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01.
arXiv (CS.LG) 2026-06-19

Indexed Bellman Information Complexity

作者:

arXiv:2606.11171v2 Announce Type: replace Abstract: We develop indexed Bellman information complexity, a representation-level theory of interactive decision making centered on information indices and reference histories. The representation strips away problem-specific syntax and retains only the ingredients needed for dynamic programming and information accounting, thereby unifying the earlier framework of indexed algorithmic information ratios (AIR). On the upper-bound side, regret is controlled by Bellman supersolutions or potential identities whose gradient bracket is paid for by indexed information. Upper-confidence-bound (UCB), estimation-to-decision/decision-estimation-coefficient (E2D/DEC), and adaptive-minimax-sampling or exploration-by-optimization (AMS/EBO) methods appear as three relaxations of this same identity. On the lower-bound side, the posterior-reference trajectory supplies both the information telescope and the ghost quantile of small-regret trajectories. The resulting critical radius in the lower bound is an effective-dimension-scale quantity, as in Fano and local-prior-mass lower bounds, rather than the constant radius of a two-point Le Cam argument. The examples show that DEC is best viewed as a one-step relaxation of indexed Bellman information complexity, not as a universally tight conversion mechanism. We illustrate the framework through several applications, with particular emphasis on kernel bandits. In this setting, the active action marginal provides a concrete basis for comparing UCB, E2D, and AMS/EBO.

02.
arXiv (CS.AI) 2026-06-19

Learner-based Concept Drift Detection: Analysis and Evaluation

arXiv:2606.20216v1 Announce Type: cross Abstract: Machine learning algorithms deployed for evolving streaming environments must handle the non-stationary data distributions, commonly referred to as concept drift. The presence of concept drift poses a major challenge for many real-world applications because it can severely degrade their predictive performance, hindering their ability to support robust decision-making. Consequently, the timely and efficient detection of drift events is critical for sustaining high accuracy over time. This study examines theoretically the concept drift characteristics and numerous drift detection algorithms across several categories. Furthermore, we evaluate their performance on both synthetic and real-world datasets exhibiting diverse streaming scenarios and drift characteristics, such as abrupt and gradual changes. This study aims to enhance understanding of the complex notion of concept drift characteristics and behavior of drift detectors, along with their applicability to diverse contexts.

03.
arXiv (CS.AI) 2026-06-19

Autonomous Event-Driven Multi-Agent Orchestration for Enterprise AI at Scale

arXiv:2606.20058v1 Announce Type: new Abstract: Enterprise AI aims to move toward continuous event monitoring, detection, and action across specialist agents, yet existing multi-agent systems largely assume discrete request-response workflows and remain underexplored at enterprise scale. We evaluate DAG Plan and Execute and ReAct across 208 production-derived enterprise scenarios spanning Persona (

04.
medRxiv (Medicine) 2026-06-22

Hyperlipidemia Pharmacotherapy in Skilled Nursing Facilities: A Real-World Evidence Study

Objectives: To estimate hyperlipidemia medication order prevalence and associated variables in U.S. skilled nursing facility (SNF) residents. Design: Retrospective, observational study. Setting and Participants: Electronic Health Record data from 447,080 SNF residents with a hyperlipidemia diagnosis identified in PointClickCare's Life Sciences clinical database (January-April 2025) were reviewed. Methods: The presence and absence of medication orders for hyperlipidemia treatments recommended by the American Heart Association were assessed. Descriptive analyses summarized demographic and clinical characteristics, and a modified Poisson regression model was used to estimate risk ratios for having a medication order, adjusting for demographic, clinical, and facility characteristics. Results: Overall, 83.3% of residents diagnosed with hyperlipidemia had at least one hyperlipidemia medication order. Statins were ordered by 96.2% of active order residents, while other medication classes i.e., omega-3 fatty acids, cholesterol absorption inhibitors, fibrates were less common (

05.
arXiv (CS.CL) 2026-06-15

The Culture Funnel: You Can't Align What isn't in the Data

Current cultural alignment approaches focus on inference-time interventions, assuming models already contain sufficient cultural knowledge. We argue modern LLM pipelines suffer from a cultural data funnel. Using a multidimensional tagging framework across pretraining, fine-tuning, alignment, and reasoning datasets, we show explicit cultural signals decline sharply during post-training, while geographically concentrated, task-specialized data dominates. Multilinguality enhances geographic diversity of cultural knowledge but does not ensure balanced representation. Our tags improve downstream cultural benchmark performance, demonstrating that advances require shifting focus in training data pipelines. To facilitate future research, we release our culturally tagged dataset with 5.6M samples at https://huggingface.co/datasets/CohereLabs/CultureMarkers.

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

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

作者:

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

07.
arXiv (quant-ph) 2026-06-15

OQMD: Single-Qubit Rotation Control Improves Low-CNOT Multiclass Quantum Classification

arXiv:2606.14088v1 Announce Type: new Abstract: Near-term variational classifiers incur substantial error and latency from two-qubit gates, yet practitioners often assume that additional entangling depth is the default route to higher accuracy. This work studies Optimal Quantum Measurement Decoding (OQMD): optimizing how quantum outcomes are mapped to classical labels by training a readout layer before measurement, jointly with the variational circuit, without adding CNOTs. Experiments use trainable triple single-qubit rotations as one concrete, hardware-native realization of OQMD; other single-qubit parametrizations fit the same classical outer loop. On the Iris benchmark with a 30-point stratified test split, the best observed 0-CNOT configuration with OQMD reaches 83.33\% accuracy, with a 96\% at 9 CNOTs, exceeding the best 18-CNOT controls (56.67\%) and the best 18-CNOT configuration with OQMD (66.67\%) under a common protocol. A six-point CNOT-depth series from 0 to 18 (fixed optimizer, iteration budget, random-seed count, and ZXZ readout) shows that the highest raw scores need not occur at the largest template, so aggregate complexity is not summarized by CNOT count alone. Because run-level accuracies are discrete and non-Gaussian, we emphasize best-observed scores and, where a global comparison of pooled runs is required, Mann–Whitney $U$ tests rather than parametric tests on means. Across architectures, OQMD shows statistically consistent but magnitude-dependent gains: large peak lifts on minimal circuits coexist with a small pooled mean shift on complex 18-CNOT runs ($p\approx 0.03$) that is not ``universal'' in the sense of uniformly large practical effects.%

08.
arXiv (CS.CL) 2026-06-16

Follow the Latent Roadmap: Navigating Revocable Decoding for Diffusion LLMs with Anchor Tokens

Diffusion Large Language Models (dLLMs) offer a promising avenue for parallel generation but face a trade-off between decoding speed and quality. While revocable decoding strategies attempt to mitigate errors by verifying and remasking tokens, they typically operate within a mixed-quality context. This leads to two critical failures: Error Propagation, where new tokens absorb toxic information from erroneous context, and Local Error Reinforcement, where errors mutually reinforce each other to evade detection. To alleviate these challenges, we propose ASRD (Anchor Supervised Revocable Decoding), a training-free framework that operates within the embedding space. ASRD explicitly decouples the decoding context into trusted Anchor Tokens, which are identified via temporal consistency, and uncertain candidates. Leveraging a dynamic Anchor Tokens Cache, we introduce two complementary mechanisms: (1) Anchor-Guided Generation, which injects entropy-weighted anchor signals into masked positions to implicitly rectify attention toward the reliable global skeleton; and (2) Anchor-Perturbed Verification, which applies orthogonal perturbations to uncertain candidate tokens, destabilizing and remasking errors driven by fragile local consensus. Extensive experiments on math and coding benchmarks demonstrate that ASRD outperforms recent remasking baselines, achieving accuracy improvements of up to 6.4\% while accelerating inference throughput by up to 7.2$\times$.

09.
medRxiv (Medicine) 2026-06-11

Parent and physiotherapist perceptions about movement skills of young children with juvenile idiopathic arthritis

Objective: The onset of juvenile idiopathic arthritis (JIA) in the early years ([≤]5 years) may negatively impact movement skill (encompassing related concepts of gross motor skills, fundamental movement skills, and functional ability) development. Few studies have explored the perceptions and needs of parents and physiotherapists towards children's difficulty with these movement skills, essential to identify potential areas for added support. The objective of this study is to understand the perceptions of physiotherapists and parents towards movement skills of children with JIA. Methods: Seventeen parents and 24 physiotherapists completed an online questionnaire consisting of multiple choice and open-ended questions about the movement skills of young children with JIA. Demographic and multiple choice questions were quantitively analysed using descriptive statistics. Open-ended responses were analyzed using qualitative conventional content analysis. Results: About half (47%) of parents perceived their children to have movement difficulties, and 75% of physiotherapists described the movement skills of children with JIA as worse than other children of the same age. Our qualitative analysis revealed three general themes including: functional task difficulties; clinical variability in movement skills; and psychosocial components of movement skill difficulties. Conclusion: This study provides an analysis of perceptions of physiotherapists and parents towards the movement skills of young children with JIA. A significant proportion of parents and physiotherapists identify movement difficulties among children with JIA that impact daily life. Future interventions co-designed with both parents and care providers targeting movement skills are needed.

10.
arXiv (CS.CL) 2026-06-11

Massive Open-Vocabulary Keyword Spotting

Automatic speech recognition systems have been shown to under-perform when it comes to transcribing words rarely seen in the training data, namely specialized terminology. Open-vocabulary keyword spotting, combined with contextual biasing, has been shown to mitigate this issue. However, existing systems can only handle glossaries of a few hundred terms without becoming an infeasible bottleneck. We propose a system that stores features with a memory footprint up to 128 times smaller than a comparable baseline and allows users to process massive databases while remaining open-vocabulary. Without fine-tuning the speech recognition model, our system achieves a comparable entity recall as uncompressed solutions, even in languages not seen during training.

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

Zero-Shot Cross-City Generalization in End-to-End Autonomous Driving: Self-Supervised versus Supervised Representations

End-to-end autonomous driving models are typically trained on multi-city datasets using supervised ImageNet-pretrained backbones, yet their ability to generalize to unseen cities remains largely unexamined. When training and evaluation data are geographically mixed, models may implicitly rely on city-specific cues, masking failure modes that would occur under real-world domain shifts when generalizing to new locations. In this work, we formulate zero-shot cross-city transfer as a controlled representation-level stress test for end-to-end autonomous driving and ask how visual pretraining affects transfer behavior under geographic domain shift. We conduct a comprehensive study by integrating self-supervised backbones I-JEPA, DINOv2, and MAE into planning frameworks. We evaluate performance under strict geographic splits on nuScenes in the open-loop setting and on NAVSIM in the closed-loop evaluation protocol. Our experiments reveal a substantial generalization gap when transferring models across cities with different road topologies, traffic conventions, and visual environments. In open-loop evaluation, a supervised backbone exhibits severe degradation when transferring between cities, yet some domain-specific self-supervised methods can substantially reduce both displacement and collision degradation. In closed-loop evaluation, self-supervised pretraining improves average out-of-distribution PDMS in several single-city training settings. Our results provide empirical evidence that representation learning influences the robustness of cross-city planning and motivate zero-shot geographic transfer as an important stress test for evaluating end-to-end autonomous driving systems.

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

LiteOdyssey: A Lightweight Reasoning AI Agent for Interpretable Rare-Disease Diagnosis

arXiv:2606.16149v1 Announce Type: new Abstract: Most medical AI systems improve by scaling additional machinery: more fine-tuning data, more agents, and/or larger retrieval databases. In rare-disease diagnosis, however, such scaling can produce systems that are difficult to deploy, audit, and maintain. We asked whether state-of-the-art diagnostic performance could instead be achieved by extending the reasoning chain of a single AI agent: guiding it with a diagnostic policy, developed through human-AI collaboration and augmenting with freely available biomedical tools. We introduce LiteOdyssey, a lightweight rare-disease diagnostic framework that guides reasoning language model through a clinical genetics workflow. This framework was developed through Policy Iteration with Human Feedback (PIHF) and uses dynamic access to public biomedical tools. On two challenging benchmarks that provide only patient clinical features, LiteOdyssey achieved state-of-the-art performance, with an overall disease Recall@1 of 59.3% over the combined 1,243 cases of LIRICAL (n = 370) and the PhenoPacket Store (n = 873). Both benchmarks have a high proportion of ultra-rare disease (a prevalence below 1 in 1,000,000, with ultra-rare shares of approximately 45% and 52.8%, respectively). On the more difficult PhenoPacket subset, where causal diseases were not mapped to Orphanet in our rarity-mapping pipeline, LiteOdyssey achieved 60.7% Recall@1, compared with 10.7% for the same baseline model (GPT-5.4) without tools. This performance was achieved without fine-tuning, multi-agent ensembles, or a large case-retrieval database. Gains were also observed in the following: on cases never seen during development, on a private cohort of real-world rare disease patients, and on a smaller open-weights model. LiteOdyssey suggests a path toward rare-disease AI systems that are accurate, easier to deploy, and more transparent for physician review.

13.
arXiv (CS.CL) 2026-06-19

Where to Place the Query? Unveiling and Mitigating Positional Bias in In-Context Learning for Diffusion LLMs via Decoding Dynamics

While In-Context Learning (ICL) is extensively studied in Autoregressive (AR) LLMs, its mechanism within Diffusion Large Language Models (dLLMs) remains largely unexplored. Unlike AR models restricted by unidirectional causal masking, dLLMs intrinsically utilize bidirectional attention, offering extensive spatial flexibility for query placement. Unfortunately, current practices conventionally inherit AR-style trailing-query templates, often overlooking the structural paradigm shift. This paper presents a comprehensive analysis unveiling that query position is actually a first-order variable in dLLMs. Through empirical decoupling, we demonstrate that positional variance impacts generation quality on par with example semantic quality. Internally, this positional sensitivity stems from a spatial ``Recency Effect'' in attention flow and task-dependent shifts in decoding trajectories. To mitigate this instability without ground-truth labels, we reveal that traditional single-step confidence ($C_{decoded}$) fails in dLLMs. Instead, we propose Average Confidence ($\overline{C}$), a novel metric tracking the iterative decoding process. By establishing the foundational spatial ICL baselines, we introduce Auto-ICL, a training-free adaptive routing strategy that dynamically optimizes query placement, robustly approaching oracle performance across heterogeneous reasoning and perception tasks.

14.
arXiv (CS.AI) 2026-06-17

MODE: Modality-Decomposed Expert-Level Mixed-Precision Quantization for MoE Multimodal LLMs

arXiv:2606.17118v1 Announce Type: cross Abstract: Mixture-of-Experts Multimodal Large Language Models (MoE-MLLMs) offer remarkable performance but incur prohibitive GPU memory costs, making compression essential. Among PTQ methods, expert-level mixed-precision quantization has proven effective for MoE-LLMs, yet suffers notable degradation on MoE-MLLMs due to two overlooked biases in expert importance estimation. (1) At the cross-modal level, the numerical dominance of vision tokens causes expert selection frequency to be dominated by vision tokens, masking experts that are critical to the text modality; (2) at the intra-vision level, the large proportion of redundant vision tokens further skew frequency statistics, obscuring experts critical for informative visual content. To bridge gaps, we propose MODE, a modality-decomposed expert-level mixed-precision quantization framework for MoE-MLLMs that decomposes expert selection frequency by modality, filters redundant vision tokens to obtain denoised visual frequency, and further evaluates quantization sensitivity per modality as a complementary signal to frequency-based estimation. These signals are integrated into an Integer Linear Programming formulation to assign per-expert bit-widths under a given budget. Extensive experiments show that MODE is particularly well-suited for MoE-MLLMs, limiting average performance loss to within 2.9% at W3A16, with larger gains at the extreme 2-bit setting.

15.
arXiv (CS.AI) 2026-06-11

GEAR-VLA: Learning Geometry-Aware Action Representations for Generalizable Robotic Manipulation

arXiv:2606.08530v2 Announce Type: replace-cross Abstract: Vision-Language-Action (VLA) models achieve strong benchmark performance but still struggle in real-world deployment with unseen objects, background shifts, and different robot embodiments. We argue that this stems from the lack of a unified geometry-aware manipulation representation, leaving existing VLAs vulnerable to low-level trajectory supervision, misaligned 3D features, and embodiment differences. To address this, we propose GEAR-VLA, a VLA framework for learning unified geometry-aware action representations for generalizable robotic manipulation. GEAR-VLA adopts coarse-to-fine action learning, where multi-source embodied pretraining equips the VLM with embodied reasoning and discrete action understanding before latent action tokens connect action semantics to a gradient-decoupled DiT continuous action expert. It further performs semantic-aligned 3D integration by aligning a trainable 3D spatial backbone with the VLA representation while freezing the original VLM-aligned visual pathway. To share this representation across robots, GEAR-VLA uses embodiment canonicalization, where embodiment-aware states and embodiment-invariant actions confine robot differences to the low-level interface. Extensive simulation and real-world experiments demonstrate strong generalization: GEAR-VLA achieves state-of-the-art performance on LIBERO, zero-shot LIBERO-Plus, and RoboTwin 2.0, reaches 85.9% success on AgileX and 81.0% on the pretraining-unseen LDT-01 embodiment, and obtains 90.1% success on a 6,360-trial universal grasping benchmark with 212 unseen objects. Code and models will be released at https://github.com/babynabeauty/GEAR-VLA.

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

Robust Local Polynomial Regression with Similarity Kernels

arXiv:2501.10729v3 Announce Type: replace-cross Abstract: Local Polynomial Regression (LPR) is a widely used nonparametric method for modeling complex relationships due to its flexibility and simplicity. It estimates a regression function by fitting low-degree polynomials to localized subsets of the data, weighted by proximity. However, traditional LPR is sensitive to outliers and high-leverage points, which can significantly affect estimation accuracy. This paper revisits the kernel function used to compute regression weights and proposes a novel framework that incorporates both predictor and response variables in the weighting mechanism. The focus of this work is a conditional density kernel that robustly estimates weights by mitigating the influence of outliers through localized density estimation. The proposed method is implemented in Python and is publicly available at https://github.com/yaniv-shulman/rsklpr. The population analysis quantifies the bias induced by density-based robust weighting, and the reported experiments show lower empirical bias than iterative robust LOWESS while remaining competitive with standard LOWESS. This advancement provides a promising extension to traditional LPR, opening new possibilities for robust regression applications.

17.
arXiv (quant-ph) 2026-06-11

Emergent mirror symmetry in the optimization of the central-spin quantum battery

arXiv:2606.11557v1 Announce Type: new Abstract: Quantum batteries provide a useful setting for exploring nonequilibrium many-body effects in energy storage. Here we investigate the optimization of a quantum battery based on the central-spin model. We identify two complementary structural indicators associated with the effective charging dynamics: one yields an upper bound on the average charging power, while the other characterizes the buildup of stored energy. We show that these two indicators are jointly optimized at a distinguished initial charger excitation number, which selects a particular Dicke sector of the model. At this common optimal point, the effective charging Hamiltonian becomes exactly mirror symmetric, suggesting mirror symmetry as a useful structural indicator for optimizing quantum batteries. We further show that the corresponding optimal dynamics can be closely approximated by product initial states, in particular by spin coherent states whose excitation-number distribution is centered at the symmetry-selected point. Our results establish a direct connection between charging performance, optimal-state structure, and emergent symmetry in the central-spin quantum battery, and suggest symmetry as a useful organizing principle for efficient charging in interacting many-body quantum systems.

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

PEFT-MedSAM: Efficient Fine-Tuning of Medical Foundation Models for Explainable Skin Lesion Segmentation

Automated segmentation of skin lesions using deep learning models for dermoscopic images can be very helpful in finding melanomas earlier than they would normally be detected. However, most deep learning methods available do not perform well. The aim of this paper is to present a parameter-efficient fine-tuning method called PEFT-MedSAM for adapting the Medical Segment Anything Model (MedSAM) to automatically segment dermoscopic skin lesions. The PEFT-MedSAM method uses only the lightweight mask decoder for training the model while keeping the pre-trained image encoder and prompt encoder frozen. The experiments performed on the ISIC 2018 benchmark dataset shows that PEFT-MedSAM obtains a dice coefficient of .9411 and an intersection over union value of .8918 when compared to both a fully trained U-Net baseline (.8715 dice coefficient) and zero-shot MedSAM inference (.8997 dice coefficient). The external validation of the model using PH2 dataset shows .9467 dice coefficient with +/- .0310 standard deviation. Supportive evidence for these claims include a p-value less than .0001 for Wilcoxon signed rank tests comparing the two datasets and bootstrap-estimated 95% confidence intervals of [.9364,.9447] that represent the estimated range of possible values for the average dice coefficient obtained by repeating the test. To increase clinical trustworthiness, we used Grad-CAM explainability along with a pointing game based evaluation methodology to evaluate the CNN baseline model on the validation set. The results showed that we had an accuracy rate of 98.27% on the validation set of 519 images and confirmed that the model classified regions containing skin lesions.

19.
arXiv (CS.AI) 2026-06-12

Benchmarking Counterfactual Prediction in Epidemic Time Series with Time-Varying Interventions

arXiv:2606.05692v2 Announce Type: replace-cross Abstract: Deep learning has enabled significant advances in time-series causal inference, yet progress remains constrained by the lack of realistic benchmarks with observable counterfactual outcomes. Existing datasets either rely on real-world observations without ground-truth counterfactuals or on simplified simulations that fail to capture complex causal dynamics. To address this gap, we develop a large-scale benchmark for counterfactual prediction in epidemic time series under dynamic interventions. Unlike existing benchmarks, it supports static and time-varying treatments, as well as both single-policy and multi-policy intervention settings, enabling evaluation of causal inference methods across a broad range of causal inference scenarios. Leveraging a calibrated agent-based model grounded in real-world demographic, mobility, epidemiological, and policy data, we generate realistic counterfactual trajectories across more than 150 U.S. counties. Using this benchmark, we evaluate widely used and state-of-the-art causal inference methods, revealing substantial performance differences and highlighting the challenges of realistic time-series causal reasoning.

20.
medRxiv (Medicine) 2026-06-11

Long-term exposure to PM2.5 components and lipid profiles in WTC Health Program general responders

Fine particulate matter (PM2.5) was found to be associated with elevated blood lipids, but fewer studies have examined the associations with specific constituents of PM2.5. We studied the associations between exposure to annual PM2.5 and its 14 constituents, and repeated blood lipid measurements among general responders enrolled in the World Trade Center Health Program between 2003 and 2019 (n = 44,876). We used generalized additive mixed effect models to investigate the single-pollutant associations with repeated measures of blood total cholesterol (TC), high and low-density lipoprotein (HDL-C and LDL-C) levels. We then used linear generalized weighted quantile sum regression with a random intercept for participant ID to account for the clustering of repeated measures and evaluate the combined associations with the component mixture. A decile increase in the mixture of 14 PM2.5 chemical components was associated with 0.375 mg/dL increase in TC levels (95% confidence Interval (CI): 0.174-0.577) and 0.302 mg/dL increase in LDL-C (95% CI: 0.063, 0.540). Lead, organic carbon, and iron were major drivers of both associations. Component-specific models also show higher TC and LDL levels associated with interquartile range increases in organic carbon (0.472, 95% CI [0.027, 0.918] and 0.648 95% CI [0.136, 1.160]) and iron exposure (1.081, 95% CI [0.630, 1.532] and 0.748, 95% CI [0.318, 1.178]). In conclusion, we found PM2.5 exposure to be associated with elevated lipid levels. The associations differed by PM2.5 composition, highlighting organic carbon, lead, and iron and major drivers. These findings are highly significant for a population exposed to extreme air pollution event and susceptible to lipid alterations that might trigger cardiovascular events.

21.
bioRxiv (Bioinfo) 2026-06-19

Perturbation Curve models continuous transcriptional response trajectories and improves prediction of genetic modulations

Single-cell CRISPR screens, Perturb-seq, have revolutionized functional genomics by revealing biological causality. However, although perturbation assignments are typically represented as discrete labels, the cell-level effective strength of perturbations is often continuous and diverse. Current analytical frameworks struggle to decouple the variability in perturbation strength from the diversity of downstream responses. Here, we present Perturbation Curve (PertCurve), a nonlinear, curve-based computational framework that models the trajectories of transcriptomic responses by explicitly incorporating diverse perturbation magnitudes and strengths. By ordering cells by perturbation strength, we demonstrate that PertCurve accurately recapitulates the response magnitudes and reveals the distinct modularity and asynchrony patterns of downstream gene behaviors. These patterns are categorized into archetypes, including proportional, sensitive, and threshold responses. By applying this framework across CRISPRi/a modalities, we identify universal response patterns in viral infection, apoptosis, and proliferation genes, and reveal previously overlooked context-specific regulatory features in cell differentiation. Finally, incorporating PertCurve into perturbation prediction models and evaluation metrics enhances predictive performance, delivering actionable insights for refining established models.

22.
medRxiv (Medicine) 2026-06-18

Maternal and fetal HLA heterozygosity in preeclampsia: Insights from a large multi-ancestry pregnancy cohort

Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity, with immune dysregulation at the maternal-fetal interface central to its pathogenesis. The highly polymorphic human leukocyte antigen (HLA) region mediates maternal immune tolerance of the semi-allogeneic fetus, yet the contribution of HLA diversity to PE risk remains poorly defined. Whether the HLA heterozygote advantage observed in other immune disorders is relevant to PE has not been systematically evaluated. Using data from the multi-ancestry TOPMed Boston-Colombia Collaborative for Adverse Pregnancy Outcomes (n = 12,790; 4,770 PE, 8,020 controls; 10,808 maternal, 1,982 fetal, including 1,848 pairs), we evaluated associations between heterozygosity across eight classical HLA loci and PE and four sub-phenotypes, adjusting for genetic ancestry. HLA heterozygosity was common across most loci (>80%). No individual maternal HLA locus was associated with overall PE; however, heterozygosity across class I loci showed a protective effect in preterm PE (OR=0.82, 95%CI:0.69-0.97), with a similar pattern for HLA-A heterozygosity (OR=0.78, 95%CI:0.64-0.96). In contrast, fetal heterozygosity at HLA-DQB1 was nominally associated with increased risk of PE (OR=1.36, 95%CI:1.03-1.79) and preterm PE (OR=1.73, 95%CI:1.13-2.73). No individual maternal or fetal HLA alleles were associated with PE. Maternal-fetal mismatch analysis demonstrated locus-specific associations with preterm PE, including increased risk with HLA-DQA1 mismatch and reduced risk with HLA-C mismatch. These findings highlight distinct maternal and fetal immunogenetic contributions to PE risk and underscore the importance of considering HLA diversity-rather than individual alleles alone-in studies of PE etiology.

23.
arXiv (CS.LG) 2026-06-12

Enhanced Low-Density Region Exploration in Classifier-Guided Diffusion Models Through Modified Reverse Diffusion Sampling

arXiv:2606.13347v1 Announce Type: new Abstract: Diffusion models have emerged as state-of-the-art generative models for high-fidelity image synthesis, particularly in their classifier-free guided and classifier-guided forms. However, standard classifier guidance concentrates probability mass around high-density class mean, leading to poor coverage of rare samples in the tails of the class-conditional distributions. Recent work on diffusion-based tail sampling mitigates this by training an additional low-density-seeking classifier with a synthetic-vs-real discriminator, at the cost of additional networks and training. In parallel, a number of samplers and distillation techniques accelerate or refine diffusion sampling, but do not explicitly address long-tail coverage. We propose a purely sampling-time, density-aware extension of classifier-guided conditional diffusion model that targets low-density regions without any additional training. We have applied guidance at noisy images not on predicted noise like most diffusion models. Starting from a pretrained conditional diffusion model and classifier on ImageNet, we modify the guided reverse dynamics by steering trajectories toward low-confidence regions via the modified classifier gradient, and at each time step, we also guide the sampling process toward the predicted real image. 1st guidance helps explore low-probability samples, and 2nd guidance helps to generate samples to be close to the real data manifold. The proposed sampler consistently improves ADM model recall at 64x64 resolution while maintaining a comparable FID, and with a 256x256 ADM model, we showed the results visually with different combinations of both guidance. We also showed that standard ADM classifier guidance, combined with predicted real image guidance, helps generate high perceptual quality samples with a 256x256 ADM model on ImageNet.

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

TivTok: Broadcasting Time-Invariant Tokens for Scalable Video Tokenization

Video tokenization is fundamental to scalable video generation, as the number of tokens directly determines the computational cost and the length of videos that can be modeled. Existing tokenizers mainly improve scalability by compressing videos into fewer tokens, but they often continue to represent persistent content, such as static backgrounds and consistent object appearances, repeatedly across frames and chunks. In this paper, we propose TivTok (Time-Invariant Tokenizer), a reuse-aware video tokenizer that makes persistent information reusable across time. TivTok represents a clip with Time-Invariant (TIV) tokens that encode information shared across frames and Time-Variant (TV) tokens that encode frame-specific residuals. To obtain this factorization, we introduce Scope-Induced Factorization (SIF), which assigns different attention scopes to the two token groups: TIV tokens attend to the full clip, whereas each TV token only accesses its corresponding frame together with the TIV tokens. In the decoder, Invariant Broadcasting (IB) reuses the same TIV tokens across frames and chunks for parallel reconstruction and long-video tokenization. Experiments show that TivTok achieves an rFVD of 12.65 on the standard $16{\times}256{\times}256$ benchmark and improves compression efficiency by 2.91$\times$ for 128-frame videos compared with the evaluated baselines, while using only 1.1\% of the tokens required by downsample-based tokenizers in our evaluation.

25.
arXiv (CS.AI) 2026-06-12

Contextual Invertible World Models: A Neuro-Symbolic Agentic Framework for Colorectal Cancer Drug Response

arXiv:2603.02274v3 Announce Type: replace-cross Abstract: Precision oncology is currently limited by the small-N, large-P paradox, where high-dimensional genomic data is abundant but pharmacological response samples are sparse. While deep learning achieves predictive accuracy, it frequently fails to provide the mechanistic clarity required for clinical adoption. We present the Contextual Invertible World Model (CIWM), a Neuro-Symbolic Agentic Framework that bridges this gap by integrating a quantitative machine learning emulator with a Large Language Model reasoning layer. Utilising a stringently curated, high-fidelity data engineering pipeline on the Sanger GDSC dataset (\( N=83 \)), we isolate true biological signals from in vitro artifacts to establish a rigorous baseline predictive correlation for complex transcriptomics (\( r=0.268 \)). Through Inverse Reasoning, we perform in silico CRISPR perturbations across the colorectal landscape. The framework autonomously overturns classical mechanistic assumptions, identifying a hierarchical dominance of mutant KRAS over the APC/Wnt-axis in driving 5-fluorouracil resistance (\( \Delta=-0.0469 \)) via a "KRAS Shield" mapped to MAPK/PI3K networks. Furthermore, the agentic layer identified a "PIK3CA Paradox", revealing that repairing PIK3CA inadvertently increases chemoresistance (\( \Delta=+0.0085 \)) by triggering a compensatory feedback loop that hyperactivates the dominant MAPK survival pathway.