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01.
arXiv (CS.AI) 2026-06-12

Structured Testbench Generation for LLM-Driven HDL Design and Verification-Oriented Data Curation

arXiv:2606.12983v1 Announce Type: new Abstract: Automated testbench generation has become a critical bottleneck in large language model (LLM)-driven Register Transfer Level (RTL) workflows, where large numbers of candidate designs must be verified rapidly and reliably. Existing prompt-based approaches treat testbench generation as unconstrained code synthesis, yielding stochastic outputs with high token cost, low reproducibility, and insufficient coverage. To address this gap, we present STG, a Structured Testbench Generation framework that exploits the inherent structure of hardware designs to generate deterministic testbenches. As a direct verification tool, STG runs 720x faster than an iterative LLM-based testbench generation flow and higher rate of successful compilation, achieves higher coverage, and reduces false-pass verdicts on incorrect DUTs. STG also helps identify errors in RTL generation benchmarks by exposing faulty benchmark testbenches. As a data curation engine, it is 11x faster than LLM-based filtering on a single CPU core with 127x less energy, and the resulting distilled models provide state-of-the-art performance in our multi-benchmark evaluation. As a test-time scaling oracle, it reduces node count by 14-47\%. Our models are available at https://huggingface.co/collections/AS-SiliconMind/siliconmind-v12.

02.
bioRxiv (Bioinfo) 2026-06-19

HTS-Oracle v2: Prospective AI-Guided Discovery and Experimental Validation of Small Molecule Modulators Across Multiple Targets

High-throughput screening (HTS) remains the cornerstone of early-phase small molecule discovery yet consistently underperforms against immunotherapy targets, yielding validated hit rates below 0.1%. Here we introduce HTS-Oracle v2, which features rigorous cross-validation that ensures honest performance estimates. HTS-Oracle v2 was trained and validated across four clinically significant immune checkpoint targets (CD28, ICOS, LAG-3, and TIGIT) achieving ROC-AUC values of 0.968, 0.969, 0.875, 0.928 respectively under rigorous cross-validation. For prospective experimental validation, HTS-Oracle v2 was applied to an 8,960-compound Enamine Protein Mimetic Library, selecting only 25 compounds per target for experimental testing using temperature-related intensity change (TRIC) technology, a 99.7% reduction in screening burden. HTS-Oracle v2 identified 4, 5, 4, and 6 validated binders from 25 prospectively selected compounds per target, corresponding to validated hit rates of 16%, 20%, 16%, and 24%, respectively. Notably, 67-80% of all experimentally confirmed hits across the full 8,960-compound library were captured within just 25 model-selected compounds per target. For CD28, this represents a 28-fold improvement over HTS-Oracle v1 (239x versus 8.4x), establishing HTS-Oracle v2 as an efficient platform for AI-guided prospective hit discovery across immunotherapy targets.

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

BrainFusionNet: a deep learning and XAI model to understand local, global, and sequential features of MRI images for improved brain tumour detection

The noise of Magnetic Resonance Imaging MRI poses challenges for Deep Learning DL when tumor boundaries are obscured tumor location and appearance are complex Therefore we develop BrainFusionNet that combines Convolutional Neural Networks CNNs Vision Transformers ViT and Gated Recurrent Units GRUs to extract spatial contextual and sequential features from MRI images for improved brain tumor classification Furthermore explainable AI such as SHAP LIME and GradCAM are integrated to visualise and highlight image regions that contribute to BrainFusionNets decisionmaking process The proposed BrainFusionNet model is evaluated on two publicly available MRI datasets Kfold validation suggests 98 accuracy on both datasets The model was compared with the six stateoftheart SOTA CNNs and transfer learning Among the SOTA CNNs DenseNet121 and VGG16 achieved the highest accuracy of 96 The novelty of BrainFusionNet is that the hybrid model effectively extracts local and global features from MRI images even in smallscale tumor regions and small tumor sizes The model has a balanced sequential CNN architecture to capture lowlevel and deeperlayer features a customized ViT that captures local features stabilizes gradient flow and reduces the risk of vanishing gradients during MRI image training The CNN and ViT outputs are fed into a GRU for final classification Furthermore we analyze pixel intensities to determine whether MRI image quality affects image classification Our findings are very novel in image interpretation as we found that the distribution of pixel intensities in MRI images affects DL performance

04.
medRxiv (Medicine) 2026-06-15

Mucosal and Systemic Antibodies Associated with Clinical Protection in a Pertussis Controlled Human Infection Model

Background The engagement of mucosal and systemic immunity in preventing Bordetella pertussis colonization and infection in humans, the impact of prior vaccination on host immunity and protective outcomes, and the dynamics of the host response following exposure remain poorly understood. Methods Healthy adults were challenged with increasing colony-forming units (CFUs) doses, 106-108, of B. pertussis D420 intranasally (NCT05136599). Shedding (PCR and culturing) and symptom development were monitored up to 21 days post-challenge. Serum and nasal wash IgA and IgG were measured before challenge (baseline) and up to 6 months post-challenge. Findings Antibodies increased post-challenge only in infected individuals, primarily nasal IgA. Participants who remained uninfected had higher baseline levels of filamentous hemagglutinin (FHA)- specific mucosal IgA and IgG, and higher serum IgA against fimbriae 2/3 (FIM). FHA was negatively associated with bacterial load and was a key discriminator between shedders and non-shedders, up to one week post-challenge. By day 14 post-challenge, pertussis toxin (PT) IgG and FIM IgA in both serum and mucosal samples were negatively associated with bacterial colonization. The majority (96.7%) of acellular pertussis (aP) vaccine recipients (n=23, median age 2.0 years) became infected, compared to 69.4% of those who received whole-cell pertussis vaccine (n=36; median age 32.0 years), and their antibody responses remained distinct following infection. Interpretation Nasal FHA antibodies emerged as early predictors of protection against pertussis infection, while PT IgG and FIM IgA antibodies may reflect clearance after infection. aP-primed individuals were more susceptible to infection, despite their younger age and more recent vaccination. Funding CDC Contract #75D30122C15467 and CDC IPA Agreement #24IPA2417512 Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention, US Department of Health and Human Services.

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

SuperCarver: Texture-Consistent 3D Geometry Super-Resolution for High-Fidelity Surface Detail Generation

Conventional production workflow of high-precision mesh assets necessitates a cumbersome and laborious process of manual sculpting by specialized 3D artists/modelers. The recent years have witnessed remarkable advances in AI-empowered 3D content creation for generating plausible structures and intricate appearances from images or text prompts. However, synthesizing realistic surface details still poses great challenges, and enhancing the geometry fidelity of existing lower-quality 3D meshes (instead of image/text-to-3D generation) remains an open problem. In this paper, we introduce SuperCarver, a 3D geometry super-resolution pipeline for supplementing texture-consistent surface details onto a given coarse mesh. We start by rendering the original textured mesh into the image domain from multiple viewpoints. To achieve detail boosting, we construct a deterministic prior-guided normal diffusion model, which is fine-tuned on a carefully curated dataset of paired detail-lacking and detail-rich normal map renderings. To update mesh surfaces from potentially imperfect normal map predictions, we design a noise-resistant inverse rendering scheme through deformable distance field. Experiments demonstrate that our SuperCarver is capable of generating realistic and expressive surface details depicted by the actual texture appearance, making it a powerful tool to both upgrade historical low-quality 3D assets and reduce the workload of sculpting high-poly meshes.

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

HSQ-VLM: A Novel Spatially-Constrained Quadrant Segmentation VLM Model for Explainability in Diabetic Retinopathy

Diabetic Retinopathy (DR) is an aggressive retinal disease and a leading cause of global blindness, yet its clinical management is currently hindered by the black-box nature of diagnostic AI. While deep learning models achieve high classification accuracy, there is a critical lack of explainability methods capable of detailing the exact anatomical landmarks and lesion distributions that lead to a clinical decision for DR. Therefore, we propose HSQ-VLM, a novel quadrant segmentation pipeline on fundus images that utilizes a Landmark-Anchored Cartesian Cross-Attention mechanism to unify visual feature extraction with structured clinical reasoning. Unlike traditional methods that rely on arbitrary image partitioning, our pipeline implements 4-quadrant Topological Latent Partitioning (TLP) to dynamically align retinal features with a fovea-centered coordinate system. This allows the Vision-Language Model to generate natural language reports that quantify pathology with anatomical precision. On a dataset of 3,500 high-resolution fundus images, this innovative methodology achieved a lesion detection sensitivity of 99.6% for hemorrhages and 96.4% for microaneurysms, while demonstrating a significant reduction in boundary-ambiguity errors compared to standard segmentation baselines.

07.
arXiv (CS.CV) 2026-06-18

Semantic Router: On the Feasibility of Hijacking MLLMs via a Single Adversarial Perturbation

Multimodal Large Language Models (MLLMs) are increasingly deployed in stateless systems, such as autonomous driving and robotics. This paper investigates a novel threat: Semantic-Aware Hijacking. We explore the feasibility of hijacking multiple stateless decisions simultaneously using a single universal perturbation. We introduce the Semantic-Aware Universal Perturbation (SAUP), which acts as a semantic router, "actively" perceiving input semantics and routing them to distinct, attacker-defined targets. To achieve this, we conduct theoretical and empirical analysis on the geometric properties in the latent space. Guided by these insights, we propose the Semantic-Oriented (SORT) optimization strategy and annotate a new dataset with fine-grained semantics to evaluate performance. Extensive experiments on three representative MLLMs demonstrate the fundamental feasibility of this attack, achieving a 66% attack success rate over five targets using a single frame against Qwen.

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

Aligning Quantum Operators with Large Language Models

arXiv:2606.13811v1 Announce Type: cross Abstract: Can Large Language Models (LLMs) understand and reason about quantum operators? Despite their remarkable capabilities in mathematics and symbolic reasoning, LLMs remain inherently blind to quantum representations such as unitary matrices. In this work, we take a step toward bridging this gap by introducing an approach that maps unitary operators into the latent space of an LLM, enabling unified modeling over quantum and linguistic inputs. We instantiate this idea on Clifford+T circuit synthesis over a Pauli rotation gate set, where our model achieves results competitive with state-of-the-art methods and scales consistently with training data, with no signs of saturation. Our approach further enables language-conditioned synthesis, allowing gate constraints unseen during training to be specified directly in natural language. This work suggests a path toward quantum–aware foundation models that can natively interpret and reason about quantum operations, which could have broader implications reaching across quantum compilation and algorithm discovery.

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

Multi-Bitwidth Quantization for LLMs Using Additive Codebooks

As large language models (LLMs) are increasingly deployed across heterogeneous hardware with varying resource constraints, the ability to adaptively manage the trade-off between performance and efficiency without retraining is critical. We propose Drop-by-Drop, a novel multi-bitwidth post-training quantization framework that enables inference-time precision control over LLM weights from a single trained model. Our method is theoretically grounded in information theory and successive refinement. We establish that LLM weights, which commonly follow a Gaussian distribution, can be optimally reconstructed with increasing fidelity as additional bits are incorporated, under a weighted mean squared error distortion motivated by LLM loss functions. To realize this in practice, Drop-by-Drop incorporates Matryoshka-style supervision into the loss function, exploiting the structure of additive codebooks. Drop-by-Drop produces a single model where ordered subsets of codebooks yield accurate partial reconstructions at each precision level. This approach significantly reduces storage and memory overhead by allowing a single checkpoint to serve multiple bitwidths, while maintaining competitive perplexity and accuracy across major architectures, such as Qwen, LLaMA, Gemma, and Mistral.

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

S-GBT: Smooth Growth Bound Tensor for Certified Robustness Against Word Substitution Attacks in NLP

Despite recent progress in Natural Language Processing (NLP), models remain vulnerable to word substitution attacks. Most existing defenses focus on first order sensitivity and measure how much the output changes when the input is slightly perturbed. However, they ignore how this sensitivity evolves, which is described by curvature. When gradients vary sharply, models can still fail. This paper introduces the Smooth Growth Bound Tensor (S-GBT), a second order method that bounds the Hessian element-wise, for which we provide formal theoretical proofs on the resulting robustness bounds. A regularization term is added during training to minimize these bounds. This yields tighter certified robustness against word substitution attacks. The change in the output under word substitution is bounded by both a linear term and a quadratic term. S-GBT is derived for two architectures: Long Short-Term Memory (LSTM) and Convolutional Neural Networks (CNN). The method is integrated directly into the training objective. Its effectiveness is evaluated on multiple benchmark datasets. The results show that combining first and second order regularization improves certified robust accuracy by up to 23.4% compared to prior methods, while clean accuracy remains competitive. These findings indicate that controlling both the gradient and its variation is a promising direction for building more robust models.

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

Shattering the Autoregressive Curse: Dynamic Epistemic Entropy Orchestrated Erasable Reinforcement Learning for LLMs

arXiv:2606.17735v1 Announce Type: new Abstract: Although reinforcement learning (RL) has expanded the cognitive boundaries of large language models (LLMs), it often remains vulnerable to the autoregressive curse in long-horizon logical reasoning: small epistemic perturbations introduced early in generation can propagate irreversibly along the Markov decision process flow, triggering cascading failures that drive the reasoning trajectory toward collapse. To overcome this autoregressive cascade, in which a single early mistake can compromise all subsequent reasoning steps, we propose dynamic epistemic entropy orchestrated erasable reinforcement learning ($E^3RL$). $E^3RL$ eliminates reliance on external signals by grounding the model's endogenous local autoregressive cross-entropy as an intrinsic coordinate of epistemic uncertainty. By introducing segment-level adaptive dynamic thresholds and advantage allocation, $E^3RL$ enables the model to precisely excise localized logical defects while reusing historical key-value (KV) cache streams, thereby endowing the reasoning process with a self-healing capability. We train $E^3RL$ on the DeepMath-103k dataset. Experimental results show that $E^3RL$ reshapes the exploration efficiency of long-sequence reasoning and improves sample efficiency while maintaining linear memory overhead. On mathematical reasoning benchmarks such as AIME, $E^3RL$ achieves substantial performance gains, with the 4B and 8B parameter models surpassing previous state-of-the-art (SOTA) results by 5.349\% and 6.514\%, respectively. These findings suggest that $E^3RL$ shatters the autoregressive curse in long-sequence reasoning and establishes a theoretical and systems-level foundation for the next generation of self-healing artificial general intelligence (AGI).

12.
arXiv (CS.CL) 2026-06-16

Less is More: Improving LLM Reasoning with Minimal Test-Time Intervention

Recent progress in large language models (LLMs) has focused on test-time scaling to improve reasoning via increased inference computation, but often at the cost of efficiency. We revisit test-time behavior and uncover a simple yet underexplored phenomenon: reasoning uncertainty is highly localized-only a small subset of high-entropy tokens dominantly affects output correctness. Motivated by this, we propose Minimal Test-Time Intervention (MTI), a training-free framework that enhances reasoning accuracy and stability with minimal overhead. MTI includes: (i) Selective CFG intervention, applying classifier-free guidance only at uncertain positions; and (ii) Lightweight negative-prompt guidance, reusing the main model's KV cache to approximate unconditional decoding efficiently. MTI yields consistent gains across general, coding, and STEM tasks-e.g., +9.28% average improvement on six benchmarks for DeepSeek-R1-7B and +11.25% on AIME2024 using Ling-mini-2.0-while remaining highly efficient.

13.
arXiv (CS.AI) 2026-06-18

TMR-GGNN: Credit Card Fraud Detection based on Time-Aware Multi-Relational Guided Graph Neural Network

arXiv:2606.18444v1 Announce Type: cross Abstract: In recent years, credit card fraud detection has faced significant challenges due to highly imbalanced data, evolving fraud patterns, and complex relational structures among transaction entities. To address these issues, this research proposes a novel framework called Timeaware Multi Relational Guided Graph Neural Network (TMR GGNN). Particularly, the proposed TMR GGNN extends the encoder decoder Graph Neural Network GNN architecture by modeling heterogeneous interactions across customers, merchants, devices, and IPs over temporal windows. Subsequently, the proposed TMR GGNN approach constructs a dynamic, multi relational graph and incorporates a time aware relational attention mechanism within the encoder to adaptively weigh the transaction relevance based on temporal proximity and semantic context. Consequently, the decoder employs a contrastive learning module to distinguish between real and synthesized transaction patterns, while improving the models generalization of rare fraud cases. Additionally, to effectively manage severe class imbalances and emphasize discriminative learning, a composite loss function combining Information Noise Contrastive Estimation (InfoNCE) based contrastive loss with Focal Loss is introduced. This integration assists in improving fraud identification while mitigating false negatives.

14.
arXiv (CS.AI) 2026-06-18

NeSyCat Torch: A Differentiable Tensor Implementation of Categorical Semantics for Neurosymbolic Learning

arXiv:2606.19279v1 Announce Type: new Abstract: Neurosymbolic semantics is fragmented: classical, fuzzy, probabilistic and neural systems each define truth by their own inductive rules. NeSyCat, extending ULLER, subsumes them under a single inductive definition of truth, parametric in a strong monad and an aggregation structure on truth-values. NeSyCat has so far lacked an account of predicates and functions learned by neural networks. We provide NeSyCat Torch as the missing link and interpret computational symbols via neural networks, implementing the framework in probabilistic programming and tensor-based backends. We use the distribution monad for reference semantics and metric evaluation, and complement it by a monad for numerically stable, differentiable training: the lazy log-tensor monad over the log-semiring. For efficient training in batches, we furthermore employ a batch monad. The axioms are the source code: written once in monad-based do-notation, monadic bind performs marginalisation, lazily pruning unneeded branches. On MNIST addition, our HaskTorch, JAX, and PyTorch implementations outperform LTN and DeepProbLog in speed and accuracy, while achieving nearly the accuracy of DeepStochLog. However, unlike DeepStochLog, we stay in a uniform framework that applies to many first-order NeSy approaches. Namely, the construction is parametric in the monad; instantiating it with, e.g., the Giry monad extends the approach to continuous probability (working out a neural representation here is left for future work).

15.
medRxiv (Medicine) 2026-06-20

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

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

16.
medRxiv (Medicine) 2026-06-22

Sex-specific multimorbidity clusters and all-cause mortality in relatively healthy older adults: findings from the ASPREE cohort

Background: Multimorbidity is common in older adults, but sex differences in chronic condition clustering remain unclear. This study explored multimorbidity clusters and their associations with all-cause mortality among community-dwelling adults aged 70 years and over. Methods: This was a secondary analysis of data from 16,095 Australian ASPREE participants aged at least 70 years without prior dementia or cardiovascular disease. Fifteen baseline chronic conditions were grouped using latent class analysis (LCA). Observed-to-expected (O/E) ratios characterised conditions over-represented within clusters, and Cox proportional hazards models assessed associations with all-cause mortality. Results: Among 16,095 participants (mean age 74 years), 88.3% had multimorbidity at baseline; 4,217 deaths occurred over a median follow-up of 10.85 years. Five clusters were identified overall: hypertension and dyslipidemia (52.1%), gout and metabolic (14.4%), depressive symptoms, osteoporosis and frailty (10.0%), anaemia and kidney disease (10.2%), and hypotension, thyroid disorder and past cancer (13.3%). Sex-stratified analyses revealed three clusters in males and four in females. The frailty, depressive symptoms and osteoporosis cluster was associated with higher mortality in both sexes (aHR 1.56 [95% CI 1.40-1.73] in males; 1.68 [1.49-1.89] in females). Higher mortality was also observed for the metabolic, gout and kidney disease cluster in males (aHR 1.63 [1.47-1.81]) and the gout, anaemia and kidney disease cluster in females (aHR 1.96 [1.74-2.21]). Conclusions: Distinct multimorbidity clusters differed by sex and were associated with increased all-cause mortality. These findings may support risk stratification, targeted screening, and more person-centred management of older adults with multimorbidity.

17.
arXiv (quant-ph) 2026-06-15

New Identity for Cayley's First Hyperdeterminant with Applications to Symmetric Tensors and Entanglement

作者:

arXiv:2512.03093v3 Announce Type: replace Abstract: In this article, a new formula for computing Cayley's first hyperdeterminant in terms of the Levi-Civita symbol is given. It is then shown that this formula can be used to compute the hyperdeterminant of symmetric tensors in polynomial time with respect to their order (assuming fixed side length). Applications to quantifying the entanglement of states of bosonic quantum systems are then discussed. Additionally, in order to obtain the fast calculation of the hyperdeterminant on symmetric tensors, generalized elimination and duplication matrices are defined and their explicit formulas are derived.

18.
bioRxiv (Bioinfo) 2026-06-17

Beyond phylogeny: Genome-wide DNA sequence patterns suggest DNA physical properties associated with thermal adaptation in extremophile microbes

Temperature is a fundamental constraint on biological systems, yet how it is reflected in genome sequence organization remains unclear. Here, we show that genome-wide distributions of short DNA sequences contain a robust signal of thermal adaptation that is largely independent of phylogeny. Using Structural Topic Modelling (STM), a machine-learning approach for identifying groups of co-occurring sequence motifs, we analyze canonical 6-mer and 9-mer frequency profiles of bacterial and archaeal genome proxies (randomly sampled genomic regions) and identify motif families systematically associated with thermophiles and psychrophiles. In bacterial thermophiles, the identified motif families are dominated by highly specific, overrepresented and co-occurring C- and G-stacked hexamers, and a distinct family of CG-periodic hexamers recurring across multiple temperature comparisons. In contrast, bacterial psychrophile-associated motifs are dominated by low-complexity A-, T-, and AT-run hexamers. Thermophilic archaea generally exhibit a distinct CTAG-centred hexamer family, suggesting that different domains may adapt to similar environmental constraints through different sequence-level solutions. However, this domain-level contrast is not absolute: in a targeted analysis of two thermophilic bacterium–archaeon pairs, we find unusually similar frequencies of all the STM-identified thermophile-associated hexamer families, suggesting that shared high-temperature environments can, in specific cases, partially override phylogenetic divergence. Notably, the identified motif families constitute only a small and highly selective subset of the vast space of possible G+C-rich or A+T-rich sequences. This indicates that thermal adaptation is associated with specific sequence architectures rather than broad shifts in nucleotide composition. Accordingly, the observed signal cannot be explained by overall base composition alone, but instead arises from structured combinations and positional arrangements of nucleotides within short sequence contexts. Related motif families are recovered at both k=6 and k=9, indicating that the signal reflects systematic shifts in genome-wide sequence organization rather than isolated sequence motifs. These patterns are consistent with known sequence-dependent DNA physical properties documented in biochemical and biophysical studies, including differences in base-stacking interactions and conformational flexibility. Together, our results suggest that genome-wide sequence organization reflects sequence-dependent DNA physical properties associated with thermal adaptation, revealing a previously underappreciated physical layer of genomic information beyond phylogenetic history.

19.
medRxiv (Medicine) 2026-06-22

Early-life nutritional environment is associated with late-life cognition in the Health and Retirement Study, a pellagra epidemic natural experiment

Early-life exposures are important to several late-life health outcomes. We sought to study the effect of an in utero nutritional environment and its interaction with Alzheimer's disease (AD) genetic risk on late-life cognitive function. We used a natural experiment created by the pellagra epidemic, a nutritional disease caused by a vitamin B3 deficiency, to evaluate the association between in utero pellagra epidemic exposure and late-life cognitive function in the Health and Retirement Study (N = 18,285). We also evaluated whether the in utero exposure could modify the AD polygenic score's (PGS) effect on cognition. In utero pellagra epidemic exposure was significantly associated with cognition ({beta} = -0.025). However, these effects were not isolated to the prenatal period as exposure during childhood periods also had an effect. The interaction between the in utero exposure and the AD PGS was significant, where the genetic effect on cognition was amplified with increasing (progressively worse) in utero exposure levels. These associations imply that the early-life nutritional environment affects late-life cognitive function and that these effects can modify genetic risk.

20.
arXiv (CS.LG) 2026-06-16

TS-ICL: A Flexible Time-Indexed Foundation Model for Time Series via In-Context Learning

arXiv:2606.05878v2 Announce Type: replace Abstract: Foundation models mark a profound paradigm shift in time series modeling, with task-specific models being superseded by general-purpose zero-shot models. Yet, current approaches primarily focus on forecasting, while real-world time series are often irregularly and partially observed, requiring models that can jointly forecast, impute missing values, and handle degraded sampling conditions. To address these challenges, we introduce TS-ICL, a novel probabilistic In-Context Learning encoder–regressor Transformer that unifies forecasting and imputation. TS-ICL formulates time series tasks as timestamp-aligned regression and naturally incorporates covariates by training on synthetic dependency structures generated from a novel causal data prior. Empirically, TS-ICL achieves a new state-of-the-art in imputation, while remaining competitive with leading forecasting foundation models across both univariate and covariate-aware benchmarks. It shows particularly strong performance in forecasting with partially observed look-back windows.

21.
arXiv (math.PR) 2026-06-16

Higher-order spectral perturbation expansions II: Kernel matrices and manifold learning

arXiv:2606.16373v1 Announce Type: cross Abstract: We study spectral concentration bounds for kernel matrices as approximation of the corresponding kernel integral operator. Results are established under weak assumptions on the data setting and the reproducing kernel relying only on a Mercer condition and a local Weyl law. This allows us to deal with key features of kernel matrices, such as large multiplicities, large effective dimension, and heavy-tailed distributions. Our results apply to infinite dimensional principal component analysis, manifold learning, and Bayesian nonparametric statistics. We illustrate this via two prototypical examples: The heat kernel on the sphere and a wavelet prior from Bayesian nonparametrics.

22.
arXiv (CS.LG) 2026-06-15

MOSIC: Model-Agnostic Optimal Subgroup Identification with Multi-Constraint for Improved Reliability

arXiv:2504.20908v3 Announce Type: replace Abstract: Current subgroup identification methods typically follow a two-step approach: first estimate conditional average treatment effects and then apply thresholding or rule-based procedures to define subgroups. While intuitive, this decoupled approach fails to incorporate key constraints essential for real-world clinical decision-making, such as subgroup size and propensity overlap. These constraints operate on fundamentally different axes than CATE estimation and are not naturally accommodated within existing frameworks, thereby limiting the practical applicability of these methods. We propose a unified optimization framework that directly solves the primal constrained optimization problem to identify optimal subgroups. Our key innovation is a reformulation of the constrained primal problem as an unconstrained differentiable min-max objective, solved via a gradient descent-ascent algorithm. We theoretically establish that our solution converges to a feasible and locally optimal solution. Unlike threshold-based CATE methods that apply constraints as post-hoc filters, our approach enforces them directly during optimization. The framework is model-agnostic, compatible with a wide range of CATE estimators, and extensible to additional constraints like cost limits or fairness criteria. Extensive experiments on synthetic and real-world datasets demonstrate its effectiveness in identifying high-benefit subgroups while maintaining better satisfaction of constraints.

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

Auditing Reward Hackability in Code RL Training Environments

arXiv:2606.16062v1 Announce Type: new Abstract: We measure the rate at which code RL environments accept incorrect solutions as correct. On a 49-task sample of SWE-bench Verified, 28.5% of tasks have test suites weak enough that a Docker-verified incorrect patch passes them. On 20 R2E-Gym tasks across 6 repositories, the same pipeline at single-shot exploit generation yields 25.0%. A random-effects meta-analysis over 134 frontier model submissions to SWE-bench Verified finds, within the same human-rated difficulty stratum, model Pass@1 is +14.14 percentage points higher on flagged-hackable tasks than on robust ones (95% CI [+11.80, +16.48]; one-sided p < 10^-6; I^2 = 0%; 123 of 134 models positive). We then describe a procedure for hardening the broken tasks. An inline LLM judge with a Docker gold-sanity gate runs each generated test against the gold solution before the judge is consulted. On the 11 broken tasks in the audit, the gate flags 65 of 105 decisive LLM-generated tests as failing on the gold patch itself, a 61.9% per-augmentation defect rate the LLM judge alone misses. With diversity-biased retry, the loop converges 9 of 11 tasks to a gated upgrade.

24.
arXiv (CS.CV) 2026-06-15

Prompt2Effect: Training-Free Image-to-Video Model Specialization via LoRA Generation

Personalizing Image-to-Video (I2V) diffusion models with specific visual effects is increasingly demanded for high-end video generation. Current practice requires training a separate Low-Rank Adaptation (LoRA) module for each effect, incurring substantial data curation and iterative optimization costs that hinder interactive control. We present Prompt2Effect, a weight-driven hypernetwork that amortizes per-effect training by directly synthesizing effect-specific LoRA weights in a single forward pass. Unlike prior hypernetworks that regress adapter weights purely from semantics, Prompt2Effect is explicitly conditioned on the frozen base model weights, grounding weight prediction in the structural geometry of each layer. Furthermore, instead of predicting raw LoRA matrices, we introduce an SVD-canonicalized parameterization that resolves factorization ambiguity and stabilizes large-scale weight synthesis. Together, these design principles enable accurate and scalable LoRA prediction for high-dimensional I2V diffusion models. Extensive experiments demonstrate that Prompt2Effect achieves on-par or superior video quality and effect alignment compared to conventional LoRA fine-tuning, while reducing the computational cost from 56 GPU training hours to 3.3 seconds of hypernetwork inference. When used as initialization for subsequent fine-tuning, our predicted weights further improve final performance and accelerate optimization by approximately 10x.

25.
medRxiv (Medicine) 2026-06-22

Efficacy and safety of semaglutide for obesity and hyperphagia in adults with Prader-Willi syndrome

Context: Prader-Willi syndrome is a genetic neurodevelopmental disorder characterized by hyperphagia and early-onset obesity from hypothalamic dysfunction with endocrinopathies and learning disability. Management is challenging with strict control of the food environment needed. While newer glucagon-like peptide-1 receptor agonists, such as semaglutide, have efficacy in non-PWS obesity, there have been limited case reports in PWS. Objective/Design/Setting: Retrospective records review of 12 adults with PWS and overweight/obesity treated with semaglutide at a UK academic hospital centre specialist clinic. Patients: mean +/- SD age 28.3 +/- 10.1 years, 83% female, BMI 46.6 +/- 8.2kg/m2, 75% type 2 diabetes mellitus. Intervention: Median follow-up 17.2 months (range 8.7-36.1) with median semaglutide dose 2.4mg once weekly (1.0-2.4). Results: Although there was no significant weight loss on semaglutide, there was stabilisation of the weight gain prior to treatment over previous 12.4 months (7.6-23.0) (post -3.1 +/- 9.9% vs. pre +5.7 +/- 5.6%: d -0.72, P=0.037). There was a significant decrease in hyperphagia on semaglutide from hyperphagia questionnaire for clinical trials (n=11, -7.3 +/- 6.1 (max 36), d -1.19, P=0.003), having been stable before treatment. HbA1c improved in those with elevated baseline levels (n=6, -4.2 +/- 4.9%, d -0.74, P=0.13). Mild gastrointestinal side effects were seen in 25% but did not lead to discontinuation. Conclusions: In adults with PWS, semaglutide produced weight maintenance, reduced hyperphagia, and improved glycaemic control, with good tolerability. Larger placebo-controlled trials are needed to confirm these findings in adults and adolescents with PWS, especially in those without T2DM, where efficacy may be greater.