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01.
arXiv (quant-ph) 2026-06-19

Near-Optimal Learning of Local Lindbladians

arXiv:2606.20535v1 Announce Type: new Abstract: We study the problem of learning local Lindbladians from black-box access to the physical evolution, and the goal is to estimate all Hamiltonian and dissipative coefficients. We give an algorithm built directly from finite-time channel probes, which runs the unknown evolution for short times, estimates the corresponding Pauli transfer matrices from classical shadows, and converts these estimates into Lindbladian coefficients by stable local Fourier inversions. For fixed locality and bounded dissipative site degree, the uses of the dynamical evolution and total evolution time scale as $\widetilde{O}(\Lambda^2/\varepsilon^2)$ and $\widetilde{O}(\Lambda/\varepsilon^2)$ respectively, in the local dynamical strength bound $\Lambda$ and target accuracy $\varepsilon$, with only logarithmic dependence on the number of qubits. The algorithm is non-adaptive, uses no ancillas, and uses only random product states as inputs followed by random Pauli measurements. The method does not require knowing the support of the Lindbladian in advance. We complement the algorithm with matching lower bounds, showing that the learning algorithm is near-optimal both in physical dynamics accesses and in total evolution time. We construct a single-qubit dephasing Lindbladian family that already requires $\Omega(\Lambda^2/\varepsilon^2)$ channel uses and $\Omega(\Lambda/\varepsilon^2)$ total evolution time, even for adaptive algorithms with arbitrary ancillas and measurements. In particular, the lower bounds imply that the Heisenberg-limited scaling achievable for Hamiltonian learning is information-theoretically impossible once dissipative coefficients must be estimated.

02.
arXiv (CS.LG) 2026-06-18

Strategic Feature Selection

arXiv:2606.18867v1 Announce Type: new Abstract: When algorithmic predictors inform resource allocation in high-stakes domains such as healthcare, these predictors must account for strategic manipulation of input features. The typical solution is to redesign the predictor itself to explicitly account for strategic interactions. In practice, however, decision makers are often constrained to adjusting coarser levers within existing prediction pipelines. For example, healthcare organizations often select which features to exclude based on perceived manipulability, while using standard regularization procedures to shrink the coefficients of retained features. In this work, we initiate a formal study of strategic classification through feature selection and its interaction with ridge regularization. Our main finding is that excluding individual features based on their manipulability alone is generally suboptimal. We provide a fine-grained characterization of the performance of a feature subset under optimal regularization, yielding new insights for policy design. Motivated by this characterization, we develop a practical algorithm for jointly choosing the feature set and the level of ridge regularization. Through a real-world case study on a healthcare payments benchmark, we illustrate how our algorithm can guide the design of coarse policy levers in practice. Our results provide a principled, practical framework for mitigating the effects of strategic behavior in algorithmic decision-making systems.

03.
arXiv (CS.CV) 2026-06-25

HaineiFRDM: Structure-Preserving Diffusion for Film Restoration under Fast Motion and Diverse Defects

Existing film-restoration methods frequently fail under fast motion, producing limb disappearance and structural distortion due to inaccurate motion modeling. Moreover, high-resolution restoration under spatially-persistent and mixed defects remains insufficiently studied. We propose HaineiFRDM, a Film Restoration Diffusion Model that leverages the content modeling capability of diffusion models for content-aware restoration, removing defects while preserving scene structure.To enable scalable high-resolution restoration, we adopt a patch-wise strategy with position-aware global fusion modules to maintain cross-patch coherence. We further introduce a frequency-based module to enhance texture consistency and a patch-consistent inference framework to alleviate blocking artifacts introduced by patch-based processing.We also construct a film restoration dataset comprising categorized defect templates, professionally restored films, and realistic synthetic degradations.Extensive experiments demonstrate our superior restoration quality with strong structural consistency. Our design also reduces memory requirements, enabling high-resolution restoration on a single 24GB-VRAM GPU.Code and the dataset will be released at https://anonymous.4open.science/r/HaineiFRDM.

04.
arXiv (CS.CV) 2026-06-16

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

Authors:

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.

05.
arXiv (CS.AI) 2026-06-16

A Causal Model of Theory of Mind in Conflict for Artificial Intelligence

arXiv:2606.16944v1 Announce Type: new Abstract: Theory of mind (ToM), the capacity to ascribe mental states to others and use those ascriptions for prediction and inference, is widely assumed to be essential for effective human-machine integration. Existing AI-ToM models address how to mentalize, but leave the question of when largely unaddressed. The central question is: under what situational and agent-level conditions is ToM engagement causally warranted in conflict? This paper presents a structural causal model formalized as a directed acyclic graph (DAG), treating ToM as a mechanism activated by situational and agent-level conditions rather than as an always-on capacity. The model specifies four exogenous variables capturing situational and agent-level conditions, five endogenous mediators, and a mechanistic ToM node producing engagement states through three distinct causal pathways: a tractability pathway, a reasoning-depth pathway, and an enabling-cause pathway. The primary outcome is epistemic accuracy, which decouples social reasoning from behavioral policy and generalizes across social phenomena beyond conflict. The framework gives AI systems a principled, resource-rational decision procedure for mentalizing, with implications for efficiency, trust, and the development of robust artificial social intelligence. Simulation validation, empirical human-machine teaming studies, and ethical considerations arising from conflict-optimized mentalizing are discussed.

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

A Red-Team Study of Anthropic Fable 5 & Opus 4.8 Models

Authors:

We evaluate the adversarial robustness of two frontier large language models (LLMs) developed by Anthropic, Fable 5 and Opus 4.8, against four families of automated jailbreak attack across 7 826 harmful intents spanning a ten-category harm taxonomy. Using the HackAgent red-teaming framework, hundreds of thousands of adversarial attempts were generated and every apparent success was independently re-adjudicated by a panel of three judge models (majority vote). Both models resist the majority of attacks, but the residual surface is larger than aggregate framing suggests: it is dominated by adaptive iterative attacks, while static obfuscation is near-fully neutralised. The strongest adaptive search (tree-of-attacks) breaks Opus 4.8 on 11.5% of intents overall, whereas Fable 5 stays in the single digits (6.1% worst-case). Aggregate rates therefore should not be read as reassurance. Even in these hardened configurations, the two models produced 1 620 (Opus 4.8) and 702 (Fable 5) panel-confirmed harmful completions spanning every harm category, located automatically, cheaply, and within the first one or two refinement steps by an attacker model with no human expert in the loop. The reasonable conclusion is that even the best, most-tested frontier models remain reliably breakable under sustained automated pressure.

07.
arXiv (CS.CV) 2026-06-17

Gaussian Light Field Splatting: A Physical Prior-Driven Vision Transformer for Unsupervised Low-Light Image Enhancement

Existing unsupervised low-light image enhancement methods often encounter local exposure imbalance and color distortion under complex non-uniform illumination. In addition, most Vision Transformers lack an explicit mechanism for modeling the physical priors of illumination degradation. To address these limitations, we propose GLFS, a Gaussian light field splatting-based Vision Transformer that integrates continuous physical illumination modeling from Gaussian splatting into the Transformer architecture. In GLFS, scene illumination is represented by a superposition of anisotropic Gaussian basis functions. Physics-guided biases are introduced into self-attention to adaptively infer a spatial gain field, enabling accurate and uniform restoration under complex illumination. To reduce color bias and structural degradation during enhancement, a color-vector angular loss and a luminance-edge loss are further developed. These losses enforce hue consistency and improve the structural fidelity of local details. Extensive ablation studies and quantitative evaluations show that GLFS provides clear advantages in illumination correction and detail preservation. It achieves state-of-the-art performance and offers a new representation paradigm for low-light image enhancement.

08.
arXiv (CS.LG) 2026-06-11

Least-Action-Guided Diffusion for Physical Extrapolation

arXiv:2606.11277v1 Announce Type: new Abstract: Reliable extrapolation remains a central challenge for generative models in computational physics, because models trained over finite ranges of time, parameters, or geometries may produce physically inconsistent predictions outside the training distribution. We introduce a least-action-principle-guided diffusion, LAPG, a framework that promotes physical consistency during inference rather than relying solely on constraints imposed during training. The method combines a conditional score-based diffusion model with an action-derived physical guidance score. In the first stage, the learned score model generates an in-distribution proposal; in the second, an action-based variational prior refines this proposal toward the target out-of-distribution condition. This formulation turns the principle of least action into a differentiable inference-time correction mechanism and provides an alternative to pointwise residual penalties that often require empirical loss balancing. We evaluate LAPG on representative ordinary- and partial-differential-equation systems, including free fall, conservative and dissipative spring-mass dynamics, interacting point vortices, and potential flow over parameterized airfoils. In temporal, parameter, and geometric extrapolation tests, LAPG reduces phase drift, preserves dissipative decay, captures vortex motion, and improves the lift response of airfoil flows compared with training-time physics-informed baselines.

09.
Nature (Science) 2026-06-24

Crude oil turns cheap porous membrane into a sieve to refine itself without heat

Authors: Unknown Author

An inexpensive, porous polymer membrane helps to separate raw crude oil, without heat or selective coating. Heavy hydrocarbons self-assemble inside the pores to create channels that are likely to be less than 2 nanometres wide, enriching the resulting permeate mix into light, ‘naphtha range’ hydrocarbons with 30% less energy cost and carbon dioxide emissions than conventional distillation. Long hydrocarbons are deposited on pore walls, narrowing channels until only smaller molecules can pass through.

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

Lesion-DDPM: Lesion-Enhanced 3D Diffusion for MS MRI Synthesis

3D FLAIR MRI is widely recommended as one of the standard MRI sequences for brain imaging in multiple sclerosis (MS), but publicly available MS datasets remain relatively small and vary across scanners, acquisition protocols, and lesion patterns. This scarcity and variability hinder the development of robust neuroimaging machine learning models and are particularly challenging for generative models that aim to synthesize images while preserving small, sparse lesions. We propose Lesion-DDPM, a 3D conditional diffusion framework for lesion-aware FLAIR synthesis that incorporates multi-level anatomical mask injection together with a lesion-weighted reconstruction loss to emphasize lesion voxels while maintaining global brain structure. Using a curated subset of the MSLesSeg dataset, we compare Lesion-DDPM with representative state-of-the-art GAN- and diffusion-based models, assessing both image-generation metrics and downstream 3D U-Net segmentation. In our experiments, Lesion-DDPM achieved the lowest lesion-region reconstruction error among all methods. In a downstream 3D U-Net lesion segmentation task, a model trained only on Lesion-DDPM-generated scans and evaluated on real MRIs reached a Dice score of 0.616 compared with 0.569 for the best competing synthetic dataset. When Lesion-DDPM images were added to the real training set, the Dice score further increased to 0.685.

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

DAM-VLA: Decoupled Asynchronous Multimodal Vision Language Action model

Vision-language-action (VLA) models inherit a shared synchronous clock from vision-language pretraining, processing every input at one rate. This is misaligned with physical interaction, where a high-frequency modality changes at hundreds of hertz, vision evolves more slowly, and language stays constant across an episode. A synchronous VLA oversamples slow modalities, undersamples fast ones, and caps action generation at the lowest effective frequency. We hypothesize that decoupling temporal processing per modality, letting each update and retain information at its own sensor rate, yields stronger representations and more robust control. We present DAM-VLA, which maintains per-modality latent buffers refreshed at sensor rates and read continuously by the action head, integrating new high-frequency modalities through gated cross-attention that leaves the pretrained backbone intact. Across seven contact-rich real-world manipulation tasks, DAM-VLA more than doubles the average success rate of the strongest synchronous baseline (95.2\% vs.\ 40.95\%) while sustaining smooth, reactive 100\,Hz control. Project website: \href{https://intuitive-robots.github.io/DAM-VLA/}{intuitive-robots.github.io/DAM-VLA/}

13.
arXiv (CS.LG) 2026-06-11

Mitigating Disparate Impact of Differentially Private Learning through Bounded Adaptive Clipping

arXiv:2506.01396v2 Announce Type: replace Abstract: Differential privacy (DP) has become an essential framework for privacy-preserving machine learning. Existing DP learning methods, however, often have disparate impacts on model predictions, e.g., for minority groups. Gradient clipping, which is often used in DP learning, can suppress larger gradients from challenging samples. We show that this problem is amplified by adaptive clipping, which will often shrink the clipping bound to tiny values to match a well-fitting majority, while significantly reducing the accuracy for others. We propose bounded adaptive clipping, which introduces a tunable lower bound to prevent excessive gradient suppression. Our method improves worst-class accuracy by over 10 percentage points on Skewed and Fashion MNIST compared to unbounded adaptive clipping, 7 points compared to Automatic clipping, and 5 points compared to constant clipping. The code is available at https://github.com/TrustworthyMLHelsinki/adaptive-clipping-fairness.

14.
arXiv (CS.CL) 2026-06-16

EvoMemBench: Benchmarking Agent Memory from a Self-Evolving Perspective

Recent benchmarks for Large Language Model (LLM) agents mainly evaluate reasoning, planning, and execution. However, memory is also essential for agents, as it enables them to store, update, and retrieve information over time. This ability remains under-evaluated, largely because existing benchmarks do not provide a systematic way to assess memory mechanisms. In this paper, we study agent memory from a self-evolving perspective and introduce EvoMemBench, a unified benchmark organized along two axes: memory scope (in-episode vs. cross-episode) and memory content (knowledge-oriented vs. execution-oriented). We compare 15 representative memory methods with strong long-context baselines under a standardized protocol. Results show that current memory systems are still far from a general solution: long-context baselines remain highly competitive, memory helps most when the current context is insufficient or tasks are difficult, and no single memory form works consistently across all settings. Retrieval-based methods remain strong for knowledge-intensive settings, whereas procedural and long-term memory methods are more effective for execution-oriented tasks when their stored experience matches the task structure. We hope EvoMemBench facilitates future research on more effective memory systems for LLM-based agents. Our code is available at https://github.com/DSAIL-Memory/EvoMemBench.

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

CrossPool: Efficient Multi-LLM Serving for Cold MoE Models through KV-Cache and Weight Disaggregation

arXiv:2606.24506v1 Announce Type: cross Abstract: Emerging LLM services increasingly host many sparse MoE models, yet most models receive sparse requests and remain cold. This creates a GPU memory problem: model weights are stable and model-determined, while KV-cache is transient and demand-determined. Because cold models rarely reach peak KV-cache demand at the same time, reserving worst-case KV capacity per model wastes memory; a shared KV-cache pool can instead provision aggregate active demand. However, KV-cache sharing is not sufficient when weights and KV-cache remain in a monolithic GPU memory pool. Static weights compete with dynamic KV-cache, and KV-head-limited attention under cold, low-concurrency traffic exposes only a fraction of replicated KV capacity, leading to low GPU memory utilization and weak long-context support. We present CrossPool, a serving engine for cold MoE models that separates FFN weights and KV-cache into two GPU memory pools: a weights pool that consolidates FFN weights across cold models, and a KV-cache pool that dynamically serves active requests while keeping attention local to KV-cache. CrossPool combines a KV-cache planner and virtualizer, a layer-wise pipeline scheduler that hides hidden-state transfers, and persistent kernels with control lowering to reduce CPU-GPU control overhead. With efficient GPU memory pooling, CrossPool underpins bursty long-context requests and outperforms the state-of-the-art kvcached-based multi-LLM serving system, reducing P99 TBT by up to $10.4\times$.

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

Mask-Proof: An LLM-based Automated Data Curation Pipeline on Mathematical Proofs

arXiv:2606.15258v1 Announce Type: new Abstract: Large language models (LLMs) are increasingly capable of mathematical problem solving and can even assist with research-level proofs, yet we still lack a scalable and reproducible way to measure step-level reasoning in long proofs across diverse sources. This evaluation gap limits trustworthy AI assistance in proof-certified scientific progress. Existing evaluations often emphasize final answers or rely on costly expert grading, while end-to-end proof generation remains open-ended and hard to verify automatically. We introduce Mask-Proof, a pipeline that turns real proofs into automatically checkable masked-step tasks. It masks key formula steps, provides the necessary surrounding context, and evaluates model reconstructions with an LLM-based equivalence judge using repeated votes for stability. The resulting Mask-ProofBench contains 292 curated problems across diverse research areas. Experiments with 17 models show that reasoning-enhanced models outperform standard models by 12% to 27%. Our evaluator achieves 96.8% agreement with expert annotators, enabling faithful, reproducible, and comparable measurement of step-level mathematical reasoning. Benchmark, annotations, and code are available at https://github.com/weating/Mask-Proof.

17.
medRxiv (Medicine) 2026-06-24

Structural ethnic inequities in maternal mortality between Indigenous and non-Indigenous women in Paraguay, 2014-2023: a national analysis of territorial, institutional, and preventable factors.

Background: Indigenous women in Paraguay continue to experience disproportionately high maternal mortality despite national efforts to improve maternal health. Evidence on the structural factors underlying these disparities remains limited. Objectives: To analyze structural ethnic inequities in maternal mortality between Indigenous and non-Indigenous women in Paraguay, focusing on territorial patterns, institutional access, and potentially preventable causes of death. Design: National population-based study using maternal mortality records registered in Paraguay between 2014 and 2023. Maternal mortality ratios (MMRs), incidence rate ratios (IRRs), and absolute differences were estimated according to Indigenous status. Logistic regression models were used to assess associations with deaths occurring outside healthcare institutions and specific preventable causes of death. Results: A total of 907 maternal deaths were identified, including 112 among Indigenous women (12.3%). Indigenous women were overrepresented by a factor of 4.8 relative to their population share. Maternal mortality remained consistently higher among Indigenous women throughout the study period, with mortality ratios ranging from 317.7 to 773.6 per 100,000 live births, compared with 58.7 to 145.1 among non-Indigenous women. Absolute inequalities remained persistently high over time. Overall, 24.3% of maternal deaths occurred outside healthcare institutions, with a substantially higher proportion among Indigenous women (44.6% versus 21.5%). After adjustment for age and educational level, Indigenous women had more than three times greater odds of dying outside healthcare institutions (aOR = 3.41; 95% CI: 2.20-5.29). Potentially preventable causes accounted for 42.4% of maternal deaths. Obstetric hemorrhage was strongly associated with Indigenous status (aOR = 3.83; 95% CI: 2.31-6.37). Conclusion: Indigenous women in Paraguay experience a disproportionate burden of maternal mortality characterized by persistent ethnic disparities, higher occurrence of deaths outside healthcare institutions, and a substantial burden of preventable causes of death. These findings suggest the presence of enduring territorial, institutional, and healthcare access barriers that contribute to structural ethnic inequities in maternal health.

18.
arXiv (CS.CL) 2026-06-24

MMed-Bench-IR: A Heterogeneous Benchmark for Multilingual Medical Information Retrieval

Retrieval-augmented generation (RAG) in clinical settings increasingly requires multilingual retrieval against predominantly English evidence corpora. Multilingual medical retrieval demands three capabilities: cross-lingual alignment, concept discrimination, and evidence retrieval. However, existing benchmarks evaluate these only in isolation, leaving the interaction between biomedical expertise and multilingual coverage unmeasured. We introduce MMed-Bench-IR, a benchmark designed to disentangle these axes across 6 languages and three structurally heterogeneous tasks: (1) cross-lingual medical QA retrieval with 6,127 queries grounded in the Unified Medical Language System (UMLS), (2) concept discrimination over 4,975 confusion sets at three difficulty tiers, and (3) multilingual evidence retrieval for RAG with 2,040 quality-assured queries. The three tasks share zero concept and query overlap by design, ensuring that aggregate scores reflect genuine capability breadth. Evaluation of ten systems across six paradigm families reveals severe cross-lingual failure: biomedical encoders that score 0.818 nDCG@10 in English drop to 0.056 in Japanese, a gap that English-only benchmarks cannot detect.

19.
Nature (Science) 2026-06-09

A unicellular relative links aggregative multicellularity to animal origins

Authors:

How animals evolved complex multicellularity from their unicellular ancestors remains unanswered. Unicellular relatives of animals exhibit simple multicellularity through clonal division, formation of multinucleate coenocytes, or aggregation. 1 Therefore, animal multicellularity may have evolved from one (or a combination) of these behaviours. Aggregation has classically been dismissed as a means to complex multicellularity. 2 However, aggregation occurs in many extant animal cells and has also been recently described in three close unicellular relatives of animals (the choanoflagellates Salpingoeca rosetta and Choanoeca flexa, and the filasterean Capsaspora owczarzaki). 3-5 It is unclear whether aggregation in these species is derived or ancestral, and its relevance for animal origins remains unknown. To fill this gap, we investigated whether an additional close unicellular relative of animals can undergo aggregation. We discovered that the marine free-living bacterivorous filasterean Ministeria vibrans 6 forms homogeneous aggregates with reproducible kinetics that have long-term stability, and that improved feeding and mating may be evolutionary drivers of this aggregation. Notably, we found that homologs of many animal multicellularity genes involved in cell adhesion, signalling, and transcriptional regulation were deployed during the aggregation process, indicating that they may have been used for aggregation in the unicellular ancestors of animals before being co-opted into animal multicellular development. Thus, our results imply that aggregative multicellularity was key to the development of the multicellular animal genetic toolkit.

20.
arXiv (CS.CL) 2026-06-11

When Does Language Matter? Multilingual Instructions Reveal Step-wise Language Sensitivity in Vision-Language-Action Models

Vision-Language-Action (VLA) models have shown strong performance in language-conditioned robotic manipulation, yet their robustness to linguistic variation remains poorly understood. In this work, we present the first systematic multilingual evaluation of VLA models by translating the LIBERO benchmark into ten languages, revealing severe performance degradation under non-English instructions, with success rates dropping by 30-50%. Through fine-grained analysis of task executions, we find that language influence is highly non-uniform across steps: certain steps exhibit strong language dependence and dominate overall task failure, while others are largely language-agnostic. Based on this insight, we propose a step-wise inference-time intervention that aligns representations according to step language sensitivity, substantially improving performance under linguistic variation. Our results indicate that language robustness in VLA models is fundamentally a step-wise control problem, highlighting the importance of temporally structured analysis for reliable embodied agents.

21.
arXiv (quant-ph) 2026-06-24

Exponential speedup in quantum simulation of Kogut-Susskind Hamiltonian via orbifold lattice

arXiv:2506.00755v2 Announce Type: replace Abstract: We demonstrate that the orbifold lattice Hamiltonian – an approach known for its efficiency in simulating SU($N$) Yang-Mills theory and QCD on digital quantum computers – can reproduce the Kogut-Susskind Hamiltonian in a controlled limit. While the original Kogut-Susskind approach faces significant implementation challenges on quantum hardware, we show that it emerges naturally as the infinite scalar mass limit of the orbifold lattice formulation, even at finite lattice spacing. Our analysis provides both a general analytical framework applicable to SU($N$) gauge theories in arbitrary dimensions and specific numerical evidence for $(2+1)$-dimensional SU($N$) Yang-Mills theories ($N=2,3$). Using Euclidean path integral methods, we quantify the convergence rate by comparing the standard Wilson action with the orbifold lattice action, matching lattice parameters, and systematically extrapolating results as the bare scalar mass approaches infinity. This reformulation resolves longstanding technical obstacles and offers a straightforward implementation protocol for digital quantum simulation of the Kogut-Susskind Hamiltonian with exponential speedup compared to classical methods and previously known quantum methods, modulo a standard assumptions made also for the original Kogut-Susskind approach.

22.
arXiv (CS.CL) 2026-06-19

CombEval: A Framework for Evaluating Combinatorial Counting in Large Language Models

We present CombEval, a dynamic benchmark for evaluating combinatorial counting in large language models. CombEval represents each problem as a typed Cofola specification over entities, combinatorial objects, object dependencies, and constraints, enabling controlled generation of natural-language counting problems with exact solver-verified answers. Unlike static collections, CombEval supports systematic variation of object type, entity scale, constraint count, and reasoning depth. We evaluate 11 LLMs under direct and code-augmented settings and find that models remain brittle on ordered objects, indistinguishable elements, relatively positional constraints, and nested object dependencies. Error analysis further identifies failures in constraint interpretation and counting principles. CombEval provides a diagnostic testbed for studying when and why LLMs fail at combinatorial reasoning. The code and generated benchmark suites are publicly available at \url{https://github.com/YuxuZhou-CN/combination-problem-generation}.

23.
Nature Medicine 2026-06-22

<b>PROTEUS trial heralds perioperative therapy for prostate cancer</b>

Perioperative androgen-deprivation therapy plus apalutamide could represent a new treatment option for patients with high-risk, localized prostate cancer. Perioperative androgen-deprivation therapy plus apalutamide could represent a new treatment option for patients with high-risk, localized prostate cancer.

24.
bioRxiv (Bioinfo) 2026-06-14

Somatic variant detection in normal tissues from single-cell sequencing data

A crucial advantage of single-cell sequencing (SCS) is its ability to identify somatic variants in individual cells, enabling phylogenetic analysis of cellular populations within bulk tissues. While identifying somatic variants in tumor tissues via SCS has become a common practice, doing so in normal tissues remains challenging due to the rarity of somatic variants in normal cells. To evaluate the feasibility of somatic variant calling from widely available single-nucleus RNA-seq (snRNA-seq) and single-nucleus ATAC-seq (snATAC-seq) data, we profiled a Cell-line mix of six HapMap samples prepared by the SMaHT consortium using 10x Genomics 5' snRNA-seq (12k cells with 36k mean reads per cell) and snATAC-seq (11k cells with 14k median high-quality fragments per cell) for variant calling. PacBio long-read whole genome sequencing (WGS) data (109x) generated from individual cell lines were used as ground truth. Two computational tools, Monopogen and SComatic, were used for somatic variant calling from the SCS data. Monopogen achieved single nucleotide variant (SNV) detection accuracies of 93.30% in the snRNA-seq and 99.64% in the snATAC-seq data, both of which outperformed SComatic (74.35% and 94.29%, respectively). Monopogen also consistently detected somatic SNVs at cellular fractions as low as 0.5% (2.54% in snRNA and 0.81% in snATAC) in individual samples. Notably, snATAC-seq exhibited higher genomic coverage breadth and larger number of variants detected than snRNA-seq. While the SCS data have lower overall genome coverage than that of the bulk WGS, the single-cell level variant resolution allows Monopogen to assign variants to their cells of origin with over 80% accuracy in both RNA and ATAC modalities, thereby facilitating studies of clonal evolution and cell-type-specific mutagenesis. Other benchmarking methods were also evaluated (DeepVariant, Cellsnp-lite and Mutect2) for comparison. In conclusion, our study demonstrated the feasibility of performing reliable single-cell somatic mutation calling in a cell-line mixture and discussed the strengths and limitations of current computational methods when applied to normal tissues.

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

Re-mixing Embeddings for Patient Augmentation in Data Scarce Multiple Instance Learning

Data scarcity is a major bottleneck in medical Multiple Instance Learning (MIL), especially for rare diseases or expensive modalities. We introduce a statistically grounded patient augmentation approach that generates realistic patients directly in embedding space. Using Gaussian Mixture Models as a probabilistic clustering approach on pooled instance embeddings from all patients, our method learns disease-specific "recipes"-statistical distributions of instances across unsupervised clusters. New patients are then generated by sampling embeddings from clusters based on learned recipes. Unlike existing methods that require examples from all categories, our method can generate patients offline by re-mixing pooled embeddings. Generated patients are further selected based on uncertainty quantification to improve MIL performance. We evaluate our method across three clinically relevant scarcity scenarios: (i) cross-dataset transfer, where an entirely missing "healthy" class is generated using statistics from an external cohort; (ii) low-data regimes, where class sizes are extremely limited; and (iii) small-cohort non-image tasks, including single-cell RNA-seq and flow cytometry. Across all experiments, our method improves performance over baseline, often outperforming other bag-mixing strategies. Notably, in the missing-class scenario, a performance comparable to full-dataset training is achieved, demonstrating its potential for rare disease diagnostic and privacy-preserving patient augmentation. The code is available at https://github.com/marrlab/RECIPE