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01.
arXiv (quant-ph) 2026-06-15

A Collective-Spin Derivation of the Uniform Magnon Hamiltonian in Cavity Magnonics

arXiv:2606.13830v1 Announce Type: cross Abstract: We present a direct collective-spin derivation of the effective uniform-mode Hamiltonian used in cavity magnonics. Starting from a nearest-neighbor Heisenberg ferromagnet coupled to long-wavelength magnetic fields, we show that the relevant dynamics can be restricted to the fully symmetric spin sector, where the exchange interaction contributes only a constant energy shift and the ferromagnet behaves as a macrospin of length $Ns$. Applying the Holstein–Primakoff transformation directly to this total spin yields the usual uniform magnon mode and its leading nonlinear corrections without first introducing site-resolved bosonic operators. This collective formulation makes explicit the interpretation of the ferromagnet as a synthetic large-spin atom and provides a compact route to the effective Hamiltonians used in driven and Floquet cavity magnonics. As a physical consequence, the leading nonlinear correction produces an occupation-dependent reduction of the effective magnon–photon coupling, providing a simple signature of finite-spin saturation under strong uniform-mode driving.

02.
arXiv (CS.CL) 2026-06-17

Incumbent Advantage: Brand Bias and Cognitive Manipulation Dynamics in LLM Recommendation Systems

Large language models (LLMs) are becoming a major way for consumers to find products, but we do not yet understand how brands compete in this new channel. We study brand dynamics in LLM recommendations using skincare products – a category where consumers cannot easily judge quality before buying and must rely on brand reputation – across three commercial LLMs (GPT-4o-mini, Claude Sonnet, Gemini 3 Flash), with a robustness check on search goods. In three experiments, we find: (1) a Conditional Monopoly where well-known brands get recommended 100% of the time (IAI = 10.0) when all products have the same specifications, but this dominance disappears with less than a +0.1-star rating advantage for a competitor; (2) authority-style marketing language, including fabricated clinical-evidence claims, breaks this monopoly at a Bias Surplus Value equal to +0.17 rating points, with each model responding differently; and (3) a social dilemma in multi-brand GEO competition: when all brands adopt the same optimization strategy, individual payoff falls from +0.802 to +0.007 in our payoff proxy, and non-participating brands receive zero recommendations in our tests. Our results suggest that generative engine optimization (GEO) should be studied not only as a security risk, but also as an emerging marketing practice that shapes market competition.

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

Asynchronous Decentralized Federated Learning over Lossy Wireless Links via Reception- and Age-Aware Aggregation

arXiv:2606.10774v2 Announce Type: replace Abstract: Decentralized Federated Learning(DFL) enables collaborative model training across wireless edge nodes, including IoT deployments, autonomous vehicles, UAV swarms, and satellite constellations. Operating over lossy wireless links under constraints, these systems cannot rely on retransmissions, so model parameters must be accepted as partial chunks, leading to two key failure modes, which are selection bias, where poor-quality links are systematically under-represented in gossip aggregation, and update staleness, where asynchronous nodes contribute outdated models. We prove that classical gossip aggregation introduces irreducible selection bias proportional to the link-loss rate. We propose DFL-AA (Decentralized Federated Learning with Adaptive AoI-weighted Aggregation), which corrects selection bias using Inverse Probability Weighting (IPW) with online channel estimation and mitigates staleness via Age-of-Information (AoI) decay without requiring a global clock. We prove that DFL-AA removes link-quality distortion in expectation and consistently outperforms state-of-the-art baselines across varying loss rates and heterogeneous channel conditions on fixed directed topologies.

04.
medRxiv (Medicine) 2026-06-22

Reliable quantification of renal function from frozen blood samples

BACKGROUND: Differences in renal function may affect Alzheimer disease (AD) blood biomarker levels independent of AD pathology. Although renal function was unaccounted for in foundational AD blood biomarker studies, there is potential to address this through quantification of estimated glomerular filtration rate (eGFR) from frozen serum and plasma samples. However, the validity of eGFR evaluation from long-term frozen blood samples is unknown. METHODS: Adults aged 50-85 with at least 2 vascular risk factors were recruited from vascular surgery or cardiology clinics in Tucson, Arizona from 2022-2025. Individuals with creatinine assessments in point-of-care whole blood (POC-WB) and frozen serum and plasma samples using the iSTAT (Abbott) were included. eGFR was calculated using the 2021 CKD-EPI creatinine equation without race. Agreement between POC-WB and frozen blood samples was assessed using Cohen's kappa with linear weights. RESULTS: 134 participants (mean [SD] age: 72.6 [7.5] years, 39.6% female, 23.1% chronic kidney disease) had POC-WB eGFR available. Frozen serum and plasma samples had strong agreement with POC-WB for eGFR (Kw= 0.90-0.95, P

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

Deep-Unfolded Coordination

arXiv:2606.19920v1 Announce Type: cross Abstract: Distributed optimization is a highly scalable and structurally transparent technique to solve multi-agent robotics problems; however, such methods often suffer from the need for highly-specialized, problem-specific hyperparameter tunings. In this work, we propose Deep Coordinator, a deep-unfolding framework that learns to dynamically adjust the hyperparameters of ADMM-DDP, a popular distributed solver for robotics tasks, at solve-time in response to optimizer performance. Our architecture consists of unrolling a fixed number of ADMM-DDP iterations into a neural network with learnable functions between layers mapping the optimizer state to the next hyperparameters. To the best of our knowledge, Deep Coordinator is the first deep-unfolding framework to adapt the penalty parameters of a non-convex optimizer at solve-time; we show that the mainstream supervised approach can yield degenerate solutions when training such models, and propose an unsupervised learning scheme. On simulations with fleets of cars and quadrotors, Deep Coordinator produces trajectories of comparable quality 6.18-9.44x faster than conventional solvers. Furthermore, Deep Coordinator retains its performance benefits when deployed to systems up to 8x larger than trained on.

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

Learning What to Remember: A Cognitively Grounded Multi-Factor Value Model for Agentic Memory

arXiv:2606.12945v1 Announce Type: new Abstract: Long-running LLM agents accumulate interaction histories far larger than any context window, forcing a standing decision: what to encode deeply, what to forget, and what to retrieve under a fixed memory budget. Production systems answer with semantic similarity or recency – both mis-specified for the forgetting decision, which is made at consolidation time before the future query is known. We propose a multi-factor memory value function V(m)=\sum_i w_i f_i(m) over seven interpretable factors (emotional intensity, goal relevance, value alignment, self/user relevance, task utility, reliability, and usage history) drawn from cognitive psychology, whose weights are learned from a downstream objective by a gradient-free optimiser, and whose single scalar uniformly controls encoding depth, forget risk, and retrieval rank. We make a methodological point: on LongMemEval, scoring goal relevance against the held-out evaluation question saturates gold-evidence retention at \approx 0.98 – this measures retrieval, not forgetting. In the realistic blind regime, a learned multi-factor value retains 0.770 \pm 0.011 of gold evidence across 479 usable cases, versus 0.657 for uniform weights, 0.518 for the best single factor, and 0.368 for recency; every paired gap's 95% bootstrap CI is above zero, and a neural network over the same factors ties the linear model. The learned weights are interpretable – reliability, emotional intensity, and self/user relevance dominate, while query-time goal similarity is correctly down-weighted for the forgetting decision. A controlled synthetic task with planted confounds confirms the learner recovers a separating weighting (1.00 retention) where uniform weighting fails (0.62). The substrate is open-source; all experiments run on a single CPU with no API calls.

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

Latent space mapping of interpretable structural coordinates from stochastic single-molecule signals

arXiv:2606.16950v1 Announce Type: cross Abstract: Nanopores are versatile single-molecular sensors, but their utility is fundamentally constrained by stochastic translocation dynamics warping any encoded information. We resolve it by shifting from time-domain analysis to a learned latent-space mapping via a contrastive encoder trained exclusively on simulated signals from a physics-informed model. This encoder maps solid-state nanopore signals of engineered DNA barcodes into an interpretable molecular coordinate system. The learned representation is responsive to structural barcode parameters while remaining invariant to acquisition conditions and translocation conformation, allowing data pooling across devices. Molecule identification requires a single pass through the encoder, reducing computational cost by three orders of magnitude relative to alignment-based methods. We experimentally validate through mixture quantification, rare-variant detection, consensus barcode reconstruction, and real-time signal acquisition. This shift from temporal analysis to mapping structural coordinates into a latent space changes the paradigm behind analyzing stochastic sensor signals by linking classification to interpretable encoded molecular information.

08.
arXiv (CS.LG) 2026-06-15

Closed-loop discovery of out-of-distribution processing protocols by evolutionary search and uncertainty-aware learning

arXiv:2606.13859v1 Announce Type: cross Abstract: Many materials and chemical systems exhibit history-dependent responses, where functional outcomes are governed not only by final-state variables but by the time-dependent sequence of fields, temperatures, or chemical potentials applied during operation. Discovering new processing protocols is therefore a high-dimensional search problem in which the control variable is an entire waveform or sample history, and conventional strategies either remain confined to conservative interpolative families or become prohibitively measurement intensive. Here, a closed-loop workflow is introduced that couples evolutionary search over a compact waveform representation with uncertainty-aware deep kernel learning to generate, rank, and experimentally validate candidate protocols. Applied to ferroelectric thin films, with the scanning-probe tip-bias waveform as the protocol and the nonlinear electromechanical response as the reward, the workflow discovers waveform families that enhance nonlinearity by de-aging the film. Spatially resolved before/after measurements show that the best-performing waveforms selectively activate pre-existing, weakly pinned domain-wall segments, whereas the worst drive long-range irreversible switching. This framework reframes protocol tuning as out-of-distribution discovery, generalizable to synthesis and annealing trajectories, battery formation protocols, and other high-dimensional control problems.

09.
arXiv (CS.CV) 2026-06-16

Leptomeningeal Collateral Detection on DSA via Vessel-Graph Neural Networks

Leptomeningeal collaterals (LMCs) are an important prognostic factor in acute ischemic stroke. Existing automated methods rely on CT angiography (CTA), but individual LMCs are often too small to be resolved on CTA, limiting these methods to coarse collateral scoring. Digital subtraction angiography (DSA) visualizes individual collaterals at superior resolution, yet current assessment remains subjective, relying on manual grading scales that suffer from poor inter-rater agreement. We present a framework that formulates collateral detection as the classification of individual vessel segments on a graph derived from DSA. A hybrid graph-pixel architecture combines a topology-aware graph branch with a dense pixel branch, fused in a shared node-probability space. In a five-fold cross-validation setting, the fused model achieves a PR-AUC of 0.434, outperforming the graph-only (0.403) and pixel-only (0.362) baselines. To our knowledge, this is the first method to enable the individualization of LMCs in DSA, allowing for precise per-vessel quantitative assessment. This integration shifts DSA assessment toward objective evaluation, supporting future biomarker and pattern discovery for individual LMCs.

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

Mixing Makes Markovian Contexts Cheap for Linear Bandits

arXiv:2603.12530v2 Announce Type: replace Abstract: Recent work shows that when contexts are drawn i.i.d., linear contextual bandits can be reduced to single-context linear bandits. This ``contexts are cheap'' perspective is highly advantageous, as it allows for sharper finite-time analyses and leverages mature techniques from the linear bandit literature, such as those for misspecification and adversarial corruption. However, this reduction crucially relies on the independence of contexts and does not extend to settings with temporally correlated (e.g., Markovian) contexts, which arise frequently in practice. Motivated by applications with temporally correlated availability, we extend this perspective to linear bandits with Markovian context processes, where the action set evolves via an exogenous Markov chain. Our main contribution is a reduction that applies under uniform geometric ergodicity. We construct a stationary surrogate action set to solve the problem using a standard linear bandit oracle, employing a delayed-update scheme to control the bias induced by the nonstationary conditional context distributions. We further provide a phased algorithm for unknown stationary distributions that learns the surrogate mapping online. In both settings, we obtain a high-probability worst-case regret bound matching that of the underlying linear bandit oracle in sufficiently fast mixing regimes. We then validate our results on a real-world instance, where we show practical gains over a LinUCB baseline.

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

Vero: An Open RL Recipe for General Visual Reasoning

What does it take to build a visual reasoner that works across charts, science, spatial understanding, and open-ended tasks? The strongest vision-language models (VLMs) suggest that broad visual reasoning is within reach, yet their closed data and reinforcement learning (RL) pipelines make their gains difficult to study, reproduce, or extend. We introduce Vero, a family of fully open VLMs that match or exceed existing open-weight models across diverse visual reasoning tasks. We scale RL data and rewards across six broad task categories, constructing Vero-600K, a 600K-sample dataset from 59 datasets, and designing task-routed rewards that handle heterogeneous answers. Across VeroEval, our 30-benchmark suite, Vero-600K outperforms existing RL datasets under controlled comparisons. Applied to five starting models, Vero variants gain 2.9-5.4 points on average over their initial models. Notably, Vero-Qwen3I-8B, trained on the Instruct model, surpasses Qwen3-VL-8B-Thinking by 3.8 points on average without additional distillation. Systematic ablations reveal that different task categories elicit distinct reasoning patterns and that broad gains depend on learning them jointly rather than in isolation. All data, code, and models are publicly available.

12.
bioRxiv (Bioinfo) 2026-06-11

EditorForge: An Active-Site-Aware Framework for Inverse-Folding-Based Protein Redesign

Inverse-folding models can rapidly generate protein sequences compatible with a supplied backbone, but unconstrained redesign is poorly suited to enzyme and genome-editor-associated domains, where catalytic, substrate-proximal, and conserved structural regions must remain protected. In this paper, we present EditorForge, a modular constraint-and-audit suite for editor-domain protein redesign that wraps fixed-backbone inverse folding with explicit design masks, fixed-position enforcement, active-site-proximity auditing, active-site-shielded regeneration, and downstream structural quality control. Using full-length Moloney murine leukemia virus reverse transcriptase structure 4MH8 (MMLV RT 4MH8) as a demonstration target, EditorForge first restricted redesign to a bounded 25-position envelope while fixing 428 residues. An initial audit detected active-site-proximal failure modes despite fixed-position integrity. Later, the Active Site Shield module then removed five unsafe design positions, replaced them with lower-contact alternatives, and regenerated candidates under stricter constraints. Post Shield Audit evaluated 24 regenerated candidates, all of which satisfied the hard sequence/mask and active-site-shield constraints. For the eight candidates that were selected or returned for structure-prediction/refolding quality control. Enhanced RefoldQC found that all 8 evaluated predicted structures passed the computational structure-QC screen. That said, the selected 8 candidates passed the computational structure-QC screen, with global C RMSD values of 1.2061–1.5555~[A], active-site C RMSD values of 0.4098–1.8397~[A], mutation-neighborhood C RMSD values of 1.3155-1.6848~[A], and average pLDDT-like confidence values of 94.87-95.11. In short, EditorForge provides a reproducible triage layer that converts general inverse-folding output into constrained and editor-specific candidate sets for downstream structural and biological review on top of existing structural prediction tools.

13.
arXiv (CS.CV) 2026-06-25

Pulmonary Embolism Risk Stratification from CTPA and Medical Records: Vascular Graphs Are Not All You Need

Risk stratification for pulmonary embolism (PE) is critical for clinical decision-making. Stratification guidelines are based on patient medical records, parameters measured from computed tomography pulmonary angiography (CTPA), and blood tests. However, blood tests are often missing in routine practice. This work studies whether state-of-the-art models can accurately classify risk stratification from only medical records and biomarkers extracted from CTPA images. We benchmark different approaches to combine medical records and cardiac biomarkers with rich pulmonary vascular information; we add vascular biomarkers to tabular models and apply graph neural networks (GNNs) on the vascular tree's intrinsic graph representation. We use a private dataset (n=353) with uniquely complete data for PE risk stratification. Our results show that, among global features, medical records and cardiac biomarkers are the most significant predictors, while vascular biomarkers do not further improve stratification. Even more surprising, even GNNs on vascular graphs fail to outperform strong tabular baseline on global features. We consider hypotheses, on both models and data, that could explain this suboptimal performance. Our investigation suggests that, counter-intuitively, vascular graphs might hold no discriminative information for PE risk stratification. Code is available from https://github.com/creatis-myriad/GENESIS.

14.
arXiv (CS.CL) 2026-06-24

Block-wise Codeword Embedding for Reliable Multi-bit Text Watermarking

Recent multi-bit watermarking methods for large language models (LLMs) prioritize capacity over reliability, often conflating decoding with detection. Our analysis reveals that existing ECC-based extractors suffer from catastrophic false positive rates (FPR), and applying rejection thresholds merely collapses detection sensitivity (TPR) to random guessing. To resolve this structural limitation, we propose BREW (Block-wise Reliable Embedding for Watermarking), a framework shifting the paradigm to designated verification. BREW employs a two-stage mechanism: (i) blind message estimation via independent block voting, followed by (ii) window-shifting verification that rigorously validates the payload against local edits. Experiments demonstrate that BREW achieves a TPR of 0.965 with an FPR of 0.02 under 10% synonym substitution, demonstrating that the high-FPR issue is not an inherent trade-off of multi-bit watermarking, but a solvable structural flaw of prior decoding-centric designs. Our framework is model-agnostic and theoretically grounded, providing a scalable solution for reliable forensic deployment.

15.
arXiv (CS.AI) 2026-06-25

The Token Not Taken: Sampling, State, and the Stochasticity of AI Agents

arXiv:2606.08998v2 Announce Type: replace Abstract: Agentic AI systems can behave differently across runs: the same request may produce a different plan, a different tool call, a different code edit, or a different final answer. Such variability arises from several layers that are often conflated. At the core of many current agents is a foundation model, a large pretrained model adaptable to many downstream tasks, embedded in an orchestration loop that plans, calls tools, observes results, and updates state. One explicit intrinsic source of variability in such systems is token generation: the model computes scores over possible next tokens, the scores are converted into probabilities, and a decoder may sample tokens using a pseudo-random number generator. A small sampled token difference can then propagate upward into a different tool call, code path, search query, or agent state. Other sources of variability are extrinsic to token sampling, including changing environments, live data, serving infrastructure, batch effects, and numerical details. By separating these layers, this tutorial clarifies what it means to call agentic AI systems stochastic, when such variability can be reproduced under matched conditions, and why deterministic execution need not imply identical behavior in deployed settings.

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

Loss Landscape Diagnosis for Gradient-Based Gray-Scott System Inversion: Disentangling the Roles of PINN Components

Authors:

arXiv:2606.11258v1 Announce Type: new Abstract: Gradient-based inversion of reaction-diffusion systems is typically approached via surrogate models or physics-informed neural networks (PINNs), while the most direct route, backpropagation through the PDE's structure itself, has largely been avoided. We pursue this direct route as a diagnostic probe, backpropagating a steady-state loss through unrolled Gray-Scott simulation to recover its parameters, with no surrogate or neural-network augmentation. Optimization fails to converge, and plotting the landscape directly locates the failure in its geometry – flat plateaus with no gradient signal, bounded by sharp cliffs that align with bifurcation boundaries – a structure that recurs across loss functions and is inherited however the gradients are routed to parameters. Reading this minimal setup as an ablation of PINN, we disentangle each component's role: with the neural network fixed, the residual loss is quadratic in the PDE parameters and yields a smooth landscape, so it alone already avoids the pathology, by implicitly encoding the full PDE dynamics across all initial conditions. The neural network, for its part, cannot repair an ill-posed parameter subspace, and so serves only to complete the observed data – a division of labor not previously made explicit. These findings carry concrete design implications for PINN-type methods and a broader heuristic on when added dimensions actually help.

17.
medRxiv (Medicine) 2026-06-15

Multidimensional nutritional assessment in Crohns disease: cross-sectional comparison of active disease and remission

Malnutrition is common in Crohns disease (CD), and its assessment requires multiple tools. Comprehensive evaluation of nutritional status in a population with CD, predominantly characterized by metabolic phenotype, was inadequately reported. This study evaluated the nutritional status of CD patients using anthropometric, clinical, and biochemical measures and compared patients with active disease with those in remission. This cross-sectional study included 127 adults with CD: 63 with active disease and 64 in remission. Disease activity was classified using the Crohns Disease Activity Index, the Simple Endoscopic Score for Crohns Disease, and magnetic resonance enterography. Nutritional assessment included body mass index (BMI), mid-upper arm circumference, calf circumference, triceps skinfold thickness, mid-arm muscle circumference, Mini Nutritional Assessment-Short Form (MNA-SF), and biochemical markers including hemoglobin, serum iron, folate, vitamin B12, albumin, and zinc. Malnutrition was defined using the Global Leadership Initiative on Malnutrition criteria. Overall, 47.2% of participants were malnourished. Malnutrition was significantly more frequent in active disease than in remission (81.0% vs. 14.1%, P

18.
arXiv (CS.AI) 2026-06-17

Confusion-Aware Transfer Teacher Curriculum Learning Framework: Disentangling Scoring and Pacing Effects

arXiv:2606.17706v1 Announce Type: cross Abstract: Curriculum learning couples two design choices, how samples are scored by difficulty and how harder samples are paced into training, making it difficult to attribute observed gains to either component. We disentangle these factors with two evaluation protocols: stage-wise test subsets that validate scoring functions independently of curriculum training, and a baseline that applies the same pacing schedule to randomly ordered data. Within the Transfer Teacher framework (TTF), we use these protocols to evaluate a confusion-aware difficulty score that considers both correct-class confidence and the probability distribution over incorrect classes. On CIFAR-10 with ResNet-18 and VGG-16, the proposed score produces model-interpretable difficulty rankings that align with human intuition. However, at full data, neither curriculum nor anti-curriculum ordering improves accuracy over standard training, indicating that improving the scoring function alone is insufficient to overcome the known failure modes of curriculum learning in TTF. In contrast, We find that confusion-aware curriculum ordering result in consistent data-efficiency benefits, outperforming random ordering by up to 8.7% points at the 20% data regime, suggesting the potential of TTF as a data-efficient training method.

19.
arXiv (CS.CL) 2026-06-15

Token-Level LLM Collaboration via FusionRoute

Large language models (LLMs) exhibit strengths across diverse domains. However, achieving strong performance across these domains with a single general-purpose model typically requires scaling to sizes that are prohibitively expensive to train and deploy. On the other hand, while smaller domain-specialized models are much more efficient, they struggle to generalize beyond their training distributions. To address this dilemma, we propose FusionRoute, a robust and effective token-level multi-LLM collaboration framework in which a lightweight router simultaneously (i) selects the most suitable expert at each decoding step and (ii) contributes a complementary logit that refines or corrects the selected expert's next-token distribution via logit addition. Unlike existing token-level collaboration methods that rely solely on fixed expert outputs, we provide a theoretical analysis showing that pure expert-only routing is fundamentally limited: unless strong global coverage assumptions hold, it cannot in general realize the optimal decoding policy. By augmenting expert selection with a trainable complementary generator, FusionRoute expands the effective policy class and enables recovery of optimal value functions under mild conditions. Empirically, across both Llama-3 and Gemma-2 families and diverse benchmarks spanning mathematical reasoning, code generation, and instruction following, FusionRoute outperforms both sequence- and token-level collaboration, model merging, and direct fine-tuning, while remaining competitive with domain experts on their respective tasks.

20.
medRxiv (Medicine) 2026-06-22

Histologically validated diffusion MRI signatures of neuroinflammation and neurodegeneration in Alzheimer disease

Noninvasive neuroinflammation measurement remains a major barrier for Alzheimer disease (AD) therapeutics. We present generalized diffusion basis spectrum imaging (g-DBSI), a diffusion MRI framework that decomposes the tissue signal into biologically interpretable microstructural compartments. In postmortem Knight ADRC brains, g-DBSI-derived restricted isotropic fraction (RIF) and restricted anisotropic fraction (RAF) mapped cellularity and neurofilament density, while their ratio (RIF/RAF) tracked inflammatory cell density and peri-plaque amyloid-beta with higher specificity and regional consistency than RIF alone. In 112 living Knight ADRC participants stratified by PET amyloid, g-DBSI metrics showed amyloid-dependent trajectories: in low-amyloid individuals, RIF and RAF rose together with amyloid, consistent with early neuropil expansion and glial elaboration, whereas in high-amyloid individuals, RIF/RAF increased, and RAF declined, indicating established neuroinflammatory remodeling and neurofilament loss. CSF proteomics linked RIF/RAF to glia-enriched immune and vascular pathways, supporting g-DBSI as a clinically compatible MRI biomarker of neuroinflammation and neurodegeneration in AD.

21.
medRxiv (Medicine) 2026-06-17

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

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

22.
arXiv (CS.AI) 2026-06-24

HOLMES: Evaluating Higher-Order Logical Reasoning in LLMs

arXiv:2606.23238v2 Announce Type: replace Abstract: Logical reasoning is essential for reliable AI, yet existing benchmarks are largely first-order-logic-centric, focusing on object-level deduction over fixed predicates. This misses many realistic scenarios where models must reason over rules, predicates, functions, constraints, and decision procedures themselves. We introduce HOLMES (Higher-Order Logic Meets real-world Explainable Symbolic reasoning), the first real-world benchmark for higher-order symbolic reasoning in LLMs, containing 1379 instances. Built on higher-order logic, HOLMES pairs natural-language problems with HOL formalizations, ground-truth answers, verifiable reasoning traces, and fine-grained controllable reasoning factors across law and finance. Experiments show that current LLMs still struggle on HOLMES, with an average accuracy of only 50.64% and the best model reaching 59.54%. Our analyses further reveal that high final-answer accuracy can mask shortcut reasoning in conflict-resolution settings, while performance drops sharply under scope-conditioned and compositional reasoning. These findings identify higher-order symbolic reasoning as a key bottleneck for building reliable and verifiable LLMs. The project code and dataset are publicly available at https://github.com/wuyucheng2002/HOLMES.

23.
arXiv (math.PR) 2026-06-25

Spectral Collapse Under Geometric Alignment of Extreme Events

arXiv:2606.25810v1 Announce Type: new Abstract: Let Q_n = B_n + J_n be the quadratic covariation matrix of a high-dimensional semimartingale, where J_n is the jump component and B_n is the diffusion component. We prove that spectral collapse occurs – meaning the ratio of the leading eigenvalue to the trace converges to 1 and the effective rank converges to 1 – if and only if the jump directions are geometrically aligned in a weighted sense and the background diffusion is asymptotically negligible. The proof separates into two steps: geometric alignment of jump directions forces spectral concentration of J_n; background negligibility then propagates this to the full system. We extend to the stochastic setting and prove convergence in probability under natural conditions on the jump process. The framework gives a scalar diagnostic for detecting when a high-dimensional system is dominated by extreme events.

24.
arXiv (CS.AI) 2026-06-17

Skill-Constrained Model Predictive Control for Resilient Manufacturing Supply Chains

arXiv:2606.17269v1 Announce Type: new Abstract: In skill-constrained production-inventory systems, the qualified human capacity available tomorrow depends on training decisions made today: production requires certified workers, certifications decay unless maintained, and training consumes the same scarce worker hours that production needs now. We study a closed-loop skill-constrained model predictive controller that, at every shift, solves a finite-horizon mixed-integer program over production, inventory, backlog, and training, with binary predicted certification, hard production eligibility, and an interpretable terminal value that prices certified-capacity gaps at the horizon boundary; only the first-period action is applied before replanning. On synthetic, seed-controlled SkillChain-Gym scenarios - announced and surprise new-skill shocks, demand shocks, absenteeism, forecast- and availability-quality modes, capacity-boundary and training-rate sweeps, and negative controls - we evaluate the controller against production-only and maintenance-only ablations, static cross-training insurance plans, and a strong reactive heuristic, under an ex-ante locked configuration and paired statistics. The result is regime dependence, not superiority: no policy class dominates. Predictive control helps when skill or labor bottlenecks are forecastable early enough for training to complete; lean static insurance remains hard to beat under surprise shocks, near the demand-capacity boundary, and wherever pre-shock slack makes insurance cheap. Attribution ablations separate certification maintenance, re-acquisition of lapsed certifications, and greenfield skill acquisition. Forecastability, not adaptivity per se, decides when predictive control pays.

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

Hidden Anchors in Multi-Agent LLM Deliberation

arXiv:2606.19494v1 Announce Type: new Abstract: Multi-agent LLM deliberation, where agents exchange and revise answers over several rounds, is increasingly used to improve reasoning and accuracy, yet how and why it works is rarely modelled. Such deliberation mirrors how humans reach decisions. As social animals we are pulled both by the group, the herd effect that classical opinion-dynamics models such as DeGroot and Friedkin–Johnsen capture, and by our own internal belief, which they do not. We model multi-agent deliberation as a closed-loop dynamical system in which each agent carries a hidden internal belief, its anchor, that continually pulls its opinion regardless of its neighbours. We show this anchor can be recovered from the deliberation alone, and that it explains a behaviour classical consensus rules forbid: an agent's confidence in the correct answer can climb past where any agent started, escaping the space (convexhull) formed by the initial beliefs. Checking whether the recovered anchor also predicts held-out runs (generalizes) gives a simple test for when a model is truly driven bysuch an anchor. Across three open-weight model families this is a spectrum, not all-or-nothing. All anchors' influence are about equally strongly, but they differ in where the anchor sits, and only when it sits far from the initial opinions does deliberation escape the hull and need the full closed-loop model.