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01.
arXiv (CS.LG) 2026-06-11

Quantum Occam Learning: Sample-Supported Expressibility for Circuit-Based Quantum Learning

arXiv:2606.12211v1 Announce Type: cross Abstract: A central principle in quantum machine learning is that an ansatz should be expressive enough to represent the quantum data of interest. Yet, the expressibility is statistically meaningful only insofar as it can be learned from finitely many copies of an unknown quantum state. In this work, we develop an information-theoretic Occam theory for quantum data generated by finite-size quantum circuits. For the class $S_{n,G}$ of $n$-qubit pure states preparable with at most $G$ two-qubit gates, a metric-entropy argument gives the realizable sample law $\widetilde{\Theta}(G/\epsilon^2)$ in the circuit-limited regime. For an arbitrary source $\hat{\rho}$, we introduce the best $G$-gate approximation error $d_G(\hat{\rho})$ and the approximate circuit complexity $C_\eta(\hat{\rho})$. We prove an agnostic quantum Occam theorem: with $M$ copies, one can learn up to the best $G$-gate approximation error plus a statistical penalty $\widetilde{O}(\sqrt{G/M})$. We then remove the need to know $G$ in advance through an adaptive model-selection theorem whose oracle inequality selects the circuit complexity justified by the data. Matching lower bounds yield a sample-supported expressibility law: at trace-distance accuracy $\epsilon$, $M$ samples can support only $G_supported \simeq M\epsilon^2$ gates, up to logarithmic factors and tomography saturation at $2^n$. Thus, the circuit complexity becomes an adaptive statistical resource rather than a static promise. Our framework turns bounded circuit complexity into a model-selection principle for quantum machine learning.

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

ToolChain-CRC: Conformal Risk Control for Agentic AI Under Retrieval and Tool-Use Drift

arXiv:2606.18467v1 Announce Type: cross Abstract: Modern AI agents retrieve documents, call tools, check intermediate information, and then produce a final answer or action. This creates a risk-control problem that is not visible from the final answer alone. A final response may look acceptable even when the retrieval was weak, a tool output was wrong, or an earlier step was unsupported. We propose ToolChain-CRC, a conformal risk-control method for retrieval-augmented and tool-using agents under drift. The method treats each agent run as a full trajectory of actions, observations, and final output. It builds step-level risk scores, combines them into a trajectory risk score, calibrates an accept-or-intervene rule, and adds an anytime alarm that can stop risky runs before the final answer. We prove trajectory-level risk control under exchangeable calibration runs, give a drift-aware extension with auditable constants, and prove an anytime escalation rule through a supermartingale construction. Experiments cover synthetic tool-chain drift, RAG/tool-use stress tests, public SQuAD-derived retrieval tasks, an API-free agentic QA case study, ablations, target-risk sensitivity checks, 20-seed robustness checks, a drift-margin audit, and a live RAG/tool-use agent benchmark. Across these settings, final-answer-only calibration can miss retrieval and tool failures, while trajectory-level calibration keeps accepted-trajectory risk below the target.

03.
bioRxiv (Bioinfo) 2026-06-22

HTS-Oracle X: AI-Guided Prospective Discovery of Small Molecule Immune Checkpoint Binders

Targeting immune checkpoint protein-protein interactions (PPIs) using small molecules remains limited by the shallow, featureless binding surfaces of co-stimulatory and co-inhibitory receptors and the characteristically low hit rates of conventional high-throughput screening against these interfaces. Here we report HTS-Oracle X, a multimodal deep learning platform that integrates bidirectional cross-attention fusion of ChemBERTa SMILES embeddings with extended RDKit descriptors, trains on continuous biophysical binding signals rather than binary labels, and employs Monte Carlo Dropout uncertainty quantification for uncertainty-adjusted compound selection. Trained on 45,760 Dianthus TRIC-screened compounds per target under scaffold-aware cross-validation, HTS-Oracle X was applied prospectively to a 100,160-compound Enamine library against CD28, TIM-3, and VISTA. From 150 model-selected compounds, 45 dose-response confirmed binders were identified (30.0% overall hit rate), yielding enrichment factors of 234-408x over experimentally established random prospective baselines and 16 sub-micromolar hits. The top hits, HX-CD28-1 (KD = 233 nM), HX-TIM3-1 (KD = 249 nM), and HX-VISTA-1 (KD = 345 nM), demonstrated on-target functional activity in immune cell and tumor co-culture assays. HTS-Oracle X represents a scalable AI-guided framework for small molecule discovery against non-enzymatic immune checkpoint targets.

04.
arXiv (CS.CL) 2026-06-17

Variable-Width Transformers

Scaling model size, specifically depth and width, has driven significant progress in transformer-based language models. However, most architectures maintain a constant width across all layers, allocating a fixed parameter and computation budget evenly despite different layers potentially playing distinct computational roles. In this work, we empirically investigate nonuniform capacity allocation across network depth by proposing a $\times$-shaped >

05.
arXiv (CS.AI) 2026-06-19

Lagrange: An Open-Vocabulary, Energy-Based Sparse Framework for Generalized End-to-End Driving

arXiv:2606.20274v1 Announce Type: new Abstract: Scaling end-to-end autonomous driving to complex, open-world environments requires perceptual models that generalize to anomalous scenarios and planners that produce kinematically valid trajectories. Existing paradigms face a distinct dichotomy between representational efficiency and generalization capacity. Dense models (e.g., occupancy networks), while geometrically robust, incur critical computational bottlenecks and struggle with high-level semantic reasoning. Conversely, sparse, query-based planners are efficient but reliant on closed-set definitions, rendering them vulnerable to out-of-distribution (OOD) events. Although recent Vision-Language-Action (VLA) models offer open-vocabulary reasoning, their autoregressive, discrete token generation fundamentally conflicts with the continuous, high-frequency control requirements of vehicle dynamics. To address this, we propose Lagrange, an open-vocabulary, computationally sparse driving framework based on Masked Latent Fields (MLF). Rather than relying on dense volumetric reconstructions or closed-set query mechanisms, Lagrange exploits Vision-Language Models (VLMs) to encode class-agnostic object proposals into continuous semantic visual tokens. We introduce an intent-driven masked cross-attention module that temporally filters irrelevant entities, decoding the attended tokens into an implicit continuous energy field defined over spatial coordinates. By framing decision-making as a Lagrangian action minimization problem spanning this energy field, we enforce strict compliance with vehicle kinematics while executing collision avoidance. Extensive offline evaluations on both standard (nuScenes) and long-tail (CODA) benchmarks demonstrate that Lagrange establishes a promising framework for robust, interpretable, and kinematically feasible open-world autonomy.

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

LOCUS: Local Visual Cue Search for Enhancing Fine-Grained Perception in Multimodal Large Language Models

Multimodal Large Language Models (MLLMs) remain unreliable on fine-grained visual perception, even when high-resolution inputs preserve the necessary local details. We identify this limitation as visual context rot: decisive evidence may exist in the full image, yet fail to be reliably selected and used amid redundant visual context. We propose LOCUS (LOcal visual CUe Search), a training framework that teaches MLLMs to internalize local evidence search through a verifiable proxy task. During training, LOCUS provides a local crop as a visual cue and optimizes the model to recover its spatial support in the full image using an IoU-based reward. The visual cue is used only during training, leaving the standard image-question inference interface unchanged. Experiments across fine-grained perception, hallucination, general understanding, and reasoning benchmarks show that LOCUS improves localization-sensitive visual understanding while preserving broad capabilities. Attention analyses further indicate stronger focus on task-relevant evidence regions, suggesting that training-time visual cue search provides an effective route to internalized fine-grained evidence selection.

07.
arXiv (CS.CV) 2026-06-15

Stream3D: Sequential Multi-View 3D Generation via Evidential Memory

View-conditioned 3D generators such as SAM 3D, TRELLIS, and Hunyuan3D produce high-quality object reconstructions from a single view, but real-world visual observation often arrives as long monocular streams. Naively applying these generators to each streaming frame independently leads to severe temporal inconsistency in the generated results. To address this problem, we propose Stream3D, the first training-free streaming mechanism that turns a frozen view-conditioned 3D generator into a streaming generator with constant cross-chunk memory. Stream3D achieves this by maintaining a compact evidential memory, which selectively caches the most informative historical frames based on a proposed evidence score mechanism. As the stream progresses, the memory dynamically updates to retain a fixed number of informative frames, preventing the memory footprint from growing linearly with sequence length. This also prevents degradation over long sequences and keeps the underlying generator completely unchanged without retraining, architectural modifications, or auxiliary losses. Evaluated on both realistic and synthetic streaming benchmarks, Stream3D outperforms latent-transport baselines, including KV-cache reuse and flow-based feature editing, across both photometric and geometric metrics. More details can be found at: https://stream-3d.github.io/stream3d.github.io/.

08.
arXiv (math.PR) 2026-06-18

On two overlooked stick-breaking constructions of the normalized inverse Gaussian process

arXiv:2606.19306v1 Announce Type: new Abstract: We shed light on two alternative stick-breaking constructions of the normalized inverse Gaussian (NIG) random discrete distribution which appear to have been overlooked so far in the Bayesian nonparametric setting. The first is derived from a result in Aldous and Pitman (1998) for the conditional Brownian excursion partition, mixing over the local time at zero up to time one. The second arises as a particular case of a result in James (2013) for priors obtained by a random spatial and temporal change of the normalized generalized Gamma subordinator. Both constructions are in terms of straightforward transformations of standard random variables and can be easily generalized to provide the stick-breaking construction of any element, respectively, in a) the family of mixed Poisson-Kingman models driven by the $1/2$ stable Lévy measure and b) the family of Poisson-Gamma processes driven by the Inverse Gaussian subordinator.

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

Augmenting Game AI with Deep Reinforcement Learning

arXiv:2606.20210v1 Announce Type: new Abstract: Immersion in video games depends not only on graphics, audio, and game mechanics, but also on the quality of in-game characters. Producing believable characters, or game AI, remains a significant challenge as behavioral complexity is hard to capture with hand-coded systems. Game AI is a source of immersion and engagement; however, the limitations stemming from the challenges of creating game AI often lead to frustration and the breaking of the illusion of realism within the game. The introduction of machine learning models opens the door to creating more believable, authentic, and relatable characters in games. The promise is that they either learn from interacting with the game, or from player data, to develop true human-like behavior. In this paper, we envision more applications of reinforcement learning for game AI in the future. For this to materialize, current research limitations are prohibitive to broad deployment across game genres. Therefore, we propose a framework for training reinforcement learning models with a set of requirements in mind that are suited towards game AI and game development. We present examples of games with reinforcement learning-augmented game AI and describe the practicalities of deploying player-facing machine learning agents in modern games. Furthermore, we identify bottlenecks and hard problems in these areas, which we believe offer promising research directions to accelerate the adoption of machine learning in game AI for the video game industry.

10.
PLOS Medicine 2026-06-04

Comparative impacts and cost-effectiveness of tuberculosis systematic screening strategies in prisons in Brazil, Colombia, and Peru: A mathematical modeling study

作者:

by Yiran E. Liu, José Victor Bortolotto Bampi, Ronan F. Arthur, Argita D. Salindri, Caroline Busatto, Pedro Avedillo Jiménez, Daniele Maria Pelissari, Fernanda Dockhorn Costa Johansen, Robert Arana-Narvaez, Alvaro Fernando Moreno Roca, Wilfredo Santos Solís Tupes, Esther Mori Jiu, Christian Alfredo Moreno Roca, Erika Albertina Abregú Contreras, Valentina Antonieta Alarcón Guizado, Julián Trujillo Trujillo, Belkys Marcelino, Mónica Alonso Gonzalez, Mayra Cecilia Córdova Ayllon, Ted Cohen, Moises A. Huaman, Jeremy D. Goldhaber-Fiebert, Julio Croda, Jason R. Andrews Background Incarceration is a leading driver of tuberculosis in Latin America. Systematic screening in prisons may reduce tuberculosis burden, but optimal strategies and cost-effectiveness remain uncertain. We examined the population-wide health impacts and cost-effectiveness of systematic screening in prisons in Brazil, Colombia, and Peru, comparing different timepoints, frequencies, and screening algorithms. Methods and findings Using dynamic transmission models calibrated to Brazil, Colombia, and Peru, we simulated annual or biannual (twice-yearly) prison-wide screening, alone or combined with entry and exit screening from 2026 to 2035. We evaluated four algorithms: (1) symptom screening, (2) chest X-ray with computer-aided detection (CXR-CAD), (3) symptoms and CXR-CAD (follow-up testing if either is positive), and (4) GeneXpert Ultra (Xpert) with pooled sputum. Individuals screening positive then received individual Xpert. We projected impacts on within-prison and population-level tuberculosis incidence in 2035, along with discounted costs (2023 US dollars) and disability-adjusted life years (DALYs). Model projections showed that combined entry, exit, and biannual screening with CXR-CAD was highly impactful and cost-effective across countries, reducing tuberculosis incidence by 61%–87% in prisons and 18%–28% population-wide. Compared to only biannual CXR-CAD (the next best strategy), the incremental cost per DALY averted of adding entry and exit screening was $2,984 (Brazil), $2,925 (Colombia), and $645 (Peru). Adding symptom screening to CXR-CAD marginally increased benefit and was only cost-effective in Peru’s higher-incidence prisons. Biannual screening alone remained cost-effective at prison incidence levels well below national averages, as well as at far lower willingness-to-pay thresholds. In settings without CXR-CAD, pooled Xpert was an impactful, cost-effective alternative. Key limitations include the model’s simplified representation of tuberculosis disease states and lack of stratification by age, gender/sex, HIV, or drug resistance. Conclusions These modeling results support immediate national-level adoption of prison-wide tuberculosis screening twice-yearly and at entry and exit, using CXR-CAD or pooled Xpert.

11.
arXiv (math.PR) 2026-06-18

Extrema of microscopically slowed-down Gaussian fields

作者:

arXiv:2606.19207v1 Announce Type: new Abstract: We introduce a family of Gaussian fields whose covariance structure exhibits an inhomogeneous, microscopic slowdown and it interpolates between a $\log$ profile (for a certain interpolation parameter $\alpha=0$) and a $\log\log$ profile (when the interpolation parameter is $\alpha=1/2$). We consider both one dimensional such objects (which we call {\it Branching Brownian Motions in a cooling environment}) as well as higher dimensional, spatial fields. We identify the correct centering of the maximum at time $T$ and prove tightness of the recentered maximum. While the exponent in the first-order growth varies linearly with $\alpha$, giving a leading order of $T^{1-\alpha}$, the second-order correction exhibits a phase transition at $\alpha=1/3$.

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

Trajectory-Level Redirection Attacks on Vision-Language-Action Models

Vision-language-action (VLA) policies bring natural language into closed-loop robot control, enabling robots to execute manipulation tasks directly from text instructions. The same interface gives text a recurring role in control because the prompt is reused at every replanning step, and each prompt-conditioned action changes the future observations on which the policy acts. Existing VLA attacks study adversarial prompts that elicit targeted low-level actions or make such actions persist across changing images. We identify a stronger trajectory-level failure mode: a prompt that still $appears$ to specify the intended task but redirects the final physical outcome. We mathematically formalize this setting as $command-preserving trajectory redirection$, a prompt-only threat model in which the attacker chooses one prompt before the episode, all policy and environment components remain fixed, and the prompt must stay close to the benign instruction while omitting target words and correction language. To find such prompts, we introduce an on-policy prompt search method that uses rollouts to discover perturbations whose closed-loop behavior tracks a target task while satisfying the command-preserving constraints. Experiments in simulation and on hardware show that near-benign prompt perturbations can redirect VLA rollouts to attacker-specified targets. These results expose a trajectory-level vulnerability in VLA instruction grounding: text that appears to preserve the intended command can still give an adversary control over the robot's final physical outcome. Project website: https://vla-redirection-attack.github.io/

13.
arXiv (CS.AI) 2026-06-15

Federated Causal Inference from Multi-Site Observational Data via Propensity Score Aggregation

arXiv:2505.17961v4 Announce Type: replace-cross Abstract: Causal inference typically assumes centralized access to individual-level data. Yet, in practice, data are often decentralized across multiple sites, making centralization infeasible due to privacy, logistical, or legal constraints. We address this problem by estimating the Average Treatment Effect (ATE) from decentralized observational data via a Federated Learning (FL) approach, allowing inference through the exchange of aggregate statistics rather than individual-level data. We propose a novel method to estimate propensity scores via a federated weighted average of local scores using Membership Weights (MW), defined as probabilities of site membership conditional on covariates. MW can be flexibly estimated with parametric or non-parametric classification models using standard FL algorithms. The resulting propensity scores are used to construct Federated Inverse Propensity Weighting (Fed-IPW) and Augmented IPW (Fed-AIPW) estimators. In contrast to meta-analysis methods, which fail when any site violates positivity, our approach exploits heterogeneity in treatment assignment across sites to improve overlap. We show that Fed-IPW and Fed-AIPW perform well under site-level heterogeneity in sample sizes, treatment mechanisms, and covariate distributions. Theoretical analysis and experiments on simulated and real-world data demonstrate clear advantages over meta-analysis and related approaches.

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

Training-Free Open-Vocabulary Visual Grounding for Remote Sensing Images and Videos

Remote sensing visual grounding (RSVG) aims to localize a referred target in a remote sensing image or video according to a natural language expression. Existing RSVG methods usually rely on task-specific manual annotations, which are costly to collect and inevitably limited in covering the diversity of real-world geospatial scenarios. As a result, they often struggle to generalize to open-vocabulary queries involving novel objects, fine-grained attributes, complex spatial relationships, and functional semantics. In this paper, we propose RSVG-ZeroOV, a training-free framework that leverages frozen generic foundation models for zero-shot open-vocabulary RSVG. RSVG-ZeroOV follows an Overview-Focus-Evolve paradigm, which exploits the distinct yet complementary attention patterns of vision-language models (VLMs) and diffusion models (DMs) to progressively generate precise grounding results. Specifically, (i) Overview utilizes a VLM to extract cross-attention maps that capture semantic correlations between the referring expression and visual regions; (ii) Focus leverages the fine-grained modeling priors of a DM to compensate for object structure and shape information often overlooked by VLM attention; and (iii) Evolve introduces a simple yet effective attention evolution module to suppress irrelevant activations, yielding purified object masks. To handle video inputs, we further present Video RSVG-ZeroOV, which extends image-level grounding to spatio-temporal grounding through a query-relevant key-frame selector and a temporal propagator, enabling efficient and temporally coherent video grounding without video annotations or fine-tuning. Extensive experiments on six image and video grounding benchmarks show that RSVG-ZeroOV consistently outperforms existing zero-shot baselines and achieves competitive or superior performance compared with weakly- and fully-supervised methods.

15.
arXiv (quant-ph) 2026-06-17

Optimal Probe State for Phase Estimation Under Covariant Measurement

arXiv:2606.18169v1 Announce Type: new Abstract: We study the optimization of input states for phase estimation under covariant measurements. Building on Holevo's framework, which provides the optimal covariant measurement for a fixed input state, we further optimize over the input state itself. For a general even $2\pi$-periodic cost function with non-negative Fourier coefficients, we derive a necessary and sufficient condition for the optimal input state: Its Fock coefficients are determined, up to arbitrary phases, by the eigenvector corresponding to the largest eigenvalue of a Toeplitz matrix defined by the cost function. This characterization yields an explicit expression for the attainable lower bound of the average cost under optimal covariant measurements and shows that this bound asymptotically approaches zero in the infinite-energy limit. For the specific cost function $W(\theta,\tilde{\theta})=4\sin^2[(\theta-\tilde{\theta})/2]$, we obtain the optimal input state and the corresponding minimum average cost in closed form, demonstrating Heisenberg scaling with respect to the mean photon number.

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

Triangular-Reference Schrödinger Bridges for Time Series Generation

arXiv:2605.27478v3 Announce Type: replace-cross Abstract: Schrödinger bridges for time series (SBTS) generate synthetic paths by projecting, in relative entropy, a Brownian reference onto the path laws that match the joint distribution of the data on the observation grid. The Brownian reference, however, fixes the quadratic variation of the generated paths, which is restrictive when stochastic volatility, correlated noise, or rank-deficient covariance structures must be reproduced. We introduce "Triangular-Reference Schrödinger Bridges for Time Series" (TR-SBTS), which keeps the entropy-projection backbone of SBTS but replaces the Brownian reference by a triangular, volatility-informed, intervalwise frozen reference on a state augmented with latent covariance descriptors. The construction remains a single entropy projection on the augmented state: the minimiser is the \(h\)-transform of the reference, and on each frozen interval the optimal drift has the logarithmic-gradient form \(b^\star(t,x)=A\,\nabla\log H(t,x)\), intrinsic to the active covariance directions when the frozen covariance \(A\) is degenerate. We prove stability of the frozen approximation and consistency of the associated regularised kernel estimators, describe a reference-aware Nadaraya–Watson implementation of the conditional next-increment law, and evaluate the construction on numerical experiments.

17.
arXiv (quant-ph) 2026-06-16

The Optimal Rate Function in Covariant Quantum State Tomography

arXiv:2606.16948v1 Announce Type: new Abstract: The problem of quantum tomography is to estimate an unknown quantum state $\rho$ from a measurement of $n$ copies of $\rho$. One can ask which tomography protocol, i.e.\ which choice of multi-copy measurement, gives the best possible estimate of $\rho$. To do so, we characterize tomography protocols by their rate function, which governs the exponential rate at which a protocol assigns probability to a particular estimate $\sigma$ of the true state $\rho$. This rate function is a quantum mechanical generalization of the classical relative entropy between the true state and its estimate, and depends on the choice of protocol. It is bounded by the quantum relative entropy, and we show that this bound is sharp: for any $\rho$ and $\sigma$ we construct a family of protocols whose rate functions converge to the quantum relative entropy $D(\sigma\|\rho)$. We consider the family of covariant tomography protocols; these are the basis independent state estimation schemes that assume no prior information about $\rho$ and $\sigma$. Keyl described a specific tomography protocol based on Schur sampling, and conjectured that among all covariant tomography protocols it has the largest possible rate function for all $\sigma$ and $\rho$. We prove this conjecture. The resulting rate function is an annealed version of quantum relative entropy, due to the cost of learning the eigenbasis in covariant quantum state tomography.

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

Lost in a Single Vector: Improving Long-Document Retrieval with Chunk Evidence Aggregation

Dense retrieval ranks one query vector against one document vector. On long documents, this interface can fail when a short but decisive span is weakened during document encoding before ranking. We study this failure mode as document-side early compression and introduce the Evidence Dilution Index (EDI) to measure how far a document-level representation falls below the strongest chunk-level evidence within the same gold document. Guided by this view, we propose DICE (Document Inference via Chunk Evidence), a training-free document-side strategy that splits documents into chunks, encodes them independently with a frozen model, and aggregates them back into a single vector while preserving the standard one-query-one-document interface. On LongEmbed, DICE improves retrieval across four backbones, with the largest gains on slices beyond 4k tokens: for Dream, Passkey >4k rises from 30.0 to 90.0 and Needle >4k from 23.3 to 74.0. Across 12,779 filtered samples, DICE yields lower EDI than the single-vector baseline in 92.8% of cases. These results establish document-level encoding as a practical and underexplored lever for long-document retrieval.

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

COSMOS: Model-Agnostic Personalized Federated Learning with Clustered Server Models and Pseudo-Label-Only Communication

arXiv:2605.11165v2 Announce Type: replace Abstract: Federated learning (FL) in heterogeneous environments remains challenging because client models often differ in both architecture and data distribution. While recent approaches attempt to address this challenge through client clustering and knowledge distillation, simultaneously handling architectural and statistical heterogeneity remains difficult. We introduce COSMOS, a model-agnostic framework that enables server-side personalization using only pseudo-label communication. Clients train local models and predict on the public data; the server clusters clients by prediction similarity, trains a cluster-specific model for each group using its own compute, and distills the resulting models back to clients. We provide the first theoretical analysis showing that distillation from the learned cluster models can yield exponential personalization risk contraction, going beyond the convergence-to-stationarity guarantees typically provided in model-agnostic FL. Experiments across benchmarks demonstrate that COSMOS consistently outperforms all model-agnostic FL baselines while remaining competitive with state-of-the-art personalized FL methods. More broadly, our results highlight personalized server-side learning with pseudo-labels as a promising paradigm for scalable and model-agnostic federated learning in highly heterogeneous environments.

20.
Nature Medicine 2026-06-08

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

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

21.
medRxiv (Medicine) 2026-06-18

MOSAIC: Methylation-Oriented Site Analysis and Information Classifier for Robust Epigenomic Classification of Acute Leukemia in Clinical Cohorts with Variable Tumor Purity

DNA methylation-based classification offers a rapid diagnostic complement to conventional molecular workflows in acute leukemia. Existing classifiers are trained on array-derived reference cohorts whose construction favors specimens with adequate tumor content, leaving clinically relevant low-purity specimens underrepresented and classifier robustness in this regime uncharacterized. On held-out low-purity specimens, existing classifiers were concordant with expert pathology in only 7 of 10 (MARLIN) and 5 of 10 (ALMA) cases, motivating a classifier built to maintain accuracy at low tumor purity. We developed MOSAIC (Methylation-Oriented Site Analysis and Information Classifier), a neural network classifier built to maintain accuracy across the full range of tumor purities encountered in clinical practice. MOSAIC is a neural network trained on publicly available array-based methylation data augmented with native methylation calls from Oxford Nanopore sequencing. MOSAIC was evaluated on low-purity specimens held out entirely from training. On these held-out low-blast leukemia specimens, all below 25% blasts and including a case at 1.4%, MOSAIC was concordant with expert pathology in every case, recovering the correct subtype where diluted disease signal would otherwise be mistaken for normal or unrelated tissue. Gradient-based saliency analysis showed that the network relies on a partially distinct set of discriminative CpG probes when classifying low-blast specimens. MOSAIC demonstrates that augmenting training with clinically representative clinical specimens yields methylation-based leukemia classification that maintains effectiveness under the variable tumor purity of real clinical cohorts.

22.
arXiv (CS.LG) 2026-06-16

Towards Data-Efficient Cross-Device Generalization of Grad-Shafranov Equilibria via Transfer Learning Neural Operator

arXiv:2606.15512v1 Announce Type: new Abstract: Real-time reconstruction of magnetohydrodynamic equilibria is essential for plasma shaping, stability assessment and feedback control in magnetic confinement fusion. However, Grad-Shafranov equilibrium calculations remain largely device-specific and iterative, limiting their use in latency-constrained control settings. Existing neural approaches can accelerate individual equilibrium predictions, but they do not generally provide reusable models across changing plasma boundaries or tokamak geometries. Here we show that equilibrium reconstruction can be recast as a cross-device operator learning problem. We develop a domain-specific neural operator framework that maps geometry and profile parameters directly to the poloidal flux field, replacing repeated solve-on-demand computation with amortized operator inference. Using the analytically tractable Solov'ev family as a controlled Grad-Shafranov testbed, we generate equilibria across eight geometrically distinct tokamak-like configurations and benchmark five neural operator architectures under four transfer-learning strategies. Single-geometry pretraining gives poor transfer to unseen devices, whereas multi-geometry pretraining enables data-efficient adaptation. The Wavelet Neural Operator gives the strongest cross-geometry performance, reaching mean relative L2 errors below 4% with 100 labelled target equilibria and below 2% with full fine-tuning. The predicted magnetic fields satisfy the divergence-free constraint to numerical precision, and four architectures achieve millisecond or sub-millisecond inference. These results identify neural operator pretraining as a route towards reusable, real-time equilibrium inference across fusion device configurations.

23.
arXiv (quant-ph) 2026-06-12

To Cool, or Not to Cool? Displacement Sensing with Hot Quantum States

arXiv:2606.13650v1 Announce Type: new Abstract: Quantum-enhanced displacement sensing with bosonic systems is typically formulated assuming that the oscillator is cooled close to its ground state before nonclassical probe preparation. We investigate whether such near-ground-state initialization is necessary, or whether sensitive probes can instead be generated directly from thermal states. We analyze hot quantum probes produced by squeezing, number-raising, and Schrödinger-cat-state generation applied to thermal inputs. We identify two distinct mechanisms by which thermal mixedness can remain compatible with enhanced displacement sensitivity. First, projecting a mixed probe onto a definite parity sector removes the usual thermal suppression of the displacement quantum Fisher information, which can then increase with initial thermal occupation. Second, coherent superpositions of opposite displacements can retain sensitivity through coherence between their displaced components, even when the underlying state is mixed. We use these two mechanisms to classify hot-state protocols according to whether their sensitivity comes from parity selection, coherence between displaced components, or both. Finally, we formulate an experimentally relevant optimization problem comparing initial cooling with direct hot-state preparation under realistic decoherence and show that complete cooling is not universally optimal. Our results establish hot-state engineering as a route to quantum-enhanced bosonic displacement sensing without mandatory ground-state initialization.

24.
bioRxiv (Bioinfo) 2026-06-22

Drug-Prot: A query system for statistical inference of drug effects and interactions in dynamic proteomic networks

Understanding drug effects and drug-drug interactions is essential for developing combination therapies. We present Drug-Prot, a computational framework that leverages large-scale perturbation proteomics to quantify causal drug effects, drug-drug interactions, and dynamic protein relationships. Using data from 63 single drugs and 59 drug combinations applied to 18 breast cancer cell lines at 6, 24, and 48 hours, Drug-Prot estimates drug effects on protein expression and reconstructs directed temporal protein dependency networks. The publicly available software enables targeted analyses of user-defined protein sets, substantially reducing the multiple-testing burden. Through an interactive web application, users obtain corrected p-values for single-drug and combination effects, directed temporal dependency networks, and downloadable results without requiring access to the underlying proteomic dataset. As a use case, we apply invariance-regularized Random Forests to triple-negative breast cancer cell lines to identify proteins associated with drug response. Querying these proteins in Drug-Prot reveals drug-specific and interaction effects at the protein-network level, illustrating how the framework links candidate causal protein features to actionable drug combinations.

25.
arXiv (CS.LG) 2026-06-15

Adaptive Oscillatory-State Alignment for Time Series Forecasting

arXiv:2606.06010v2 Announce Type: replace Abstract: Long-term time series forecasting benefits from inductive biases that expose recurring temporal structure. Existing periodic forecasting methods typically model recurrence through predefined periods, global spectral components, or fixed learnable templates. However, real-world temporal dynamics are rarely rigidly periodic: around a nominal cycle, oscillatory behavior often exhibits non-rigid periodicity (NRP), where cycle magnitude, cycle alignment, and local cycle duration vary over time. Under these conditions, fixed-template periodic modeling can become fundamentally mismatched to the underlying temporal states. We propose AOSNet, a Hilbert-guided forecasting framework that reformulates periodic forecasting from fixed template matching to adaptive oscillatory-state alignment. AOSNet extracts analytic-signal descriptors from both the observed sequence and a learnable global oscillatory prior, then adaptively aligns local states through a descriptor-conditioned gate that selectively preserves reliable observations while softly correcting mismatched regions. The learned prior serves not as a rigid repeated template but as a flexible oscillatory reference interpreted through local state dynamics. Experiments on eight public benchmarks and two cloud workload traces demonstrate leading or highly competitive accuracy with a compact model size and low inference latency, supporting repeated forecasting settings such as capacity planning and autoscaling. Controlled synthetic studies that isolate cycle-magnitude and cycle-alignment variation and combine them with cycle-duration changes show that the advantage of oscillatory-state alignment increases as NRP intensifies.