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

Ultra Flash: Scaling Real-Time Streaming Video Generation to High Resolutions

While recent autoregressive video diffusion models achieve remarkable streaming quality, they remain confined to low resolutions (e.g., 480P), leaving efficient, scalable, real-time high-resolution video generation a fundamental open challenge. To bridge this gap, we present Ultra Flash, a cascaded streaming framework capable of real-time high-resolution video generation. Ultra Flash achieves ~30 FPS at 1K resolution and ~18 FPS at 2K resolution on a single GPU through three key contributions: (1) an architecture-preserving T2V-to-TV2V super-resolution training paradigm coupled with an AIGC-oriented data degradation pipeline that effectively preserves the generative capability of the base model, enabling enhanced high-resolution detail when cascaded after mainstream low-resolution generative models; (2) a causal streaming latent upsampler paired with a high-resolution decoder, which enhances spatiotemporal coherence while enabling efficient latent spatial scaling and precise high-resolution decoding with negligible computational overhead; and (3) a cascade high-resolution streaming video generation optimization scheme that first performs hybrid-reward-enhanced sparse causalization and single-step distillation of the super-resolution model, then introduces cascaded streaming self-forcing preference optimization with dynamic cache management, jointly enhancing overall coherence, improving quality, and enabling real-time high-resolution streaming video generation. Extensive experiments demonstrate that Ultra Flash reliably produces ultra-high-resolution streaming video while maintaining state-of-the-art visual quality and superior efficiency. Project Page: https://xin1u.github.io/UltraFlash/

02.
Nature Medicine 2026-06-10

Dual-target gene therapy in Parkinson’s disease: a multicenter phase 1 trial

Authors:

Restoring striatal dopamine synthesis is a promising gene therapy strategy for Parkinson’s disease. Previous adeno-associated virus-mediated aromatic L-amino acid decarboxylase (AADC) monotherapies remain dependent on exogenous levodopa, whereas multigene delivery is constrained by strict adeno-associated virus packaging limits. A ‘dual approach’ targeting the two rate-limiting enzymes, tyrosine hydroxylase (TH) and AADC, offers the potential for autonomous dopamine synthesis. We report the 12-month primary safety and tolerability outcomes of a multicenter, open-label, dose-escalation, phase 1 trial evaluating BBM-P002, a new adeno-associated virus vector—AAVT42—codelivering constitutively active TH and AADC. Ten participants with moderate-to-advanced Parkinson’s disease were enrolled and received bilateral intraputaminal infusions across doses of 4.0 × 1011 vg (Cohort 1; n = 1), 6.0 × 1011 vg (Cohort 2; n = 2), 1.0 × 1012 vg (Cohort 3; n = 2) and 1.2 × 1012 vg (Cohort 4; n = 5). The trial achieved its primary outcome, as BBM-P002 demonstrated a favorable safety and tolerability profile within 12 months post-treatment. No dose-limiting toxicities or drug-related serious adverse events occurred. A total of 23 adverse events were reported, all judged unrelated to BBM-P002 and primarily mild and transient. Systemic toxicity and clinically meaningful immunogenicity were absent. In conclusion, intraputaminal delivery of BBM-P002 was safe and well tolerated in this phase 1 trial, supporting continued clinical development. ClinicalTrials.gov registration: NCT05822739 . Phase 1 results reveal that BBM-P002, a dual-target gene therapy co-delivering TH and DDC, is safe and well tolerated in Parkinson’s disease, with 12-month motor improvements signaling therapeutic potential.

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

Variable Bound Tightening for Nash Equilibrium Computation in Multiplayer Imperfect-Information Games

Authors:

arXiv:2606.25997v1 Announce Type: cross Abstract: There has been significant recent progress in algorithms for approximation of Nash equilibrium in large two-player zero-sum imperfect-information games and exact computation of Nash equilibrium in multiplayer strategic-form games. While counterfactual regret minimization and fictitious play are scalable to large games and have convergence guarantees in two-player zero-sum games, they do not guarantee convergence to Nash equilibrium in multiplayer games. Recently, an approach has been presented for exact computation of Nash equilibrium in multiplayer imperfect-information games that solves a quadratically constrained program based on a nonlinear complementarity problem formulation derived from the sequence-form game representation. This formulation was solved using Gurobi's nonconvex quadratic solver, which employs spatial branch-and-bound to iteratively refine variable bounds by solving convex relaxations of bilinear terms via McCormick envelopes. During presolve, Gurobi introduces auxiliary variables and, in some cases, binary variables, leading to an internal MIQCP reformulation. This approach was demonstrated to outperform prior algorithms from the Gambit software suite and quickly solve three-player Kuhn poker after removal of dominated actions; however, the algorithm was not able to solve the full version of the game within 24 hours. In this paper, we derive finite bounds on slack and multiplier variables in the nonlinear complementarity formulation. These bounds strengthen the convex relaxations used within spatial branch-and-bound and lead to substantial computational improvements. We demonstrate the impact of the proposed bounds on exact Nash equilibrium computation in three-player Kuhn poker.

04.
medRxiv (Medicine) 2026-06-24

Epidural versus Transcutaneous Spinal Cord Stimulation for Motor Recovery after Spinal Cord Injury: A Comparative Analysis

Spinal cord injury (SCI) is a devastating neurological injury that results in the profound loss of voluntary motor function and marked reduction in quality of life. Rehabilitation remains as the standard of care for recovery after SCI; however, it often falls short in recovering meaningful motor function. Spinal cord stimulation (SCS) has emerged as a promising neurostimulation approach to fill this gap and recover lost voluntary motor function. Two main approaches of SCS have been designed and implemented for human use: epidural and transcutaneous SCS. Over the last two decades, several clinical studies have shown convincing evidence that both epidural and transcutaneous SCS can be used in conjunction with rehabilitation to improve motor function of individuals after SCI. Yet fundamental clinical questions remain unanswered: when should clinicians choose epidural or transcutaneous SCS, which technique provides the most durable outcomes, and for whom is each therapy best? Without these answers, widespread and meaningful adoption of either approach into clinical practice will remain limited. To address these questions, in this Review, we define the distinct therapeutic goals, intended use cases, clinical parameters, and responder profiles for both epidural and transcutaneous SCS to guide their eventual adoption into clinical practice. We found that indeed epidural and transcutaneous SCS serve distinct therapeutic roles. Epidural SCS is designed as an assistive therapy that can restore muscle activity and single joint movements immediately within one week of implantation, while transcutaneous SCS is designed as a long-term therapeutic device with cumulative functional gains observed over treatment periods of up to 18 weeks. Lastly, epidural SCS produced benefits for all participants (AIS A-D) despite the extent of their injury, while transcutaneous SCS only consistently benefits individuals with incomplete motor injuries (AIS C-D).

05.
arXiv (CS.CL) 2026-06-24

Reinforcement Learning Towards Broadly and Persistently Beneficial Models

As AI systems are deployed across increasingly diverse and high-stakes settings, model alignment must generalize beyond the tasks and domains seen during training. This is especially important for reinforcement learning (RL), which can introduce unexpected misalignment through reward hacking, deception, or other unintended strategies. We study whether RL on beneficial behavior, instantiated in realistic domains, can produce broad and persistent alignment generalization beyond the training distribution. We construct a dataset of realistic situations designed to measure and train beneficial traits, such as truthfulness, fairness, risk awareness, and corrigibility, spanning varied domains, including health, science, and education. We then train models with RL on this dataset and evaluate them on more than 50 independent benchmarks of alignment and beneficial behavior. Compared to a compute-matched baseline, beneficial trait RL improves performance on over 80% of these out-of-distribution benchmarks. We observe substantial out-of-distribution alignment transfer: a beneficial-behavior RL intervention entirely limited to one domain, health, produces broad improvements on non-health alignment evaluations, including reduced reward hacking, deception, and general misalignment. Finally, we study alignment persistence: whether behavior remains robustly aligned under attempts to steer models towards misalignment. Models trained with beneficial trait RL show improved persistence, including greater resistance to adversarial prompting and harmful finetuning; further work is required to isolate the sources of these effects. These results suggest that RL to reinforce beneficial behavior in realistic domains can produce models that are more robustly aligned with human flourishing.

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

TensorLDM: A Component-Wise Latent Diffusion Model for Volumetric DTI Reconstruction from Sparse DWIs

Reconstructing diffusion tensors from sparse DWIs is critical for accelerating Diffusion Tensor Imaging (DTI) in clinical settings, yet current deep learning approaches frequently yield anatomically inconsistent or physically implausible tensors. We introduce TensorLDM, a component-wise latent diffusion model that processes the six tensor components through two group-specific encoders (for diagonal and off-diagonal elements) while maintaining anatomical consistency via shared DWI conditioning. TensorLDM uses an Anatomy-Conditioned Autoencoder that encourages the latent to focus on tensor properties rather than re-encoding structural information. A shared Cross-Component Attention (CCA) mechanism, applied in both autoencoder refinement and diffusion fine-tuning, models inter-component dependencies, while a Mixture-of-Experts (MoE) DWI conditioner provides component-adaptive conditioning. On the Human Connectome Project (HCP) dataset under a single-shell, four-volume sparse acquisition, TensorLDM produces the most accurate downstream tractography and tensors with near-ground-truth physical validity (SPD-violation rate 1.54% vs. 1.40%), with the best or comparable voxel-wise reconstruction accuracy. Geodesic tensor error measured by the Log-Euclidean Metric (LEM) corroborates these gains.

07.
medRxiv (Medicine) 2026-06-12

The Clinical Characteristics and mortality outcomes of Atrial fibrillation complicating Heart failure with reduced ejection fraction: A prospective study from South Africa

Background: A growing burden of cardiovascular risk factors has raised cardiovascular disease-related mortality in Sub-Saharan Africa (SSA), driving higher prevalence of heart failure with reduced ejection fraction (HFrEF) and its complication with atrial fibrillation (AF). No prospective study has examined AF's clinical impact on HFrEF in SSA. Aim: To determine AF prevalence in HFrEF, describe HFrEF-AF clinical characteristics, and determine AF's impact on mortality. Methods: In this prospective observational study at a tertiary hospital in Johannesburg, 136 HFrEF patients were enrolled and categorised as HFrEF- SR (sinus rhythm) or HFrEF-AF. Baseline clinical characteristics and biochemistry were recorded. Comprehensive echocardiography including left atrial strain by 2D speckle-tracking was performed. Median follow-up was 30.6 months. Results: AF was present in 28 patients (21%). The mean age was 58.7 {+/-} 14.9 years (52.9% male) and differed between groups (p < 0.001). Hypertensive heart disease was the leading cause of HFrEF (36%). Compared with SR, HFrEF-AF patients had poorer health status (KCCQ 27 [16-43] vs 45 [32-60], p < 0.001) and lower left atrial strain (26.2 {+/-} 11.3%, p < 0.001). Guideline-directed medical therapy was suboptimal in the AF group: anticoagulation use was higher than SR (60% vs 9.5%, p < 0.001) but overall inadequate; HFrEF-AF patients received lower median doses of carvedilol (15.6 mg vs 25 mg, p = 0.002) and enalapril (10 mg vs 20 mg, p = 0.004), and fewer received spironolactone (50% vs 75.3%, p = 0.013). Survival was significantly lower in HFrEF-AF (0.41 [0.22-0.61]) versus SR (0.73 [0.61-0.82], p < 0.001). Independent predictors of mortality included prior stroke, lower TAPSE and KCCQ, and higher E/e' and heart rate. Conclusion: AF is common among HFrEF patients in this SSA cohort (though lower than in high-income countries) and associates with worse clinical status, suboptimal therapy, and higher mortality.

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

LLM agent safety, multi-turn red-teaming, jailbreak benchmarks, adversarial robustness, safety-critical systems

arXiv:2606.20408v1 Announce Type: cross Abstract: Large language model (LLM) agents are increasingly proposed as supervisory components for safety-critical systems, yet their robustness under sustained, adaptive adversarial pressure remains poorly characterized. We present NRT-Bench, a benchmark for multi-turn red-teaming of LLM agents acting as operators of a safety-critical system, instantiated in a simulated nuclear power plant control room. A five-role operator team, each backed by a configurable LLM, runs a plant governed by six critical safety functions (CSFs), while adversaries inject messages over four channels in bounded multi-turn sessions with per-turn feedback. Harm is an objective signal rather than LLM-judged text: a run terminates the moment any CSF is lost, attributed to the causing message. Evaluating four frontier operator models under a fixed-attack paired-replay protocol, we find that adaptive multi-turn attacks reliably push the operator team past a safety limit: across the four models, between 8.7% and 12.1% of attack sessions end with the plant losing a critical safety function. Although the four models look almost equally robust by this aggregate rate, their failures barely overlap: of $149$ sessions, none defeat all four models while a third defeat at least one, so vulnerabilities are nearly disjoint across models rather than nested. The effect of added defences is strongly model-dependent: the same guardrail stack or safety-advisor agent that lowers attack success for one model can raise it for another. We release the simulation venue, attack dataset, and replay tooling for reproducible safety evaluation of LLM agents.

09.
arXiv (quant-ph) 2026-06-15

Reaffirming a Challenge to Bohmian Mechanics

arXiv:2509.06584v4 Announce Type: replace Abstract: In our recent work, we reported the first measurement of the speed of tunnelling particles using a coupled waveguide system. The measured speed is operationally defined through a comparison of two orthogonal motions in a coupled waveguide system, is compatible with the standard definition of dwell time and with the Büttiker-Landauer tunnelling time, and does not presuppose a trajectory picture. Here we respond to objections raised in comments, referee reports, preprints, and articles. We distinguish two questions that are often conflated: whether Bohmian mechanics reproduces the measured density, and whether the standard guiding equation assigns the correct state of motion to the particles. The first point follows under the usual quantum equilibrium assumptions. The second is a separate physical assumption, since the standard guiding equation does not follow from the Schrödinger equation alone. We argue that, in the evanescent regime, the state of motion assigned by the standard guiding equation is in disagreement with the measured speed. To make the distinction explicit, we also present a bidirectional Bohmian model that reproduces the same stationary density while assigning finite speeds compatible with the speed inferred in the evanescent regime.

10.
arXiv (CS.CV) 2026-06-16

Are Neuro-Inspired Multi-Modal Vision-Language Models Resilient to Membership Inference Privacy Leakage?

In the age of agentic AI, the growing deployment of multi-modal models (MMs) has introduced new attack vectors that can leak sensitive training data in MMs, causing privacy leakage. This paper investigates a black-box privacy attack, i.e., membership inference attack (MIA) on multi-modal vision-language models (VLMs). State-of-the-art research analyzes privacy attacks primarily to unimodal AI-ML systems, while recent studies indicate MMs can also be vulnerable to privacy attacks. While researchers have demonstrated that biologically inspired neural network representations can improve unimodal model resilience against adversarial attacks, it remains unexplored whether neuro-inspired MMs are resilient against privacy attacks. In this work, we introduce a systematic neuroscience-inspired topological regularization (tau) framework to analyze MM VLMs resilience against image-text-based inference privacy attacks. We examine this phenomenon using three VLMs: BLIP, PaliGemma 2, and ViT-GPT2, across three benchmark datasets: COCO, CC3M, and NoCaps. Our experiments compare the resilience of baseline and neuro VLMs (with topological regularization), where the tau > 0 configuration defines the NEURO variant of VLM. Our results on the BLIP model using the COCO dataset illustrate that MIA attack success in NEURO VLMs drops by 24% mean ROC-AUC, while achieving similar model utility (similarities between generated and reference captions) in terms of MPNet and ROUGE-2 metrics. This shows neuro VLMs are comparatively more resilient against privacy attacks, while not significantly compromising model utility. Our extensive evaluation with PaliGemma 2 and ViT-GPT2 models, on two additional datasets: CC3M and NoCaps, further validates the consistency of the findings. This work contributes to the growing understanding of privacy risks in MMs and provides evidence on neuro VLMs privacy threat resilience.

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

CPS4: Class Prompt driven Semi-Supervised Spine Segmentation with Class-specific Consistency Constraint

Vision Language Model (VLM) has great potential to enhance the quality of pseudo labels in semi-supervised spine segmentation by leveraging textual class prompts to generate segmentation map, but no one has studied it yet. Although promising, it lacks explicit constraints to ensure consistency between spine class prompts and spine unit region, resulting in unsatisfactory performance in multi-class segmentation map generation. In this paper, we propose CPS4, the first text-guided semi-supervised spine segmentation network using class prompts to enhance the quality of spine pseudo labels. Specifically, CPS4 is implemented through two training stages. (i) Class-specific consistency constrained VLM pretraining stage: we propose token- and pixel-level attention loss to optimize the consistency between class prompts and spine units, forcing the textual class prompt to be closely coupled with the target spine unit in the semantic space. (ii) Class Prompt driven semi-supervised spine segmentation stage: using the pretrained vision-text encoder, we derive each class-specific binary segmentation map for the unlabeled spine image and integrate them into an unified multi-class segmentation map, improving the quality of the spine pseudo label generated by the semi-supervised spine segmentation network. Experimental results show that our CPS4 achieves superior spine segmentation performance with Dice of 80.44%, only using 5% labeled data on the public spine segmentation dataset, surpassing popular semi-supervised learning and VLM methods. Our code will be available.

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

Closing the Auto-Research Loop: An AI Co-Scientist for Production Search Ranking

arXiv:2603.22376v2 Announce Type: replace-cross Abstract: We present an AI Co-Scientist framework that closes the research loop for the production search-ranking system of a large online travel platform – pairing LLM agents with direct cloud-compute access so that idea generation, code implementation, GPU experimentation, and result analysis iterate end-to-end with a human scientist in the loop. The framework uses a hybrid agent architecture: single-LLM agents handle routine work, while multi-LLM consensus (GPT-5.2, Gemini Pro 3, Claude Opus 4.5) is invoked for higher-stakes decisions. On the production ranking task, a human-designed transformer baseline (V2) yielded $+0.118\%$ over a pre-transformer baseline (V1); the AI Co-Scientist's automated loop on top of V2 contributed an additional $+0.083\%$, for a combined $+0.201\%$ offline gain delivered in roughly one extra week of wall-clock time (single-run numbers; statistical limits discussed in the paper). The most useful AI proposals – unified long-sequence layouts, slot-type embeddings, and multi-phase learning-rate schedules – are standard practice in NLP and Vision but were absent from our production stack, suggesting that LLM agents can serve as cross-disciplinary connectors for ranking teams. We also report deployment context, negative results, and lessons learned.

13.
arXiv (CS.AI) 2026-06-12

Definitional alignment before capability alignment: a Design-Science framework for adjudicating claims about AGI

arXiv:2606.12713v1 Announce Type: new Abstract: Claims that artificial general intelligence has already arrived and claims that it remains decades away are often defended from overlapping evidence. "AGI" lacks a single shared and stable referent and competing operationalizations can return different verdicts on the same system. This article treats that under-specification as a design and governance problem. Following Design Science Research Methodology, it develops DAF-AGI, a second-order conceptual artifact with two coupled components: five ordinal criteria for assessing the adjudicative fitness of candidate definitions and a structured governance audit of authorship, interest, certification, external verification and revision authority. The artifact is demonstrated on five prominent measurement families and one deflationary boundary position in a documented corpus and then stress-tested against a stylized strong arrival claim: that current generative systems constitute AGI because they outperform a well-educated adult on many cognitive tasks. On evidence from the cited 2024-2025 sources, the claim was certifiable only under a performance-based operationalization; capability-ontology, psychometric and skill-acquisition approaches did not certify it, the economic family remains indeterminate and the deflationary position refuses binary adjudication. The contribution is a novel integration and operationalization, not an empirical validation: independent application, inter-rater testing and author-external cases remain necessary. The paper further proposes definitional sovereignty as an enabling component of algorithmic sovereignty: the institutional capacity to contest, certify and revise imported technological categories under public accountability.

14.
arXiv (CS.AI) 2026-06-15

Quantized Evolution Strategies: High-precision Fine-tuning of Quantized LLMs at Low-precision Cost

arXiv:2602.03120v2 Announce Type: replace-cross Abstract: Post-Training Quantization (PTQ) is essential for deploying Large Language Models (LLMs) on memory-constrained devices, yet it renders models static and difficult to fine-tune. Standard fine-tuning paradigms, including Reinforcement Learning (RL), fundamentally rely on backpropagation and continuous weights to compute gradients. Thus they cannot be used on quantized models, where the parameter space is discrete and non-differentiable. While Evolution Strategies (ES) offer a backpropagation-free alternative, optimization of the quantized parameters can still fail due to vanishing or inaccurate gradient estimation. This paper introduces Quantized Evolution Strategies (QES), an optimization paradigm that performs full-parameter fine-tuning directly in the quantized space. QES is based on two innovations: (1) it integrates accumulated error feedback to preserve high-precision weight updating signals, and (2) it utilizes a stateless seed replay to reduce memory usage to low-precision inference levels. QES significantly outperforms the state-of-the-art zeroth-order fine-tuning methods on a variety of tasks, making direct fine-tuning for quantized models possible. It therefore opens up the possibility for scaling up LLMs entirely in the quantized space. The source code is available at https://github.com/dibbla/Quantized-Evolution-Strategies .

15.
arXiv (CS.LG) 2026-06-16

Distribution Alignment for One-Shot Federated Learning via Optimal Transport

arXiv:2606.16655v1 Announce Type: new Abstract: One-Shot Federated Learning (OSFL) addresses extreme communication regimes in which clients interact with the server only once, amplifying the impact of heterogeneous client data distributions. In particular, the interaction of domain shift and label shift across clients induces misaligned feature representations that cannot be corrected through iterative optimization. Existing OSFL methods rely on distillation, server-side generation or ensemble-based aggregation, but assume aligned representations or address domain and label shift separately. We introduce SLOT-Align (Single-round, Learning-free Optimal Transport Alignment), a geometry-aware feature harmonization framework for OSFL. SLOT-Align uses a shared frozen encoder to extract compact feature statistics, constructs a global reference via Bures-Wasserstein barycenters, and aligns local representations using closed-form geodesic optimal transport maps. The method is computationally efficient and can be combined with existing OSFL pipelines relying on frozen encoders without modifying their training procedures. Extensive experiments across multiple benchmarks, pretrained backbones, and OSFL methods show that SLOT-Align consistently improves accuracy and robustness under joint domain and label shift.

17.
arXiv (CS.CL) 2026-06-18

Output Vector Editing for Memorization Mitigation in Large Language Models

Large language models memorize and reproduce sequences from their training data, creating privacy, copyright, and security risks. Existing neuron-level mitigation methods equate editing with zeroing out neuron activations, but the activation only controls whether a neuron engages; the output vector is what writes to the residual stream and, through superposition, encodes multiple features. We propose output vector editing, a constrained-optimization weight edit that locates a small set of MLP neurons responsible for a memorized continuation and minimally modifies their output vectors to introduce a distractor in vocabulary space, redirecting their residual-stream contributions while leaving activations unchanged. Evaluating on four models from 360M to 7B parameters (SmolLM-360M, OLMo-1B, OLMo-7B, Llama2-7B), we center on OLMo-7B (whose open weights and pretraining corpus enable systematic mining) and mine 6831 memorized sequences, achieving up to 87.9% suppression. The 2.7$\times$ gap over zero ablation on the same located neurons shows the suppression comes from the output-vector edit, not localization alone. Four edit modes span a spectrum from aggressive suppression to minimal redirection; in ensemble they cover 96.5% of memorized sequences, while our recommended single-mode configuration reaches 81.5% with no catastrophic locality failures. We further identify a mechanistic boundary at ${\sim}14%$ of sequences unreachable by MLP-only editing; while these failures are not attention-driven overall, ablating the top contributing attention heads recovers 60–64% of them, with stronger recovery on continuations that copy tokens from the prefix, positioning attention as a complementary fallback rather than a primary mechanism. Edit mode ordering and the success-locality trade-off transfer across all four models, with success rates scaling with model size rather than family.

18.
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.

19.
arXiv (CS.LG) 2026-06-11

How Low Can You Go? Active Learning for Sparse Model Discovery in the Ultra-Low-Data Limit

arXiv:2606.12182v1 Announce Type: new Abstract: Identifying the governing equations of complex dynamical systems remains a fundamental challenge across science and engineering. While early approaches relied on empirical data and heuristics, modern data-driven methods offer greater flexibility and fewer assumptions. However, data acquisition in real-world settings is often expensive. This work addresses this challenge by introducing an active learning strategy for dynamics discovery in the ultra-low data limit. Rather than sampling randomly, our method iteratively prioritizes regions that are most informative for model identification. This approach builds on Sparse Identification of Nonlinear Dynamics (SINDy), and utilizes an ensemble extension, E-SINDy, to estimate epistemic uncertainty and guide the sampling for both ordinary and partial differential equations (ODEs/PDEs). For ODEs, an exhaustive analysis is conducted on the Lorenz system across varying data budgets and noise levels. For PDEs, two systems with contrasting dynamical characteristics are examined: the Burgers' equation, where a sharp shock front creates a distinction between informative and uninformative regions, and the Kuramoto-Sivashinsky equation, which presents a more spatially complex sampling landscape. Across all scenarios, the proposed method accurately identifies the governing dynamics with significantly fewer data samples than random sampling.

20.
medRxiv (Medicine) 2026-06-22

Burden of Cardiovascular Disease in Brazil, 1996-2023: A Retrospective Descriptive Study of the Epidemiology and Impact on Public Healthcare with Emphasis on Acute Myocardial Infarction

Background Cardiovascular diseases (CVD) are the leading cause of death worldwide, and their epidemiology is correlated with genetic predisposition, exposure to risk factors, sex, age, access to medical care, and other sociodemographic characteristics. Brazil is a developing country with a vast territory, which leads to structural inequalities. Estimates of CVD in Brazil, in its regions, and in its population are poorly evaluated and analysed. Methods We obtained CVD-related data from the Brazilian Unified Health System (SUS) and analysed mortality and morbidity from 1996 to 2023 by sex, race/ethnicity, age, and region. We calculated the risk of death from the most prevalent diseases, the average length of hospital stay, and the costs associated with heart transplantation. Findings In Brazil, acute myocardial infarction was the pathology that led to the highest number of deaths across all variables analysed during the evaluated period. Other CVD were also related to causes of death and morbidity, such as hypertensive diseases and heart failure. Interpretation Brazil presents a serious challenge to the public health system due to the high number of deaths and the progressive mortality rate. This study represents a fundamental contribution to the basis for formulating public health policies aimed at reducing the growing impact associated with these diseases. Funding CNPq, CAPES, FAPEMIG, INCT

21.
bioRxiv (Bioinfo) 2026-06-18

Accounting for allelic diversity and multicopy gene detection improves the accuracy of antibiotic resistance genotypic determination

Background Genomic prediction of antimicrobial resistance (AMR) relies on the accurate detection of resistance genes or allelic variants of core genes from raw or assembled genomes sequences. For several bacterial species and antibiotics, AMR genotype-phenotype discrepancies are common, indicating that important sources of error remain unresolved. For Enterococcus faecium, we focused on identifying the sources of discrepancies for tetracycline resistance, for which genotypic detection had shown particularly low accuracy. We investigated the effect of structural variation in antibiotic resistance genes (ARGs), including gene duplications, truncations, interruptions, and mixed configurations of complete and partial gene copies, as a source of genotype-phenotype discrepancies from short-read data. We conduct further extended investigations to other antibiotic families and into another bacterial species: Escherichia coli. Methods We analyzed collections of E. faecium and E. coli genomes, integrating high-quality complete assemblies, simulated Illumina short reads, and matched AMR phenotypic data. The integrity, copy number, and allelic diversity of ARGs were examined for multiple antibiotic classes, and their impact on ARG detection and accuracy of AMR determination was assessed using several commonly used bioinformatic tools (SRST2, ARIBA and AMRFinderPlus). Results For E. faecium, after ruling out the effect of specific tet allelic variants on tetracycline susceptibility, we found that the integrity and copy number of tet(M) had a major effect on detection accuracy. Duplicated and incomplete ARGs are also common in E. faecium genomes, particularly for macrolides (erm(B)) and aminoglycosides (ant(6)-Ia and aph(3')-IIIa). In E. coli, similar patterns were observed for tet(A), erm(B) and aminoglycoside-associated genes (aph(3')-IIIa and ant(6)-Ia). Across ARGs in both species, short-read mapping methods wrongly reported interrupted genes as complete in some instances, while assembly-based methods often failed to resolve complete copies of duplicated genes. Detection accuracy improved when tools were adapted to account for gene integrity and when extended AMR databases incorporating species-specific alleles were included. Conclusions Our findings reveal that bioinformatic limitations in dealing with ARG copy number and completeness, and in accounting for allelic variation, underly a substantial source of genotype-phenotype errors, highlighting the need for improved AMR databases and bioinformatic tools that consider these factors to achieve reliable genomic prediction of AMR.

22.
arXiv (quant-ph) 2026-06-12

Electric Field Distortions in Surface Ion Traps with Integrated Nanophotonics

arXiv:2503.20387v3 Announce Type: replace Abstract: The integration of photonic components into surface ion traps provides a scalable approach for trapped-ion quantum computing, sensing, and metrology, enabling compact systems with enhanced stability and precision. However, the introduction of optical apertures in the trap electrodes can distort the trapping electric field. This can lead to excess micromotion (EMM) and ion displacement which degrade the performance of quantum logic operations and optical clocks. In this work, we systematically investigate the electric field distortion in a surface ion trap with integrated waveguides and grating couplers using Finite Element Method (FEM) simulations. We analyze methods to reduce these distortions by exploiting symmetries and transparent conductive oxide materials.

23.
arXiv (CS.CV) 2026-06-11

ViT-FREE: Efficient Face Recognition via Early Exiting and Synthetic Adaptation

Vision Transformers (ViTs) have gained significant attention in computer vision and shown strong potential for face recognition (FR). However, their high computational cost makes deployment on resource-constrained devices challenging, motivating the need for methods that balance efficiency and accuracy. In this work, we investigate early exiting in pretrained ViTs as a simple yet effective training-free strategy for efficient FR inference. Leveraging the uniform feature dimensionality across transformer encoder blocks, we introduce ViT-FREE, a multi-exit framework that enables face verification directly from intermediate representations without modifying or retraining the backbone model, and thus, reducing inference cost. Empirically, we show that patch embeddings and attention maps evolve progressively across depth, exhibiting high similarity between consecutive ViT blocks and increasing alignment with the final representation. This indicates gradual feature refinement and attention convergence, suggesting that intermediate layers already provide stable and discriminative representations suitable for early exiting. Through extensive experiments on multiple FR benchmarks, we systematically analyze the accuracy-efficiency trade-off across exit depths. Our results demonstrate that later exits achieve a highly favorable balance, with exiting at layer 10 yielding up to a 20% speedup while incurring only a 1.5 drop in verification performance on benchmarks such as IJB-C. Also, we propose ViT-FREE_FT, a lightweight exit-specific fine-tuning strategy that adapts only the projection layers using a small synthetic dataset while keeping the transformer backbone frozen. This approach improves the performance of shallow exits while preserving the efficiency benefits and leaving deeper exits largely unaffected.

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

Coercivity and Local Convergence of Physical Learning in Linear Circuits

arXiv:2606.15443v1 Announce Type: cross Abstract: Physical learning methods train physical networks to perform computational tasks using only local update rules, exploiting the physics of the system to handle the global transfer of information. We provide the first local convergence analysis of three such methods – Equilibrium Propagation (EP), Coupled Learning (CL), and a new method we call Adjoint Coupled Learning (AL) – for linear circuits, in the limit of small-nudging for both discrete and continuous time. EP and AL perform gradient descent on a natural loss function, while CL follows modified dynamics with an additional cubic correction. Assuming the existence of a solution, we identify a coercivity condition, expressed as a rank condition on a matrix built from the network's incidence structure, under which the training loss decays exponentially and the parameters converge to the solution manifold. We show that coercivity can fail by exhibiting a kite circuit in which a symmetry causes the coercivity constant to degenerate on the solution manifold, but prove using Sard's theorem that such degeneracies are non-generic: coercivity holds at every point of the solution manifold for almost every choice of desired output.

25.
arXiv (CS.AI) 2026-06-19

RACL: Reasoning-Agent Control Layers for Continuous Metaheuristic Learning

arXiv:2606.20142v1 Announce Type: new Abstract: This paper introduces RACL, a Reasoning-Agent Control Layer for metaheuristics. RACL places a reasoning agent above an existing optimizer. The agent does not replace the optimizer and does not modify business constraints. Instead, it controls the optimizer's internal search behavior by observing operational memory, reasoning over past behavior, formulating bounded hypotheses, testing interventions, evaluating outcomes, applying guardrails, consolidating useful policies and explaining its decisions. The experiment uses vehicle routing as a testbed, but the contribution is not a new routing solver, a particular ALNS configuration or a specific set of routing rules. The contribution is the RACL method: a way for a reasoning agent to discover, validate, consolidate and explain algorithmic control rules for a metaheuristic. In the current experimental setting, RACL improves or ties the Operational Memory Policy in 21 of 21 feasible cases and improves or ties a non-reasoning Stagnation-Triggered Policy in 18 of 21 feasible cases, with an average RACL vs STP cost delta of -0.641%. In the Sevilla-9/10 runtime sample, RACL improves average cost by -8.337% versus Fixed and -1.605% versus STP without showing material computational overhead. During the proof-of-concept, Codex was used as an in-the-loop reasoning agent observing executions, interpreting logs and proposing live bounded interventions. The policy proxy was later used only to make quantitative evaluation reproducible.