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

Denoising Implicit Feedback for Cold-start Recommendation

arXiv:2606.19658v1 Announce Type: new Abstract: Implicit feedback is widely used in recommender systems due to its accessibility and generality, yet it usually presents noisy samples (e.g., clickbait, position bias). Meanwhile, recommenders inevitably face the item cold-start problem due to the continuous influx of new items. We identify that cold items are more prone to noisy samples due to the aforementioned factors, and researchers often overlook the significance of denoising implicit feedback for cold items. Previous denoising studies usually identify noisy samples based on heuristic patterns, such as higher loss values, and mitigate noise through sample selection or re-weighting. However, these methods have limited adaptability and are ineffective in cold-start scenarios. To achieve denoising implicit feedback for cold-start recommendation, we propose a model-agnostic denoising method called DIF. First, user preferences for content remain stable, which allows us to infer pseudo-labels indicating whether a user is interested in a cold item through content-similar warm items. Furthermore, to improve pseudo-label accuracy, we model the confidence of pseudo-labels based on the content similarity between the cold item and warm items, and then aggregate multiple pseudo-labels for each sample. Finally, we explicitly estimate the uncertainty of the noisy sample label by considering its relative entropy and the cold-start status of the item, which adaptively guides the role of pseudo-labels to correct the noisy labels at the sample level. DIF's superiority is supported by both theoretical justification and extensive experiments on real-world datasets. The method has been deployed on a billion-user scale short video application Kuaishou and has significantly improved various commercial metrics within cold-start scenarios.

02.
arXiv (CS.LG) 2026-06-11

Scaling Laws of Global Weather Models

arXiv:2602.22962v2 Announce Type: replace Abstract: Data-driven models are revolutionizing weather forecasting. To optimize training efficiency and model performance, this paper analyzes empirical scaling laws within this domain. We investigate the relationship between model performance (validation loss) and three key factors: model size ($N$), dataset size ($D$), and compute budget ($C$). Across a range of models, we find that Aurora exhibits the strongest data-scaling behavior: increasing the training dataset by 10x reduces validation loss by up to 3.2x. GraphCast demonstrates the highest parameter efficiency, yet suffers from limited hardware utilization. Our compute-optimal analysis indicates that, under fixed compute budgets, allocating resources to more total training data yields greater performance gains than increasing model size. Furthermore, we analyze model shape and uncover scaling behaviors that differ fundamentally from those observed in language models: weather forecasting models consistently favor increased width over depth. These findings suggest that future weather models should prioritize wider architectures and larger effective training datasets to maximize predictive performance.

03.
arXiv (CS.LG) 2026-06-16

Tangram: Unlocking Non-Uniform KV Cache Compression for Efficient Multi-turn LLM Serving

arXiv:2606.06302v2 Announce Type: replace Abstract: Multi-turn LLM serving accumulates dialogue history whose Key-Value (KV) cache grows with every turn and every user, quickly exceeding the model weights themselves and making memory – not compute – the binding constraint on throughput. Non-uniform KV compression, which allocates heterogeneous budgets across attention heads, preserves accuracy far better than uniform schemes, yet remains impractical: modern serving stacks assume identical KV lengths across heads, so heterogeneity traps freed memory as page fragmentation, spends up to 25% of prefill time reclaiming scattered pages, and skews GPU workloads that inflate decode latency by up to $1.7\times$ or burn 15–20% of each decode step on re-planning. We observe that this heterogeneity need not be discovered at runtime: head-wise retention follows a two-level structural regularity – an input-invariant head ranking with narrowly bounded per-head ratios – that can be calibrated offline from as few as 50 samples. Building on this insight, we present Tangram, a serving framework that statically resolves what prior systems handle dynamically: Budget Reservation fixes each head's post-compression footprint at scheduling time, eliminating page reclamation; Ragged Paging clusters similar-budget heads into independent page tables, turning fragmentation into reclaimable memory; and Ahead-of-Time Load Balancing precomputes balanced GPU partitions with zero runtime planning. Implemented on vLLM, Tangram serves as a drop-in substrate for existing non-uniform compression methods, matching their accuracy while improving end-to-end throughput by up to $2.6\times$ over the full-KV baseline. Our implementation is publicly available at https://github.com/aiha-lab/TANGRAM.

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

Model Graph Inductive Learning for Knowledge Graph Completion

arXiv:2606.16509v1 Announce Type: new Abstract: Link prediction in knowledge graphs fundamentally depends on the quality of learned embeddings for entities and relations. However, most existing methods derive these embeddings by aggregating only the local neighborhood of each entity, neglecting the global structure of the knowledge graph. This limited view prevents models from capturing higher-level structural patterns that are essential for accurate and generalizable link prediction. To address these limitations, we introduce Model Graph Inductive Learning (MGIL), a framework that constructs a model graph by clustering entities based on the similarity of their incoming and outgoing relational structures or their entity types. A GNN is then applied to this model graph to produce embeddings that capture the global view of the knowledge graph. These embeddings subsequently serve as high-quality initial features %embeddings for the original knowledge graph, replacing random initialization and leading to more stable and expressive representations. Extensive experiments on standard and recently proposed inductive benchmarks demonstrate that MGIL achieves state-of-the-art or highly competitive performance in inductive link prediction, highlighting its effectiveness across diverse graph settings.

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

Causal Object-Centric Models for Planning with Monte Carlo Tree Search

arXiv:2606.14418v1 Announce Type: new Abstract: We introduce COMET (Causal Object-centric Model for Efficient Tree search), a model-based reinforcement learning algorithm that performs Monte Carlo Tree Search in a slot-structured latent space. COMET pairs a frozen unsupervised object-centric encoder with a transformer-based world model, in which actions are bound to objects through a novel action-slot fusion mechanism that is used in slot transition prediction. Policy and value heads use object-causal attention, modulating token interactions by learned per-slot relevance scores so that decision-making concentrates on task-relevant entities. COMET adds an explicit object-level inductive bias to MuZero-style latent planning. Across eight visually and dynamically diverse tasks from the Object-Centric Visual RL benchmark, ManiSkill, Robosuite, and VizDoom, COMET achieves a higher mean normalized score during the early stages of training compared to object-centric and monolithic baselines.

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

Detecting Functional Memorization in Code Language Models

Large language models (LLMs) are increasingly used to generate code at scale. Meanwhile, prior work has investigated whether training data may be recoverable from model outputs, by auditing the textual overlap between training examples and model generations. Code, however, can be functionally equivalent while textually dissimilar. In this work, we study functional memorization: extraction of functional logic beyond what verbatim metrics detect. We construct a counterfactual setup for Olmo-3-32B, comparing a midtrained model (exposed to target code) against a pretrained reference (not exposed). We prompt both models with Python function signatures and measure both textual and functional similarity (i.e., LLM-as-a-judge, execution-based). Our results show clear evidence of functional memorization, highlighting the need for auditing metrics that go beyond textual overlap.

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

A unified complexity bound for logconcave sampling

arXiv:2606.12694v1 Announce Type: cross Abstract: We give a simple, unified, and nearly tight bound for sampling arbitrary logconcave distributions from a warm start using the In-and-Out algorithm along with exponential lifting. The main new ingredient in the analysis is an improved bound on the Poincaré constant of a lifted distribution. As a consequence, the resulting convergence rate is nearly tight for both constrained settings (e.g., Gaussian restricted to a convex body) and well-conditioned settings (e.g., strongly logconcave and smooth densities).

08.
bioRxiv (Bioinfo) 2026-06-12

ProMiSE: Protein Multi-State Evaluation Benchmark in Biological Contexts

Proteins are inherently dynamic, with biological functions often emerging from transitions between multiple conformational states. While recent breakthroughs have largely addressed the static structure prediction problem, no systematic benchmark exists to demonstrate how well current models capture functionally relevant dynamics. We introduce ProMiSE, the first benchmark that provides both a dataset and an evaluation scheme, based on native biological assemblies and integrating major conformational change mechanisms - intrinsic, ligand-induced, and protein-induced - within a single curated dataset. We conducted a comprehensive evaluation of state-of-the-art structure prediction models, including AlphaFold3 and recent generative approaches. Our findings reveal that current models exhibit a limited ability to sample intrinsic multi-states and are often insensitive to biological context in induced scenarios. Internal representation analysis suggests that training-data exposure can shift predictions toward dominant conformational states over alternative biologically relevant states, primarily at the structure module. In contrast, results from BioEmu indicate that reducing decoding-stage bias can substantially improve multi-state sampling without major changes to upstream pair representations.

09.
arXiv (CS.CV) 2026-06-17

EventDrive: Event Cameras for Vision-Language Driving Intelligence

Event cameras sense the world through asynchronous brightness changes with microsecond latency and high dynamic range, offering motion fidelity far beyond frame-based sensors and capturing temporal structure that conventional exposures often miss. These properties make events a powerful complement to RGB in autonomous driving, especially under blur, glare, and rapid motion, where frame-based perception can become unreliable. However, existing event-aware vision-language models remain limited to generic perception and do not reveal how event sensing contributes to reasoning and decision-making across the full driving loop. We present EventDrive, a large-scale benchmark and model suite that unifies event streams, RGB frames, and language supervision across four core dimensions: Perception, Understanding, Prediction, and Planning, covering captions, structured QA, grounding, motion-state recognition, trajectory forecasting, and planning tasks. Building on this foundation, EventDrive-VLM introduces a multi-horizon event pyramid and a temporal-horizon mixture-of-experts module to adaptively encode and fuse asynchronous and frame-based information for downstream reasoning. Comprehensive evaluation across diverse tasks shows that event streams provide substantial gains in temporal precision, motion awareness, and robustness, bringing event sensing into the center of driving intelligence.

10.
bioRxiv (Bioinfo) 2026-06-13

Testing the reliability of AI-generated protein structures

Although AlphaFold2 and its competitors have demonstrated remarkable abilities to predict protein structure, more work is needed to explore the limitations of these methods. Here we investigated the reliability of AlphaFold2 and ColabFold by creating a set of realistic but false protein sequences, using ColabFold to predict their structure, and then asking how often the program produces a high-scoring structure for a sequence that does not represent a protein. We determined that AlphaFold2 has a very small but non-zero false positive rate, estimated here at approximately 1 in 435 if one uses a threshold pLDDT score of 70 to define positive predictions. We also discovered, serendipitously, that some high-scoring sequences in the human genome were not false positives, but instead were previously unknown and un-annotated pseudogenes. These latter findings indicate that some well-established human annotations of protein-coding genes may have incorrectly extended the 5-prime untranslated regions too far. They also suggest that the false positive rate of AlphaFold2 is low enough that almost any high-scoring structure, even in a noncoding region, is worthy of further investigation.

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

Cramér-Type Moderate Deviations for Engel's Series via a Martingale Approach

arXiv:2606.18866v1 Announce Type: new Abstract: Let $x$ be uniformly distributed on $(0,1)$, and let $(q_n)_{n\geq1}$ be the digits of its Engel series expansion. We establish a Cramér-type moderate deviation expansion for $(\log q_n-n)/\sqrt n$. The proof is based on a martingale decomposition and asymptotic results for martingales. As consequences, we obtain a moderate deviation principle over the full range of scales between the central limit theorem and the law of large numbers, without the additional lower rate restriction required in several earlier works. We also derive a uniform Berry–Esseen bound of order $(\log n)/\sqrt n$.

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

3D Scene Graphs: Open Challenges and Future Directions

3D Scene Graphs (3DSGs) have emerged as a powerful representation for spatial AI by combining geometric grounding with semantic and relational abstractions of the environment. Their expressiveness has made them relevant to a broad range of problems in robotics and computer vision, including manipulation, navigation, task planning, scene understanding, and many others. However, the field remains fragmented: different communities adopt distinct formulations, construction pipelines, and evaluation protocols, making it difficult to compare methods, identify common assumptions, and assess remaining challenges for robust real-world deployment. This survey provides a unified and critical review of 3DSGs, with particular emphasis on open challenges and future directions. We first formalize 3DSGs under a common definition and analyze the principal modeling choices that characterize existing formulations, including node and edge attributes, hierarchical structure, dynamic scene representations, and affordance-aware extensions. We then review how 3DSGs are built from raw sensory observations, discussing the most common terminologies, conventions, and techniques. Finally, we examine downstream applications and evaluation strategies, from intrinsic graph quality to task-level performance. To support the community, we also provide a dedicated website that organizes and extends the surveyed content, accessible at https://3dscenegraphs.com/.

13.
arXiv (quant-ph) 2026-06-16

Semiclassical Gravity Efficiently Solves $\mathsf{NP}$-Complete Problems

arXiv:2606.14806v1 Announce Type: cross Abstract: Assuming the gravitational field is classical and that it couples to quantum fields via the semiclassical Einstein field equations, we show that the weak-field dynamics of a massive and non-relativistic qubit can in principle be used to solve an $\mathsf{NP}$-complete problem in polynomial time. We attribute this vast computational power to the non-linear dynamics afforded by the semiclassical Einstein field equations. Consequently, the above two assumptions entail a violation of the Physical Extended Church–Turing Thesis, which we regard as evidence for the quantization of gravity.

14.
arXiv (CS.AI) 2026-06-19

Leveraging systems' non-linearity to tackle the scarcity of data in the design of Intelligent Fault Diagnosis Systems

arXiv:2606.20323v1 Announce Type: new Abstract: Deep Transfer Learning (DTL) allows for the efficient building of Intelligent Fault Diagnosis Systems (IFDS). On the other hand, DTL methods still heavily rely on large amounts of labelled data. Obtaining such an amount of data can be challenging when dealing with machines or structures faults. This document proposes a novel approach to the design of vibration-based IFDS using DTL in condition of strong data scarcity. A periodic multi-excitation level procedure leveraging intrinsic non-linearities of real-world systems is used to produce images that can be conveniently analysed by pre-trained Convolutional Neural Networks (CNNs) to diagnose faults. A new data visualization method and its augmentation technique are proposed in this paper to tackle the typical lack of data encountered during the design of IFDS. Experimental validation on a railway pantograph structure provides effective support for the proposed method.

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

Visualizing Uncertainty: Spatial Maps of Missing and Conflicting Evidence in Deep Learning

arXiv:2606.15767v1 Announce Type: cross Abstract: Understanding when and why deep neural networks are uncertain is crucial for deploying reliable machine learning systems in safety-critical domains. While existing uncertainty quantification methods provide scalar measures of model confidence, they offer limited insight into which spatial regions of an input contribute to different types of uncertainty. We propose a novel visualization framework, Uncertainty Activation Map (UAM), that combines Evidential Deep Learning (EDL) with Full-Gradient Class Activation Mapping (FullGrad) to generate interpretable spatial uncertainty activation maps. Our approach distinguishes between two fundamental types of uncertainty: vacuity, representing lack of evidence, and dissonance, capturing conflicting evidence between competing hypotheses. By leveraging the complete gradient decomposition property of FullGrad and the principled uncertainty quantification of Subjective Logic, our method produces theoretically grounded visualizations that highlight specific image regions responsible for model uncertainty. With this framework, vacuity and dissonance activation maps are generated by computing belief-weighted attributions, enabling identification of where models lack knowledge versus where they encounter ambiguous evidence. Extensive evaluations across multiple benchmark datasets demonstrate that the proposed framework effectively addresses the critical gap between uncertainty quantification and explainability, providing intuitive visual feedback to assess model reliability in complex visual recognition tasks.

16.
arXiv (CS.LG) 2026-06-19

Pseudo-Feature Padding: A Lightweight Defense Against False Data Injection in Power Grids

arXiv:2606.20415v1 Announce Type: new Abstract: Deep Neural Networks DNNs have achieved remarkable accuracy in various tasks including their application in CyberPhysical Systems CPS for detecting False Data Injection Attacks FDIA during critical operations However the unique infrastructure of CPS makes DNNs vulnerable to exploitation by attackers aiming to evade detection Additionally the distinct nature of CPS presents challenges for conventional defense mechanisms against FDIA This paper proposes an innovative defense framework that strengthens DNNs against such attacks by introducing an additional input layer that performs padding in the input samples using pseudofeature values derived from the inputs statistical distribution This padding increases the input dimensionality in a randomized and dataaware manner making adversarial attacks computationally infeasible due to the nontransferable nature of crafted perturbations and the unpredictability of the padded structure Our method is lightweight modelagnostic and requires no modifications to the core architecture making it highly deployable in realworld CPS settings We evaluated our framework on critical power grid applications such as state estimation using the IEEE 14bus 30bus 118bus and 300bus systems Experiments under adversarial settings demonstrate that our padding strategy significantly improves model robustness with negligible impact on performance and effectively mitigates attacks that would otherwise bypass conventional defenses

17.
arXiv (quant-ph) 2026-06-19

Quantum Dynamics from Lax Pair Theory: A Reconstruction from Spectrum Preservation

arXiv:2606.19664v1 Announce Type: new Abstract: We reconstruct unitary quantum dynamics from a minimal axiomatic foundation built on Hilbert-space observables and isospectral evolution. The only dynamical assumption is that physical time evolution is a continuous one-parameter flow of Hermitian observables that preserves their spectra, i.e. the possible outcomes of measurement. We show that this assumption is already sufficient to force the Lax form of quantum dynamics. The Heisenberg equation, the time-dependent and time-independent Schrödinger equations, conservation laws, and good quantum numbers then follow as theorems rather than postulates. In this formulation, Lax pair theory supplies the missing dynamical bridge between the measurement structure of a Hilbert space and standard quantum evolution: the Hamiltonian is not assumed, but emerges as the generator required for an isospectral observable flow.

18.
arXiv (CS.AI) 2026-06-16

InvDesMobility: a reliability-gated first-principles feedback framework for closed-loop materials discovery

arXiv:2606.16133v1 Announce Type: cross Abstract: Inverse materials design starts from target functionality and searches for structures that can realize it. Its value in closed-loop discovery depends not only on prediction performance, but also on whether expensive first-principles results are independently validated, provenance-recorded, and admitted as feedback only when evidence is sufficient. This is especially important for composite properties such as carrier mobility, where a final scalar value hides intermediate quantities, fit quality, convergence history, and workflow assumptions. Here we present InvDesMobility, a reliability-gated first-principles feedback framework that integrates multi-agent automated DFT, evidence stratification, generative structure proposal, acquisition ranking, and auditable release. Using 516 2DMatPedia-derived candidates, the workflow produced 280 QC-passed materials and 573 retained carrier-direction seed channels after channel-level reliability gating. These records were split into two feedback objects: relaxed structures updated the generative model, while retained mobility channels trained the acquisition model and set validation priority. Over multiple iterations, InvDesMobility screened 2.4 x 10^6 structures, submitted 102 candidates for DFT validation, and retained 86 reliability-gated generated channels across 41 formulas. Overall, the main contribution is not a fixed list of high-mobility materials, but a transferable feedback contract that makes closed-loop inverse design both useful and auditable when learning from expensive calculated properties. All source data, retained feedback records, and workflows are available at https://github.com/DreamLufei/invDesMobility, with an accompanying evidence website at https://dreamlufei.github.io/invDesMobility/.

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

SkMTEB: Slovak Massive Text Embedding Benchmark and Model Adaptation

We introduce SkMTEB, the first comprehensive MTEB-style text embedding benchmark for Slovak, a low-resource West Slavic language, comprising 31 datasets across 7 task types – nearly 4$\times$ the depth of existing multilingual benchmark coverage for Slovak. Our evaluation of 31 embedding models reveals that large instruction-tuned multilingual models achieve the strongest performance, while existing Slovak-specific models trained for NLU tasks transfer poorly to embedding tasks. To address the need for efficient, locally-deployable Slovak embeddings, we develop \texttt{e5-sk-small} (45M parameters) and \texttt{e5-sk-large} (365M) by applying vocabulary trimming and fine-tuning to Multilingual E5 models. Despite size reductions of up to 62\%, our open-source models achieve competitive performance with proprietary APIs while remaining locally deployable for semantic search and retrieval-augmented generation (RAG). We release the benchmark, models, datasets, and code openly, hoping our approach offers a replicable path for other under-resourced languages.

20.
arXiv (CS.AI) 2026-06-19

LOKI: Memory-Free Null-Space Constrained Lifelong Knowledge Editing

arXiv:2606.19679v1 Announce Type: cross Abstract: Lifelong knowledge editing aims to efficiently and sequentially update language models over time, as new knowledge becomes available or when the model makes mistakes, while preserving acceptable performance on past knowledge. One unresolved challenge is that existing methods modify a fixed set of layers for all new knowledge samples, reducing flexibility and increasing catastrophic forgetting. Another is requiring access to previous knowledge and extensive pre-processing to obtain data statistics. To address these challenges, we introduce LOKI, a novel approach that uses dynamic layer selection based on the Hilbert-Schmidt Independence Criterion and projects gradient updates onto the null-space of the model weights, bypassing the requirement for previous knowledge access. We show that LOKI achieves superior performance to existing approaches across a wide variety of experiments, achieving up to a 14\% improvement in average accuracy.

21.
arXiv (CS.AI) 2026-06-17

Reversal Q-Learning

arXiv:2606.17551v1 Announce Type: cross Abstract: Iterative generative modeling techniques, such as flow matching, provide powerful tools to model complex behaviors for effective offline reinforcement learning (RL). In this work, we propose a new off-policy RL algorithm that trains a flow policy based on prior data. Our idea starts from the "expanded" Markov decision process (MDP) framework, which treats individual flow refinement steps as separate actions in an MDP. To enable off-policy RL within this framework, we apply two techniques: we generate virtual on-policy trajectories (by "reversing" flows) to make this framework compatible with prior data, and we apply a bias-and-variance reduction technique to mitigate the curse of horizon in off-policy RL. We call the resulting algorithm Reversal Q-learning (RQL). RQL has several advantages over previous flow-based RL methods: it does not suffer from backpropagation through time, makes better use of the learned value function, and directly trains the full, expressive flow policy. Through our experiments on 50 challenging simulated robotic tasks, we show that RQL leads to the best average offline RL performance compared to state-of-the-art flow-based offline RL algorithms.

22.
arXiv (math.PR) 2026-06-15

Longest weakly increasing subsequences of discrete random walks on the integers with heavy tailed distribution of increments

arXiv:2603.29047v2 Announce Type: replace-cross Abstract: We investigate the behavior of the length of the longest weakly increasing subsequences (weak LIS) of $n$-step random walks with nonzero integer increments $k = \pm 1, \pm 2, \dots$ given by a symmetric heavy tailed mass distribution proportional to $|k|^{-1-\alpha}$ for several values of the real parameter $\alpha > 0$ together with that of the simple random walk ($k=\pm 1$), to which the $n$-step heavy tailed walks reduce when $\alpha$ grows large enough that step jumps beyond $\pm 1$ become essentially absent on the scale of $n$. By means of exploratory fits, weighted nonlinear least squares, and nested-model comparisons, we found that the sample average length $\langle{L_{n}}\rangle$ scales like $\langle{L_{n}}\rangle \sim \sqrt{n}\log{n}$ when the distribution of increments has finite variance ($\alpha > 2$) and $\langle{L_{n}}\rangle \sim n^{\theta}$ with a varying exponent $\theta > 0.5$ when the variance is infinite ($\alpha \leq 2$). Distributional diagnostics indicate that the bulk of the $L_{n}$ distribution is very well-approximated by a lognormal model, though systematic deviations are observed in the tails. Our results corroborate and expand upon previous results for the LIS of other types of heavy-tailed random walks and raise a conjecture as to whether the distribution of $L_{n}$ is given, or can be effectively described, by a lognormal distribution.

23.
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.

24.
arXiv (quant-ph) 2026-06-16

Information Is Not Physical: Possibility Spaces, Erasure, and the Structure of Unrealized Alternatives

arXiv:2606.15120v1 Announce Type: cross Abstract: The slogan ``information is physical,'' introduced by Rolf Landauer and developed through quantum information theory and black-hole thermodynamics, has achieved near-axiomatic status in modern physics. Yet the ontological status of information remains surprisingly underexamined: most discussions either reduce information to a form of energy or treat it as a purely mathematical object. This paper proposes a third position. I argue that information is neither a physical substance nor a free-floating abstraction, but rather the structure of physically realizable alternatives – a counterfactual structure that a physical system instantiates in virtue of the possibility space available to it. Building on Shannon's combinatorial definition, the Landauer principle, the no-cloning theorem, and the black-hole information paradox, I show that the informational content of any physical event is constituted by the set of outcomes that could have occurred but did not. This counterfactual reading dissolves several persistent confusions: it explains why erasing information dissipates heat without making information ``material,'' why quantum superposition is informationally richer than any classical mixture, and why information loss in black holes is physically significant beyond mere bookkeeping. The proposal sits within a structural-realist framework but departs from standard structural realism by locating the relevant structure in modal, not merely actual, relations. I conclude by sketching implications for the foundations of quantum mechanics, quantum gravity, and scientific ontology more broadly.

25.
medRxiv (Medicine) 2026-06-18

Development and Initial Validation of the Quality of life Evaluation in NF2-related Schwannomatosis Trials (QUEST) Assessment

Individuals with NF2-related schwannomatosis (NF2-SWN) experience a complex constellation of physical, emotional, and social symptoms that substantially impact quality of life (QoL). Although disease-specific patient-reported outcome measures are increasingly important for evaluating treatment benefit in clinical trials, existing NF2-SWN QoL measures have limitations in content coverage and sensitivity to change. This study describes the development and initial validation a new disease-specific QoL assessment – the Quality of Life Evaluation in NF2-related Schwannomatosis Trials (QUEST). Using a three-phase, mixed-methods approach, items were generated through concept elicitation interviews with individuals with NF2-SWN and clinicians, prioritized via patient survey data, and refined through iterative cognitive debriefing procedures. The resulting 21-item QUEST assesses the extent to which NF2-SWN has negatively impacted a persons daily life over the past seven days. Initial psychometric evaluation was conducted in an international sample of 174 individuals with NF2-SWN aged 15 years and older (117 women (67%), 158 White individuals (89%)). Exploratory factor analysis supported a four-factor structure, and the total score demonstrated excellent internal consistency and strong test-retest reliability. Evidence of construct validity was demonstrated through hypothesized associations with disease-specific, generic, and domain-specific QoL measures, as well as known-groups validity based on self-reported disease severity and number of prior surgeries. Incremental validity analyses indicated that QUEST explained unique variance beyond existing measures. Together, findings support the QUEST as a reliable and valid disease-specific QoL measure with strong content validity and feasibility for use as a clinical trial endpoint in NF2-SWN.