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01.
medRxiv (Medicine) 2026-06-12

Order-Based Bayesian Network Modeling of Early Detection and Post-Diagnosis Control for Cardiovascular Disease Risk in Type 2 Diabetes

Patients diagnosed with type 2 diabetes (T2D) are at increased risk of developing cardiovascular disease (CVD), the leading cause of morbidity and mortality in this population. Early detection and glycemic control within the first year after diagnosis reduce CVD risk. However, gaps remain in how to operationalize early detection of T2D using Electronic Health Record (EHR) data and quantify its relationship with subsequent CVD risk using longitudinal observations. We developed a probabilistic graph model to analyze the interdependencies between early detection of T2D, post-diagnosis glycemic control, and CVD occurrence. Using a temporally structured Bayesian Network (BN) learned from EHR data of 9,450 primary care patients between 2017 and 2023, we quantified probabilistic dependencies between demographics, diagnostic delay surrogates, glycemic control, and post-diagnosis CVD occurrence. Percentile based thresholds defined risk groups, where individuals with predicted probabilities in the bottom decile ([≤] 10th percentile) were classified as low risk, and those in the top decile ([≥] 90th percentile) as high risk. Results demonstrated heterogeneity in predicted risks across glycemic and cardiovascular outcomes. Predicted probability of developing CVD within the first year after T2D diagnosis ranged from a mean of 5.2% in the low-risk group to 28.9% in the high-risk group, while predicted probabilities of mean Hemoglobin A1c (HbA1c) [≥] 8% during the first year post-diagnosis ranged from 1.6% in low-risk to 55.1% in high-risk group. Patients with HbA1c at diagnosis [≥] 8% had higher predicted probabilities of first-year post-diagnosis mean HbA1c [≥] 8% (53.3% vs. 1.9%) and high HbA1c coefficient of variation (18.7% vs. 3.1%) compared with those with HbA1c [≤] 6.5%. Incorporating early clinical outcomes refined later risk predictions, with long-term CVD risk reaching 33.5% among high-risk individuals. The proposed model achieved predictive performance comparable to conventional machine learning approaches while providing interpretable relationships for risk stratification in primary care populations.

02.
medRxiv (Medicine) 2026-06-15

Association of Genetic Liability to Psychiatric Disorders with Peripheral Metabolic Dysregulation

Importance: Individuals with psychiatric disorders face elevated cardiometabolic risk which is linked to increased mortality. The extent to which this reflects shared pathogenesis or the downstream effects of illness and treatment remains poorly understood. Objective: To characterize the direct pleiotropic effects of psychiatric genetic liability on circulating metabolites and aggregate cardiometabolic risk, independent of psychiatric diagnosis and psychotropic medication use. Design: Cohort study. Setting: Mass General Brigham Biobank (MGBB). Participants: MGBB participants with metabolomic profiling, genomic data, and linked electronic health records. Exposures: Genetic liability to nine psychiatric disorders quantified using polygenic risk scores (PRS): attention deficit/hyperactivity disorder (ADHD), anorexia nervosa (ANO), anxiety disorder (ANX), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), PTSD, schizophrenia (SCZ), and substance use disorder (SUD). Main Outcomes and Measures: 249 circulating metabolites and four metabolomic risk scores (MRS) for type 2 diabetes, myocardial infarction, ischemic stroke, and vascular dementia. PRS-metabolite associations were estimated using nested models adjusting for lifetime psychiatric diagnosis and psychotropic medication use. Results: Across 25,290 participants, we identified 604 significant PRS-metabolite associations (Bonferroni p< 1.36 x 10-4), of which 89% persisted after adjustment for lifetime diagnosis and medication use, suggesting that the direct genetic effects on metabolism are largely independent of illness or treatment. PRS for MDD, PTSD, and ADHD showed the most extensive dysregulation, with a transdiagnostic pattern of elevated lipids and systemic inflammation, specifically triglycerides ({beta} = 0.04 to 0.05, all p< 4.4 x10-13) and glycoprotein acetyls ({beta} = 0.05, all p< 2.2 x10-16). Notably, PRS for SCZ and BD showed minimal metabolite dysregulation despite having the strongest association with their target diagnoses. PRS for MDD, PTSD, ADHD, and SUD were associated with increased MRS across cardiometabolic conditions ({beta} = 0.03 to 0.08, all p< 2.1 x10-4). Sensitivity analyses controlling for BMI or excluding participants without any psychiatric history (N: 21,305 and 11,150, respectively) showed a similar pattern. Conclusions and Relevance: Psychiatric genetic liability is associated with systemic metabolic dysregulation independent of illness onset or treatment, supporting a partially pleiotropic basis for psychiatric-cardiometabolic comorbidity.

03.
arXiv (CS.LG) 2026-06-24

Hessian-augmented Supervised Learning for Hamilton-Jacobi-Bellman PDEs

arXiv:2606.23827v1 Announce Type: cross Abstract: A data-driven method is developed for approximating value functions in deterministic optimal control problems with nonlinear control-affine dynamics. The Pontryagin Maximum Principle optimality system is solved from multiple initial conditions to generate training data consisting of values, gradients, and Hessians of the value function, where Hessian information is obtained from a matrix Riccati equation along optimal trajectories. These quantities augment a weighted least-squares regression over sparse polynomial bases on hyperbolic cross index sets, with gradients and Hessians contributing additional linear equations per sample and substantially reducing sample complexity compared to value-only regression. Feedback laws are recovered analytically from the learned value function. In high dimensions, a partial Hessian strategy controls the cost of data generation. The approach is validated on problems of increasing state dimension, where second-order data augmentation is shown to improve approximation accuracy and closed-loop performance, with up to an order-of-magnitude reduction in the number of training samples required relative to lower-order methods.

04.
arXiv (CS.CL) 2026-06-11

ChartFI: Benchmarking Faithfulness and Insightfulness of Chart Descriptions from Multimodal Large Language Models

Chart descriptions are essential for accessibility, cross-modal retrieval, and assisting readers in extracting insights from complex visualizations. As multimodal large language models (MLLMs) are increasingly adopted for automated chart description generation, a critical question arises: how faithfully and insightfully do these models actually describe charts? Current benchmarks fall short on two fronts: existing datasets consist of simple, homogeneous charts paired with shallow, fact-enumerating descriptions; and prevailing metrics fail to capture the multi-faceted nature of description quality. To address these gaps, we present the Chart Faithfulness and Insightfulness Benchmark (ChartFI-Bench). We first summarize four dimensions that characterize high-quality chart descriptions: factual accuracy, salient feature emphasis, domain-informed guidance, and chart-text complementarity. Guided by these dimensions, we construct a high-quality benchmark comprising 896 chart-description pairs, which feature visually complex charts and semantically rich descriptions. Furthermore, we design four aligned evaluation metrics – Faithfulness, Coverage, Informativeness, and Acuity – to systematically assess the quality of descriptions across these dimensions. Experiments conducted on mainstream MLLMs demonstrate the effectiveness of the proposed framework and reveal common weaknesses among existing models.

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

Optimizing Agentic Reasoning with Retrieval via Synthetic Semantic Information Gain Reward

arXiv:2602.00845v3 Announce Type: replace Abstract: Agentic reasoning enables large reasoning models (LRMs) to dynamically acquire external knowledge, but yet optimizing the retrieval process remains challenging due to the lack of dense, principled reward signals. In this paper, we introduce InfoReasoner, a unified framework that incentivizes effective information seeking via a synthetic semantic information gain reward. Theoretically, we redefine information gain as uncertainty reduction over the model's belief states, establishing guarantees, including non-negativity, telescoping additivity, and channel monotonicity. Practically, to enable scalable optimization without manual retrieval annotations, we propose an output-aware intrinsic estimator that computes information gain directly from the model's output distributions using semantic clustering via bidirectional textual entailment. This intrinsic reward guides the policy to maximize epistemic progress, enabling efficient training via Group Relative Policy Optimization (GRPO). Experiments across seven question-answering benchmarks demonstrate that InfoReasoner consistently outperforms strong retrieval-augmented baselines, achieving up to 5.4% average accuracy improvement. Our work provides a theoretically grounded and scalable path toward agentic reasoning with retrieval. The code is available at https://github.com/dl-m9/InfoReasoner

06.
arXiv (CS.AI) 2026-06-11

A Survey of Reasoning and Agentic Systems in Time Series with Large Language Models

arXiv:2509.11575v3 Announce Type: replace Abstract: Time series reasoning treats time as a first-class axis and incorporates intermediate evidence directly into the answer. This survey defines the problem and organizes the literature by reasoning topology with three families: direct reasoning in one step, linear chain reasoning with explicit intermediates, and branch-structured reasoning that explores, revises, and aggregates. The topology is crossed with the main objectives of the field, including traditional time series analysis, explanation and understanding, causal inference and decision making, and time series generation, while a compact tag set spans these axes and captures decomposition and verification, ensembling, tool use, knowledge access, multimodality, agent loops, and LLM alignment regimes. Methods and systems are reviewed across domains, showing what each topology enables and where it breaks down in faithfulness or robustness, along with curated datasets, benchmarks, and resources that support study and deployment (https://github.com/blacksnail789521/Time-Series-Reasoning-Survey). Evaluation practices that keep evidence visible and temporally aligned are highlighted, and guidance is distilled on matching topology to uncertainty, grounding with observable artifacts, planning for shift and streaming, and treating cost and latency as design budgets. We emphasize that reasoning structures must balance capacity for grounding and self-correction against computational cost and reproducibility, while future progress will likely depend on benchmarks that tie reasoning quality to utility and on closed-loop testbeds that trade off cost and risk under shift-aware, streaming, and long-horizon settings. Taken together, these directions mark a shift from narrow accuracy toward reliability at scale, enabling systems that not only analyze but also understand, explain, and act on dynamic worlds with traceable evidence and credible outcomes.

07.
arXiv (quant-ph) 2026-06-16

Synthesizing Arbitrary Non-Hermitian Hamiltonian with Stochastic Floquet Engineering

arXiv:2606.15664v1 Announce Type: new Abstract: The conventional Floquet engineering scheme synthesizes a given target Hamiltonian with a deterministic temporal periodic driving field. In this work, we introduce the stochastic Floquet engineering scheme that can synthesize an arbitrary non-Hermitian target Hamiltonian using a time-periodic driving field with noisy amplitude. Our method is rooted in the Hermitian dynamics taking noise as a valuable quantum resource with no need for loss or gain in prior. We apply our method to engineer a cavity Hamiltonian with dissipative coupling between Fock states, and to prepare a given quantum state from a generally arbitrary quantum state. The stochastic Floqut engineering also provides a way to generate non-unitary quantum gates, which take advantage in certain tasks compared to unitary quantum computing, without the need for ancillae or state-dependent updating.

08.
arXiv (quant-ph) 2026-06-16

The Inverse Born Rule Equivalence. On the Informational Limits of Real-Valued Amplitude Encodings and the Measurement of Quantum Advantage in Data Embeddings

arXiv:2602.21350v2 Announce Type: replace Abstract: When does quantum data encoding provide genuine quantum advantage, and when does it merely rephrase a classically solvable problem? We prove an Equivalence Theorem demonstrating that any encoding mapping classical data to real-valued amplitudes, $\vert\psi_c\rangle = \sum_i c_i \vert i\rangle$ with $c_i \in \mathbb{R}$ and $\sum_i c_i^2 = 1$, composed with a data-independent parameterised unitary and computational-basis measurement, yields exactly the class of classical quadratic forms. We identify the geometric mechanism driving this collapse: the restriction to $\mathbb{R}$ forces a vanishing Berry connection, removing the complex phases required for data-dependent quantum interference. To operationalize this boundary, we introduce encoding diagnostics – phase complexity $C[\Phi]$ and mode-wise von Neumann mutual information $I[\Phi]$ – and link them to the information-geometric excess $\Delta g$. We show that for all real-valued encodings, $\Delta g = 0$ identically. We term the misidentification of such models as evidence of quantum computational power the Inverse Born Rule Fallacy. Supported by numerical experiments, our results establish that complex-phase structure is a strictly necessary condition for data-driven (Type~B) quantum advantage.

10.
arXiv (quant-ph) 2026-06-12

Coupling-Grouped XY-QAOA for Joint Anomaly-Feature Selection

Authors:

arXiv:2606.13244v1 Announce Type: new Abstract: Selecting anomalous samples and explanatory features under fixed budgets defines a coupled constrained-optimization problem. Sequential feature-first selection ranks features before choosing samples, which can overlook features whose utility depends on which samples are selected, especially when scores are calibrated from reference data that may be limited, noisy, or drifting. We instead formulate the task as joint sample-feature selection under the same fixed counts. In the analyzed formal model, calibration-error sensitivity grows linearly with the number of samples for feature-first ordering but stays constant for joint selection. We introduce Coupling-Grouped XY-QAOA, a constraint-preserving grouped-angle variant for the resulting optimization problem. On matched sparse IBM Heron R3 benchmarks, a hardware-aware implementation reduces circuit depth by 45.9%-61.3% and two-qubit gates by 2.6%-5.2% relative to Qiskit optimization level 3 on the CZ-basis target. It enables, to our knowledge, the largest reported width-depth configurations for constraint-preserving bipartite-selection QAOA hardware executions with feasible-sector retention: 64 qubits at p=2 and 36 qubits at p=3. The 20-qubit p=5 runs retain 63% valid samples. Across 36-64 qubits, fixed-angle runs yield lower-energy feasible samples than matched random-feasible sampling. Warm starts reduce the gap to strict-feasible classical references by 57.5%-80.5%, and near-budget repair matches the sparse classical reference at 36 qubits. Benchmarks show gains in balanced fixed-budget regimes, and noiseless simulations show that problem-structured angle grouping improves over same-depth XY-QAOA and matched-parameter, type-preserving randomization controls. Overall, the results support calibrated joint selection and hardware-realizable constrained-mixer execution in the tested regimes.

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

Unified Multimodal Model for Brain MRI Imputation and Understanding

Multimodal large language models (MLLMs) hold great potential for medicine, as they inherit knowledge from LLM and allow multiple data modalities to be integrated, analysed and interpreted in natural language. However, the field of medical MLLMs is constrained by non-trivial challenges, notably the scarcity of high-quality training data and the frequent occurrence of missing data in the real-world clinical setting. Here, we propose a novel unified multimodal model, UniBrain, for brain magnetic resonance image (MRI) analysis. To address potential missing brain MRI modalities, we employ a unified training strategy to perform joint imaging modality imputation and brain image understanding. During training, an interleaved and description-enriched data flow is constructed to train the model in an autoregressive manner, enabling medical reasoning with generated multimodal data. A self-alignment strategy is introduced to leverage dense image embeddings to learn fine-grained anatomical features without requiring detailed image captions. Furthermore, we propose a dynamic hidden state mechanism to alleviate the exposure bias during long-context multimodal inference. Extensive experiments on multi-disease brain MRI dataset demonstrate that UniBrain achieves high performance for brain image imputation, understanding, and disease diagnosis under various extents of modality incompleteness.

12.
PLOS Computational Biology 2026-06-22

Integrative modelling of innate immune response dynamics during virus infection

by Ramya Boddepalli, Harsh Chhajera, Rahul Roya Positive-sense RNA viruses that constitute a large class of human pathogens employ various strategies to suppress and evade host immune defenses. Understanding the dynamic interaction between the viral life cycle and immune signaling is crucial to designing effective antiviral strategies. Although significant progress has been made, quantitative models that can accurately capture the intricate interactions and the intertwined dynamics during viral infection of cells remain missing. In this study, we develop a comprehensive mathematical model that integrates the intracellular viral life cycle with key cellular innate immune pathways, including RIG-I-mediated detection and JAK-STAT signaling. The model provides mechanistic insights into long-standing observations, capturing both virus-specific dynamics and innate immune response, and the key components driving their coupled dynamics. For example, a comparison of viruses shows how the Japanese Encephalitis virus undergoes a dramatic reduction in viral load in cells, due to its rapid replication that robustly activates the RIG-I pathway, in contrast to the poor immune control of Hepatitis C virus. More importantly, our model demonstrates how virus-host interactions exhibit a sharp transition boundary behavior, where minor differences in immune strength or viral suppression capacity can determine whether infections resolve or persist. We propose that ISG mRNA translation and viral replication predominantly dictate these bimodal infection outcomes. Additionally, the model not only recapitulates IFN desensitization but also identifies the molecular players involved. We demonstrate how our model’s ability to capture IFN dynamics allows us to predict optimal timing and dosing strategies for interferon-based prophylactic therapies. Together, our approach reveals fundamental features that govern the delicate balance between the establishment of infection and immune control in RNA virus infections.

13.
arXiv (CS.CV) 2026-06-11

PT-WNO: Point Transformer with Wavelet Neural Operator for 3D Point Cloud Semantic Segmentation

Point cloud semantic segmentation requires architectures that capture both fine-grained local geometry and broad global scene structure. Transformer-based networks have demonstrated strong performance by focusing on detailed local feature aggregation; however, global context is conveyed primarily through skip connections across encoder-decoder stages, which we argue is insufficient for full scene understanding. We hypothesize that augmenting skip connections with a learnable global feature extraction module allows the network to acquire scene-level knowledge before descending into local detail, leading to richer and more contextually grounded representations. To this end, we propose Point Transformer with Wavelet Neural Operato (PT-WNO), which integrates a shared Wavelet Neural Operator (WNO) branch alongside the skip connections of a point cloud transformer backbone. At each encoder-decoder transition, point features are projected onto a dense 3D volumetric grid where the WNO captures multi-scale global spectral context through learnable wavelet decomposition and reconstruction. These global features are fused back into the network via lightweight adapters, complementing rather than replacing the existing skip connections. Experiments on four large-scale 3D point cloud benchmarks demonstrate the effectiveness of PT-WNO. On S3DIS (Area 5), PT-WNO achieves 71.59% mIoU, outperforming the Point Transformer v3 (PTv3) baseline by +1.03 points. On DALES it achieves 81.05% mIoU (+1.47 over the baseline). On ScanNet~v2, PT-WNO obtains 76.19% mIoU, remaining competitive with the baseline (76.36%).

14.
arXiv (quant-ph) 2026-06-11

Additivity and chain rules for quantum entropies via multi-index Schatten norms

arXiv:2502.01611v3 Announce Type: replace Abstract: The primary entropic measures for quantum states are additive under the tensor product. In the analysis of quantum information processing tasks, the minimum entropy of a set of states, e.g., the minimum output entropy of a channel, often plays a crucial role. A fundamental question in quantum information and cryptography is whether the minimum output entropy remains additive under the tensor product of channels. Here, we establish a general additivity statement for the optimized sandwiched Rényi entropy of quantum channels. For that, we generalize the results of [Devetak, Junge, King, Ruskai, CMP 2006] to multi-index Schatten norms. As an application, we strengthen the additivity statement of [Van Himbeeck and Brown, 2025] thus allowing the analysis of time-adaptive quantum cryptographic protocols. In addition, we establish chain rules for Rényi conditional entropies that are similar to the ones used for the generalized entropy accumulation theorem of [Metger, Fawzi, Sutter, Renner, CMP 2024].

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

MedAI: Evaluating TxAgent's Therapeutic Agentic Reasoning in the NeurIPS CURE-Bench Competition

arXiv:2512.11682v2 Announce Type: replace Abstract: Therapeutic decision-making in clinical medicine constitutes a high-stakes domain in which AI guidance interacts with complex interactions among patient characteristics, disease processes, and pharmacological agents. Tasks such as drug recommendation, treatment planning, and adverse-effect prediction demand robust, multi-step reasoning grounded in reliable biomedical knowledge. Agentic AI methods, exemplified by TxAgent, address these challenges through iterative retrieval-augmented generation (RAG). TxAgent employs a fine-tuned Llama-3.1-8B model that dynamically generates and executes function calls to a unified biomedical tool suite (ToolUniverse), integrating FDA Drug API, OpenTargets, and Monarch resources to ensure access to current therapeutic information. In contrast to general-purpose RAG systems, medical applications impose stringent safety constraints, rendering the accuracy of both the reasoning trace and the sequence of tool invocations critical. These considerations motivate evaluation protocols treating token-level reasoning and tool-usage behaviors as explicit supervision signals. This work presents insights derived from our participation in the CURE-Bench NeurIPS 2025 Challenge, which benchmarks therapeutic-reasoning systems using metrics that assess correctness, tool utilization, and reasoning quality. We analyze how retrieval quality for function (tool) calls influences overall model performance and demonstrate performance gains achieved through improved tool-retrieval strategies. Our work was awarded the Excellence Award in Open Science. Complete information can be found at https://curebench.ai/.

16.
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

17.
arXiv (CS.LG) 2026-06-16

SPICE: Synergy and Partial Information Based Curriculum Evolution

arXiv:2606.16639v1 Announce Type: new Abstract: Multimodal learning exploits complementary information across heterogeneous modalities. The informativeness of each modality can vary widely across samples and training stages. Existing multimodal curriculum learning strategies often assume that the relative complexity of samples remains unchanged throughout training and therefore cannot adapt to model evolution. We propose SPICE (Synergy and Partial Information based Curriculum Evolution), a novel progressive curriculum framework for multimodal interaction learning. Guided by Partial Information Decomposition (PID) theory, our approach decomposes multimodal interactions into redundant, unique, and synergistic information components, enabling an interpretable and dynamic characterization of sample complexity. Building on this decomposition, we design a progressive curriculum that evolves throughout training, allowing the model to transition from learning shared cross-modal cues to modality-specific patterns and, finally, to complex synergistic interactions. Adapting to model evolution, sample ordering is refined in real-time using PID information estimates derived from unimodal and multimodal predictions. Experiments across multiple multimodal benchmarks demonstrate consistent improvements over conventional training and state-of-the-art baselines, highlighting the effectiveness of PID information decomposition and adaptive sample ordering for multimodal curriculum learning.

18.
medRxiv (Medicine) 2026-06-18

Artificial Intelligence-informed mobile behavioural interventions to support adolescents mental health in schools: protocol for a randomised controlled trial using the MindCraft app

Background: Children and young people (CYP) are particularly affected by mental health problems. Mobile apps provide a scalable and accessible approach to adolescent mental health support, and schools are well-positioned to address multiple risk factors and deliver large-scale interventions. By combining active (self-reported) and passive (sensor-derived) data, mobile apps can model mental states and deliver context-aware support. Artificial Intelligence (AI) enables adaptive, context-aware recommendations tailored to each user. However, there is limited research on AI-based mental health interventions in community CYP. MindCraft is a mobile app designed to monitor adolescents mental health using active and passive data and provide AI-informed recommendations ("nudges"). This study aims to investigate the effectiveness of personalised AI nudges delivered through MindCraft on improving mental health outcomes among adolescents in schools in the United Kingdom. Methods: The study is a three-arm RCT using a prospective cohort of secondary school students aged 14-19. Following informed consent, participants complete a baseline online assessment at school and download MindCraft. The primary outcome is the Strengths and Difficulties Questionnaire global and subscale scores. Secondary outcomes include the Eating Disorders Diagnostic Scale, the Sleep Condition Indicator Questionnaire, the Self-Injurious Thoughts and Behaviours Interview, the Self-Efficacy Questionnaire for Children and the World Health Organisation-Five Well-Being Index. Participants are randomised to: (1) an AI-informed intervention group receiving personalised nudges, (2) an active control receiving non-personalised nudges, or (3) a control group with self-monitoring only. Participants use the app for four weeks, with follow-up at one month. Repeated-measures analyses will assess changes across time points. Discussion: We hypothesise that AI nudges will have a greater positive effect on mental health outcomes at one month than general nudges and self-monitoring. Our findings will provide key evidence on the effectiveness of personalised mobile AI recommendations for adolescents mental health and inform school-based mental health prevention and early intervention. This study will contribute evidence on the ethical, acceptable, and scalable integration of AI-enabled digital mental health tools within public health and educational systems, with implications for the design of future digital public health interventions and policies supporting their safe integration in schools.

19.
medRxiv (Medicine) 2026-06-22

An integrated AI-microfluidic platform reveals the broad persistence and developmental potential of rare sperm in non-obstructive azoospermia

Non-obstructive azoospermia (NOA) represents the most severe form of male infertility, severely limiting a patient's prospects for biological fatherhood when surgical retrieval fails. However, the true biological limits of NOA remain obscured by the inherent limitations of conventional gamete recovery protocols: standard centrifugation frequently causes substantial cell loss, masking extremely rare sperm, while surgical interventions are constrained by spatial sampling biases. Here we report SpermSeek, an integrated AI-guided microfluidic platform for real-time, non-destructive isolation of single sperm directly from semen. Operating at scalable throughput (0.36 mL/h), the system achieves 98.3% detection precision and a 95.5% target encapsulation efficiency, suppressing background debris. In a 59-patient NOA cohort, SpermSeek detected morphologically identifiable sperm in 64.4% (38/59) of cases, spanning diverse genetic etiologies, including AZFb/c microdeletions, and severe histopathological phenotypes, such as Sertoli-cell-only syndrome (SCOS). Notably, among a sub-cohort of 41 patients who remained consistently sperm-negative despite prior medical or micro-TESE interventions, our platform identified gametes in 53.7% (22/41) of these cases. Comprehensive safety profiling in healthy human donors and wild-type mice confirmed that processed sperm retain high DNA integrity and epigenomic concordance (r=0.98), supporting transgenerational developmental stability in mice. Furthermore, in a 26-patient validation cohort, SpermSeek recovered rare sperm in 11 cases. Utilizing gametes from a subset (n=5), we demonstrated their capacity to support early human embryogenesis, yielding high-quality cleavage-stage embryos with confirmed genomic euploidy. This work establishes a highly sensitive framework for re-examining the biological limits of human spermatogenesis, laying the foundation to expand autologous reproductive options for patients refractory to conventional retrieval protocols.

20.
arXiv (CS.AI) 2026-06-17

Belief-Space Control for Personalized Cancer Treatment via Active Inference

arXiv:2606.10376v2 Announce Type: replace Abstract: Cancer treatment is at the core a sequential decision-making problem with partial observability, latent patient heterogeneity, and explicit constraints on the budget for medical measurements. Unlike standard Reinforcement Learning (RL) approaches that control state trajectories, cancer treatments permanently modify patients' transition dynamics, changing how states evolve over time. We model cancer treatment as a belief-space planning problem using active inference, deriving an expected free-energy objective that unifies goal-directed control and information acquisition under measurement budgets without. We implement this framework using real clinical cancer data from the AACR Project GENIE Biopharma Collaborative dataset. Results on clinical data demonstrate a simultaneous patient categorization and high treatment efficacy, under real measurement and treatment constraints.

21.
arXiv (CS.LG) 2026-06-16

Fantastic Pretraining Optimizers and Where to Find Them II: Hyperball Optimization

arXiv:2606.16899v1 Announce Type: new Abstract: Matrix based optimizers such as Muon can substantially speed up language model pretraining, but their gains over AdamW are observed to shrink as model size and data scale grow when using standard constant decoupled weight decay. We propose Hyperball, a simple optimizer wrapper that addresses this issue. Given a base optimizer such as Adam or Muon, Hyperball sets the Frobenius norms of weight matrices and their corresponding optimizer updates to fixed constants. On Qwen3 style models up to 1.2B parameters, Muon Hyperball achieves 20–30% token equivalent speedup over weight decay baselines. Hyperball also improves learning rate transfer across widths and depths compared to decoupled weight decay. This method is motivated by prior theory showing that training with weight decay leads to an equilibrium weight norm that only depends on the training hyperparameters. Through this mechanism, the weight decay then decides the angular learning rate, i.e. how fast the direction of the weight matrix changes.

22.
arXiv (CS.CL) 2026-06-11

ICA Lens: Interpreting Language Models Without Training Another Dictionary

Finding interpretable directions in language-model representations is critical for understanding and controlling model behavior. Sparse autoencoders (SAEs) have become the standard tool for this purpose, but using them as the default first lens often requires training, storing, and evaluating large overcomplete dictionaries. This bottleneck limits rapid exploration and raises a fundamental question: how much interpretable structure is already visible from activation geometry before training another neural dictionary? Our intuition is simple: many interpretable directions are selective on tokens, and these directions should look less Gaussian than random directions. We therefore revisit independent component analysis (ICA), a classical method for finding non-Gaussian directions, as a compact lens for language-model interpretability. We find that ICA has been underestimated for LLM interpretability, because prior uses often relied on off-the-shelf ICA implementations that are brittle on LLM activations and lacked systematic tools for inspecting and evaluating the recovered directions. To bridge these gaps, we introduce ICALens, the first practical workflow for stable, efficient, and auditable ICA analysis of LLM representations. It combines an optimized GPU-parallel FastICA pipeline with LLM-specific stability recipes and better fitting diagnostics, enabling efficient and reliable layer-wise analysis. Across GPT-2 Small, Gemma 2 2B, and Qwen 3.5 2B Base, ICALens efficiently recovers compact, human-interpretable directions without per-layer gradient-based dictionary training. On SAEBench, ICA is competitive with public SAEs in sparse probing and outperforms them in targeted probe perturbation under small-to-medium budgets. These results suggest that ICA should not be viewed as a weak baseline, but as an efficient and complementary first lens for exploring language-model representations.

23.
arXiv (quant-ph) 2026-06-16

Quantum Global Variational Learning for Quantum Error Correction

arXiv:2606.08592v2 Announce Type: replace-cross Abstract: Efficient quantum error correction is essential for the advancement of quantum computing. We propose a quantum neural network with a global structure that reduces the number of unitary matrices required in quantum circuits. This approach resulted in a 97% reduction in training time and up to a 25% improvement in the training completion rate, ultimately achieving a 100% success rate in training while surpassing the error correction performance reported in previous studies. In addition, we demonstrated the enhanced robustness of quantum error correction against internal network noise. Moreover, the fidelity of quantum error correction under internal network noise increased by up to 15% due to the reduced computational load.

24.
arXiv (CS.LG) 2026-06-15

Recursively Trained Diffusion Models: Limiting Collapse Distribution and Spectral Characterization

arXiv:2606.13796v1 Announce Type: cross Abstract: Recursive training of generative models on their own outputs can lead to model collapse, a compounding drift away from the true data distribution. Existing theoretical works bound finite-round error accumulation in the context of diffusion models, but two questions remain open:~what distribution does the recursion converge to, and how fast? We answer both, isolating a mechanism distinct from imperfect learning: even with perfect score estimation and exact sampling, the early stopping of the reverse diffusion (required for numerical stability) drives a progressive drift away from the data distribution. We prove that this recursion converges geometrically to a unique limiting distribution, which admits a closed-form characterization as an infinite mixture of increasingly Gaussian-smoothed versions of the data distribution. A Hermite spectral decomposition of this limit reveals that recursive training acts as a low-pass filter: higher-order modes, which encode fine non-Gaussian structure, are attenuated much more strongly than coarse modes. This spectral picture motivates annealed truncation schedules that progressively shrink truncation times across retraining rounds; we prove that any schedule converging to $0$ asymptotically eliminates recursive compounding. Finally, we show our idealized characterization is robust: in the presence of discretization and score estimation errors, the learned distribution remains in a Wasserstein-2 ball around the ideal limit, with mode-dependent contraction rates that contract high-order errors faster than low-order ones. We validate the theory on synthetic Gaussian mixtures and CIFAR-10.

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arXiv (CS.AI) 2026-06-16

AI-Driven Test Case Generation from Natural Language Requirements: A Survey of Techniques and Research Gaps

arXiv:2606.06563v2 Announce Type: replace-cross Abstract: Software testing is critical for verifying that systems meet specified requirements, yet remains among the most time-consuming and expensive activities in development. Requirements-based test generation allows test cases to be derived early from requirements artifacts, but generating them directly from natural language is challenging due to inherent ambiguity and imprecision. Recent advances in AI, natural language processing (NLP), and large language models (LLMs) have made automating this pipeline increasingly feasible, while introducing new risks including hallucination, reduced traceability, and inconsistent evaluation. This survey addresses four research questions: what AI and NLP techniques have been proposed for generating test cases from natural language requirements; what tools and frameworks support these approaches; how generated test cases are evaluated; and what research gaps remain. Following Kitchenham and Charters' systematic review guidelines, we searched major scholarly databases spanning 2000-2025 and, after applying strict inclusion criteria, identified 21 primary studies. The literature is organized into three evolutionary eras, revealing that no existing approach simultaneously satisfies six key quality dimensions: automation, ambiguity handling, domain applicability, traceability, evaluation thoroughness, and hallucination control. The survey makes three main contributions: a three-era evolutionary synthesis of AI-based test generation; a six-criteria gap analysis showing no current approach fully addresses all quality dimensions; and four actionable research guidelines targeting hallucination, traceability, complexity sensitivity, and compliance.