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01.
medRxiv (Medicine) 2026-06-15

Scalable estimation of temporal clustering in accelerometry: a kernel-independent dispersion index grounded in the Hawkes process

Background. Self-exciting (Hawkes) point processes are a natural model for the temporal clustering of human physical activity (PA) recorded by accelerometers, yet they have seldom been used in this setting—in part because the usual maximum-likelihood fitting is challenging due to potential estimation bias and convergence failures on these data. A moment-based alternative—estimating the Hawkes branching ratio from the dispersion index, the variance-to-mean ratio of event counts—is kernel-independent and computationally trivial, but it has not been evaluated for accelerometry or adapted to the intensity-marked recordings accelerometers provide. Methods. Treating each minute above a sedentary threshold as an event, we estimated the Hawkes branching ratio $n$ by maximum likelihood and, as a kernel-independent and far cheaper alternative, from the dispersion index. We compared four dispersion-based estimators—event-count-based, intensity-mark-weighted using the mark-moment ratio, and time-of-day (TOD) adjusted variants of each—against the marked and unmarked maximum-likelihood estimates. Estimators were evaluated for mutual agreement, goodness of fit, and finite-window results in two National Health and Nutrition Examination Survey (NHANES) accelerometry cohorts (hip-worn, $n=2{,}560$; wrist-worn, $n=3{,}132$). We related the resulting temporal clustering measures to all-cause mortality using survey-weighted Cox models, adjusting for PA frequency, Peak30 (the average of the 30 highest PA values), and demographic covariates. Results. Event-count-based dispersion estimates agreed strongly with maximum-likelihood branching ratios ($rapprox0.74$ in both cohorts); the intensity-marked variant incorporating PA intensity variability agreed less well. Marked and unmarked Hawkes models yielded similar excitation and decay parameters, suggesting PA intensity added little clustering information beyond event timing. In the survival analysis, temporal clustering was associated with all-cause mortality independently of PA frequency and Peak30; the direction of association differed between the hip- and wrist-worn cohorts. Conclusions. A scalable dispersion-index estimator recovers the Hawkes branching ratio and matches maximum-likelihood estimates without requiring kernel specification or iterative optimization. It offers a practical tool for quantifying temporal clustering in accelerometry, enabling decomposition of temporal PA patterns into its exogenous initiation and endogenous persistence. Such temporal patterns carry health-relevant information beyond PA intensity and volume. Keywords: dispersion index; Hawkes process; branching ratio; temporal clustering; point process estimation; accelerometry; mortality

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

Learner-based Concept Drift Detection: Analysis and Evaluation

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

03.
arXiv (CS.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.

04.
medRxiv (Medicine) 2026-06-11

Validity and Limitations of the Empatica E4 Wristband for Autonomic and Thermoregulatory Sleep Monitoring Against Concurrent Polysomnography: A Wearanize+ Dataset Study

The Empatica E4 wristband provides continuous multi-modal physiological monitoring including blood volume pulse (BVP), electrodermal activity (EDA) and skin temperature (TEMP) but its validity for sleep-stage-specific autonomic and thermoregulatory monitoring has not been systematically evaluated against concurrent polysomnography (PSG). Using the Wearanize+ dataset which provides synchronised PSG, Empatica E4, and Zmax EEG recordings from 100 home-recorded participants; a systematic validation of Empatica E4 physiological signals against PSG ground truth across five sleep stages was conducted. Of 100 participants, 92 had Empatica data; 69 met Zmax EEG signal quality criteria and formed the analysis sample. Heart rate (HR) from the pre-computed Empatica HR channel showed valid stage-specific patterns (Wake: 70.9 bpm, N3: 61.2 bpm) and moderate inter-device MeanNN correspondence with PSG ECG (Spearman r=0.35-0.42 across stages). Skin temperature showed the expected thermoregulatory pattern (Wake: 33.92C, N3: 35.48C) and is recommended for downstream analyses. Tonic EDA showed an inverted stage pattern attributable to wrist sweat accumulation during deep sleep, representing a known confound for wrist-worn EDA during sleep. Phasic EDA showed plausible patterns and may be used with caution. These findings establish a validated feature set for Empatica E4 sleep research and directly inform multimodal psychiatric biomarker studies using the Wearanize+ dataset.

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

Divide-and-Denoise: A Game-Theoretic Method for Fairly Composing Diffusion Models

The abundance of pre-trained diffusion models provides an opportunity for composition. Combining several models, however, runs the risk of one model dominating or models disagreeing with each other. Here, we propose Divide-and-Denoise, a method for coordinating multiple pre-trained diffusion models during sampling. Much like managing a specialized workforce, our method creates a fair but efficient division of labor across models. Central to our method is the notion of an allocation which defines the responsibility of each model to every region of the noisy sample. At every timestep, we then denoise by (i) updating the allocation by solving a fair division game, where we divide the sample into regions that maximize total utility under fairness constraints, and (ii) aligning the models with this allocation, where we guide each model to denoise within its assigned region. This leads to a new composite denoising process that evolves in tandem with a division process. We evaluate Divide-and-Denoise on conditional image generation. Across several quality metrics, including the GenEval benchmark, our method outperforms baselines and resolves common failures including missing objects and mismatched attributes. Experiments show that Divide-and-Denoise utilizes each model's expertise without neglecting any other model.

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

A Study of Belief Revision Postulates in Multi-Agent Systems (Extended Version)

arXiv:2605.02249v2 Announce Type: replace Abstract: We investigate the belief revision problem in epistemic planning, i.e., what will be the beliefs of all agents in a multi-agent system after an agent gains the belief in some state property. Based on the standard representation in epistemic planning of agents' beliefs via a single multi-agent Kripke model, we generalize the classical AGM belief revision postulates to the multi-agent setting, with the aim to provide a formal framework for evaluating dynamic epistemic reasoning frameworks in which the beliefs of all agents as the result of actions are computed. As an example of a simple operator that satisfies all of the generalized AGM postulates, we present generalized full-meet multi-agent belief revision. We moreover define a generalization of the standard postulates for iterated revision, present a more sophisticated, event model based revision operator, and discuss the potential issues in defining an epistemic operator on Kripke models that can satisfy all of the generalized postulates for iterated multi-agent belief revision.

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

Strategic Decision Support for AI Agents

arXiv:2606.12587v1 Announce Type: new Abstract: Traditionally, decision support studies how humans use machine learning models to make better decisions. In modern agentic systems, this division of roles is increasingly reversed: AI agents act on behalf of users, while humans and tools becomes support mechanisms around them. This role reversal brings reliability concerns to the forefront, since agentic errors can be consequential and agent behavior must remain aligned with human goals and constraints. Departing from the classical view of decision support, we revisit its two basic principles, the cost–value tradeoff of seeking support and the role of uncertainty quantification, in a setting where AI agents are the central actors. We propose a framework for strategic decision support for AI agents through an optimization problem that minimizes support usage subject to controlling a counterfactual missed-support error: the probability that the agent acts alone on instances where support would have materially improved its output. At the population level, we show that the optimal policy is a threshold rule on the value of support. Building on this structure, we develop an online algorithm that adaptively thresholds such a score and uses randomized exploration to control missed-support error without distributional assumptions. We further introduce a calibration-on-the-fly method that reduces unnecessary support calls online. We instantiate this framework across diverse scenarios, including information gathering, human–AI collaboration, and tool use, showing how each can be modeled through the same strategic decision-support lens. Experiments across these settings show that our method reliably controls the target error while substantially reducing support usage in practice.

08.
medRxiv (Medicine) 2026-06-11

Dissecting the functional landscape of rare diseases through genomic variation in a heterogeneous cohort of 11,000 patients

Rare diseases (RDs) remain a major diagnostic challenge. Genetic and phenotypic heterogeneity, incomplete knowledge of disease mechanisms, and limitations in variant clinical interpretation leave many patients without a molecular diagnosis. Meanwhile, the growing volume of genomic data generated in clinical practice offers an opportunity to develop data-driven methodologies for exploring disease mechanisms and improving the reanalysis of unsolved cases. We aggregated real-world genomic data from 11,084 unrelated patients with suspected RD. Patients were clinically classified into 122 diseases. We built a multi-disease genomic variant frequency database (FJD-DB), which enabled the development of variant and gene-disease association scores by means of case-control subcohort comparisons across 32 disease groups. Functional enrichment analyses were then used to highlight disease-associated protein domains, pathways, biological processes, and phenotypes. Finally, the resulting knowledge was integrated into a data-driven framework for the guided reanalysis of unsolved RD patients applied to Inherited Retinal Dystrophies (IRD) patients as first use case. FJD-DB contained more than 45 million unique variants, including ~185,000 potentially pathogenic variants. Disease-specific analyses identified disease-associated pathogenic variants and highlighted both established and candidate disease genes. We detected 179 significantly enriched protein domains across 23 diseases, 124 Human Phenotype Ontology terms across 13 diseases, 79 Reactome pathways across 10 diseases, and 72 Gene Ontology biological processes across 8 diseases, revealing highly disease-specific functional signatures. Integration of disease-specific variant, gene, and functional association signals enabled the development of a data-driven framework for guided reanalysis of unsolved RD cases. Applied to more than 1,100 unsolved IRD cases, the framework generated clinically relevant findings in 26 patients, including four molecular diagnoses, seven candidate diagnoses, and 15 cases upgraded from non-informative findings to variants of uncertain significance. Aggregated real-world genomic data can be leveraged to identify disease-associated molecular signals generating novel biological hypotheses. A unified analytical framework provides a scalable strategy for knowledge discovery and guided reanalysis, facilitating the identification of overlooked and potentially novel genetic causes of RDs.

09.
arXiv (CS.CV) 2026-06-12

EquiDexFlow: Contact-Grounded SE(3)-Equivariant Dexterous Grasp Generative Flows

Most learned dexterous grasp generators relegate contact forces to a downstream verification step, so a kinematically-plausible pose can still violate the conditions for a stable physical grasp. We address this with EquiDexFlow, an SE(3)-equivariant flow-matching model that jointly predicts wrist pose, joint angles, fingertip contacts, surface normals, and contact forces from an object point cloud. Our architecture projects contacts onto the object surface and forces into the Coulomb friction cone by construction, so placement and friction compliance hold without loss penalties. We prove end-to-end SE(3) equivariance and verify it empirically over 200 rotations, with wrist residuals below $0.04^\circ$ and exactly zero joint deviation. Trained on 8,100 force-closure grasps across 81 objects for the 16-DoF Allegro Hand, our model achieves zero friction violations, the best composite score, and the lowest wrench residual among all ablation variants. We retarget decoded fingertip contacts to a 16-DoF LEAP Hand via per-finger inverse kinematics, and our hardware-feasible refinement places every joint at least 5% inside its actuator envelope while preserving wrench balance. On the physical robot, retargeted EquiDexFlow-decoded grasps complete open-loop pick-and-hold trials on all six test objects, with every asymmetric object succeeding at both the canonical pose and a $120^\circ$ co-rotation. Videos, code, and checkpoints are available at https://equidexflow.github.io.

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

Stop the Sampler! Classifier-Based Adaptive Stopping for Sampling Kernels

arXiv:2606.16073v1 Announce Type: new Abstract: Sampling from complex, unnormalized probability densities is a fundamental challenge in Bayesian inference and probabilistic modeling. While Markov chain Monte Carlo (MCMC) methods provide asymptotic guarantees, they often suffer from slow mixing and high computational costs due to fixed or manually tuned trajectory lengths. In this work, we propose a novel framework that treats trajectory termination as a learnable component of the sampling dynamics. By framing MCMC within the theory of non-acyclic generative flow networks (GFlowNets), we train state-dependent neural classifiers to decide when a trajectory has reached a high-density region and should terminate. We theoretically establish the connection between optimal classifiers and the target density via detailed balance conditions and introduce a multilevel training scheme to facilitate exploration in complex geometries. Experimental results across various benchmark densities demonstrate that our approach significantly reduces average trajectory lengths while improving mode coverage and mixing compared to standard MCMC baselines.

11.
medRxiv (Medicine) 2026-06-17

Perceptions of aging well among older adults with heart failure: insights from a qualitative study

Background: Heart failure (HF) is a prevalent and often debilitating cardiovascular condition among older adults, frequently accompanied by multimorbidity, functional limitations, and the need to age in place. Traditional models of successful aging emphasize disease absence and preserved function, yet most individuals with HF live with ongoing symptoms and chronic health challenges. How older adults with HF define aging well, particularly across different socioeconomic contexts, remains underexplored. Objectives: To explore how older adults with HF conceptualize aging well and to identify perceived facilitators and barriers across more and less resourced New York City neighborhoods. Methods: We conducted semi-structured interviews with 20 adults diagnosed with HF residing in Manhattan and Brooklyn neighborhoods classified by 2019 United States Census data. Interviews were guided by Rowe and Kahn's model. Transcripts were analyzed using an inductive-deductive thematic approach and interpreted in alignment with the Healthy People 2030 framework. Results: Participants had a mean age of 69 years; 50% identified as Black and 50% were women. Despite functional limitations, 65% reported aging well. Five themes emerged: maintaining physical function, maintaining cognitive function, sustaining social relationships, avoiding pain, and promoting overall well-being. Avoiding pain and promoting well-being extended beyond traditional models. Neighborhood context shaped priorities, with financial stability emphasized in more affluent areas and social cohesion prioritized in less affluent communities. Conclusions: Older adults with HF frequently perceive themselves as aging well despite chronic illness, reframing successful aging beyond disease avoidance. These findings support a patient-centered, place-informed model of aging well with implications for healthcare delivery and policy.

12.
arXiv (CS.LG) 2026-06-17

Continuous-time Optimal Stopping through Deep Reinforcement Learning

arXiv:2606.17545v1 Announce Type: new Abstract: Simulation based solvers for optimal stopping problems must discretize the stopping decision. Under classical dynamic programming, a coarse exercise grid with only a few stopping opportunities can materially undervalue the optimal expected reward, whereas on a very fine grid, approximation errors accumulate through the backward recursion. To remove this limitation, we develop a new reinforcement-learning inspired algorithm that enables us to learn the exercise rule at arbitrarily fine time resolution. Our CARLOS (Continuous-time Adaptive Reinforcement Learning for Optimal Stopping) algorithm utilizes an aggregate deep neural network (ADNN) to learn a joint space-time decision boundary. Starting from a coarse time grid, we progressively increase the frequency of stopping opportunities, while in parallel training the ADNN to refine its timing-value estimates. We moreover design an adaptive sampling strategy that gradually concentrates training effort near the stopping boundary. Benchmarked results show that CARLOS delivers higher prices than existing Bermudan solvers, approaching the American upper bound, and achieves high computational efficiency relative to non-RL comparators.

13.
medRxiv (Medicine) 2026-06-16

Cross-sectional study of the association between depressive symptoms and attentional bias to emotional stimuli in patients with acute stroke: Study protocol

Post-stroke depression affects approximately 30% of patients after stroke and is associated with delayed recovery in activities of daily living, reduced rehabilitation effectiveness, and poorer quality of life. Attentional bias modification may provide a low-burden, nonpharmacological approach for patients in the acute phase of stroke. However, before such an intervention can be implemented in clinical practice, it is necessary to clarify whether attentional bias is present in patients with acute stroke and depressive symptoms, whether cognitive function influences the manifestation of this bias, and which task and stimulus formats are most appropriate for assessment. This multicenter, cross-sectional observational study will enroll patients with acute stroke between 7-30 days after stroke onset. Depressive symptoms will be assessed using the depression subscale of the Hospital Anxiety and Depression Scale. Attentional bias will be measured under four task conditions based on the dot-probe task and the cue-target task, using face and word stimuli. Secondary assessments will include cognitive function, anxiety symptoms, activities of daily living, health-related quality of life, and clinical background variables. The aims of this study are to investigate the association between depressive symptoms and attentional bias in patients with acute stroke, compare attentional bias characteristics across task and stimulus types, and examine the potential influence of cognitive function on this association. The findings are expected to provide an empirical basis for designing future attentional bias modification protocols targeting post-stroke depression in the acute phase. This study has been registered with the UMIN Clinical Trials Registry (UMIN000059166).

14.
arXiv (quant-ph) 2026-06-12

A Robust Strontium Tweezer Apparatus for Quantum Computing

arXiv:2601.16564v2 Announce Type: replace-cross Abstract: Neutral atoms for quantum computing applications show promise in terms of scalability and connectivity. We demonstrate the realization of a versatile apparatus capable of stochastically loading a 5x5 array of optical tweezers with single $^{88}$Sr atoms featuring flexible magnetic field control and excellent optical access. A custom-designed oven, spin-flip Zeeman slower, and deflection stage produce a controlled flux of Sr directed to the science chamber. In the science chamber, featuring a vacuum pressure of $3 \times 10^{-11}$ mbar, the Sr is cooled using two laser cooling stages, resulting in $\sim 3 \times 10^5$ atoms at a temperature of 5(1) $\mu$K. The optical tweezers feature a $1/e^2$ waist of 0.81(2) $\mu$m, and loaded atoms can be imaged with a fidelity of $\sim 0.997$ and a survival probability of $0.99^{+0.01}_{-0.02}$. The atomic array presented here forms the core of a full-stack quantum computing processor targeted for quantum chemistry computational problems.

15.
arXiv (CS.CV) 2026-06-17

ActWorld: From Explorable to Interactive World Model via Action-Aware Memory

Interactive world models aim to simulate environment dynamics under real-time user actions. However, their action vocabulary is largely confined to navigation: most actions correspond to motion (e.g., walk, turn, look around), while interaction with objects in the scene (e.g., pick up plates, open doors, or trigger physical responses) is either absent, restricted to game domains, or relegated to prompt-to-full-video scenarios. The resulting worlds are visually explorable but not truly actionable. In this work, we present ActWorld, an interactive world model that extends prior navigation-centric generators to support mid-rollout object interaction within a chunk-autoregressive framework. We argue that the navigation-interaction gap stems from two bottlenecks. First, a data bottleneck: the lack of human-object interaction data with accurate, dense labels. Second, a memory bottleneck: recency-biased history compression in existing world models discards the event-transition frames that causally determine subsequent object states, leading to an action-forgetting pathology. On the data side, we construct a 100K interaction video dataset, each annotated with per-chunk captions via chain-of-thought reasoning. On the model side, we introduce a hierarchical action-aware memory design that routes history compression by interaction importance, complemented by a persistent memory bank that maintains event-update and object-identity tokens across long rollouts. Experiments show that ActWorld supports both flexible navigation and rich object interaction within a single model, substantially improving interaction fidelity over navigation-only baselines without sacrificing viewpoint control. Project page is available at https://interactwm.github.io/ActWorld.

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

Rethinking Air-Ground Collaboration: A Progressive Cross-Task Benchmark and Socialized Learning Framework

Air-ground collaborative perception is crucial for robust visual understanding in real-world dynamic environments. However, existing studies typically formulate collaboration as single-task cross-view fusion, overlooking the functional dependencies among localization, target association, and fine-grained parsing. In addition, the heterogeneous nature of aerial and ground views introduces substantial geometric, scale, and occlusion discrepancies, making uniform feature sharing vulnerable to negative transfer. To tackle these issues, we model air-ground perception as a progressive cross-task collaboration task and construct the Air-Ground Progressive Collaboration (AGPC) benchmark, a spatio-temporally aligned benchmark comprising more than 745K raw video frames. Built upon this benchmark, we propose Socialized Co-Perception (SCP), a coarse-to-fine framework that organizes collaboration progressively from aerial global localization to ground target association and identity-aware parsing. Its core module, the Dual-Layer Router (DLR), decouples input-side multi-scale expert selection from output-side task-conditioned modulation, enabling selective cross-view and cross-task interaction while suppressing harmful interference. Extensive experiments demonstrate the effectiveness of SCP. It achieves a 3.73\% coevolutionary gain and a 7.86\% improvement in average downstream performance. These results show that task-conditioned collaboration is more effective than uniform fusion for heterogeneous air-ground perception. The code is available at https://github.com/g1136639260-spec/AGSCP.

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

Learning Cardiac Electrophysiology Digital Twins Through Agentic Discovery of Hybrid Structure

arXiv:2606.18154v1 Announce Type: new Abstract: Building personalized cardiac electrophysiology (EP) digital twins requires identifying the appropriate model structure for each patient, not merely fitting parameters. Traditional methods rely on experts to manually prescribe hybrid physics-neural architectures, which requires deep domain expertise and does not transfer across patients. Recent works have applied large language models (LLMs) to generate or act as hybrid models. However, despite their promising generalization capacity, these LLM-based methods lack the structural priors needed for stable cardiac simulations. Hence, we propose LEADS, a framework that formulates cardiac EP domain knowledge as a structured action space and utilizes an LLM agent to discover hybrid models. The agent follows an iterative reasoning-and-action loop to select, combine, and refine hybrid models, whilst gradient descent handles parameter fitting. The proposed LEADS designs every candidate model towards physically grounded, interpretable, and numerically stable, while allowing open-ended architectural discovery. We validate LEADS on synthetic data with three ground-truth reaction models and on real cardiac EP data, demonstrating that it outperforms both human-designed hybrid models and other LLM-based hybrid modeling.

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

The Road to Artificial SuperIntelligence: A Comprehensive Survey of Superalignment

arXiv:2412.16468v4 Announce Type: replace Abstract: The emergence of large language models (LLMs) has sparked discussion on Artificial Superintelligence (ASI), a hypothetical AI system that surpasses human intelligence. Although ASI remains hypothetical and far beyond current AI capabilities, discussing its potential and exploring its feasibility and potential risks is critical for the development of future AI systems. The idea of superalignment originates from scalable oversight, which studies how to supervise increasingly capable AI systems when direct human supervision becomes insufficient. In this paper, we focus on the superalignment problem: "The process of supervising, controlling, and governing artificial superintelligence." We first review scalable oversight paradigms-Sandwiching, Self-Enhancement, and Weak-to-Strong Generalization – then analyze the limitations of current paradigms through the lens of possibility and impossibility, discuss key challenges, and propose pathways for the safe and continual improvement of future AI systems.

19.
arXiv (CS.AI) 2026-06-15

Korzhinskii-Net: Physics-Informed Neural Network for Sub-Surface Mineral Prospectivity Modelling

作者:

arXiv:2606.13695v1 Announce Type: cross Abstract: Mineral prospectivity modelling (MPM) underpins exploration economics, yet most operational pipelines reduce to data-driven classifiers trained on shallow surface proxies. Such models are blind to the subsurface physics that actually localises ore: heat advection, fluid flow, and lithology-dependent precipitation. We present Korzhinskii-Net, a 2-D radial physics-informed neural network (PINN) that couples Darcy flow, advective-diffusive heat transport, and a softplus-saturated reaction rate into a single differentiable forward model, weakly supervised by surface and remote-sensing proxies. The network is named after Dmitri S. Korzhinskii (1899-1985), whose theory of infiltration metasomatism provides the physical scaffold. We evaluate Korzhinskii-Net on five ore provinces spanning four commodity classes – Norilsk (Ni-Cu-PGE), Pechenga (Ni-Cu sulphide), Udokan (sandstone-hosted Cu), Sukhoi Log (orogenic Au), and Mirny (kimberlitic diamond) – under a fair, leakage-controlled 5-fold cross-validation protocol with hard ring-shaped negatives. Korzhinskii-Net attains a mean PR-AUC of 0.885 versus 0.281 for the strongest classical baseline (gradient boosting), and a mean fractional rank of 0.019 versus 0.413. The improvement is consistent across all five provinces and four commodity systems, suggesting that physics-informed differentiable simulators, even when constrained only by global open-data proxies, can recover localisation patterns that pure feature-based learners systematically miss. We release the full pipeline and evaluation harness as open source.

20.
arXiv (quant-ph) 2026-06-17

Probing PbTe-Pb nanowire devices with radio-frequency reflectometry

arXiv:2606.04544v2 Announce Type: replace-cross Abstract: We report the implementation of radio-frequency (rf) reflectometry on selective-area-grown PbTe-Pb nanowire devices on a CdTe substrate. These nanowires are predicted to host Majorana zero modes. We demonstrate the compatibility of the rf technique, including both resistive and capacitive sensing, with these nanowires. The effect of dielectric loss from the CdTe substrate is quantitatively characterized. Furthermore, the feasibility of rf reflectometry is verified under finite magnetic fields where zero-energy modes can emerge. Our results establish the fast control of PbTe quantum devices, paving the way for their applications in topological quantum computation.

21.
Nature Medicine 2026-06-09

Adjuvanted inactivated rabies virus-vectored Lassa virus vaccine in healthy adults: a phase 1 trial

Lassa fever causes substantial morbidity and mortality in West Africa, and no licensed vaccine is available. We evaluated LASSARAB, an inactivated rabies virus-vectored Lassa virus (Josiah strain) glycoprotein complex vaccine. We conducted a randomized, controlled, dose-escalation phase 1 trial. Participants (total n = 54) received two intramuscular doses of LASSARAB containing 700 (n = 15), 1,400 (n = 15) or 2,800 (n = 14) relative units of antigen formulated with the TLR-4 agonist 3D-6-acyl PHAD-SE adjuvant, or licensed rabies vaccine control (n = 10), administered 28 days apart. This protocol-defined interim analysis reports the primary safety evaluation and secondary immunogenicity assessments through day 61. There were no prespecified hypotheses or formal power calculations. All primary safety end points demonstrated an acceptable safety profile. After dose 1, local solicited adverse events occurred in 86.7–100.0% of LASSARAB groups and 80% of controls; systemic events in 33.3–71.4% and 60.0% of controls. After dose 2, local solicited adverse events occurred in 66.7–86.7% of LASSARAB groups and 55.6% of controls; systemic events in 53.3–71.4% of LASSARAB groups and 55.6% of controls. Events were predominantly mild and self-limited. Unsolicited adverse events occurred in 28.6–60.0% of LASSARAB groups and 20.0% of controls. No serious adverse event, immune-mediated condition or sensorineural hearing loss occurred. Safety laboratory abnormalities occurred in 13.3–66.7% of LASSARAB groups and 30.0% of controls (14 mild, 6 moderate and none severe). After two doses, Lassa virus GPC IgG ELISA seroconversion (≥fourfold rise) was achieved in 100.0% (44 of 44) of LASSARAB recipients and 0.0% (0 of 10) of controls. Rabies glycoprotein IgG ELISA seroconversion (≥fourfold rise) and neutralizing antibody by rapid fluorescent focus inhibition test (RFFIT) seroprotection (≥0.5 IU ml−1) were also 100% across all groups, including controls. LASSARAB + 3D-6-acyl phosphorylated hexaacyl disaccharide (PHAD)-SE demonstrated a favorable safety profile and immunogenicity against Lassa and rabies viruses. The per-protocol final study report will include safety and durability through day 394. ClinicalTrials.gov identifier NCT06546709 . An interim report of a first-in-human phase 1 trial found an adjuvanted, combination inactivated rabies-vectored, Lassa fever vaccine (LASSARAB + 3D-6-acyl PHAD-SE) to be safe and induced immunogenicity to both Lassa and rabies viruses in healthy participants.

22.
medRxiv (Medicine) 2026-06-22

Longitudinal multi-omics characterization of the malignant evolution in multirelapsing glioblastoma

Linking glioblastoma (GBM) evolution to clinical progression is challenged by multiple factors, including tumor location for repeated sample collection, and short patient survival. In a single individual, we collected and analysed samples from 11 operations distributed across 31 months of multi-relapsing and multifocal GBM, including terminal leptomeningeal progression. All samples shared genomic ancestry of the retinoblastoma protein 1 (RB1) and neurofibromin 1 (NF1) mutations while advanced progression and extracranial metastases featured mutations of tuberous sclerosis complex 2 (TSC2), PBRM1, CD22 and Fanconi anemia supplementation group I (FANCI), correlated with clinical resistance to immunotherapies and DNA-damaging agents. Single-cell analytics revealed distinct yet reversible shifts in response to the precision medicine arsenal. GBM parenchymal dissemination and extracranial progression were associated with strengthening of neuron-like cell phenotypes. Our multidimensional study describes GBM evolution over a rarely reported time scale, and provides a valuable resource linking genetic, molecular, cellular and clinical progressions.

23.
bioRxiv (Bioinfo) 2026-06-15

Multi-platform reassessment of human mitochondrial DNA methylation reveals signals consistent with technical artifacts

The existence and functional relevance of mitochondrial DNA methylation remain controversial. Here, we systematically profiled cytosine methylation and hydroxymethylation across human brain and blood tissues spanning healthy and malignant states using orthogonal sequencing approaches that avoid chemical conversion during library preparation. While nuclear DNA exhibited canonical methylation patterns, mitochondrial DNA consistently showed negligible signal, indistinguishable from background technical noise. By mapping cytosine-guanine sites between mitochondrial DNA and nuclear-embedded mitochondrial sequences, we demonstrate the potential of these nuclear counterparts to confound not only cytosine methylation but also hydroxymethylation measurements, corroborating and extending prior findings implicating nuclear contamination as a potential source of apparent mitochondrial epigenetic signals. Additional technical factors that inflate apparent mtDNA methylation signals were identified, including sequence context biases, flow cell chemistries, and coverage-dependent discrepancies between the heavy and light strands. Collectively, these results provide convergent evidence against the presence of biologically meaningful cytosine methylation or hydroxymethylation in mitochondrial DNA. These findings caution against interpreting apparent mtDNA methylation signals in human adult tissues as meaningful without rigorous orthogonal validation and comprehensive consideration of technical and analytical confounding factors.

24.
arXiv (CS.CL) 2026-06-11

When Generic Prompt Improvements Hurt: Evaluation-Driven Iteration for LLM Applications

Evaluating Large Language Model (LLM) applications differs from conventional software testing because outputs are probabilistic, semantically variable, and sensitive to prompt and model changes. This technical report proposes the Minimum Viable Evaluation Suite (MVES), an audit-oriented structure for application-level LLM evaluation. MVES links application categories to failure modes, metrics, required artifacts, and validation evidence across general LLM applications, retrieval-augmented systems, and agentic workflows. We pair the framework with a reproducible local evaluation harness covering structured extraction, RAG citation/content-compliance, and instruction-following checks. Using Ollama with Llama 3 8B Instruct and Qwen 2.5 7B Instruct, we evaluate five prompt conditions over expanded 30-case-per-suite ablations. The results show that, in the tested local conditions, generic prompt additions do not produce monotonic improvements: stronger output-contract prompts improve strict extraction for both models, while RAG citation/content-compliance declines under some generic-rule conditions. The largest observed decline occurs for Qwen 2.5 on RAG when generic rules are appended to the user prompt, from 26/30 to 9/30. These findings support evaluation-driven prompt iteration: prompt changes should be treated as potential regression risks and tested against task-specific suites before deployment. The accompanying repository contains the test suites, prompt variants, evaluation harness, raw result logs, and scripts needed to reproduce the reported local ablations.

25.
bioRxiv (Bioinfo) 2026-06-17

In silico characterization of lysis and host-recognition modules in Staphylococcus aureus bacteriophage genomes

Background/aim: Antimicrobial resistance in methicillin-resistant Staphylococcus aureus (MRSA) requires precision non-antibiotic therapeutics, yet phage lytic efficacy is poorly predicted by phenotypic assays, as shown by paradoxical biofilm responses. This study characterized the genomic architecture of lytic S. aureus bacteriophages, focusing on the conservation of the lysis module and the variability of host-recognition modules, to provide a rational basis for phage candidate selection. Materials and methods: Twenty-two complete S. aureus phage genomes were retrieved from NCBI GenBank. Genomic features were extracted with custom Biopython scripts. Lysis (endolysin, holin) and host-recognition (tail fiber/receptor-binding protein) modules were annotated and validated by InterPro domain analysis, with disrupted endolysins resolved by tBLASTn. Phylogeny was reconstructed from large terminase subunit (TerL) sequences using maximum likelihood. Results: Genome size spanned three classes, from 17.5 to 148.6 kb. The LysK-type endolysin (CHAP, Amidase, SH3b) was highly conserved, whereas tail fiber/RBP genes were detected in only 14 of 22 phages. Domain analysis reclassified two proteins annotated as endolysins as virion-associated peptidoglycan hydrolases, and identified two independent mechanisms, HNH endonuclease insertion and intron splitting, that interrupt lysis-module genes and confound automated annotation. Maximum likelihood analysis recovered a strongly supported, highly conserved core clade with EW and SA13 as divergent lineages. Conclusion: Lysis modules are conserved whereas host-recognition modules are variable, indicating that host recognition rather than the lytic enzyme is the principal determinant of host range and the more rational target for phage selection and engineering.