomenon from the perspective of GRPO-style reinforcement learning (RL) post-training, framing it as a training-time credit-assignment problem rather than merely a decoding-time stopping problem. In rollouts sampled at the onset of GRPO training, we observe that successful trajectories can exhibit a slightly higher degree of overthinking than unsuccessful trajectories for the same prompts. This early imbalance provides a starting point for an undesirable feedback loop: because GRPO assigns sequence-level credit, it cannot distinguish the solution-reaching prefix from the unnecessary continuation that lengthens a successful trajectory. Both receive positive update signal, allowing the initial imbalance to grow into more severe overthinking during training. To address this issue, we introduce Dynamic Rollout Editing (DRE), a training-time intervention for successful trajectories that continue thinking after answer emergence. DRE preserves the accepted verified prefix, edits the remaining thinking, and prefers the edited trajectory within the same RL group, weakening the preference signal for unnecessary thinking without penalizing the reasoning needed to reach the answer. Experiments across diverse tasks show the effectiveness of DRE.

11.
Nature Medicine 2026-06-12

Efficacy and target engagement of dopamine agonist pramipexole for anhedonic depression: a randomized placebo-controlled trial

Anhedonia is a core and disabling symptom of mood disorders with limited treatment options. We evaluated the efficacy and safety of the dopamine agonist pramipexole in patients with mood disorders characterized by clinically significant anhedonia. In this single-center, randomized, double-blind, placebo-controlled trial, adults with major depressive disorder, dysthymia or bipolar depression and elevated Snaith−Hamilton Pleasure Scale (SHAPS) scores were assigned (1:1) to flexible dose, once-daily oral pramipexole as add-on treatment or placebo for 9 weeks. The primary outcome was change in SHAPS score from baseline to week 9. Analyses were conducted in the modified intention-to-treat population. Eighty-five participants were randomized, and 82 were included in the analysis. The primary outcome was met: pramipexole was associated with a greater reduction in SHAPS scores compared to placebo (mean difference: −4.04, 95% confidence interval: −6.89 to −1.18, P = 0.006, Hedges’ g = 0.62). Exploratory analyses indicated that pramipexole was associated with increased light physical activity and relative preservation of reward-related ventral striatal activation. Improvements in anhedonia were sustained during a 6-month open-label extension. Pramipexole was generally well tolerated compared to placebo. Pramipexole significantly improved anhedonia and showed a favorable safety profile, supporting its potential as an augmentation strategy in mood disorders. ClinicalTrials.gov identifiers: NCT05355337 and NCT05825235 . Pramipexole, in patients with major depressive disorder, dysthymia or bipolar depression, reduced Snaith−Hamilton Pleasure Scale scores significantly compared to placebo.

12.
arXiv (quant-ph) 2026-06-15

Quantum codes and optimal pure quantum $(r,\delta)$-LRCs via the MP construction

arXiv:2606.14253v1 Announce Type: new Abstract: In this paper, we employ MP codes whose defining matrices are $\tau$-optimal defining ($\tau$-OD) matrices to construct new quantum codes and quantum $(r,\delta)$-LRCs. Specifically, we report the following results: We establish a unified $\tau$-monomial decomposition theorem for invertible self-adjoint matrices over finite fields of arbitrary characteristic, which generalizes the result in "Quantum codes using the $\tau$-OD MP construction" where the characteristic was required to be odd. Based on this theorem, we prove the existence of $\tau$-OD matrices over $\mathbb{F}_{q^2}$ for any characteristic and demonstrate that there exist several new infinite families of $\tau$-OD matrices over $\mathbb{F}_{q^2}$ of characteristic $2$. As an application of MP codes involving $\tau$-OD matrices, we construct several infinite families of quantum codes with flexible parameters. Within this framework, we present $222$ record-breaking quantum codes that surpass the best-known records maintained in Grassl's database. We propose two effective schemes for constructing optimal pure quantum $(r,\delta)$-LRCs via MP codes. Accordingly, we construct four new infinite families of optimal pure quantum $(r,\delta)$-LRCs with flexible parameters. Notably, we report an interesting phenomenon by exhibiting $30$ optimal pure quantum $(r,\delta)$-LRCs derived from our framework; that is, there exist quantum codes that are not only optimal pure quantum $(r,\delta)$-LRCs but also, according to Grassl's database, best-known, optimal, or record-breaking quantum codes. To the best of our knowledge, the new discovery that quantum codes are simultaneously optimal pure quantum $(r,\delta)$-LRCs and record-breaking quantum codes has not been previously reported in the literature.

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

Critical Percolation as a Synthetic Data Model for Interpretability

arXiv:2606.20347v1 Announce Type: new Abstract: Neural networks learn features that reflect the hierarchical, multi-scale structure of natural data. Synthetic datasets used to evaluate interpretability methods typically lack this structure, limiting their value as realistic toy models. To close this gap, we introduce a family of synthetic datasets consisting of hierarchical functions defined on critical mean-field percolation clusters embedded in a high-dimensional data space. The percolation data consists of sparse, low-dimensional fractal clusters with a power-law size distribution. Latent variables modeling a taxonomic hierarchy generate each data point's target value. The data model is analytically tractable with known critical exponents that fix its properties without requiring hyperparameter tuning. We leverage a mapping between percolation clusters, random trees, and additive coalescence to propose an almost linear-time algorithm to jointly sample a random tree and its hierarchical latent decomposition, enabling data generation at arbitrary scale. Using probing experiments, we find that the model's ground-truth latent variables can be linearly decoded from neural network activations. Together, sparsity, self-similarity, power-law statistics, and analytical tractability make critical percolation a principled testbed for interpretability research.

14.
arXiv (math.PR) 2026-06-17

Persistence diagrams of random triangular matrices over finite fields

arXiv:2606.17895v1 Announce Type: cross Abstract: Let us consider a random infinite lower triangular matrix, where the entries on and below the diagonal are i.i.d. uniform random elements of a fixed finite field. We investigate the evolution of the span of the first $n$ rows of this matrix as $n$ grows. Many properties of this evolving subspace can be captured with the help of the verbose persistence diagram, which is a standard tool in stochastic topology and topological data analysis. We give an explicit formula for the distribution of the persistence diagram. We prove a law of large numbers for the distribution of lifetimes. We also describe the fluctuations of the persistent Betti numbers.

15.
arXiv (CS.CV) 2026-06-11

XPR: An Extensible Cross-Platform Point-Based Differentiable Renderer

Point-based differentiable rendering underpins modern 3D reconstruction, novel-view synthesis, and learning-based graphics pipelines, but developing new rendering methods often requires extensive low-level implementation, hardware-specific kernels, and manually written backward passes. This limits rapid prototyping, reproducibility, exploration, and deployment, especially across diverse hardware platforms. This paper presents XPR, an extensible cross-platform framework for point-based differentiable rendering. XPR introduces a high-level programming interface that separates method-specific logic from the shared rendering pipeline, allowing users to implement new methods in a few lines of code. Its pipeline decomposes rendering into modular, statically shaped parallel operations that can be lowered by a cross-platform compiler to GPUs, TPUs, CPUs, and other ML accelerators. We demonstrate implementations of 3DGS, 3DGUT, and LinPrim, with only a few 100s lines of Python code, each of which can be compiled to a range of hardware platforms with the XLA compiler. These results show that XPR enables fast experimentation and portable execution for emerging point-based differentiable rendering systems.

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

RAIL: Rethinking Auditory Intelligence in Large Audio-Language Models with a CHC-Grounded Benchmark

arXiv:2606.11260v1 Announce Type: cross Abstract: Humans process rich auditory environments through tightly integrated cognitive capabilities such as audio perception, audio reasoning, and memory. Despite recent progress in large audio-language models (LALMs) across speech understanding and multimodal audio reasoning, current evaluation paradigms remain largely task- or modality-centric, focusing on end performance while overlooking underlying auditory cognitive behaviours. This reveals a fundamental gap between how auditory cognition is understood in humans and how it is evaluated in LALMs, particularly in the lack of frameworks that operationalise cognitive principles beyond task-level metrics to systematically capture model behaviour. In this work, we introduce RAIL, a human-centric evaluation paradigm grounded in the Cattell-Horn-Carroll (CHC) cognitive framework. RAIL formalises auditory cognition into five core capabilities and develop them into structured evaluation tasks that probe how models process, retain, and integrate auditory information. We further construct a cognitively grounded benchmark with principled data curation and human-aligned evaluation protocols. Evaluating 26 state-of-the-art LALMs, we find that current models exhibit highly uneven performance across cognitive abilities. RAIL establishes a new evaluation paradigm that moves beyond task-centric benchmarking toward cognitively grounded assessment of auditory intelligence.

17.
arXiv (math.PR) 2026-06-17

Optimal Impulse Control for Cyber Risk Management

arXiv:2410.17706v2 Announce Type: replace-cross Abstract: We explore an optimal impulse control problem wherein an electronic device owner strategically calibrates protection levels against cyber attacks. Utilizing epidemiological compartment models, we qualitatively characterize the dynamics of cyber attacks within the network. We determine the optimal protective measures against effective hacking by formulating and solving a stochastic control problem with optimal switching. We demonstrate that the value function for the cluster owner constitutes a viscosity solution to a system of coupled variational inequalities associated with a fully coupled reflected backward stochastic differential equation (BSDE). Furthermore, we devise a comprehensive algorithm alongside a verification procedure to ascertain the optimal timing for network protection across various cyber attack scenarios. Our findings are illustrated through numerical approximations employing deep Galerkin methods for partial differential equations (PDEs). We visualize the optimal protection strategies in the context of two distinct attack scenarios: (1) a constant cyber attack, (2) an exogenous cyber attack strategy modeled with a Poisson process.

18.
arXiv (CS.LG) 2026-06-19

Flow Map Denoisers: Traversing the Distortion-Perception Plane for Inverse Problems

arXiv:2606.19802v1 Announce Type: new Abstract: Image restoration faces a fundamental tradeoff: methods that minimize error produce blurry reconstructions, while those that maximize perceptual quality yield sharp but less faithful images. Existing approaches either commit to a single operating point on this distortion perception (DP) frontier or require paired-data supervision, auxiliary models, or hyperparameter tuning of the sampler to access different points. We show that flow map models, a recent extension of flow matching for few-step sampling that learns an average field, implicitly define a one-parameter family of denoisers that continuously spans the DP frontier. The lookahead parameter t acts as a control knob between the MMSE and perceptual regimes. For Gaussian targets, we prove that varying t exactly recovers the optimal DP frontier; for natural images, we observe similar behavior empirically. Within a Plug-and-Play solver, the same mechanism extends to general inverse problems, where it controls a tradeoff between perceptual alignment and data consistency. Despite the lack of exact optimality guarantees in this setting, a single trained flow map spans the DP tradeoff, matching or exceeding specialized baselines at both extremes. Extensive experiments on CelebA ($128\times 128$) and AFHQ ($256\times 256$) across several linear and nonlinear inverse tasks validate our findings.

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

Programmable Gauge-Field Textures with Ultracold Atoms in Momentum Space

arXiv:2606.15124v1 Announce Type: cross Abstract: Synthetic gauge fields with ultracold atoms offer a route to quantum matter in which electromagnetic environments can be designed rather than merely imposed. While the Harper-Hofstadter model has been realized in several cold-atom systems, existing implementations are largely limited to spatially uniform magnetic fluxes. Here we experimentally realize a highly programmable two-dimensional momentum-state lattice of ultracold atoms with local control over the Peierls phase pattern, enabling direct implementation of Harper-Hofstadter Hamiltonians with tunable and spatially structured synthetic gauge fields. We observe a crossover from ballistic to strongly flux-modified bulk dynamics with suppressed transport. By introducing a synthetic electric field through site-dependent energy gradients, we further demonstrate Hall-type transverse drift arising from the interplay between electric and magnetic fields. In addition, we engineer a synthetic flux domain wall separating regions with opposite magnetic fluxes and observe anisotropic propagation guided along the interface. These results move cold-atom gauge-field engineering from uniform magnetic backgrounds toward designer gauge textures, providing an experimental setting for transport across programmable topological interfaces.

20.
arXiv (quant-ph) 2026-06-19

All-valid-state HOBO encoding for constrained combinatorial optimization on NISQ devices

arXiv:2606.20017v1 Announce Type: new Abstract: Continued advancements in quantum computing have stimulated growing interest in translating quantum technologies into real-world applications. Consequently, the investigation of practically motivated NP-hard problems is of significant value. This study investigates the performance of a variational quantum eigensolver (VQE) in addressing the traveling salesperson problem (TSP) through noiseless simulations representative of noisy intermediate-scale quantum (NISQ) devices using higher-order binary optimization (HOBO) encodings. We construct a HOBO Hamiltonian with an efficient binary representation and propose an all-valid-state HOBO (AVS-HOBO) scheme based on cyclic mapping that eliminates one penalty term and reuses states that would otherwise be invalid. Using TSP instances of up to 20 cities, we compare the original HOBO and AVS-HOBO encodings from multiple perspectives, including the energy convergence behavior and the approximation, tour-length, and feasibility ratios. In addition to simulations, we perform computations on real quantum hardware with different device architectures, where we not only compare the performances of different chips but also investigate the effects of different error-mitigation methods on actual quantum machines. The results indicate that AVS-HOBO encoding enhances the practical reliability of VQE on NISQ devices and improves scalability for larger TSP instances, with broader applicability to constrained quantum optimization problems.

21.
medRxiv (Medicine) 2026-06-12

An integrative multi-omics framework identifies epigenetic dysregulation of HAND2 as a potential primary driver of impaired enteric neural crest cell differentiation in Hirschsprung Disease

Hirschsprung disease (HSCR) is a congenital neurodevelopmental disorder characterized by segmental aganglionosis due to impaired developmental processes of enteric neural crest cells (NCCs). Despite being the leading genetic cause of functional intestinal obstruction in early childhood, HSCR represents a paradigmatic challenge in precision medicine: its multifactorial etiology, complex gene-environment interactions and limited resolution of single-modality analyses have long hindered mechanistic understanding and therapeutic translation. Here, we applied an integrative multi-omics approach combining genetic, phenotypic, epigenomic and transcriptomic analyses of matched ganglionic and aganglionic formalin-fixed paraffin-embedded (FFPE) patient tissues, complemented by patient-specific in vitro models. Beyond established genetic contributors, our integrative approach reveals novel regulatory pathways predominantly affecting enteric NCC differentiation, with convergent evidence pointing to epigenetic dysregulation as a primary disease mechanism. Notably, we identified over 1,300 differentially methylated positions between ganglionic and aganglionic FFPE samples, with HAND2 emerging as a key candidate due to multiple hypermethylated sites and consistently reduced expression levels in aganglionic tissues and in vitro models, suggesting a potential role in HSCR pathophysiology. We propose that our multi-omics approach offers a powerful and comprehensive framework for dissecting disease mechanisms. Beyond advancing biological understanding, this strategy holds promise for paving the way for molecularly informed patient stratification and supporting the development of personalized treatment and postoperative management strategies.

22.
medRxiv (Medicine) 2026-06-16

Deployment-readiness audit of calibration, clinical utility, and fairness in perioperative infection prediction

Objective: Clinical risk scores intended to guide patient-level decisions can show strong average performance. However, predicted probabilities can be systematically too high or too low in specific subgroups even when overall performance is strong. We audited deployment readiness of a strong end-of-surgery postoperative infection model across clinically relevant subgroups and tested mitigation strategies in miscalibrated subgroups. Materials and Methods: We analyzed out-of-fold predictions for 10,719 surgical procedures at a Swiss tertiary hospital, with 504 postoperative bacterial infection events. Prespecified axes were recorded sex, age stratum, and an EHR-derived physiological-reserve proxy. Within subgroups and pairwise intersections, we evaluated discrimination, calibration, threshold-specific errors, and decision-curve net benefit at the prespecified operating threshold. We compared group-specific isotonic recalibration with Wasserstein-barycenter postprocessing and demonstrated portability in SUPPORT2. Results: Overall AUROC was 0.876. While sex-marginal discrimination was similar in women and men (0.878 vs 0.875), age and reserve stratification revealed deployment-readiness failures. Calibration-in-the-large ranged from -0.86 in frail patients to -2.47 in non-frail patients. At the 0.10 operating threshold, decision-curve net benefit was positive in frail patients but negative in pre-frail and non-frail patients. Isotonic recalibration corrected average physiological-reserve-stratified calibration without worsening Brier scores, whereas Wasserstein postprocessing worsened calibration in most procedure clusters. Discussion: Discrimination-only or sex-marginal evaluation would have missed subgroup failures with clinical-utility implications. Conclusion: Subgroup fairness audits for clinical deployment should jointly evaluate discrimination, calibration, and utility. We implemented the audit as the open-source isitfair framework for identifying deployment-relevant subgroup failures, comparing mitigation strategies, and generating structured reports.

23.
arXiv (CS.AI) 2026-06-11

When Do Data-Driven Systems Exhibit the Capability to Infer?

arXiv:2606.11769v1 Announce Type: new Abstract: The European AI Act is the first comprehensive regulation of artificial intelligence (AI), setting out extensive obligations, particularly for so-called high-risk and general-purpose AI systems. A key distinguishing feature of AI systems under the AI Act is the capability to infer. Since the AI Act does not clearly define what inference is, there is a gray area for certain data-driven systems. A specific example is credit scoring systems, which are listed by Annex III of the AI Act. At the same time, however, these are often implemented using statistical models for which it is unclear whether they have the capability to infer and thus fall under the AI definition of the AI Act at all. Motivated by statistical learning theory, this work develops a framework for grading different levels of the capability to infer. Based on the AI Act and the Commission Guidelines on the definition of an artificial intelligence system, we analyze which levels constitute sufficient capability to infer within the meaning of the AI Act and where further regulatory clarity is needed. We illustrate the framework by creating two realistic credit scoring workflows and show whether and where inference occurs in them. Our analysis illustrates that not only individual models but the entire data processing workflow must be considered. It also shows that the involvement of human experts during development can have significant influence on the capability to infer. Code can be found at https://github.com/fraunhofer-iais/inference-framework-creditscorecards.

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

Not What, But How: A Framework for Auditing LLM Responses across Positioning, Generalization, Anthropomorphism, and Maxims

Large language models (LLMs) are being increasingly used to answer subjective, information-seeking questions, where users are sensitive to how responses are communicated, not just whether the answers are correct. Existing LLM evaluations for subjective cultural queries largely focus on factual correctness, ignoring how the response is framed. To this end, we introduce FRANZ, an automated FRAmework for respoNse characteriZation to conduct communicative audit of LLM responses along four dimensions: cultural positioning, use of generalizing language, anthropomorphic cues, and adherence to conversational maxims. To enable this evaluation, we contribute SQUARE - a corpus of 376k subjective questions sourced from 57 subreddits, and mapped to 7 countries and 19 question categories. We demonstrate FRANZ's applicability by scoring responses from three open-weight LLMs. We observe that LLMs show statistically significant differences in the frequency with which they employ each response characteristic. Unlike single-dimensional audits, FRANZ reveals that insider positioning and anthropomorphism are positively coupled, with the degree of coupling varying by country, providing a diagnostic lens for identifying framing divergences.

25.
arXiv (quant-ph) 2026-06-11

Q-DICE: Quantum Distributed Interconnect Compiler and Emulator

arXiv:2606.11340v1 Announce Type: new Abstract: As distributed quantum computing (DQC) offers a leading path towards scalable quantum computation, the ability to benchmark distributed algorithms under realistic conditions becomes critical for system co-design. However, without access to physical systems, researchers lack tools to evaluate distribution protocols. We introduce Q-DICE (Quantum Distributed Interconnect Compiler and Emulator), a hardware-aware emulation environment for benchmarking distributed quantum circuits on classical simulators and on NISQ-era monolithic hardware. This work provides three core contributions: (1) a programmatic scheme to construct distributed QPU backends, utilizing two novel techniques - QPU slicing and stitching - to facilitate distributed circuit mapping, (2) a methodology for modeling nonlocal link noise using physically motivated Kraus operators and stochastic error channels, and (3) a boundary-aware circuit mapping algorithm enforcing distributed QPU topology constraints during transpilation. Together, these components constitute a distribution-aware compiler and noise-modeling engine that faithfully enforces the physical limitations of distributed quantum hardware within existing execution environments. We validate Q-DICE against a multitude of experimentally demonstrated quantum circuits, including a distributed Grover's search on optically linked trapped-ion hardware, achieving a worst-case fidelity deviation of 4% between simulated and experimental results. These findings demonstrate Q-DICE's capacity to accurately reproduce real distributed quantum system behavior across platforms, streamlining experimentation with distributed quantum algorithms and architectures.