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01.
arXiv (CS.AI) 2026-06-15

HierSVA: A Data Synthesis Pipeline, Dataset, and Benchmark for LLM-Driven Hierarchical Hardware Formal Verification

arXiv:2606.13706v1 Announce Type: cross Abstract: We present HierSVA, an integrated suite that combines a pipeline, dataset, and benchmark for LLM-driven hierarchical hardware formal verification. HierSVA-SP pairs an RTL preprocessing toolchain with an LLM-in-the-loop formal verification flow to produce reference SystemVerilog Assertions (SVA) on hierarchical RTL. Applying it to BaseJump STL yields HierSVA-DS, a dataset of 342 modules, with hierarchy metadata and depths 0–9, accompanied by a deep subset of 28 module-bug pairs with natural-language specifications and bug variants. HierSVA-B decomposes assertion quality into six metric axes: syntax correctness, assertion proof success rate, vacuity, specification faithfulness, mutation coverage, and formal core coverage. Applying HierSVA-B to twelve recent LLMs reveals three findings. First, the module-level compile rate is 67.1\%; among generated assertions in evaluable runs, 82.1\% prove non-vacuously, but the corresponding assertion sets detect only 70.2\% of eligible injected faults and cover 36.2\% of the formal core. Second, on 211 evaluable model–module entries in the deep subset, assertion sets flag buggy RTL with 0.87 recall, but 40\% of predicted-buggy outcomes are false positives on correct RTL, limiting precision to 0.60. Third, agentic mode improves S1-style provability and strength metrics, but gains plateau and oscillate. Codes and artifacts are available at \href{https://github.com/HierSVAAnon/HierSVACodeAndArtifacts}{https://github.com/HierSVAAnon/HierSVACodeAndArtifacts}. Dataset is available at \href{https://huggingface.co/datasets/AnonymousHierSVA/HierSVA}{https://huggingface.co/datasets/AnonymousHierSVA/HierSVA}.

02.
arXiv (quant-ph) 2026-06-12

Coarse-grained quantum thermodynamics: Observation-dependent quantities, observation-independent laws

arXiv:2507.15918v2 Announce Type: replace Abstract: In both classical and quantum thermodynamics, physical quantities are typically assigned objective values defined independently of our observations. We then refer to the 'work performed by a gas', or the 'entropy of the gas', regardless of how they are evaluated. Here, we question this conception in the context of quantum thermodynamics, estimating how the definition of pivotal thermodynamic quantities is affected by experimental instruments of limited precision. We find that the coarse-grained thermodynamic quantities frequently lead to different conclusions from those drawn in fine-grained scenarios. For instance, the irreversibility of a process, or its work payoff, can significantly vary with the instrument precision. We show nonetheless that coarse-grained thermodynamic quantities satisfy the same relations (i.e., the second law inequality, the relation between dissipation and distinguishability of a process from its time-reverse, and the quantum work fluctuation theorems) as their fine-grained counterparts. These results highlight the observation-independence of relations linking thermodynamic quantities which are themselves observation-dependent.

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

Essential Subspace Merging for Multi-Task Learning

arXiv:2606.19164v1 Announce Type: cross Abstract: Model merging aims to enable multi-task learning by integrating the capabilities of multiple models fine-tuned from the same pre-trained checkpoint into a single model. Its core challenge is inter-task interference among task-specific parameter updates. In this paper, we analyze the output shifts induced by task updates and observe that their energy is concentrated in a small number of principal directions. We call the subspace spanned by these directions the essential subspace. In contrast, most remaining directions carry little task-relevant energy, but their accumulation across multiple task updates can cause severe interference during merging. Motivated by this observation, we propose Essential Subspace Decomposition (ESD), which decomposes each task update according to the principal components of its activation shift. Based on ESD, we introduce Essential Subspace Merging (ESM), a training-free static merging method that orthogonalizes and fuses essential components into one compact multi-task model. We further extend ESM to ESM++, a training-free dynamic merging method that decomposes task-specific residuals into low-rank experts and selects the most relevant expert through prototype-based routing during forward inference. Extensive experiments across multiple task sets and model scales demonstrate that ESM and ESM++ effectively preserves task knowledge while reducing inter-task interference.

04.
Nature Medicine 2026-06-08

Effects of SGLT2 inhibition on incident heart failure in carriers of cardiomyopathy-associated genetic variants

Although the beneficial effects of sodium–glucose cotransporter 2 (SGLT2) inhibition in heart failure (HF) have been well established, it is unknown whether SGLT2 inhibition confers benefit in carriers of rare variants in cardiomyopathy-associated genes. Here we evaluated whole-exome sequencing data from the randomized DECLARE-TIMI 58 trial, in which adults with type 2 diabetes and increased cardiovascular risk were randomized to dapagliflozin or placebo treatment. Pathogenic or likely pathogenic variants (P/LP) in high-confidence cardiomyopathy genes were identified, and treatment effects on hospitalization for HF (HHF) were compared between carriers of such variants and noncarriers. Among 12,685 patients for whom sequence data were obtained, 121 carried a cardiomyopathy variant (76 dilated cardiomyopathy, 25 hypertrophic cardiomyopathy and 25 arrhythmogenic cardiomyopathy). Over a median follow-up of 4.2 years, dapagliflozin lowered the risk of HHF more strongly in carriers (hazard ratio 0.18, 95% confidence interval 0.04–0.86) than in noncarriers (hazard ratio 0.70, 95% confidence interval 0.57–0.86; P interaction 0.03). Absolute risk reduction was 13.0% in carriers and 1.0% in noncarriers (P interaction 0.03). Most carriers (82%) had no prior HF, and in carriers without prior HF, treatment with dapagliflozin reduced the absolute risk of HHF by 12.8%, compared with a reduction of 0.6% in noncarriers (P interaction 0.01). The findings from this cohort of older and high-risk patients raise the possibility that SGLT2 inhibitor treatment should be started early to prevent HF in individuals who carry P/LP cardiomyopathy variants. These results need to be confirmed in a prospective, dedicated trial of preventive HF treatments in carriers of P/LP cardiomyopathy-associated variants. In a whole-exome sequencing analysis, the beneficial effects of the SGLT2 inhibitor dapagliflozin in reducing the risk of future heart failure hospitalization in individuals with type 2 diabetes were markedly greater in individuals who carried a cardiomyopathy-associated genetic variant compared with noncarriers, suggesting a personalized preventative therapy based on genetic information.

05.
arXiv (CS.LG) 2026-06-11

Fixed-Parameter Tractability of Private Synthetic Data Generation

arXiv:2606.11283v1 Announce Type: cross Abstract: We study the problem of generating synthetic data under differential privacy. We establish fixed-parameter tractability (FPT) for this problem where the parameter is the treewidth of the query family's incidence graph. Our algorithms attain optimal error rates across all regimes and are realized by two different approaches: the first is based on linear programming (LP) and the FPT of the separation problem for the LP dual; the second is based on a subsampled private multiplicative weights method, where we obtain FPT for sampling from Gibbs distributions. Both approaches are unified by a dynamic programming framework over a tree decomposition.

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

MUFASA: A Multi-Layer Framework for Slot Attention

Unsupervised object-centric learning (OCL) decomposes visual scenes into distinct entities. Slot attention is a popular approach that represents individual objects as latent vectors, called slots. Current methods obtain these slot representations solely from the last layer of a pre-trained vision transformer (ViT), ignoring valuable, semantically rich information encoded across the other layers. To better utilize this latent semantic information, we introduce MUFASA, a lightweight plug-and-play framework for slot-attention-based approaches to unsupervised object segmentation. Our model computes slot attention across multiple feature layers of the ViT encoder, fully leveraging their semantic richness. We propose a fusion strategy to aggregate slots obtained on multiple layers into a unified object-centric representation. Integrating MUFASA into existing OCL methods improves their segmentation results across multiple datasets, setting a new state of the art while simultaneously improving training convergence with only minor inference overhead.

07.
medRxiv (Medicine) 2026-06-10

Developmental Associations Linking Childhood Trauma and Early Cannabis Use to Adolescent DNA Methylation and Psychotic-Like Experiences

Background. Psychotic-like experiences (PLEs) index early risk for psychotic disorders and are consistently associated with childhood trauma, yet underlying biological mechanisms remain poorly understood. DNA methylation (DNAm) may capture the biological embedding of early adversity, while adolescent exposures such as cannabis use may modify these processes. We examined epigenome-wide associations of childhood trauma and PLEs, tested the moderating role of early cannabis use, and evaluated DNAm as a potential mediator. Methods. We analysed data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK population-based birth cohort. Childhood trauma was assessed prospectively and retrospectively. Epigenome-wide DNAm was measured in peripheral blood at ~17 years using the Illumina 450K array, and PLEs were assessed at 18 using a structured interview. Epigenome-wide association studies were conducted for trauma-DNAm and DNAm-PLEs associations in the final sample (n = 1,457), adjusting for demographic, biological, and technical covariates. Differentially methylated regions (DMRs) were identified using DMRff, followed by functional enrichment analyses. Cannabis use at 15.5 was modelled as a moderator with multiple imputation for missing data. Mediation was tested using the Divide-Aggregate Composite-null Test (DACT). Results. Childhood trauma was associated with widespread DNAm differences, primarily at the regional level, with enrichment in pathways related to cellular stress responses. In contrast, DNAm associated with PLEs was more limited and implicated loci involved in epigenetic regulatory processes. These signatures were largely distinct, and there was no evidence supporting mediation after multiple testing correction. Incorporating cannabis use altered the pattern and extent of DNAm associations, with stronger and more significant signals observed at both CpG and regional levels, although these did not translate into evidence of mediation. Conclusion. Childhood trauma and PLEs show distinct DNAm signatures in adolescence, with trauma-related DNAm reflecting broad stress-related processes and PLE-associated DNAm implicating regulatory mechanisms. We found little evidence that DNAm mediates the trauma-PLE association. Instead, adolescent exposures, particularly cannabis use, may distinctly influence trauma-related epigenetic variation with limited detectable downstream effects on PLEs. These findings support a context-dependent model of epigenetic risk and highlight the need for larger longitudinal studies to clarify causal pathways linking early adversity to psychosis.

08.
arXiv (CS.AI) 2026-06-12

TimeROME-DLM: Temporal Causal Tracing and Low-Rank Inference-Time Knowledge Editing for Masked Diffusion Language Models

arXiv:2606.12841v1 Announce Type: cross Abstract: Masked diffusion language models (MDLMs) such as LLaDA now rival autoregressive (AR) LLMs, but every existing knowledge-editing and unlearning method (ROME, MEMIT, etc.) targets AR transformers and either makes assumptions that fail under iterative denoising, or requires gradient updates whose backward-pass activations cost tens of GB of extra VRAM and which collapse MDLMs at standard learning rates. We introduce TimeROME-DLM, the first training-free, gradient-free, inference-time knowledge-editing framework for MDLMs. It couples two components: a Temporal Indirect Effect (TIE) causal-tracing protocol that identifies, for each fact, the coordinate whose intervention most strongly drives the object prediction at later denoising steps; and a closed-form, low-rank residual edit memory that aggregates subject keys and target deltas across all forget facts and applies a single ridge-regularised update at that coordinate at every diffusion forward, with sparsification to limit utility spillover. Backbone weights stay frozen; only three hyperparameters (alpha, lambda, q) are tuned on a small validation split. On TOFU forget01 with TOFU-finetuned LLaDA-8B-Base, TimeROME-DLM cuts forget-set log-probability by roughly 83 nats. The same configuration transfers to LLaDA-8B-Instruct, Dream-7B, MMaDA-8B, DiffuLLaMA-7B, and LLaDA-MoE-1.4B. It keeps retain-set log-probability nearly flat (within ~1 nat at the utility-safe operating point) across 50 sequentially inserted facts, delivers a four- to fourteen-fold wall-clock speedup with zero additional VRAM over the strongest converged training-time baseline, and scales sub-linearly to 400 facts. TimeROME-DLM closes the locate-then-edit gap between AR LLMs and MDLMs at a fraction of the computational cost.

09.
arXiv (CS.CV) 2026-06-15

One Layer's Trash is Another Layer's Treasure: Adaptive Layer-wise Visual Token Selection in LVLMs

Large Vision-Language Models (LVLMs) have achieved remarkable success across diverse multimodal tasks, yet their practical deployment remains constrained by the computational burden arising from lengthy visual tokens. While visual token pruning has emerged as a promising solution, existing methods suffer from a fundamental limitation: once tokens are pruned at a specific layer, they become inaccessible to all subsequent layers, leading to premature information loss that can compromise model performance. Through empirical studies, we observe that different layers exhibit distinct visual region focus, indicating a varying optimal token subset across layers. Motivated by this insight, we propose Adaptive Layer-wise Visual Token Selection (ALVTS), a novel framework that breaks away from the conventional static token pruning paradigm. ALVTS incorporates a lightweight token selector to identify and route important tokens for further processing, while allowing less important tokens to skip the layer, thus minimizing computational redundancy. These two streams of tokens are seamlessly reintegrated before being fed into subsequent layers, facilitating adaptive compression across the entire model. Grounded in our importance consistency constrained low-rank approximation, the proposed token selection module closely emulates the full attention mechanism, effectively capturing its essential patterns without requiring model retraining. Extensive experiments on LLaVA-1.5, LLaVA-NeXT, and Qwen2.5-VL validate the effectiveness of our method. With an 89% token compression ratio, ALVTS retains 96.7% of the original model's accuracy, achieving a superior efficiency-accuracy trade-off for LVLM inference.

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

TimeVista: Exploring and Exploiting Vision-Language Models as Judges for Time Series Forecasting

arXiv:2606.16173v1 Announce Type: new Abstract: High-quality time series forecasting is pivotal for real-world decision-making. However, traditional point-wise metrics often fail to reveal complex temporal patterns and align poorly with human intuitive preferences. While the ''LLM-as-a-Judge'' paradigm has revolutionized text evaluation by providing flexible, human-aligned judgment, its application to time series remains largely unexplored. In this paper, we leverage Vision-Language Models (VLMs) as judges for time series forecasting, harnessing their ability to comprehend time series plots grounded in textual information. Specifically, we propose a novel framework integrating micro- and macro-level judgments informed by contextual information to evaluate time series forecasting. To this end, we introduce TimeVista, a comprehensive VLM-as-a-Judge benchmark comprising 5563 time series samples paired with detailed evaluation rubrics. Extensive meta-evaluations demonstrate that VLMs are highly reliable judges, achieving significantly higher consistency with human preferences than conventional metrics. Building upon our benchmark, we comprehensively assess recent Time Series Foundation Models (TSFMs) under the VLM-as-a-Judge paradigm. Our results demonstrate that VLMs serve as robust and interpretable judges, providing a comprehensive, human-aligned standard for evaluating time series models.

11.
Nature (Science) 2026-06-17

A blastoporal organizer in a ctenophore

In an iconic experiment in 1924, Hilde Mangold and Hans Spemann established that the dorsal blastopore lip of amphibian embryos functions as an organizer and induces a secondary body axis when transplanted into a host embryo1. This discovery demonstrated that specific embryonic regions can regulate embryonic patterning and lead to the establishment of an entire body axis. Subsequent studies have revealed that cnidarians, the sister group to Bilateria, also possess a blastoporal embryonic organizer2,3. However, the evolutionary origin of the organizer remains unclear. Here we report that the blastopore lip of the ctenophore Mnemiopsis leidyi, a member of the evolutionary sister group to all other metazoans4,5, exhibits organizer activity. We show that transplanted fragments of blastopore lip tissue from M. leidyi gastrula induce secondary pharynx and mouth formation. Moreover, transphyletic transplantation experiments show that the blastopore lip of M. leidyi leads to the generation of a secondary body axis in embryos of the cnidarian Nematostella vectensis. Organizer function in M. leidyi requires both β-catenin and TGFβ signalling, and the TGFβ-family ligands probably provide this inductive capacity. These findings reveal the deep homology of the blastoporal organizer in ctenophores, cnidarians and vertebrates, implying the ancestral organizer role of the blastopore lip. We propose that the emergence of the organizer was an essential innovation that facilitated the change from the temporal cell differentiation of unicellular relatives to the spatial cell differentiation of the first multicellular embryo. Experiments using the comb jelly Mnemiopsis leidyi and the sea anemone Nematostella vectensis reveal that the emergence of a core signalling pathway may have been a key innovation enabling the transition to multicellularity in animals.

12.
arXiv (CS.CL) 2026-06-11

SoftMatcha 2: A Fast and Soft Pattern Matcher for Trillion-Scale Corpora

We present SoftMatcha 2, an ultra-fast and flexible search algorithm that enables search over trillion-scale natural language corpora in under 0.3 seconds while allowing semantic variations in the form of substitution, insertion, and deletion. Our approach employs string matching based on suffix arrays that scales well with corpus size, and represents words as vectors, which underpin its semantic flexibility. To mitigate the combinatorial explosion induced by the semantic relaxation of queries, our method is built on two key algorithmic ideas: dynamic corpus-aware pruning and fast exact lookup enabled by a disk-aware design. We theoretically analyze the efficiency of the proposed method, indicating that it can mitigate exponential growth in the search space. Empirically, on FineWeb-Edu (Lozhkov et al., 2024) (1.4T tokens), it attains substantially lower search latency than existing methods: infini-gram (Liu et al., 2024), infini-gram mini (Xu et al., 2025), and SoftMatcha (Deguchi et al., 2025). As a practical application, our method uncovers benchmark contamination in training corpora that existing approaches miss, and it also benefits information retrieval and paraphrase detection. We also provide an online demo of fast, soft search across corpora in seven languages.

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

Constitutional On-Policy Safe Distillation

arXiv:2606.03089v2 Announce Type: replace-cross Abstract: On-policy self-distillation (OPSD) has emerged as an efficient post-training paradigm by using a teacher conditioned on privileged information to provide dense token-level supervision. Prior work has shown that OPSD can collapse in verifiable reasoning tasks, but safety alignment differs in that it is guided by high-level constitutions rather than explicit target answers, making it a natural setting to revisit dense distillation. However, our pilot study show that safety OPSD still suffers from severe collapse: constitutional conditioning contracts the teacher distribution toward short and overly conservative responses, and Reverse KL further amplifies this contraction into reduced expressiveness. We formalize this effect as geometric leakage under safety boundaries in a non-orthogonal semantic space, where safety pressure transfers into the expressiveness dimension. Based on this analysis, we propose Constitutional On-Policy Safe Distillation (COPSD), which first calibrates the teacher through a Cross-SFT cold-start and then performs constitution-conditioned on-policy distillation. Experiments on 12 benchmarks show that COPSD achieves a consistently stronger safety–helpfulness trade-off than baselines while substantially reducing the safety tax on general reasoning ability.

14.
arXiv (CS.AI) 2026-06-11

MobilityBench: A Benchmark for Evaluating Route-Planning Agents in Real-World Mobility Scenarios

arXiv:2602.22638v2 Announce Type: replace Abstract: Route-planning agents powered by large language models (LLMs) have emerged as a promising paradigm for supporting everyday human mobility through natural language interaction and tool-mediated decision making. However, systematic evaluation in real-world mobility settings is hindered by diverse routing demands, non-deterministic mapping services, and limited reproducibility. In this study, we introduce MobilityBench, a scalable benchmark for evaluating LLM-based route-planning agents in real-world mobility scenarios. MobilityBench is constructed from large-scale, anonymized real user queries collected from Amap and covers a broad spectrum of route-planning intents across multiple cities worldwide. To enable reproducible, end-to-end evaluation, we design a deterministic API-replay sandbox that eliminates environmental variance from live services. We further propose a multi-dimensional evaluation protocol centered on outcome validity, complemented by assessments of instruction understanding, planning, tool use, and efficiency. Using MobilityBench, we evaluate multiple LLM-based route-planning agents across diverse real-world mobility scenarios and provide an in-depth analysis of their behaviors and performance. Our findings reveal that current models perform competently on Basic information retrieval and Route Planning tasks, yet struggle considerably with Preference-Constrained Route Planning, underscoring significant room for improvement in personalized mobility applications. We publicly release the benchmark data, evaluation toolkit, and documentation at https://github.com/AMAP-ML/MobilityBench.

15.
medRxiv (Medicine) 2026-06-17

Silent Manipulation of Mental Health Treatment Recommendations from a Large Language Model

Importance. Large language models (LLMs) increasingly inform mental health decisions by patients and clinicians. Inference-time activation steering can shift model behavior on a target dimension without altering weights or prompts and without disclosure to users, allowing treatment recommendations to be silently changed for commercial or ideological reasons. Objective. To determine whether directional activation steering can shift an open-weights LLM's depression treatment recommendations. Design, Setting, and Participants. This non-human subjects study applied directional activation steering to an open-weights LLM (DeepSeek V4 Flash) responding to 12 depression-advice scenarios (4 favoring medication, 4 favoring avoidance, 4 neutral), generated at 30 amplitudes from -1.5 to +1.5 in 0.1 increments plus an unsteered baseline. Exposures. A single steering direction contrasting antidepressant medication with self-directed approaches (diet, exercise, meditation, dietary supplements), constructed from 16 paired training prompts and applied at the attention output of every transformer block; weights and system prompt were held constant. Main Outcomes and Measures. The extent to which medication and four self-care categories were addressed, scored 0 to 3 by a human-validated LLM rater (Claude Opus 4.7), the medication-versus-self-care balance, and clinician referral, estimated per unit of amplitude using mixed-effects models with a scenario random intercept. Results. Across 372 generations, steering produced a graded, dose-dependent shift in the medication-versus-self-care balance, which declined by 0.32 per unit of amplitude (beta=-0.32; 95% CI, -0.39 to -0.25; P < .001); medication extent fell and self-care extent rose. The shift was largest for scenarios with no stated treatment preference (beta = -0.44; 95% CI, -0.54 to -0.34; P < .001). A clinician referral appeared in 322 of 372 responses (87%) and did not vary with steering amplitude (P = .63). Conclusions and Relevance. In this open-weights LLM providing depression treatment information, inference-time activation steering shifted treatment recommendations without altering weights, prompt structure, or safety outputs, with the largest effect among users expressing no treatment preference. These findings suggest a need for LLM disclosure standards and independent auditing as such models inform clinical decisions.

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

How Much Can We Trust LLM Search Agents? Measuring Endorsement Vulnerability to Web Content Manipulation

Large language model (LLM)-based search agents synthesize open-web content into actionable recommendations on behalf of users, creating a risk that attacker-published pages are transformed into endorsed claims. We introduce SearchGEO, a controlled evaluation framework for measuring endorsement corruption in LLM-based web-search agents, combining a web-evidence manipulation pipeline, a five-mode attack taxonomy, and multiple output-level metrics. We evaluate 13 LLM backends on 308 cases each. Results show that vulnerability patterns vary across backends: overall attack success rate (ASR) ranges from 0.0% on Claude-Sonnet-4.6 to 31.4% on Gemini-3-Flash, the strongest attack mode differs by model family, and the same deployment scaffold could amplify or decrease ASR on different backends. An auxiliary agent-skill probe, where endorsement becomes an install command, exposes a sharp split among otherwise robust backends: Claude over-rejects while GPT over-trusts. These findings argue for treating recommendation reliability under adversarial search content as a first-class dimension of backend safety evaluation.

17.
arXiv (CS.AI) 2026-06-19

How Transparent is DiffusionGemma?

arXiv:2606.20560v1 Announce Type: cross Abstract: LLM reasoning transparency is a critical affordance for understanding model decisions, mitigating misuse and misalignment, and debugging surprising model behaviors. However, DiffusionGemma performs a larger fraction of its computation in a continuous latent space; does this make its reasoning less transparent? We study this question by decomposing transparency into two components: variable transparency, whether we understand intermediate snapshots of a model's computational state; and algorithmic transparency, whether we can use these snapshots to reconstruct the process by which the model arrived at its outputs. Naively, DiffusionGemma has poor variable transparency: its opaque serial depth, the amount of serial computation that occurs in between interpretable model states, seems at first 28.6X higher than the corresponding autoregressive Gemma 4 model. However, we show that we can map the information flowing between denoising steps through an interpretable token bottleneck with no decrease in downstream performance. Treating these intermediate states as interpretable reduces the opaque serial depth to just 1.1X that of Gemma 4. Algorithmic transparency is harder for diffusion models than for autoregressive models because all token predictions in the canvas can change at every denoising step, giving the model the power to implement complicated distributed algorithms during the denoising process. To begin bridging this gap, we conduct a suite of interpretability case studies, uncovering initial evidence of novel diffusion-specific phenomena such as non-chronological reasoning, token and sequence smearing, and intermediate-context reasoning. Finally, we test monitorability, a key application of transparency that measures whether model outputs are useful for downstream tasks. We find that DiffusionGemma is similarly monitorable to Gemma 4.

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

SegTME-UNI2: A Foundation Model-Based Framework for Generalisable Multiclass Cell Segmentation and LLM-Driven Tumour Microenvironment Characterisation in Histopathology

Characterising the tumour microenvironment (TME) from routine H&E-stained histology images requires simultaneous cell segmentation, feature extraction, and interpretable clinical reporting. We present SEGTME-UNI2, a unified framework addressing these requirements. Its core is UNI2-UPERHOVER, a dual-head segmentation model pairing the UNI2-H pathology foundation model (ViT-Giant, pretrained on >100M tiles from 100K slides) with two parallel UperNet decoders: one for six-class semantic segmentation and one for horizontal-vertical gradient regression enabling watershed-based nuclear instance separation. To address the lack of pixel-level annotations in large real-world repositories, UNI2-UPERHOVER undergoes a three-stage progressive pseudo-label curriculum. Each stage trains a fresh model without weight transfer, driving improvement entirely via increased pseudo-label quality: Stage 1: Uses human-annotated PanNuke (7,901 images, 189,744 nuclei, 0.25 um/pixel). Stage 2: Uses entropy-filtered pseudo-labels from the Stage 1 model on 271,711 TCGA-UT scale-0 patches (0.5 um/pixel). Stage 3: Uses pseudo-labels from the Stage 2 model on all 1,608,060 TCGA-UT patches across six resolution scales (0.5-1.0 um/pixel). Segmentation outputs feed a structured TME feature extraction pipeline computing 20+ per-patch compositional, morphological, spatial entropy, and intercellular distance metrics. These are encoded as JSON and passed to a fine-tuned NVIDIA BioNeMo GPT model to generate clinically interpretable TME narratives. Preliminary validation on held-out PanNuke and TCGA-UT partitions demonstrates framework feasibility and internal consistency. The pseudo-labelled TCGA-UT dataset and UNI2-UPERHOVER checkpoint are publicly released to support large-scale TME profiling and spatial biology research.

19.
medRxiv (Medicine) 2026-06-11

Genetic Susceptibility to Incisional Hernia: Evaluation of Hernia Polygenic Risk Scores

Objectives: Incisional hernia (IH) affects 13-30% of people after abdominal surgery, resulting in substantial morbidity and costs. While clinical risk factors have been studied extensively, genomic risk for IH is incompletely understood. We aimed to evaluate the impact of polygenic risk scores (PRS) on IH risk prediction. Methods] We created and evaluated three PRS for abdominal hernia, ventral hernia and latent hernia susceptibility for prediction of IH in an institutional biobank. The primary outcome was defined as the diagnosis or repair of an IH based on ICD-9/10-CM/PCS and CPT codes. Clinical covariates included age, sex, body mass index (BMI), smoking status, index procedure type, and perioperative surgical site infection. A phenome-wide association study (PheWAS) was performed to assess clinical associations with increased PRS. We then tested the ability of the PRS to improve prediction for IH by modeling clinical covariates with and without PRS in patients who underwent abdominal surgery. Model performance was assessed using 10 iterations of 5-fold cross-validation to estimate Brier scores and area under the receiver operating characteristic curve (AUROC), which were compared using cross-model Bayesian analysis of variance. Results: In 55,809 subjects, assessed PRS was significantly associated with incisional, umbilical, and ventral hernia on PheWAS, with 1.19 greater odds of developing IH per 1-SD increase in PRS (95% CI: 1.13-1.25, P < 0.001). Of 9,909 subjects who underwent qualifying abdominal surgery, 706 developed IH. In this cohort, the latent hernia susceptibility PRS was associated with a 16% increased hazard of developing IH per 1-SD increase (HR 1.16; 95% CI: 1.07-1.26; P < 0.001). Compared to a predictive model using clinical covariates (Brier score = 0.047, 95% CI: 0.046-0.048; AUROC = 0.660, 95% CI: 0.653-0.666), addition of the PRS showed similar Brier score and AUROC estimates (Brier score = 0.047, 95% CI: 0.046-0.048; AUROC: 0.667, 95% CI: 0.661-0.673) at five years. Cross-model Bayesian analysis demonstrated >99% probability of practical equivalence when trying to detect a difference of [&ge;] 0.02. Conclusion: All three PRS for hernia were independently associated with IH, suggesting that genomic factors contribute significantly to IH development. However, none of the three PRS meaningfully improved clinical IH risk prediction in patients who underwent abdominal surgery. This suggests that clinical comorbidities and surgical techniques may be equally as important as genomic architecture.

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

Neuron Level Analysis of Large Language Model in Legal Domain Reasoning

We presented a neuron-level analysis of legal-domain reasoning in LLMs, comparing it with other applied domain tasks across seven open-weight models. Using neuron attribution scores to rank and suppress influential neurons, we confirmed that suppressing the identified neurons collapses accuracy on the target task, whereas suppressing the same number of random neurons does not. We further found a small subset of neurons influential across all seven tasks; once these are removed, suppressing the remaining neurons degrades only the task they were identified from, revealing genuinely task-specific neurons in every model studied. Within the legal domain, the three benchmarks exhibit relatively high neuron overlap and tend to be affected jointly, suggesting of legal components neurons that span jurisdictions. The distribution of identified neurons in our experiments suggests that the hypothesis that influential neurons are concentrated in middle MLP layers may depend on the input format and content, rather than being a universal phenomenon.

21.
medRxiv (Medicine) 2026-06-16

Validating an Early Pregnancy HbA1c as the Screening Test for Gestational Diabetes Mellitus: Findings from PRISMA Pakistan Cohort

Background: Early identification of gestational diabetes mellitus (GDM) is critical to improving maternal and neonatal outcomes, particularly in resource-constrained settings where universal oral glucose tolerance testing (OGTT) is burdensome. We assessed whether early-pregnancy HbA1c alone or combined with common risk factors can predict GDM and reduce the burden of OGTT requirements in a peri-urban cohort in Karachi, Pakistan. Methods: We conducted a secondary analysis of the Pregnancy Risk Infant Surveillance and Measurement Alliance (PRISMA) Pakistan cohort. Women enrolled before 20 weeks' gestation with available early-pregnancy HbA1c and a 2-hour 75g OGTT at 24 to 28 weeks were included. We externally validated GDM prediction models originally developed in the STRiDE-India cohort. Model performance was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). We assessed four models: HbA1c alone (Model 1a); age, BMI, and family history of diabetes mellitus (FH DM) (Model 1b); HbA1c combined with age, BMI, and FH DM (Model 2); and an extended model, i.e., Model 2 combined with socioeconomic status, gestational age, parity, systolic and diastolic blood pressure (Model 3). A dual-threshold approach was applied to assess rule-in and rule-out performance. Results: Among 2,489 women, GDM incidence was 7.5% (n=186). Models with a broader set of predictors demonstrated higher AUC values, with Model 2 achieving an AUC of 0.61 (95% CI: 0.57, 0.66). Including additional factors (Model 3) did not further improve predictive ability (AUC: 0.62; 95% CI: 0.58, 0.66). In addition, at predefined thresholds, Model 2 achieved sensitivity of 73.7% (rule-out) and specificity of 83.5% (rule-in), with the potential to reduce OGTT requirements (58.5%). Conclusions: Early-pregnancy risk stratification using HbA1c combined with simple clinical predictors offers a pragmatic approach to streamline GDM screening among high-risk pregnant women. A dual-threshold strategy using Model 2 could reduce reliance on universal OGTT while prioritizing high-risk women for confirmatory testing.

22.
Nature (Science) 2026-06-17

Navigating a crowded developing brain leaves neurons with broken DNA

As neurons migrate to their final destinations in the forming brain, their DNA gets damaged. The brain has evolved a fix, but there can be lasting consequences if repair fails. As neurons migrate to their final destinations in the forming brain, their DNA gets damaged. The brain has evolved a fix, but there can be lasting consequences if repair fails.

23.
arXiv (CS.AI) 2026-06-17

Closing the Feedback Loop: From Experience Extraction to Insight Governance in Verbal Reinforcement Learning

arXiv:2606.17591v1 Announce Type: new Abstract: Training-free verbal reinforcement learning enables LLM agents to learn from world feedback – objective signals such as dynamic task outcomes, market returns, or demand forecasts – by extracting verbal rules from experience and injecting them as context, updating the agent's behavior without parameter changes. However, in non-stationary environments these agents face a retention-forgetting dilemma: retaining stale insights causes negative transfer, while discarding them causes catastrophic forgetting when conditions recur. We identify four requirements for navigating this dilemma – outcome-driven evaluation, persistent structured evidence, non-monotonic knowledge lifecycle, and compositional governance – and show that existing methods invest heavily in experience extraction while underinvesting in insight governance. We propose a three-layer architecture – rules, evidence, and skills – connected by a feedback-driven curation loop that closes the governance gap. Rules capture distilled experience from world outcomes; evidence logs track each rule's reliability across episodes; skills govern which rules to apply, how to resolve conflicts, and when to abstain. On financial forecasting as a case study, where world feedback is naturally abundant, noisy, and non-stationary, we show that the same accumulated experience either degrades performance below the zero-shot baseline or dramatically improves accuracy and risk-adjusted returns, depending on whether the curation loop is present.

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

Evaluating Interactive 2D Visualization as a Sample Selection Strategy for Biomedical Time-Series Data Annotation

arXiv:2603.26592v2 Announce Type: replace-cross Abstract: Reliable machine-learning models in biomedical settings depend on accurate labels, yet annotating biomedical time-series data remains challenging. Algorithmic sample selection may support annotation, but evidence from studies involving real human annotators is scarce. Consequently, we compare three sample selection methods for annotation: random sampling (RND), farthest-first traversal (FAFT), and a graphical user interface-based method enabling exploration of complementary 2D visualizations (2DVs) of high-dimensional data. We evaluated the methods across four classification tasks in infant motility assessment (IMA) and speech emotion recognition (SER). Twelve annotators, categorized as experts or non-experts, performed data annotation under a limited annotation budget, and post-annotation experiments were conducted to evaluate the sampling methods. Across all classification tasks, 2DV performed best when aggregating labels across annotators. In IMA, 2DV most effectively captured rare classes, but also exhibited greater annotator-to-annotator label distribution variability resulting from the limited annotation budget, decreasing classification performance when models were trained on individual annotators' labels; in these cases, FAFT excelled. For SER, 2DV outperformed the other methods among expert annotators and matched their performance for non-experts in the individual-annotator setting. A failure risk analysis revealed that RND was the safest choice when annotator count or annotator expertise was uncertain, whereas 2DV had the highest risk due to its greater label distribution variability. Furthermore, post-experiment interviews indicated that 2DV made the annotation task more interesting and enjoyable. Overall, 2DV-based sampling appears promising for biomedical time-series data annotation, particularly when the annotation budget is not highly constrained.

25.
bioRxiv (Bioinfo) 2026-06-18

MorphoStat: A Statistics-Aware Pipeline for Morphological Profiling Analysis

作者:

High-content imaging produces thousands of morphological measurements per cell. Interpreting these measurements requires normalization to remove plate effects, statistical tests selected on the basis of data distribution, and control over false discoveries across many features tested at once. MorphoStat is an open-source Python pipeline that applies this sequence of steps automatically. Given a CSV file from CellProfiler or a compatible imaging platform, it removes low-quality wells, normalizes each plate against DMSO controls using a MAD-scaled z-score, routes each feature to a parametric or nonparametric test based on a distributional check, applies Benjamini Hochberg correction, and writes out results and publication-ready figures. On the BBBC021 benchmark (MCF-7 breast-cancer cells, 632 wells, 473 features), MorphoStat recovered 12 of 13 known mechanism-of-action classes in principal component space, confirming that the normalization and statistical routing work as intended. The tool is available at https://github.com/Almunthir334/morphostat (DOI: 10.5281/zenodo.20354069) under the MIT license.