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01.
arXiv (CS.CV) 2026-06-16

Parameter-Efficient Adaptation of SAM 3 for Automated ITV Generation from 4DCT Images

Four-dimensional computed tomography (4DCT) captures the full respiratory cycle of thoracic anatomy, yet current Internal Target Volume contouring workflows process each phase in isolation, discarding temporal coherence and leaving contours vulnerable to phase-specific artifacts. We present a lightweight framework that applies parameter-efficient fine-tuning to the Segment Anything Model 3 (SAM 3) via low-rank adaptation (LoRA) to align its text-prompted segmentation with the medical domain using only seven annotated 3D CT volumes. Furthermore, the framework incorporates a hard negative mining strategy to improve boundary discrimination in low-contrast thoracic regions. At inference, phase-wise predictions are refined through phase-coherent temporal filtering and spatial connectivity analysis. Since respiratory motion is continuous and periodic, genuine anatomy appears in contiguous blocks of phases, whereas transient artifacts appear sporadically and are thus effectively suppressed. Experiments on pulmonary and cardiac structures yield median Dice scores of 0.968 and 0.910 with 95th-percentile Hausdorff distances of 0.998 mm and 2.931 mm, respectively. The proposed framework effectively eliminates the severe false-positive predictions inherent in the zero-shot inference of the unadapted SAM 3. With only seven annotated volumes, the framework retains over 95% of full-data accuracy, and the entire pipeline is trainable on a single consumer-grade GPU, demonstrating a scalable, data-efficient solution for adaptive radiotherapy.

02.
medRxiv (Medicine) 2026-06-13

Projected population level impact and cost-effectiveness of clinic and community-based tuberculosis screening approaches

The South Africa National Department of Health have set ambitious targets to scale up TB testing, focusing primarily on clinic attendees. In the context of declining funding for TB care and prevention, the most cost-effective approaches for targeting testing should be identified. We developed a mathematical model of TB in South Africa, explicitly incorporating clinic attendance by sex and HIV/ART status. We simulated six screening approaches over 2026-2035 (individually and in combination): three clinic-based (symptom screening, intensified targeted universal TB testing [TUTT, symptom-agnostic sputum testing of clinic attendees in key risk groups], and intensified TUTT allowing saliva samples) and three targeted community-based (community radiographic screening, symptom screening, and universal Xpert Ultra testing), each implemented at a range of coverage levels. Model outputs were combined with a mechanistic cost function to estimate potential impact and cost-effectiveness from a societal perspective. The most cost-effective standalone approach was community radiographic screening at 10% annual population coverage, with an incremental cost-effectiveness ratio (ICER) of $421 per disability-adjusted life year (DALY) averted. 10/11 scenarios along the expansion path included community radiographic screening at progressively higher coverage, combined with a clinic-based approach. Combining complementary approaches to reach both groups at increased risk of TB (e.g. clinic-based screening) and groups with lower screening coverage (e.g. community-based screening) may increase cost-effectiveness of TB screening, compared to standalone approaches. When designing TB screening strategies, both population risk and existing screening coverage should be considered.

03.
arXiv (quant-ph) 2026-06-11

An iterative Ising decoder for quantum error correction codes

arXiv:2606.12301v1 Announce Type: new Abstract: The Ising framework maps the decoding problem in quantum error correction onto ground-state optimization of a classical Hamiltonian, in which $X$-$Z$ error correlations enter as cross terms. Under phenomenological depolarizing noise, the exact joint formulation contains up to 8-body interactions for the toric code and 10-body for the $6.6.6$ color code. These high-order terms degrade solver convergence, inflate runtime, and raise the auxiliary spin overhead when embedding into native 2-body Ising hardware. In this work, we propose the iterative low-order decoding (ILOD) algorithm, which alternates between $X$- and $Z$-type sub-Hamiltonians, approximating cross-type correlations through Bayesian priors that reweight each type's couplings using the other type's inferred error configuration. This halves the maximum body count of interaction terms in the Hamiltonian, accelerating the solver, restoring convergence at larger code distances, and reducing the total spin count for 2-body embedding by a factor of $2.5$. For the toric code, ILOD attains a threshold of $4.73%$ versus $4.83%$ for the joint formulation, with the empirical runtime ratio scaling as $(0.81)^d$. For the $6.6.6$ color code, their thresholds agree within statistical uncertainty for small code distances, and ILOD remains convergent for larger distances where the joint formulation fails to converge despite a larger annealing budget.

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

Training-Free Adversarial Robustness in Computational MRI

Deep learning (DL) methods have become the state-of-the-art for reconstructing sub-sampled magnetic resonance imaging (MRI) data. However, studies have shown that these methods are susceptible to small adversarial input perturbations, resulting in major distortions in the output images. Various strategies have been proposed to reduce the effects of these attacks, but they require retraining. In this work, we propose a novel approach for mitigating adversarial attacks on MRI reconstruction models without any retraining. Based on the idea of cyclic measurement consistency, we devise a novel mitigation objective that is minimized in a small ball around the attack input. Results show that our method substantially reduces the impact of adversarial perturbations across different datasets, attack types/strengths and PD-DL networks, and qualitatively and quantitatively outperforms conventional mitigation methods. We also introduce a practically relevant scenario for small adversarial perturbations that models impulse noise in raw data, which relates to herringbone artifacts, and show the applicability of our approach in this setting. Finally, we show our mitigation approach remains effective in two realistic extension scenarios: a blind setup, where the attack strength or algorithm is not known to the user; and an adaptive attack setup, where the attacker has full knowledge of the defense strategy.

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

Optimizing LLM Inference: Fluid-Guided Online Scheduling with Memory Constraints

arXiv:2504.11320v4 Announce Type: replace-cross Abstract: Large language models now serve millions of users daily, with providers incurring costs exceeding $700,000 per day. Each request requires token-by-token inference, making GPU scheduling central to latency, capacity, and cost. The difficulty is endogenous memory growth: generated tokens expand the Key-Value (KV) cache, and overflow can evict in-progress requests and waste prior computation. We formulate inference as a multi-stage online scheduling problem with endogenous memory growth, linear iteration times, and GPU-resident KV-cache constraints. We introduce a fluid model that characterizes equilibrium batch composition, memory requirement, and stability region. Guided by the fluid model, we design WAIT (Waiting for Accumulated Inference Threshold), a threshold-based admission rule for known output lengths, and Nested WAIT, which extends the rule to unknown output lengths by regulating how requests advance across decode-stage segments. Both algorithms approximate the fluid benchmark asymptotically under the stated memory conditions. Nested WAIT uses an additional safety buffer of moderate scale to hedge against memory-overflow-induced evictions under unknown output lengths. In Vidur simulations configured for Llama-2-7B on an A100 GPU, with supplemental real-GPU validation reported in the appendix, the policies enlarge the empirically observed stable operating range relative to widely used baseline algorithms and reduce latency especially in near-overloaded and overloaded regimes.

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

CineDance: Towards Next-Generation Multi-Shot Long-Form Cinematic Audio-Video Generation

The fidelity and structural diversity of training datasets fundamentally determine the capabilities of video generation models. While commercial systems showremarkableabilitytogeneratecinematicnarratives, the progress of open-source models remains limited by the scarcity of high-quality training data. To bridge this gap, we introduce CineDance-1M, a large-scale, open research Text-to-Audio-Video (T2AV) dataset designed specifically for multi-shot, long-form joint audio-video generation. Averaging 92.8 seconds and 24.2 continuous shots per video, it provides configurable, structured annotations for both audio and video modalities. This exceptional quality is achieved through a rigorous three-stage curation pipeline: i) diverse sourcing and comprehensive cleansing, ii) film-theory-inspired narrative parsing, and iii) hierarchical dual-modal captioning. For a comprehensive assessment, we propose CineBench, featuring a diverse prompt suite and a six-dimensional, human-aligned metric system tailored for complex narrative audio-video evaluation. Furthermore, we adapt LTX-2.3 into CineDance, which demonstrates exceptional single-modality quality alongside precise audio-video alignment and robust subject and environment consistency, effectively validating our curation strategy and the high quality of CineDance-1M. We anticipate that this work will serve as a solid foundation for accelerating future research in multi-shot, long-form joint audio-video generation. Our project page is available at https://aliothchen.github.io/projects/CineDance/.

07.
arXiv (CS.CV) 2026-06-12

Ex-Omni: Enabling 3D Facial Animation Generation for Omni-modal Large Language Models

Omni-modal large language models (OLLMs) aim to unify multimodal understanding and generation, yet extending them to jointly produce speech and 3D facial animation remains largely unexplored despite its importance for natural human-computer interaction. A key challenge is the mismatch between the discrete semantic reasoning of LLMs and the dense temporal dynamics required for 3D facial motion. We propose Expressive Omni (Ex-Omni), an open-source model that augments OLLMs with native speech-accompanied 3D facial animation. Ex-Omni decouples semantic reasoning from temporal generation through a blendshape-aware speech unit generator and a blendshape decoder, where speech units provide temporal scaffolding and hidden speech representations carry facially relevant cues. We further introduce a unified token-as-query gated fusion (TQGF) mechanism for controlled semantic injection, as well as InstructS2SF-1200K, a dataset consisting of 1200K samples for pre-training. Extensive experiments show that Ex-Omni maintains competitive speech understanding and generation ability while achieving better audio-visual synchronization and lower face-generation latency than cascaded pipelines.

08.
arXiv (math.PR) 2026-06-11

Approximation Properties of Evolutionary Dynamics in Continuous-Time Finite State Space Games

arXiv:2606.11193v1 Announce Type: cross Abstract: This thesis studies the convergence of finite-population stochastic evolutionary dynamics to their deterministic mean-field limit in continuous-time finite state space games. We first develop refined ergodic theorems for Markov chains with a single positive-recurrent class, guaranteeing the existence of a unique invariant distribution and almost-sure convergence of time averages. Next, we prove that the mean-field model, described by a system of Lipschitz-continuous ordinary differential equations, admits a unique solution that depends continuously on its initial condition and that constitutes the almost-sure limit for the empirical distributions with fixed policy. Furthermore, we show that every Mixed Stationary Nash Equilibrium of the mean-field game is approximated by a Nash equilibrium of the corresponding $N$-player game within an error $\epsilon$ for sufficiently large $N$. We finally demonstrate, by Kurtz's theorem, that the empirical state-policy distribution converges in probability to the mean-field trajectory. Numerical simulations conducted in MATLAB confirm the theoretical $\mathcal{O}(N^{-1/2})$ convergence rate in both models across a range of population sizes.

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

Possibilistic Predictive Uncertainty for Deep Learning

Deep neural networks achieve impressive results across diverse applications, yet their overconfidence on unseen inputs necessitates reliable epistemic uncertainty modeling. Existing methods for uncertainty modeling face a fundamental dilemma: Bayesian approaches provide principled estimates but remain computationally prohibitive, while efficient second-order predictors lack rigorous connections between their specific objectives and epistemic uncertainty quantification. To resolve this dilemma, we introduce Dirichlet-approximated possibilistic posterior predictions (DAPPr), a principled framework grounded in possibility theory. We define a possibilistic posterior over parameters, project it to the prediction space via supremum operators, and approximate the projected posterior using learnable Dirichlet possibility functions. This projection-and-approximation strategy yields a simple training objective with closed-form solutions. Despite its simplicity, extensive experiments across diverse benchmarks show that DAPPr achieves competitive or superior uncertainty quantification performance over state-of-the-art second-order predictors while maintaining both principled derivation and computational efficiency. Code is available at https://github.com/MaxwellYaoNi/DAPPr.

10.
arXiv (quant-ph) 2026-06-11

Quantum ergodicity and semiclassical measures: mathematical results

arXiv:2606.12098v1 Announce Type: new Abstract: In this chapter we review some results describing the high-frequency eigenmodes of the Laplacian on compact manifolds, or Euclidean domains, for which the geodesic flow is chaotic. We focus on the macroscopic distribution of these eigenmodes, which is described by the concept of semiclassical measure. The main result on the question is the Quantum Ergodicity theorem, originally due to Schnirelman. We provide the detailed proof of this theorem, including the adjustments necessary to treat the case of manifolds with boundary. We also discuss the Quantum Unique Ergodicity conjecture, and some progress towards this conjecture for strongly chaotic (Anosov) systems. In particular, we describe the constraints on admissible semiclassical measures, in terms of their Kolmogorov-Sinai entropy, as well as more recent delocalization results.

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

ALAS: An Automatic Latent Alignment Score for Audio Language Models

Large Language Models (LLMs) are extended into Speech-LLMs, and the quality of the audio–text alignment they learn affects most downstream Spoken Language Understanding (SLU) behavior. Yet despite a growth of fusion strategies, there is no standard way to measure how well a Speech-LLM internally binds audio frames to text tokens. We introduce ALAS (Automatic Latent Alignment Score), a model and task-agnostic metric that probes the LLM's per-layer hidden states, scoring the cross-modal cosine similarity between audio and text representations against a Whisper-derived reference. ALAS needs only a frozen forward pass and an off-the-shelf ASR reference, with no training or fitted classifier, and is calibrated to an interpretable uniform baseline comparable across tasks. Applying ALAS to four open-source Speech-LLMs (AF3, Qwen2-Audio, Qwen-Omni, SALMONN) across emotion recognition (IEMOCAP), open-ended SQA (LibriSQA), and multi-choice audio understanding (MMAU-speech), we find that the depth and strength of alignment reflect each model's audio-encoder design and the acoustic-versus-semantic demands of the task, and that ALAS tracks but does not duplicate task accuracy, exposing models that score well without genuinely grounding in the audio. We release ALAS as an open-source library so that practitioners can probe their own Speech-LLMs or try it on new tasks.

12.
medRxiv (Medicine) 2026-06-16

Sleep regularity outweighs sleep duration as a predictor of disease

Sleep regularity, the consistency of sleep-wake timing from one day to the next, is more strongly associated with longevity than adequate sleep duration. Whether this relationship persists across common diseases is unknown. We compared sleep regularity vs. sleep duration as risk factors for 199 diseases and disorders, using ten million hours of objective sleep-wake data (N=60,998, age[mean{+/-}SD]=62.8{+/-}7.8, 55% female). Multivariable-adjusted risks of incident diseases/disorders for regular/irregular and short/adequate sleepers were compared across 9.5 years of follow-up. Irregular sleep predicted risks for 131 diseases/disorders, more than double the number predicted by short sleep duration (63). Irregular sleep was a superior predictor than short sleep duration for 90 diseases/disorders, including circulatory, metabolic, digestive, renal, infectious, neurological, and musculoskeletal conditions, and mental disorders, whereas short sleep duration was the superior predictor for only 9 diseases/disorders. For models where short sleep duration explained disease risks, 83% were improved by adding sleep regularity. Sleep regularity was a stronger predictor of diseases/disorders than sleep duration in this cohort and should be considered an essential dimension of sleep health.

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

\texttt{Range-Arithmetic}: Verifiable Deep Learning Inference on an Untrusted Party

arXiv:2505.17623v2 Announce Type: replace-cross Abstract: Verifiable computing (VC) has gained prominence in decentralized machine learning systems, where resource-intensive tasks like deep neural network (DNN) inference are offloaded to external participants due to blockchain limitations. This creates a need to verify the correctness of outsourced computations without re-execution. We propose \texttt{Range-Arithmetic}, a novel framework for efficient and verifiable DNN inference that transforms non-arithmetic operations, such as rounding after fixed-point matrix multiplication and ReLU, into arithmetic steps verifiable using sum-check protocols and concatenated range proofs. Our approach avoids the complexity of Boolean encoding, high-degree polynomials, and large lookup tables while remaining compatible with finite-field-based proof systems. Experimental results show that our method not only matches the performance of existing approaches, but also reduces the computational cost of verifying the results, the computational effort required from the untrusted party performing the DNN inference, and the communication overhead between the two sides.

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

Vector Quantized Latent Concepts: A Scalable Alternative to Clustering-Based Concept Discovery

Large language models (LLMs) encode rich semantic information in their hidden states, yet it remains difficult to understand what information these internal representations capture. Latent concepts extracted from hidden states offer a promising direction for interpreting LLMs, but existing clustering-based methods face a trade-off: hierarchical clustering produces coherent concepts but is limited to small datasets due to its quadratic memory cost, while K-Means scales efficiently but may yield less semantically coherent concepts. We propose Vector Quantized Latent Concept (VQLC), a discrete concept learning framework that learns a codebook of latent concepts on frozen hidden states. Across 12 dataset-model settings, VQLC stays close to K-Means in computational cost, scales better than hierarchical clustering, and remains competitive in faithfulness, with the clearest gains on decoder-only models. LLMs-based evaluation, qualitative analysis, and a Sparse Autoencoder (SAE) comparison demonstrate that the learned concepts are interpretable and task-relevant.

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

Trade-offs in Medical LLM Adaptation: An Empirical Study in French QA

The development of large language models (LLMs) has led to an increased focus on their adaptation to specialized domains and languages, yet the effectiveness of domain adaptation strategies remains unclear. We present a study of medical domain adaptation using French medical question-answering (QA) as a case study. We compare continual pretraining (CPT), supervised fine-tuning (SFT), and their combination across three model families, multiple sizes, and three initialization types, explicitly disentangling adaptation effects from base model choice. We evaluate both multiple-choice (MCQA) and open-ended QA (OEQA) under greedy and constrained decoding using automatic metrics and LLM-as-a-Judge evaluation. For MCQA, CPT+SFT most often achieves the best scores, but gains over SFT are small and frequently not statistically significant, making SFT a strong and cost-effective default. For OEQA, CPT consistently improves overlap-based metrics, while SFT often degrades generation quality; instruction tuning and CPT+SFT are preferred by LLM-based evaluation. Cross-lingual experiments further show effective transfer from French adaptation to English benchmarks. Overall, we provide practical guidelines for selecting adaptation strategies under computational constraints.

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

Pricing Excess-of-Loss Reinsurance and CAT Bonds under Climate Uncertainty: A Cox Process Framework with Temperature-Dependent Stochastic Intensity

arXiv:2606.14830v1 Announce Type: cross Abstract: This paper develops a climate-aware pricing framework for excess-of-loss (XL) reinsurance contracts and catastrophe (CAT) bonds under non-stationary catastrophe risk. Catastrophe arrivals are modeled as a Cox process whose stochastic intensity depends exponentially on a temperature-related climate index. To represent climate dynamics, the index is modeled as a mean-reverting Ornstein–Uhlenbeck process around a time-dependent warming trend. Within this setting, aggregate losses follow a compound Cox structure with lognormal severities. Pricing is performed under a reduced-form risk-adjusted measure, which provides a tractable valuation approach for XL reinsurance layers and binary zero-coupon CAT bond payoffs in an incomplete market setting. Because catastrophe losses are not dynamically replicable, the framework emphasizes scenario-based valuation rather than model-independent no-arbitrage bounds. A Monte Carlo valuation scheme is implemented to quantify the economic implications of climate-dependent catastrophe intensity. The numerical results show that climate dependence materially changes the loss-generation mechanism and affects the valuation of catastrophe-linked contracts. In the baseline calibration, the climate-aware model increases the excess-of-loss reinsurance premium and lowers the CAT bond price relative to the stationary benchmark. Furthermore, our analysis of the 99.5\% Tail Value-at-Risk (TVaR) indicates that stationary benchmarks may underestimate economic capital requirements by approximately 13.7\% compared to the climate-aware framework, highlighting the potential regulatory relevance of the proposed model. This finding highlights that benchmark design is critical for interpreting climate-pricing effects.

17.
arXiv (CS.CV) 2026-06-16

Gen-VCoT: Generative Visual Chain-of-Thought Reasoning via Diffusion-Based RGB Intermediate Representations

Multimodal large language models (MLLMs) excel at visual reasoning but rely on text-based chain-of-thought (CoT), lacking interpretable visual intermediates. Existing methods use opaque tokens or external tools, missing key properties. We propose Gen-VCoT, a framework using expert vision models to generate RGB images as reasoning intermediates. It has three stages: visual grounding (SAM segmentation), geometric reasoning (Marigold depth maps), and semantic reasoning (Qwen2-VL integration). An adaptive router selects reasoning depth. Evaluations show Gen-VCoT improves spatial (25% better) and depth (50% better) questions, but may hurt simple factual queries. Text CoT outperforms visual intermediates on CLEVR (91.2% vs 62.5%), showing task-dependent optimal representations. Gen-VCoT establishes a new paradigm for interpretable multimodal reasoning.

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

Beyond Perplexity: UTF-8 Validity in Byte-aware Language Models

Byte-level tokenization enables language models to handle any Unicode input, but models can generate invalid UTF-8 sequences when encountering rare or unseen characters. We investigate the relationship between training scale and UTF-8 generation reliability with a 355M parameter model trained on 80B tokens from a balanced multilingual corpus of English, Japanese, Korean, and Chinese. We introduce multiple evaluation protocols that isolate UTF-8 structural validity from language modeling. UTF-8 validity convergence lags perplexity by a roughly a factor of two: perplexity stabilizes after 2.1B tokens, but UTF-8 validity requires 4.2B tokens. In context-free generation, rare characters achieve higher structural validity than common characters, suggesting over-specialization of frequent character representations. Through experiments, we observed that reliable UTF-8 generation is a distinct capability requiring evaluation beyond perplexity.

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

PIVOT: Bridging Black-Scholes Implied-Volatility and Price Objectives via Differentiable Jäckel Operator

arXiv:2606.17065v1 Announce Type: cross Abstract: Modern option-learning systems operate in two coordinates: price space, where markets quote and no-arbitrage constraints are most naturally enforced, and implied volatility (IV) space, where volatility surfaces are smoothed, regularized, and evaluated. The bottleneck is interface, not approximation: Jäckel's seminal "Let's Be Rational" (LBR) solver already inverts the Black-Scholes price to machine precision efficiently. What is missing is a differentiable layer that preserves LBR in the forward pass and avoids backpropagating through its branch logic. Such a layer must also confront the unavoidable singularity of the inverse map in the low-vega regime, where the sensitivity 1/vega diverges as vega -> 0. We close this gap with PIVOT, the Price-Implied-Volatility Objective Translator. PIVOT keeps the LBR forward pass intact and supplies the backward pass by implicit differentiation through the smooth Black-Scholes/Black-76 price map, with an explicit gating contract: invalid domains return NaN, well-conditioned rows receive the exact 1/vega gradient, and low-vega rows are attenuated rather than silently regularized. On a single H100, a fused Triton kernel reaches 1.79e9 IV/s at machine precision (9.3e-14 max relative error vs. the reference C solver); end-to-end label generation sustains 48.9M/s on synthetic chains and 16.6M/s on SPX OptionMetrics. In a HyperIV-style one-day reproduction on SPX, PIVOT-augmented objectives Pareto-dominate the baselines, reducing held-out price MAE by up to 43.4% and the strongest three-seed gated objective improving price MAE by 38.8% and IV MAE by 21.3% jointly; cross-asset results on RUT, VIX, and NDX show directional price-MAE gains of 40.1%, 24.2%, and 16.7%, while an ungated IV-roundtrip control collapses to a degenerate near-zero surface, confirming the gate as a correctness contract rather than a tuning knob.

20.
arXiv (CS.CV) 2026-06-18

RUB: Evaluating Residual Knowledge in Unlearned Models

Machine Unlearning (MUL) has emerged as a key mechanism for privacy protection and content regulation, yet current techniques often fail to guarantee the complete removal of sensitive information. While most existing works focus on verifying the execution of unlearning, they overlook the critical question of whether models remain robust against adversarial attempts to recover forgotten knowledge. In this work, we advocate for the principle of Robust Unlearning, which requires models to be both indistinguishable from retrained counterparts and resilient against diverse adversarial threats. To instantiate this principle, we propose a unified benchmark, RUB (Robust Unlearning Benchmark), that systematically evaluates the robustness of unlearning algorithms across classification, image-to-image reconstruction, and text-to-image synthesis. Within this framework, we introduce the Unlearning Mapping Attack (UMA) as a generalizable method to detect residual information, and demonstrate how existing attack strategies can be adapted into this framework as long as they conform to the generic UMA framework. Our experiments across discriminative and generative tasks reveal that state-of-the-art unlearning methods remain vulnerable under these evaluations, even when passing standard verification metrics. By positioning robustness as the central criterion and providing a benchmark for adversarial evaluation, we hope RUB paves the way toward more reliable and secure unlearning practices. The codebase and model checkpoints in RUB will be published.

21.
medRxiv (Medicine) 2026-06-15

Association of Genetic Liability to Psychiatric Disorders with Peripheral Metabolic Dysregulation

Importance: Individuals with psychiatric disorders face elevated cardiometabolic risk which is linked to increased mortality. The extent to which this reflects shared pathogenesis or the downstream effects of illness and treatment remains poorly understood. Objective: To characterize the direct pleiotropic effects of psychiatric genetic liability on circulating metabolites and aggregate cardiometabolic risk, independent of psychiatric diagnosis and psychotropic medication use. Design: Cohort study. Setting: Mass General Brigham Biobank (MGBB). Participants: MGBB participants with metabolomic profiling, genomic data, and linked electronic health records. Exposures: Genetic liability to nine psychiatric disorders quantified using polygenic risk scores (PRS): attention deficit/hyperactivity disorder (ADHD), anorexia nervosa (ANO), anxiety disorder (ANX), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), PTSD, schizophrenia (SCZ), and substance use disorder (SUD). Main Outcomes and Measures: 249 circulating metabolites and four metabolomic risk scores (MRS) for type 2 diabetes, myocardial infarction, ischemic stroke, and vascular dementia. PRS-metabolite associations were estimated using nested models adjusting for lifetime psychiatric diagnosis and psychotropic medication use. Results: Across 25,290 participants, we identified 604 significant PRS-metabolite associations (Bonferroni p< 1.36 x 10-4), of which 89% persisted after adjustment for lifetime diagnosis and medication use, suggesting that the direct genetic effects on metabolism are largely independent of illness or treatment. PRS for MDD, PTSD, and ADHD showed the most extensive dysregulation, with a transdiagnostic pattern of elevated lipids and systemic inflammation, specifically triglycerides ({beta} = 0.04 to 0.05, all p< 4.4 x10-13) and glycoprotein acetyls ({beta} = 0.05, all p< 2.2 x10-16). Notably, PRS for SCZ and BD showed minimal metabolite dysregulation despite having the strongest association with their target diagnoses. PRS for MDD, PTSD, ADHD, and SUD were associated with increased MRS across cardiometabolic conditions ({beta} = 0.03 to 0.08, all p< 2.1 x10-4). Sensitivity analyses controlling for BMI or excluding participants without any psychiatric history (N: 21,305 and 11,150, respectively) showed a similar pattern. Conclusions and Relevance: Psychiatric genetic liability is associated with systemic metabolic dysregulation independent of illness onset or treatment, supporting a partially pleiotropic basis for psychiatric-cardiometabolic comorbidity.

22.
Science (Express) 2026-06-11

Chemically induced skin tumors arise from long-lived stem cells of the upper hair follicle | Science

作者: 未知作者

The identification of the cancer cell of origin is a fundamental question in cancer biology. We used fluorescent lineage tracing of independent mouse skin stem cell populations, single cell transcriptomics, and Duplex sequencing, to identify the origin of chemically induced skin tumors. Tumors arose predominantly from Lgr6+ and / or Lrig1+ stem cells of the upper hair follicle, but only very rarely from the Lgr5 + and Krt19 + hair follicle bulge. Lgr6 + stem cells initiated by dimethylbenzanthracene responded to tumor promoter treatment resulting in clonal expansion of initiated cells carrying the canonical Hras Q61L mutation. Spontaneous mutations in Kras also clonally expanded, but did not generate tumors unless the Hras gene was deleted, thus revealing a competitive interaction between Hras and Kras pathways that influences clonal selection.

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

Understanding Cross-Modal Contributions in Continual Vision-Language Models: A Theoretical Perspective

Continual vision-language models are commonly addressed through sequential fine-tuning; however, although this paradigm enables adaptation to new environments (tasks), it inherently emphasizes the contribution of previously learned environments (tasks) at the expense of the stability required to preserve previously acquired knowledge. While existing approaches have adequately studied continual learning and catastrophic forgetting in vision-language models (VLMs), the theoretical understanding of modality-specific contributions across a sequence of environments remains largely unexplored. In this paper, we present a new theoretical perspective to understand the cross-modal (vision-language) contributions to consecutive environments. We empirically evaluate our theoretical findings on large VLMs and demonstrate their effectiveness in capturing environment-level cross-modal contributions. Our analysis provides deeper insights into continual VLMs, highlighting their contribution robustness to varying task orders and inter-task similarities, and their improved generalization performance.

24.
arXiv (CS.CV) 2026-06-16

Propagating Structural Guidance: Synthesizing Fluorescein Angiography from Fundus Images and Sparse OCT Scans

Fundus fluorescein angiography (FFA) is critical for assessing retinal vascular abnormalities, but its acquisition is invasive and not always feasible. In contrast, color fundus photography (CFP) is non-invasive and widely accessible, which has motivated studies on CFP-to-FFA synthesis. However, prior works rely solely on CFP surface texture, fundamentally limiting the ability to reconstruct functional vascular information and subtle pathological changes. To address this, we propose a novel framework that synthesizes FFA from CFP with structural guidance provided by optical coherence tomography (OCT). We construct a multi-modal retinal imaging dataset with paired CFP, FFA, and OCT from 3,676 patient eyes–the first tri-modally aligned dataset in retinal imaging. To bridge the spatial gap between OCT and fundus modalities, we propose a Spatially Aligned Cross-Modal Fusion (SACMF) module that projects depth-resolved OCT features onto the fundus plane and injects them into the CFP encoder via adaptive layer normalization. Beyond feature fusion, we further introduce Token-wise Cross-Modality Alignment (TCMA), a token-level contrastive learning strategy that explicitly aligns CFP and FFA representations at corresponding spatial positions. Our method achieves superior synthesis performance compared to state-of-the-art methods. Moreover, extensive experiments demonstrate that the FFA images synthesized by our approach bring greater improvements in downstream disease diagnosis performance than existing methods, highlighting the clinical potential of our approach as a non-invasive decision-support tool in routine workflows. The code is available at https://github.com/while-plus/OCT-guide-FFA-Syn.

25.
arXiv (CS.LG) 2026-06-18

ActiTect: A Generalizable Machine Learning Pipeline for REM Sleep Behavior Disorder Screening through Standardized Actigraphy

arXiv:2511.05221v3 Announce Type: replace Abstract: Isolated rapid eye movement sleep behavior disorder (iRBD) is a major prodromal marker of $\alpha$-synucleinopathies, often preceding the clinical onset of Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. While wrist-worn actimeters hold significant potential for detecting RBD in large-scale screening efforts by capturing abnormal nocturnal movements, they become inoperable without a reliable and efficient analysis pipeline. This study presents ActiTect, a fully automated, open-source machine learning tool to identify RBD from actigraphy recordings. To ensure generalizability across heterogeneous acquisition settings, our pipeline includes robust preprocessing and automated sleep-wake detection to harmonize multi-device data and extract physiologically interpretable motion features characterizing activity patterns. Model development was conducted on a cohort of 78 individuals, yielding strong discrimination under nested cross-validation (AUROC = 0.95). Generalization was confirmed on a blinded local test set (n = 31, AUROC = 0.86) and on two independent external cohorts (n = 113, AUROC = 0.84; n = 57, AUROC = 0.94). To assess real-world robustness, leave-one-dataset-out cross-validation across the internal and external cohorts demonstrated consistent performance (AUROC range = 0.84-0.89). A complementary stability analysis showed that key predictive features remained reproducible across datasets, supporting the final pooled multi-center model as a robust pre-trained resource for broader deployment. By being open-source and easy to use, our tool promotes widespread adoption and facilitates independent validation and collaborative improvements, thereby advancing the field toward a unified and generalizable RBD detection model using wearable devices.