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01.
arXiv (CS.CL) 2026-06-15

Coping in Crisis: Computational Modeling of Coping Styles in Digital Crisis Discourse During the 2023 Turkiye Earthquake

How do people cope when disaster strikes and can we detect it at scale, in real time, from what they write? This study addresses that question using over one million Turkish-language tweets posted in the aftermath of the February 6, 2023 earthquake in Turkiye, which unfolded in a deeply polarized political context just months before a national election. Drawing on Lazarus and Folkman's (1984) coping theory, we develop a multi-label BERTurk classifier to detect three coping styles (problem-focused, emotion-focused, and meaning-making) across four theoretically motivated crisis phases. BERTurk achieves a macro F1 of 0.693, substantially outperforming a zero-shot mDeBERTa baseline (macro F1 = 0.324). Applied to the full corpus, the classifier reveals a clear temporal trajectory: problem-focused coping dominates the urgency phase and declines sharply, emotion-focused coping rises and stabilizes, and meaning-making increases monotonically. Anger correlates most strongly with meaning-making (Spearman r = 0.387), suggesting it functions as a mobilizing force toward blame attribution rather than practical action. These findings demonstrate that coping theory can be reliably operationalized in real-world digital crisis data and that doing so can help humanitarian organizations tailor their responses to where a population actually is.

02.
medRxiv (Medicine) 2026-06-10

A Three-Tier Operational Benchmark for Evaluating Large Language Models on Hospital Medication Safety

Objective. To introduce PsiBench, a clinically validated medication-safety benchmark for evaluating large language models (LLMs) against the standards used to certify hospital computerized provider order entry (CPOE) and electronic health record (EHR) systems, and a non-overlapping three-tier evaluation framework separating highest-stakes discrimination, the operational CDS regime, and category-correct alerting. Materials and Methods. PsiBench comprises 492 medication-safety scenarios across 11 safety categories, created by clinical pharmacology experts whose work underpins an annualized testing procedure used by more than 2,000 U.S. hospitals. The three-tier framework partitions the scenarios non-overlappingly: Discrimination (98 scenarios, 50 fatal vs 48 deception, near-balanced 51%/49%); Operational (394 scenarios, 261 serious unsafe plus 133 safe including 41 Excessive Alerts reclassified as operational negatives); and Attribution (311 alert-required scenarios). We evaluated 40 frontier LLMs from 10 providers over 3 runs per scenario at temperature 0.2 (or the provider default where temperature is not configurable), yielding 59,040 evaluations conducted April 21-23, 2026. Results. Headline binary performance on the full benchmark spans a wide range across the 40 models: F1 78.5%-92.3%, accuracy 65.4%-89.8%, sensitivity 81.4%-100.0%, specificity 6.1%-81.8%. Leading models by F1 (o4-mini 92.3%; o3 92.2%) pair high sensitivity with meaningful specificity; three models saturate sensitivity at 100% but fall below 25% specificity, indistinguishable from a naive always-alert classifier. The wide spread on a single headline metric motivates tier-specific analyses, developed in a separate clinical paper. Discussion and Conclusion. PsiBench and the three-tier framework operationalize a rigorous evaluation rubric for LLM medication safety, grounded in two decades of national hospital audit experience. The framework generalizes to any binary medication-safety classifier (rule-based, conventional ML, or LLM-driven), supporting tier-aware model selection and post-deployment surveillance.

03.
arXiv (CS.CV) 2026-06-17

RAVA: Retrieval-Augmented Viewpoint Alignment for Subject-Driven Image Generation

Reference-driven image generation has made rapid progress on identity preservation, but reliable viewpoint control across different subjects remains poorly understood. The difficulty is not merely generating a new image of the target subject: the model must infer the implicit viewpoint of one subject and transfer it to another subject using only image-level evidence, without camera poses, depth, or ray-based conditions. In this setting, existing generators conditioned on multiple image references often rely on spurious semantic correlations, which lead to viewpoint drift, part-level structural mismatches, and missing or unsupported target-specific content. We formulate this challenge as cross-subject viewpoint alignment and propose RAVA, a retrieval-augmented framework that supplies explicit geometric evidence before generation. RAVA first learns a cross-instance viewpoint embedding that retrieves target-subject images aligned with the anchor viewpoint, then applies a LogDet-based subset selection strategy to retain a compact reference set that is both view-consistent and structurally complementary. The selected references are finally consumed by a fine-tuned multi-reference image generator. Experiments show that generic semantic embeddings are nearly random for this task, while the proposed retriever substantially improves viewpoint retrieval quality. On cross-subject generation, RAVA consistently outperforms zero-shot baselines and stronger retrieval alternatives under the same generation backbone. These results indicate that cross-subject viewpoint alignment benefits from retrieval-augmented geometric grounding rather than relying on end-to-end generation alone.

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

From Correlation to Causation in Lane Change Prediction for Automated Driving: A Causal Explanation Framework

arXiv:2606.15756v1 Announce Type: cross Abstract: Lane-change prediction is a central task in intelligent vehicles, where early maneuver anticipation can support safer decision-making. However, many existing approaches mainly learn statistical associations between observed driving variables and future maneuvers, while overlooking the causal dependencies among the input variables themselves. This limits interpretability, especially when physically related variables such as longitudinal gap, relative longitudinal velocity, and Time-To-Collision (TTC) are treated as independent flat inputs. This article presents a causal-inference-based framework for lane-change prediction and explanation. The proposed approach combines linguistic feature construction, expert-constrained causal discovery, deep structural causal modeling with Deep End-to-end Causal Inference (DECI), intervention-based effect analysis, refutation testing, and recursive causal-chain explanation. The objective is not only to predict the future maneuver, but also to identify candidate variables that directly contribute to the prediction, the upstream factors influencing them, and the causal chains through which these effects propagate. The framework achieves average F1-scores above 95% during the first three seconds before the lane-marking crossing event. Beyond prediction accuracy, the framework uses intervention-based effect analysis to distinguish influential from weakly influential variables under the learned causal structure. It further distinguishes candidate direct contributors from mediated effects and generates contrastive causal-chain explanations that clarify why the predicted maneuver is favored and why the alternative maneuvers are less supported. The main contribution is therefore a mechanism-aware lane-change prediction pipeline that moves beyond correlation-based classification toward more interpretable causal reasoning for maneuver prediction.

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

Conditional Score-Based Modeling of Effective Langevin Dynamics

arXiv:2604.23952v2 Announce Type: replace-cross Abstract: Stochastic reduced-order models are widely used to represent the effective dynamics of complex systems, but estimating their drift and diffusion coefficients from data remains challenging. Standard approaches often rely on short-time trajectory increments, state-space partitioning, or repeated simulation of candidate models, which become unreliable or computationally expensive for high-dimensional systems, coarse temporal sampling, or unevenly sampled data. We introduce a data-driven calibration method based on a novel relationship between the coefficients of a stochastic reduced model and the conditional score of the finite-time transition density, defined as the gradient of the logarithm of the transition density with respect to the initial state. The resulting identity expresses derivatives of lagged correlation functions as stationary expectations over observed lagged pairs involving this conditional score and the unknown model coefficients. This formulation allows the drift and diffusion structure to be constrained directly from finite-lag statistics, without differentiating trajectories, partitioning state space, or repeatedly integrating candidate reduced models during calibration, yielding a least-squares fitting problem over stationary lagged pairs. We validate the approach on three systems of increasing complexity: an analytically tractable Cox–Ingersoll–Ross diffusion, a two-dimensional nonequilibrium diffusion with affine multiplicative noise, and a periodic soft-spin stochastic Landau–Lifshitz chain. Across these tests, the inferred models preserve the invariant statistics while reproducing finite-lag dynamical correlations. The framework provides a scalable route for learning stochastic reduced-order models from data that reproduce prescribed statistical and dynamical properties.

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

From Memorization to Parameter Interference: How Overtraining Experts Harms Model Merging

arXiv:2506.14126v2 Announce Type: replace-cross Abstract: Modern deep learning is increasingly characterized by the use of open-weight foundation models that can be fine-tuned on specialized datasets. This has led to a proliferation of expert models and adapters, often shared via platforms like HuggingFace and AdapterHub. Model merging has recently emerged as an effective way to leverage these existing resources, enabling the composition of capabilities from different model checkpoints. A natural pipeline has thus formed to harness the benefits of transfer learning and amortize sunk training costs: models are pre-trained on general data, fine-tuned on specific tasks, and then multiple checkpoints are merged to obtain a more capable model. A prevailing assumption is that improvements at one stage of this pipeline propagate downstream, leading to gains at subsequent steps. In this work, we challenge that assumption by examining how expert fine-tuning affects model merging. We show that long fine-tuning of experts that optimizes for their individual performance leads to degraded merging performance across vision and language modalities, multiple model scales, and both fully fine-tuned and LoRA-adapted models. We trace this degradation to the memorization of a small set of difficult examples that dominate late fine-tuning steps. This causes negative parameter interference and encodes knowledge that is forgotten during merging. Finally, we demonstrate that task-dependent aggressive early stopping strategies can significantly improve model merging performance.

07.
arXiv (CS.AI) 2026-06-17

Learn to Quantify Social Interaction with Constraints for Pedestrian Walking

Authors:

arXiv:2606.17897v1 Announce Type: new Abstract: Long-term human path forecasting in crowds is critical for autonomous moving platforms (like autonomous driving cars and social robots) to avoid collision and make high-quality planning. Although the current research take into account social interactions for prediction, they don't reveal the exact kinds of social interactions happened among people and how the social interactions affect the decision-making process of pedestrians, which further limits its robustness. Social interactions in pedestrian walking are intuitively massive and hard to label and quantify. In this paper, we explore creatively to quantify and interpret how pedestrians interact with others by proposing Learn to Cluster. Our clustering social interactions is probabilistic latent variable generative, learning directly from sequential trajectory observations, scalable to arbitrary number of pedestrians. Learn to cluster is label-free and can be naturally integrated into the training process of the prediction model. The latent variables will then serve as 'labels' to categorize social interactions. Extensive experiments over several trajectory prediction benchmarks demonstrate that our method is able to learn the patterns of social interactions and effectively integrate the patterns to pedestrian trajectory prediction.

08.
arXiv (CS.CV) 2026-06-15

OmniVideo-100K: A Dataset for Audio-Visual Reasoning through Structured Scripts and Evidence Chains

Current automated pipelines for audio-visual Question Answering (QA) generally adopt a ``video-caption-QA'' paradigm. However, these methods typically segment videos into short clips and generate separate descriptions for audio and visual modalities. This decoupled processing severs inherent associations between sounds and their visual sources, while independent clip processing often causes inconsistent descriptions of the same entity across segments. Furthermore, coupling long-text comprehension and QA synthesis into a single step often restricts models to localized events, yielding questions lacking long-term temporal connections and deep cross-modal reasoning. To address these issues, we propose an automated data engine featuring two mechanisms: (1) Entity-Anchored Video Scripting transforms videos into structured scripts, comprising summaries, main entity lists, and segment-wise audio-visual descriptions. The entity list serves as a global prior to ensure cross-segment referential consistency and reconstruct audio-visual associations. (2) Clue-Guided QA Generation prompts models to first mine cross-segment, multimodal clues from the script, and subsequently generate QA pairs based on these high-value clues. Leveraging this pipeline, we construct the instruction-tuning dataset OmniVideo-100K and a human-verified test set, OmniVideo-Test. Fine-tuning VITA-1.5, Qwen2.5-Omni-7B and Qwen3-Omni-30B on OmniVideo-100K yields performance gains of up to 20.59% on OmniVideo-Test, demonstrating strong generalization (up to 12.64% improvements) across established benchmarks like Daily-Omni and JointAVBench.

09.
medRxiv (Medicine) 2026-06-22

Development and validation of a risk prediction algorithm to estimate all-cause mortality among community-dwelling Canadians: the Mortality Population Risk Tool (MPoRT)

BACKGROUND: The risk of all-cause mortality can inform decision-making for chronic disease prevention. We developed a predictive algorithm to estimate the 5-year risk of death among community-dwelling adults. METHODS: We derived and validated the Mortality Population Risk Tool (MPoRT) using data from population health surveys in Canada (the Canadian Community Health Survey) and the United States (the National Health Interview Survey), survey years 2001 to 2011, linked to vital statistics. The outcome was death within five years of the survey response. The algorithm was developed using data from Ontario respondents using a Cox proportional hazards model, then modified and re-estimated to allow cross-national assessment in Canada and the United States. Twenty-three prespecified predictors were assessed: seven sociodemographic, six behavioural, and ten general health and chronic disease. RESULTS: 527,369 respondents aged 20 to 105 years were included in the Canadian and United States development and validation cohorts, with 43,758 deaths during 3.68 million person-years follow-up. The final sex-specific MPoRT algorithms each contained 21 variables, showing strong discrimination (C-statistic: females 0.874 [0.871–0.877]; males 0.867 [0.865–0.871]) and good calibration overall and in 246 of 247 subgroups. Discrimination was modestly attenuated (0.01 decrease in C-statistic) in cross-national validation between Canada and the United States, with good calibration across all 71 subgroups. INTERPRETATION: MPoRT accurately discriminated all-cause mortality using only self-reported data, enabling broad application without clinical measures. While validation outside North America is needed to confirm broader applicability, MPoRT is designed for straightforward recalibration using routinely available national mortality data. This supports targeted chronic disease prevention strategies at both the population and individual levels, though the limitations inherent to self-reported predictors should be considered when interpreting predictions.

10.
medRxiv (Medicine) 2026-06-18

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

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

11.
arXiv (math.PR) 2026-06-17

Extreme value theory for geometric Brownian motion and pricing of short maturity options

Authors:

arXiv:2505.08036v2 Announce Type: replace Abstract: We investigate the limiting distribution of geometric Brownian motion conditional on its running maximum taking large values. The Freidlin-Wentzell large deviations theory predicts that the conditional distribution of the sample paths converge weakly to a deterministic exponential curve. We complement this result by showing that the conditional sample paths in fact converge in strong sense, and obtain quantitative bounds on the rate of convergence. As an application of our results to financial mathematics, we obtain new closed form asymptotic formulae for the fair price of barrier options with general path dependent payoff in the short maturity limit, with quantitative error estimates. We provide exact formulae for Asian and lookback style payoffs.

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

Ontology Memory-Augmented ASR Correction for Long Text-Speech Interleaved Conversations

Automatic speech recognition (ASR) correction has traditionally focused on isolated utterances or short local contexts. However, as text and speech become increasingly interleaved in long interactions, ASR correction requires conversation-level contextual evidence. Existing ASR correction methods often rely on the current hypothesis or concatenate raw dialogue history. In such contexts, sparse correction evidence can be difficult to locate amid redundancy and noise. Addressing these challenges, we propose an ontology memory-augmented ASR correction framework for long text-speech interleaved conversations. The framework organizes preceding interaction history into a dynamically updatable ontology memory, where entities, terminology, surface variants, potential ASR confusions, and semantic relations are stored as retrievable nodes for context-grounded correction. To evaluate this setting, we construct RAMC-Corr, a dataset derived from MAGIC-RAMC for long-range ASR correction with grounded context. Experiments on RAMC-Corr show that our method improves over direct correction in 9 out of 10 paired backbone-setting combinations and encourages more selective and evidence-grounded corrections for context-dependent ASR errors.

13.
arXiv (math.PR) 2026-06-24

Variational Tail Bounds for Norms of Random Vectors and Matrices

arXiv:2503.17300v5 Announce Type: replace Abstract: We propose a variational tail bound for norms of random vectors and matrices under moment assumptions on their one-dimensional marginals. A simplified version of the bound that parametrizes the ``aggregating distribution'' using a certain pushforward of the Gaussian distribution is also provided. We apply the proposed method to reproduce some of the well-known bounds on norms of Gaussian random vectors, and also obtain dimension-free tail bounds for the Euclidean norm of random vectors with arbitrary moment profiles. Furthermore, we reproduce a dimension-free concentration inequality for sum of independent and identically distributed positive semidefinite matrices with sub-exponential marginals, and obtain a concentration inequality for the sample covariance matrix of sub-exponential random vectors. We also obtain a tail bound for the operator norm of a random matrix series whose random coefficients may have arbitrary moment profiles. Furthermore, we use coupling to formulate an abstraction of the proposed approach that applies more broadly. As a corollary, we derive a PAC-Bayesian-style bound in terms of a certain combination of the KL and R\'{e}nyi divergences between the prior and posterior distributions.

14.
arXiv (CS.CV) 2026-06-18

Pre-Deployment Robustness Stress Testing for CT Segmentation Systems Using Clinically Motivated Multi-Corruption Augmentation

Deep learning-based CT segmentation systems often achieve high accuracy on clean benchmark images, but their performance may degrade under heterogeneous clinical imaging conditions such as noise, resolution loss, contrast variation, intensity shift, and artifacts. This instability can limit reliable deployment in real-world medical imaging workflows. We propose Robustness via Augmented Multi-corruption Pipeline (RAMP), a robustness-oriented augmentation framework for CT segmentation. RAMP combines anatomically constrained spatial perturbations, CT intensity transformations, and stochastic multi-corruption composition to expose models to clinically plausible image degradation during training. Across two CT segmentation evaluation settings, RAMP achieved the strongest corrupted-image performance and the smallest clean-to-corrupted robustness gap. In the five-organ noisy evaluation benchmark, RAMP improved mean corrupted Dice from 0.610 to 0.753 and reduced the robustness gap from 0.264 to 0.064 compared with the nnU-Net baseline. In Abdomen1K, RAMP improved mean corrupted Dice from 0.633 to 0.789 and reduced the robustness gap from 0.290 to 0.070. Although RAMP did not achieve the highest clean-image Dice, it substantially mitigated worst-case segmentation collapse under severe image degradation. These results suggest that multi-corruption augmentation can serve as a practical pre-deployment strategy for improving the reliability of CT segmentation systems in heterogeneous clinical environments.

15.
medRxiv (Medicine) 2026-06-15

Epileptogenicity alters intrahippocampal ripple propagation

Objective: Tracing the propagation of high-frequency oscillations (HFOs) aids in localizing epileptogenic regions and improving surgical outcomes. We examined how hippocampal epileptogenicity influences the propagation properties of the HFOs it generates. Methods: We analyzed non-REM sleep stereo-EEG from 49 patients (68 hemispheres) with verified hippocampal contacts. Hippocampi were stratified by excitability: 28 seizure onset zone (SOZ), 22 more-irritative non-SOZ (>6 interictal epileptiform discharges [IED]/min), and 18 less-irritative non-SOZ (

16.
medRxiv (Medicine) 2026-06-22

Starting, stopping and restarting. Patterns of Methylphenidate Use over 14 years in a large public health system

Background Persistence with stimulant medication is poor in children and adolescents with ADHD, and the evidence base is derived predominantly from high-income countries. We describe methylphenidate utilisation patterns and predictors of 12-month retention across 14 years in a large South African public health service. Methods Retrospective cohort study using routine pharmacy data from the Western Cape provincial health service (2011-2024). Children aged 5-18 at first prescription were included. Treatment episodes were defined as continuous prescription sequences with no gap exceeding 90 days and classified as initiations or restarts. Logistic regression modelled 12-month retention against early visit frequency and formulation type as pre-specified exposures. Findings 421,925 prescription events for 23,243 children across 115 facilities generated 65,885 treatment episodes. Median age at first prescription was 10 years (IQR 8-12); 77.6% were male. Kaplan-Meier 12-month survival was 28.2% for initiations and 15.4% for restarts, substantially below high-income country comparators. A quarter of all initiating prescriptions were not followed by a subsequent dispensing event; nearly 40% of patients had three or more treatment episodes. Early visit frequency was the strongest predictor of 12-month retention (high vs low: OR 2.85, 95% CI 2.65-3.06). The sustained-release formulation effect was present but attenuated on multivariable adjustment. Treatment re-initiations showed a marked seasonal pattern consistent with the South African school calendar. Interpretation Twelve-month retention was markedly lower than high-income country rates. Against a backdrop of high attrition, both early visit frequency and sustained-release formulation access predicted persistence; clinical engagement and reducing structural barriers to access are modifiable factors in this setting. Funding None.

17.
arXiv (quant-ph) 2026-06-24

Controlled Chaos in 4D SCFTs

arXiv:2606.23785v1 Announce Type: cross Abstract: Chaotic dynamics play an important role in a number of physical systems. One of the qualitative hallmarks of this behavior is the appearance of a sufficiently "complex" spectrum of energy levels. This also makes it challenging to directly verify the onset of chaos in interacting quantum field theories. We present a class of 4D superconformal field theories (SCFTs) given by orbifolds of 4D $\mathcal{N} = 4$ Super Yang–Mills theory in which operator mixing in a controlled subsector is described by an effective spin chain in one spatial dimension with nearest neighbor interactions tuned by the marginal couplings of the SCFT. Tuning the marginal couplings results in a chaotic spectrum, while generically the spin chain exhibits Anderson localization. We diagnose the onset of chaos by analyzing the statistical distribution of eigenvalues of the dilatation operator, in particular properties such as eigenvalue level repulsion, spectral rigidity, and the spectral form factor. We also show that other diagnostics such as Krylov complexity sometimes do not faithfully capture this information. This structure defines a chaotic billiard in the target space of the stringy realization. We also comment on the large $N$ holographic dual description, where the controlled single spin chain approximation must be supplemented by multi-trace dynamics, i.e., the splitting and joining of multiple spin chains.

18.
arXiv (quant-ph) 2026-06-12

Schrödinger Symmetry in Spherically-symmetric Static Mini-superspaces with Matter Fields

arXiv:2512.13651v3 Announce Type: replace-cross Abstract: Schr\"{o}dinger symmetry has been shown to emerge in a ``fluid limit" from the full superspace to several mini-superspace models. To investigate one aspect of the robustness of this emergent symmetry, we consider two spherically-symmetric static mini-superspace models with matter fields at the classical level: (i) a Maxwell field with a cosmological constant and (ii) $n$ massless scalar fields. By developing a method based on canonical transformations, we demonstrate that for model (i), 3D Schrödinger symmetry emerges, and the solution is the (anti-)de Sitter Reissner-Nordström spacetime, and for model (ii), $(2+n)$D Schrödinger symmetry appears, and the solution is a generalized Janis-Newman-Winicour spacetime and its ``interior", a Kantowski-Sachs type closed universe. Furthermore, for the vacuum model, we find that 2D Schrödinger symmetry holds with different lapse functions and mini-superspace coordinates, suggesting the potential, yet unconfirmed, covariance of the symmetry. Finally, we propose a physical interpretation of the symmetry under the Hamiltonian constraint $H$: symmetry generators commuting with $H$ map a solution to another one, while those non-commuting with $H$ generate a new theory with the Schrödinger symmetry and the transformed configuration is a solution to the new theory. These results reinforce the robustness of the emergent Schrödinger symmetry and open new frontiers for exploring dynamics of matter and gravity.

19.
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.

20.
arXiv (CS.CL) 2026-06-12

Observable Patterns Are Not Explanations: A Causal-Geometric Analysis of Latent Reasoning Models

Latent reasoning models (LRMs) replace explicit chain-of-thought with continuous thoughts. Recent work treats observable latent-state patterns, such as BFS-like frontiers and decodable arithmetic computation, as evidence for internal reasoning mechanisms. Evaluating two LRMs (Coconut and CODI) against controls lacking the proposed recurrence or curriculum, we find these patterns also appear in the controls and do not always causally affect behavior. Causal interventions reveal that latent-thought utilization is not binary but graded, scaling with a thought's causal effect on model behavior. Geometric analyses reveal this effect concentrates in low-rank directions whose step-to-step geometry grows more structured as their behavioral influence increases. Latent thoughts should therefore be treated as hidden computation, not hidden explanation: decodability, attention, or static structure alone cannot establish mechanism. LRM interpretability thus requires matched controls and causal tests.

21.
arXiv (CS.AI) 2026-06-18

TxBench-PP: Analyzing AI Agent Performance on Small-Molecule Preclinical Pharmacology

arXiv:2606.19245v1 Announce Type: new Abstract: Artificial intelligence (AI) agents promise to accelerate drug discovery by compressing interpretation and decision-making loops, but practical deployment requires trusted evaluation on realistic program decisions. We introduce TherapeuticsBench Preclinical Pharmacology (TxBench-PP), a verifiable benchmark for small-molecule preclinical pharmacology and the first focused slice of a broader TherapeuticsBench effort across drug-discovery stages and therapeutic modalities. TxBench-PP tests whether agents can recover accurate conclusions from real-world assay data rather than memorized facts from literature. The benchmark contains 100 evaluations indexed by program stage, assay type, and task structure, spanning mechanism-of-action (MoA) and pharmacodynamic (PD) reasoning, compound-target engagement, causal target validation, developability and safety, and translational efficacy. Agents receive realistic workflow snapshots, inspect files in a coding environment, and return structured answers graded deterministically. Across 16 model-harness configurations, comprising 11 models and 4,800 trajectories, no system reliably recovered preclinical pharmacology decisions. The strongest configuration, Claude Opus 4.8 / Pi, passed 59.3\% of endpoint attempts (178/300; 95\% CI, 51.1-67.6), followed by GPT-5.5 / Pi at 55.3\% (166/300; 47.0-63.6).

22.
medRxiv (Medicine) 2026-06-23

Changes in hierarchical brain dynamics of rumination following mindfulness-based cognitive therapy for depression

Major depressive disorder (MDD) is a leading cause of disability worldwide with risk of onset and recurrence linked to depressive ruminative thought patterns. Mindfulness-based cognitive therapy (MBCT) is an evidence-based treatment for depression that targets the ability to recognise, decenter, and disengage from ruminative thought patterns. Elucidating how MBCT impacts hierarchical brain organisation may be key to understanding the processes by which MBCT can modulate ruminative tendencies. In a randomised controlled functional magnetic resonance imaging (fMRI) trial on individuals with MDD (N=80) before and after MBCT in addition to treatment as usual (TAU), we investigated changes in hierarchical brain organisation during resting-state and rumination. We built whole-brain models to obtain generative connectivity (GEC) matrices per patient and quantified brain hierarchy by measuring the global directedness and regional trophic levels in each GEC, in which greater directedness reflects more directional information flow and less recurrence. Global directedness in MBCT+TAU compared to TAU increased during rumination, with no changes during resting-state. Furthermore, increased regional breadth of hierarchy during rumination was related to improvements in clinical and behavioural outcomes following MBCT+TAU. Increased brain hierarchy during rumination following mindfulness training may be consistent with a shift away from self-reinforcing negative mental loops towards more differentiated and less coupled cognitive and bodily cycles, supporting MBCT's ability to interrupt ruminative processes. Hierarchical brain dynamics may hold promise as a treatment-sensitive marker and a potential mechanism of therapeutic change in MBCT for depression.

23.
arXiv (CS.CL) 2026-06-19

JAMER: Project-Level Code Framework Dataset and Benchmark on Professional Game Engines

Current AI-driven game development has made substantial progress in asset generation, gameplay design, and web-based game coding, yet project-level code engineering on professional game engines remains largely unexplored due to the absence of large-scale datasets and deterministic evaluation methods. We present JamSet and JamBench, the first project-level game code framework dataset and benchmark built on a professional game engine. Our key insight is that Game Jam competitions, community events where developers build complete games under tight time constraints, yield thousands of open-source projects suitable for this purpose. Building on the Godot engine's text-based format and headless execution mode, we design a deterministic verification pipeline from file integrity to runtime behavior collection, distilling 8,133 verified projects from over 240,000 repositories. Of these, 300 manually verified projects form JamBench; the rest constitute JamSet. JamBench defines theme-driven generation and code completion tasks, evaluated through a pipeline combining compilation pass rates, Structural Completeness Score (SCS), and Behavioral Alignment Score (BAS). Evaluation of 9 frontier models reveals a capability cliff as project scale increases, with runtime pass rates dropping from 80.4% on small projects to 5.7% on large ones (Task2a). Code Agents improve compilation rates yet yield no gains in runtime behavioral quality, indicating that the bottleneck lies in architectural design rather than syntactic correctness. Experiments validate JamSet as effective training data. All data and code are publicly available.

24.
arXiv (CS.AI) 2026-06-18

Externalizing Research Synthesis and Validation in AI Scientists through a Research Harness

arXiv:2606.18874v1 Announce Type: new Abstract: AI systems can increasingly automate scientific workflows, but the reasoning that links prior evidence, generated ideas, experiments and final claims often remains implicit inside model inference. Here we introduce Xcientist, a research harness that externalizes research synthesis and experimental validation into inspectable, contract-governed processes. Xcientist organizes literature evidence, idea states, implementation plans, ablation records and repair traces as persistent research artifacts, so that generated mechanisms can be grounded, executed, tested and revised without losing their evidential basis. We identify claim drift as a failure mode of automated research, where runnable artifacts no longer support the mechanism originally claimed. Across training-free memory systems, graph-structured traffic forecasting and multi-scale physics-informed neural networks, Xcientist preserves traceable trajectories from problem formulation to mechanism design, validation and bounded revision. These results suggest that AI scientists should be evaluated not only by their final artifacts, but by whether their synthesis and validation processes remain attributable, inspectable and scientifically accountable.

25.
arXiv (quant-ph) 2026-06-15

Implementation of two-qubit Rydberg operations on neutral Rb-87 atoms in systems with different intermediate states

arXiv:2606.13975v1 Announce Type: new Abstract: This work presents an experimental setup for implementing two-qubit operations on neutral atoms ($^{87}$Rb) with the possibility of using two different Rydberg excitation schemes. One of them uses 5P$_{1/2}$ as the intermediate level and applies the second-stage beam locally to the addressed atoms. The second scheme uses the 6P$_{3/2}$ level; in this scheme, the particles to be entangled are moved to a separate zone through which both Rydberg beams pass. The advantages and limitations of both schemes are analyzed. Based on numerical modeling performed with a Julia package developed by the authors, it is demonstrated that the spatial configuration has a greater effect on quantum-operation fidelity than the choice of intermediate level. An experimental implementation of the scheme using the 6P$_{3/2}$ level is demonstrated, making it possible to achieve a two-qubit operation fidelity of 94%.