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01.
Nature Medicine 2026-06-22

Biological aging and generational shifts in early-onset cancer risk

作者:

Incidence of early-onset cancer is rising globally in recent generations, which underscores the need to elucidate the influence of emerging generational risk factors. Systemic and organ-specific aging reflects the cumulative impact of exposures and may provide an integrative and complementary approach to understand early-onset cancer risk. Here among 154,169 young adults from the United Kingdom Biobank, systemic aging measured by PhenoAge increased across birth cohorts, with 23% s.d. increase for those born 1965–1974 versus 1950–1954, and was associated with early-onset solid cancer risk (hazard ratio (HR)per s.d. 1.08; 95% confidence interval (CI), 1.03–1.13), driven by lung, gastrointestinal and uterine cancers, independent of genetic risks of aging and cancer. Patterns were consistent using alternative systemic aging measures, including the Klemera–Doubal method-defined age gap and metabolomic-based age gap. These findings were validated partially among 10,262 participants in the United States All of Us Research Program. Proteomics-based organ-specific aging analyses linked immune aging with early-onset lung cancer (HRper s.d. 1.89; CI, 1.20–2.97) and adipose tissue aging to early-onset colorectal cancer (HR 1.60; CI, 1.11–2.32). Greater age gap, reflecting more advanced biological aging relative to chronological age, may serve as a driver associated with risk of early-onset solid cancers, highlighting the importance of uncovering underlying mechanisms to guide effective prevention strategies. Analyses of population cohorts found that young adults exhibited earlier systemic and organ-specific aging, which was associated with increased risk of early-onset cancer compared with older adults born decades earlier.

02.
arXiv (CS.CV) 2026-06-12

Analyzing and Improving Fine-grained Preference Optimization in Medical LVLMs

Large Vision-Language Models (LVLMs) have achieved strong performance across medical imaging tasks, yet they remain prone to factual inconsistencies, poor visual grounding, and misalignment with clinically meaningful feedback. Existing post-training alignment approaches, including Direct Preference Optimization (DPO) and its variants, face three critical limitations in the medical domain: (1) sequence-level reward signals treat clinically critical tokens identically to generic filler text; (2) reliance on static supervised fine-tuning references as preferred responses introduces an off-policy distribution shift, steering optimization toward stylistic artifacts over clinical correctness; and (3) alignment objectives lack explicit visual grounding constraints, leaving models insensitive to subtle yet diagnostically decisive pathological features. Our method leverages a bidirectional token-wise KL regularizer alongside a visual-contrastive grounding objective that pairs clean and lesion-corrupted images to penalize responses generated without adequate visual evidence. Together, these components form a fine-grained, on-policy alignment framework that constructs preference pairs by minimally editing model-generated outputs, correcting only clinically erroneous spans while preserving the original linguistic style. Extensive experiments across medical imaging tasks and clinical text generation benchmarks validate the effectiveness of our approach.

03.
Nature (Science) 2026-06-18

Daily briefing: The proteins that protect us from deadly mutations

作者:

Proteins that ‘buffer’ the effects of mutations could help to treat diseases such as cancers. Plus, goats can follow human voices and the battle over a key ocean observatory project in the United States. Proteins that ‘buffer’ the effects of mutations could help to treat diseases such as cancers. Plus, goats can follow human voices and the battle over a key ocean observatory project in the United States.

04.
arXiv (CS.CV) 2026-06-18

Conditional Latent Diffusion Model with Fourier-based Motion Modelling for Virtual Population Synthesis

In-silico trials of medical devices require the generation of virtual populations of anatomies. In cardiovascular applications, virtual anatomy is typically represented as a 3D+t mesh sampled from a generative model. However, most existing mesh generators focus on static anatomy, while sequence models often lack explicit periodicity. To this end, we propose 4D F-MeshLDM, a conditional generative framework comprising a convolutional mesh VAE to encode meshes, a structural latent space that parameterises motion using a truncated Fourier series, and a diffusion prior that learns the latent distribution over Fourier coefficient tokens. By conditioning the diffusion process on clinical covariates via affine modulation, we enable controllable synthesis. Sampling tokens and performing inverse Fourier synthesis yield cycle-consistent latent trajectories, which can be decoded into 3D+t cardiac mesh sequences. Experiments on 5,000 UK Biobank subjects demonstrate that 4D F-MeshLDM outperforms state-of-the-art baselines in anatomical fidelity and achieves near-zero cycle closure error. Furthermore, the generated cohorts accurately preserve clinical functional indices, highlighting the potential of our framework for reliable in-silico cardiac trials.

05.
arXiv (math.PR) 2026-06-18

Stable size-biasing and the positive scale-mixture order of generalized Gaussian laws

arXiv:2606.18458v1 Announce Type: new Abstract: Let $X_r\sim N_r(0,1)$ be the centered unit-scale generalized Gaussian random variable with density proportional to $\exp(-|x|^r/2)$. We prove that, for $p,q>0$, there exists a strictly positive random variable $V$, independent of $X_q$, such that $X_p\stackrel{d}{=}VX_q$ if and only if $p\le q$. Moreover, the law of $V$ is unique. For $pq$, the required Mellin quotient, viewed as the candidate characteristic function of $\log V$, is unbounded by Stirling's formula, and hence cannot be a characteristic function. The factor laws form a multiplicative cocycle, $V_{p,r}\stackrel{d}{=}V_{p,q}V_{q,r}$, for $p\le q\le r$, where the factors on the right-hand side are independent copies. Thus the Mellin quotient isolated by Dytso, Bustin, Poor and Shamai is realized constructively throughout the $p

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

Recursive Agent Harnesses

Recursive language models (RLMs) showed that recursion over model calls is an effective strategy for long-context reasoning, and production coding agents have begun to write code that spawns subagents at scale, most recently in Anthropic's dynamic workflows. We name and study the pattern between these two lines of work, where the recursive unit is a full agent harness with filesystem tools, code execution, and planning rather than a model call with no tools. We call this the Recursive Agent Harness (RAH) and frame it as harness recursion, the code-first extension to the model recursion of RLMs. A parent agent generates and runs an executable script that spawns subagent harnesses in parallel for fine-grained workloads and uses structured function calls for small subtasks. We provide a controlled evaluation on long-context reasoning. With the backbone held fixed at GPT-5 to match the published Codex and RLM baselines, RAH improves the Codex coding-agent baseline from 71.75% to 81.36% on Oolong-Synthetic (199 samples, 13 context-length buckets up to 4M tokens), a gain attributable to the harness rather than the model. With a stronger backbone, Claude Sonnet 4.5, the same design reaches 89.77%.

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

Amortized mean-shift interacting particles

arXiv:2606.15871v1 Announce Type: cross Abstract: Bayesian inference for inverse problems is run to evaluate integrals – posterior expectations, tail probabilities, and risks – across a stream of observations. The standard estimate averages the integrand over posterior samples, a Monte-Carlo average whose error decays only as the square root of the sample size, so accuracy demands many samples – prohibitive when each one calls a partial-differential-equation forward model. Mean-shift interacting particles need far fewer: they return a small set of signed-weight nodes – a deterministic quadrature whose weighted averages estimate those integrals. Finding the nodes, however, is a per-observation optimization that, in its most accurate form, reads the posterior score at every step – returning the cost it meant to save. We introduce amortized mean-shift interacting particles, a learned map that emits the weighted nodes from an observation and a few posterior samples in a single forward pass. Training asks only for joint parameter-observation samples and a posterior to draw from – a conditional normalizing flow, an empirical conditional, or any reference the user can sample – and the map learns to integrate that posterior from samples alone, evaluating neither its density nor its score. Once trained, it generalizes to unseen observations and integrands at any node budget and improves on independent samples in two ways: by reweighting them, provably no worse than the equal weights of Monte-Carlo; and by moving them, which empirically lowers it further. Across closed-form, sampled, learned, and physics-based posteriors – up to a thousand-coefficient groundwater field – it integrates more accurately than the same number of samples at every budget, and a posterior-whitened, dimension-aware kernel removes the high-dimensional wall. The result is a Pareto improvement on Monte-Carlo integration, not a competitor to drawing more samples.

08.
arXiv (CS.LG) 2026-06-19

The Significance of Style Diversity in Annotation-Free Synthetic Data Generation

arXiv:2606.20400v1 Announce Type: new Abstract: Generating high-utility synthetic data for intent classification typically requires human-annotated seed data, which is often unavailable in fast-paced industrial settings. In this paper, we propose a framework for synthetic dialogue generation that works entirely without human-annotated data, relying solely on intent definitions. Our proposed dialogue generation framework utilizes two different types of topic and style attributes to improve data diversity. Also, we propose two novel post-hoc stylization models called Univ and Exam to transform synthetic LLM-generated utterances into more varied, human-like linguistic styles. To enhance data quality, we utilize an LLM-as-a-judge filtering process. Experimental results on both industrial and public datasets demonstrate that the proposed approach achieves up to 93.3% of the performance obtained using human-annotated training data. Crucially, the findings reveal that style diversity is more critical than topic diversity for synthetic data utility, as it prevents models from learning spurious stylistic correlations. Furthermore, the study shows that incorporating style attributes during the generation process is more effective than post-hoc style adaptation.

09.
arXiv (CS.LG) 2026-06-19

Model soups need only one ingredient

arXiv:2602.09689v2 Announce Type: replace Abstract: Fine-tuning large pre-trained models on a target distribution often improves in-distribution (ID) accuracy, but at the cost of out-of-distribution (OOD) robustness as representations specialize to the fine-tuning data. Weight-space ensembling methods, such as Model Soups, mitigate this effect by averaging multiple checkpoints, but they are computationally prohibitive, requiring the training and storage of dozens of fine-tuned models. In this paper, we introduce MonoSoup, a simple, data-free, hyperparameter-free, post-hoc method that achieves a strong ID-OOD balance using only a single checkpoint. Our method applies Singular Value Decomposition (SVD) to each layer's update and decomposes it into high-energy directions that capture task-specific adaptation and low-energy directions that introduce noise but may still encode residual signals useful for robustness. MonoSoup then uses entropy-based effective rank to automatically re-weigh these components with layer-wise coefficients that account for the spectral and geometric structure of the model. Experiments on CLIP models fine-tuned on ImageNet and evaluated under natural distribution shifts, as well as on Qwen language models tested on mathematical reasoning and multiple-choice benchmarks, show that this plug-and-play approach is a practical and effective alternative to multi-checkpoint methods, retaining much of their benefits without their computational overhead.

10.
arXiv (CS.CV) 2026-06-24

FLAT: Feedforward Latent Triangle Splatting for Geometrically Accurate Scene Generation

Generating explorable 3D scenes from a single image requires strong generative priors and accurate geometric representations suitable for downstream use. Current video diffusion models offer high-quality generation and implicitly encode multi-view geometric structure in latent space. However, existing feedforward latent scene decoders typically output volumetric 3D Gaussians that lack a well-defined surface, limiting their use in simulation or standard graphics pipelines. This motivates decoding surface-aligned primitives that are not only renderable but also closer to explicit geometric assets. We ask whether compressed video diffusion latents can be mapped directly to explicit surface primitives in a single pass. To this end, we introduce FLAT and, for the first time, show that triangle splats can be decoded directly from video diffusion latents. Compared with decoding 3D Gaussians, predicting flat primitives is notoriously more challenging due to high sensitivity to primitive orientations, oftentimes leading to poor gradient flow. FLAT solves with two key ingredients: a ray-centered rotation parameterization for triangle regression and a novel product window function that improves gradient flow during differentiable triangle rendering. On standard benchmarks, FLAT achieves significantly better geometric accuracy while maintaining competitive visual quality compared to state-of-the-art feedforward baselines. We further show that a lightweight test-time refinement step converts the predicted triangle soup into a fully opaque, game-engine-ready representation that supports real-time rendering. By evaluating 3DGS, 2DGS, and triangle splatting variants under an identical training setup, we provide the first systematic analysis of representation tradeoffs in feedforward scene generation. The project page is available at https://flat-splat.github.io

11.
arXiv (CS.CV) 2026-06-18

E-VAds: An E-commerce Short Videos Understanding Benchmark for MLLMs

E-commerce short videos represent a high-revenue segment of the online video industry characterized by a goal-driven format and dense multi-modal signals. Current models often struggle with these videos because existing benchmarks focus primarily on general-purpose tasks and neglect the reasoning of commercial intent. In this work, we first propose a multi-modal information density assessment framework to quantify the complexity of this domain. Our evaluation reveals that e-commerce content exhibits substantially higher density across visual, audio, and textual modalities compared to mainstream datasets, establishing a more challenging frontier for video understanding. To address this gap, we introduce E-commerce Video Ads Benchmark, which is the first benchmark specifically designed for e-commerce short video understanding. We curated 3,961 high-quality videos from Taobao covering a wide range of product categories and used a multi-agent system to generate 19,785 open-ended Q&A pairs, which consist of five distinct tasks. Finally, we develop E-VAds-R1, an RL-based reasoning model featuring a multi-grained reward design called MG-GRPO. This strategy provides smooth guidance for early exploration while creating a non-linear incentive for expert-level precision. Experimental results demonstrate that E-VAds-R1 achieves a 109.2% performance gain in commercial intent reasoning with only a few hundred training samples. Data is available at https://github.com/TaobaoTmall-AlgorithmProducts/E-VAds_Benchmark.

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

The Dynamics of Human and AI-Generated Language: How Semantics Fluctuates across Different Timescales

Spoken language, whether produced by humans or large language models (LLM), unfolds over time with varying semantic content. However, we still lack simple, interpretable time-series features that capture how generic versus specific content is distributed over time, and that can be used to compare human and AI-generated speech. We introduce a semantic-timescale analysis pipeline that turns word-level transcripts with timestamps into semantic time-series. For each spoken narrative, we compute (i) semantic specificity using WordNet-based word depth and (ii) contextual similarity using SBERT embeddings and quantify their temporal dependence using autocorrelation-window measures (ACW-0 and related metrics). We then compare original speech to multiple shuffled controls that selectively disrupt lexical identity, temporal order, and word duration. Across human-read autobiographical narratives, TTS readings, and LLM-generated texts rendered with TTS, we find that segments with longer ACW-0 in the semantic time-series tend to contain more generic vocabulary, whereas segments with shorter ACW-0 are enriched in more specific words. These associations are strongly attenuated or abolished when word order and timing are randomized, indicating that ACW-based measures capture non-trivial temporal organization of semantic content beyond static lexical distributions. Our results suggest that ACW-based semantic timescales are a useful family of features for analyzing and comparing the temporal structure of human and AI-generated speech.

13.
arXiv (CS.CL) 2026-06-16

Re-feeding Is Not Replaying: Measuring Replay Noise in Counterfactual Token-Credit Estimation

Per-token counterfactual credit estimation asks which token in a language-model rollout caused the final answer to be right or wrong: cut the transcript at a pivot, substitute an alternative token, replay continuations, and compare outcomes. Published methods re-feed the transcript prefix as a fresh prompt, assuming this reproduces the state the model passed through during generation. We measure what that assumption costs on a stock inference engine, with a three-pass design: continuations resumed from the verified decode-time KV state, an identical second exact pass (a replica noise floor), and a re-feed pass. Across six configurations and three models (including a GRPO-trained checkpoint), at low-margin decision tokens, re-feeding changes the credit estimate at rates 14-28 percentage points above the replica floor (7-21pp under a treatment-independent conditioning; problem-clustered t = 2.9-6.4). Most changes are zero-boundary crossings of the quantized estimator rather than polarity reversals, and the perturbation is consistent with mean-zero, so averaged quantities are largely safe; but selection is not: a critical-token set chosen by thresholding $|\hat{A}_t|$ under re-feed overlaps the exact-resume selection at Jaccard 0.34-0.90, versus a 0.63-0.96 replica ceiling. A causal confirmation closes the loop: under vLLM's batch-invariant kernels all three passes are identical on every measured channel, with both disagreement rates exactly zero. Replica passes themselves disagree on 9-23% of eligible estimates: single-sample credit measurements at decision tokens are unreliable under any replay. Settings were fixed in advance; exact-pass cache hits in the second campaign are instrumented (100% hit rate, 3,434 pivots); total compute was under 10 USD. We recommend that counterfactual credit studies resume decoder state or use batch-invariant kernels, and report a replica floor.

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

TreeSeeker: Tree-Structured Trial, Error, and Return in Deep Search

arXiv:2606.11662v1 Announce Type: new Abstract: Deep search requires agents to answer complex questions through multi-step web search, browsing, evidence comparison, and synthesis. A central challenge is deciding how to search when several directions look plausible but only some will later lead to reliable evidence. If an agent greedily follows the current best-looking direction, it may keep extending a weak continuation. If it explores without discipline, it may waste budget on disconnected trials. We propose TreeSeeker, an inference-time framework for controlled trial-and-error in deep search. TreeSeeker organizes search as branch-and-return search over tree-structured states, where each branch is a tentative direction for a sub-goal. At each round, TreeSearch reads all sub-goal trees, identifies active goals, and uses textual UCB signals of value, uncertainty, and risk to select among exploiting a promising branch, exploring an uncertain alternative, or pruning an unproductive continuation and returning to an earlier branch point. TreeMem supports this control loop by keeping evidence, uncertainty, conflicts, progress, and failure cues attached to the branches that produced them, so trial outcomes can guide later decisions. Experiments on XBench-DeepSearch, BrowseComp, and BrowseComp-ZH show that TreeSeeker consistently outperforms strong open-source baselines, suggesting that explicit branch-and-return control complements stronger reasoning and tool execution.

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

HypOProto: Hyperbolic Ordinal Prototypes for Left Ventricular Filling Pressure Classification

Echocardiography (echo) is a widely used imaging modality for assessing cardiac function, with Left Ventricular Filling Pressure (LVFP) serving as a critical physiological marker for conditions such as heart failure. Standard LVFP classification into normal vs elevated categories relies on the Doppler-derived $E/e'$ ratio, which is operator-dependent and often unavailable in resource-limited settings, motivating methods that infer LVFP directly from B-mode echo. Existing deep learning approaches achieve high performance but remain largely black-box, limiting clinical interpretability. We propose HypOProto, a hyperbolic, ordinal prototype-based framework for interpretable LVFP classification using a frozen, explainable foundation model backbone. HypOProto arranges prototypes along the physiological $E/e'$ scale, placing borderline cases near the hyperboloid root where small angular differences separate similar cases, while normal and elevated cases occupy outward positions reflecting increasing diagnostic certainty. This hyperbolic geometry encodes clinically meaningful ordinal relationships and improves interpretability. We also introduce a novel Hyperbolic Prototype Angular Separation (HyperPAS) loss, enforcing inter-class prototype separation in hyperbolic space. HypOProto achieves SOTA performance while maintaining transparency, and highlights clinically relevant regions in visualizations. This work represents the first prototype-based framework for LVFP classification in echo. Our code can be found at https://github.com/DeepRCL/HypOProto.

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

Where Did It Go Wrong? Process-Level Evaluation of Web Agents with Semantic State Tracking

arXiv:2606.15673v1 Announce Type: new Abstract: Web agents act through long interaction sequences, yet existing benchmarks evaluate only terminal success, discarding all process information and offering little guidance on improvement. In this work, we conduct a process-level analysis of web agents. We introduce WebStep, a benchmark of 1,800 task instances with controlled difficulty and automatic semantic state tracking. Each website exposes a deterministic semantic MDP alongside the GUI: the agent operates on the interface, while the environment records high-level states and transitions in the background, enabling fine-grained analysis without manual annotation. Based on the semantic trajectory, we first show that process metrics reveal differences invisible to outcome evaluation: three agents whose success rates cluster within 31-33% diverge in exploration reach versus execution accuracy. Then, decomposing by skill characterizes the nature of these differences, exposing opposite per-skill rankings hidden within the same website: e.g., on Housing, OpenAI CUA outperforms Qwen3.5 by 23.7% on commit actions yet underperforms it by 15.6% on filtering, pinpointing a concrete skill to improve even within a domain. Bifurcation analysis further localizes the decisive error that loses the task and shows that this error is agent-specific rather than shared. Finally, these differences widen as tasks grow harder: success rate is similar on easy tasks but separates sharply as exploration becomes more demanding. Our process-level analysis opens a new avenue in web agent evaluation, providing fine-grained and actionable insight into where and how each agent should be improved.

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

Future Dynamic 3D Reconstruction: A 3D World Model with Disentangled Ego-Motion

Forecasting the evolution of dynamic environments is crucial for autonomous agents. While generative world models have recently achieved high photorealism in 2D video synthesis by mixing ego-motion and environmental dynamics within the image plane, they exhibit physical inconsistencies, such as morphing or vanishing objects, especially over long time horizons. In this paper, we propose FR3D, a world model that predicts a persistent 3D latent representation for future dynamic 3D reconstruction. Unlike prior works that treat the world as a sequence of image-based features, FR3D explicitly decouples the 3D evolution of the scene from the agent's trajectory, treating the inferred ego-motion as a latent proxy for action. This disentanglement resolves the ambiguities between self-motion and world-motion, ensuring geometric consistency into the future. Furthermore, we introduce a teacher-student distillation strategy that leverages the spatial "common sense" of off-the-shelf foundation models, leading to robust zero-shot generalization. Extensive experiments demonstrate FR3D's strong performance for future dynamic 3D reconstruction from monocular observations across multiple datasets, even 2 seconds into the future. Project page: https://fr3d-wm.github.io.

18.
arXiv (CS.LG) 2026-06-15

Stability of a Generalized Debiased Lasso with Applications to Resampling-Based Variable Selection

作者:

arXiv:2405.03063v3 Announce Type: replace-cross Abstract: We propose a generalized debiased Lasso estimator based on a stability principle. When a single column of the design matrix is perturbed, the estimator admits a simple update formula that can be computed from the original solution. Under sub-Gaussian designs with well-conditioned covariance, this approximation is asymptotically accurate for all but a vanishing fraction of coordinates in the proportional growth regime. The proof relies on concentration and anti-concentration arguments to control error terms and sign changes. In contrast, establishing comparable distributional limits (e.g., Gaussianity) under similar assumptions remains open. As an application, we show that the approximation significantly reduces the computational cost of resampling-based variable selection procedures, including the conditional randomization test and a local knockoff filter.

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

Compositionality Emerges in a Narrow Depth-Connectivity Regime: Architecture Constraints and Solution Manifolds

arXiv:2606.19941v1 Announce Type: new Abstract: Compositionality is believed to be the foundation for generalization, enabling models to reuse meaningful primitives in novel combinations. Yet, models trained with standard gradient-based optimization rarely, and often only weakly, exhibit compositional internal structure, and it remains unclear how or why such compositionality forms. In this work, we show that compositionality emerges in a narrow connectivity-depth sweet spot. Along the connectivity axis, compositionality only appears in some specifically sparse networks, heavily depends on which connections remain rather than on weights' sparsity alone. Along the depth axis, compositionality emerges within a narrow, target-dependent regime, peaking at specific depths, while both shallower and deeper networks fail. When either the depth or connectivity condition is violated, gradient descent silently converges to fractured solutions rather than compositional ones. To discover and exploit this emergence, we introduce (i) similarity-based pruning (SP) to recover compositional connectivity and (ii) a heuristic depth predictor to estimate where compositionality is most likely to appear. Finally, we support these empirical findings with a theoretical framework based on compositional sparsity, volume-ratio arguments, and feature-interference bounds, explaining why compositional solutions are reachable only in a narrow depth-connectivity regime.

20.
medRxiv (Medicine) 2026-06-18

The relationship between serotonin transporter occupancy and extracellular serotonin concentration is hyperbolic, not linear: implications for safely tapering antidepressants

Background: Hyperbolic tapering is an increasingly recognized approach for discontinuing serotonin reuptake inhibitor (SRI) antidepressants that involves non-linear dose reductions with equal stepwise reductions in serotonin transporter (SERT) occupancy to mitigate withdrawal symptoms. Its theoretical basis is the hyperbolic relationship between SRI dose and SERT occupancy reported in radioligand imaging studies. Hyperbolic tapering implicitly assumes that changes in SERT occupancy approximate changes in biologic effect and withdrawal risk. Because SERT occupancy plateaus across the therapeutic dose range of SRIs, this framework predicts relatively small biologic effects and withdrawal risk within this range. However, SERT occupancy influences serotonergic activity only indirectly via its effects on extracellular serotonin concentrations, and the relationship between these two variables is poorly characterized. Methods: We developed a two-pathway clearance model derived from mass-action kinetics to evaluate the steady-state relationship between SERT occupancy and extracellular serotonin concentrations under chronic SRI treatment. Results: Our analysis indicates that serotonin concentrations increase hyperbolically as transporter occupancy increases, suggesting that biologically meaningful differences in serotonergic signaling persist across the therapeutic dose range of SRIs despite plateauing occupancy. Conclusions: Our model predicts a hyperbolic relationship between SERT occupancy and extracellular serotonin concentrations, suggesting that changes in occupancy may not map proportionally onto serotonergic effect. These findings provide a potential mechanistic explanation for dose-dependent clinical effects of SRIs despite plateauing transporter occupancy and generate testable hypotheses regarding antidepressant tapering strategies. Empirical validation is warranted.

21.
bioRxiv (Bioinfo) 2026-06-21

SPA-C: an hybrid tool to accurately scaffold genomes using Hi-C and Deep-Learning

Genome assembly is a computational pipeline designed to reconstruct chromosomes from small sequencing reads. Following their assembly, contiguous sequences (contigs) are arranged into chromosome-long sequences during scaffolding. Hi-C, a long-range linkage information between regions of the genome widely used in recent large sequencing projects, is often required to correctly order contigs. Several tools have been developed to automate this task following either statistical or deep-learning approaches. Statistical approaches summarise 2D Hi-C matrices into contact densities across sequences, thus ignoring informative visual patterns. The sole existing deep-learning tool uses a transformer-based computer vision model to correct the assembly. It has been trained on several species and uses Hi-C matrices directly. Yet it comes as a supplementary step in the scaffolding process, introducing extra computation time, and has been trained on a dataset that might contain labelling errors, which could provide sub-optimal results. We propose SPA-C, an hybrid pipeline combining the strengths of both approaches. Linkage prediction is handled with a frugal CNN-based model and a graph-solving algorithm is used to generate the scaffolds. Through our input's design, the model is able to both correct errors within assemblies and link contigs, leveraging small, local Hi-C contact matrices. We handled low-complexity regions that might induce erroneous predictions using an external tool, improving the overall accuracy of generated assemblies. On a benchmark of six various genomes and four standard metrics, SPA-C outperformed four out of four state-of-the-art methods while achieving comparable start-to-end computation time.Python and Bash scripts are available on GitHub (https://github.com/SPA-C/SPA-C.git) and Zenodo (https://doi.org/10.5281/zenodo.19000361).

22.
arXiv (CS.AI) 2026-06-11

Beyond Uniform Token-Level Trust Region in LLM Reinforcement Learning

arXiv:2606.10968v2 Announce Type: replace-cross Abstract: Reinforcement learning with verifiable rewards (RLVR) has become standard for improving LLM reasoning. However, existing PPO-style trust-region mechanisms remain position-agnostic by enforcing uniform thresholds across all tokens independently. This pointwise treatment conflicts with autoregressive generation in two critical ways. First, uniform thresholds ignore autoregressive asymmetry. Early-stage deviations produce compounding sequence-level drift, causing static thresholds to under-regulate early divergence and excessively constrain late-stage exploration. Second, evaluating token-level divergence in isolation overlooks cumulative prefix drift, granting the same divergence allowance regardless of how far the conditioning history has already deviated from the rollout policy. To address this limitation, we propose CPPO (Cumulative Prefix-divergence Policy Optimization), a token-level masking rule that aligns updates with a finite-horizon policy-improvement bound via two coupled mechanisms. First, a position-weighted threshold imposes stricter limits at early positions whose effects persist longer, relaxing constraints for late-stage tokens. Second, a cumulative prefix budget tracks historical deviations, dynamically restricting further token-level deviation to prevent compounding errors along the prefix. Empirically, CPPO enhances training stability and significantly improves reasoning accuracy across various model scales.

23.
arXiv (CS.LG) 2026-06-24

SLEEPING-DISCO 9M: A large-scale pre-training dataset for generative music modeling

arXiv:2506.14293v4 Announce Type: replace-cross Abstract: We present Sleeping-DISCO 9M, a large-scale pre-training dataset for music and song. To the best of our knowledge, there are no open-source high-quality dataset representing popular and well-known songs for generative music modeling tasks such as text-music, music-captioning, singing-voice synthesis, melody reconstruction and cross-model retrieval. Past contributions focused on isolated and constrained factors whose core perspective was to create synthetic or re-recorded music corpus (e.g. GTSinger, M4Singer) and arbitrarily large-scale audio datasets (e.g. DISCO-10M and LAIONDISCO-12M) had been another focus for the community. Unfortunately, adoption of these datasets has been below substantial in the generative music community as these datasets fail to reflect real-world music and its flavour. Our dataset changes this narrative and provides a dataset that is constructed using actual popular music and world-renowned artists.

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

When LLMs Analyze Scars: From Images to Clinically-Meaningful Features

Medical image classification faces a fundamental dilemma: while deep learning models achieve remarkable performance at scale, real-world clinical scenarios often suffer from severe data scarcity due to annotation costs, privacy constraints, and disease rarity. This challenge is particularly pronounced in pathological scar classification, where differentiating keloids from hypertrophic scars requires subtle expert knowledge and labeled images are extremely limited. We propose a novel paradigm that repositions large language models (LLMs) as knowledge-driven feature engineers rather than end-to-end classifiers. We call this framework ScaFE (Scar Feature Engineering). Our key insight is that LLMs encode rich medical knowledge that can be externalized as executable feature extraction code, enabling the transformation of high-dimensional images into low-dimensional, clinically interpretable representations. Specifically, we prompt an LLM with established scar assessment criteria to generate deterministic Python code that extracts features aligned with clinical scoring systems such as the Vancouver Scar Scale. Our approach offers three key advantages: (1) data efficiency, achieving robust performance with limited training samples by decoupling knowledge acquisition from statistical learning; (2) privacy preservation, as raw images are processed locally without exposure to external LLMs; and (3) interpretability, through explicit features grounded in clinical reasoning. Extensive experiments on scar classification demonstrate that our method consistently outperforms end-to-end deep learning baselines or using LLMs as black-box classifiers under limited data conditions, establishing a promising direction for integrating LLMs into data-efficient and clinically transparent medical AI systems.

25.
arXiv (quant-ph) 2026-06-15

Digital programming of spin correlations in a fermionic lattice quantum simulator

arXiv:2606.13772v1 Announce Type: cross Abstract: Analog quantum simulation provides a highly controlled platform to study diverse quantum many-body phenomena. However, current methods for state initialisation are limited to thermal ensembles or uncorrelated product states. Here we present a hybrid approach that complements analog preparation with a digital quantum-gate protocol. This approach enables the engineering of target states with specific, long-range spin-correlations from the same initial resource state. By applying collisional gates to adiabatically prepared and filtered four-fermion singlet chains, we program diverse spin-correlation patterns, including that of a Heisenberg chain. We measure the spin correlations using a sequence of quantum gates followed by singlet-pair measurements. Our method paves the way to the targeted preparation of strongly correlated states of matter.