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01.
arXiv (CS.CV) 2026-06-12

ReFoCUS: Reinforcement-guided Frame Optimization for Contextual Understanding

Recent progress in Large Multi-modal Models (LMMs) has enabled effective vision-language reasoning, yet the ability to video understanding remains constrained by suboptimal frame selection strategies, albeit with the rapid development of video-specialized LMMs. Prior works attempted to solve this with static heuristics or external retrieval modules to feed frame-level information, but these approaches often fail to capture visual cues grounded to the given user queries conflating raw visual dynamics with true semantic relevance. In this paper, we introduce ReFoCUS (Reinforcement-guided Frame Optimization for Contextual UnderStanding), the first framework to integrate online policy-gradient reinforcement learning into frame-level optimization for video-LLMs. ReFoCUS aims to learn a frame selection policy, leveraging reward signals derived from reference models to capture their underlying scoring behavior over frame combinations that best support temporally grounded responses. To efficiently explore the large combinatorial frame space, we employ an autoregressive and query-conditional selection architecture that ensures contextual consistency while reducing complexity. Our policy learning removes the need for explicit frame-level supervision, as it implicitly discovers optimal and semantically consistent frame compositions. ReFoCUS consistently improves reasoning accuracy across multiple video QA benchmarks, demonstrating the advantage of aligning frame selection with model-internal utility.

02.
arXiv (quant-ph) 2026-06-11

Unifying Quantum Smoothing Theories with Extended Retrodiction

arXiv:2510.08447v2 Announce Type: replace Abstract: Estimating the state of an open quantum system monitored over time requires incorporating information from past measurements (filtering) and, for improved accuracy, also from future measurements (smoothing). While classical smoothing is well understood within a Bayesian framework, its quantum generalization has been challenging, leading to distinct and seemingly incompatible approaches. In this work, we demonstrate that quantum state smoothing hinges on a uniquely quantum feature: the fundamental dependence of retrodiction on prior correlations. We introduce auxiliary systems into the prior belief to capture correlations formed during preparation and evolution and develop a comprehensive framework for quantum state smoothing based on extended Bayesian retrodiction. This framework identifies all previous approaches as different choices of the extended prior, and naturally extends it to other choices that have not been considered before. We also give an information-theoretic characterization of the choices of prior, in terms of the average entropy of the smoothed states. Our results establish quantum state smoothing as a fundamentally retrodictive process just like classical smoothing, with proper quantum features clearly identified.

03.
arXiv (CS.AI) 2026-06-12

HalluJudge: A Reference-Free Hallucination Detection for Context Misalignment in Code Review Automation

arXiv:2601.19072v3 Announce Type: replace-cross Abstract: Large Language models (LLMs) have shown strong capabilities in code review automation, such as review comment generation, yet they suffer from hallucinations – where the generated review comments are ungrounded in the actual code – poses a significant challenge to the adoption of LLMs in code review workflows. To address this, we explore effective and scalable methods for a hallucination detection in LLM-generated code review comments without the reference. In this work, we design HalluJudge that aims to assess the grounding of generated review comments based on the context alignment. HalluJudge includes four key strategies ranging from direct assessment to structured multi-branch reasoning (e.g., Tree-of-Thoughts). We conduct a comprehensive evaluation of these assessment strategies across Atlassian's enterprise-scale software projects to examine the effectiveness and cost-efficiency of HalluJudge. Furthermore, we analyze the alignment between HalluJudge's judgment and developer preference of the actual LLM-generated code review comments in the real-world production. Our results show that the hallucination assessment in HalluJudge is cost-effective with an F1 score of 0.85 and an average cost of $0.009. On average, 67% of the HalluJudge assessments are aligned with the developer preference of the actual LLM-generated review comments in the online production. Our results suggest that HalluJudge can serve as a practical safeguard to reduce developers' exposure to hallucinated comments, fostering trust in AI-assisted code reviews.

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

Geometry of Reason: Spectral Signatures of Valid Mathematical Reasoning

Verifying whether a language model is genuinely reasoning or pattern-matching remains an open problem: learned verifiers are expensive, and output-based heuristics are brittle. We show that valid mathematical reasoning induces a measurable, training-free spectral signature in transformer attention. By treating each attention matrix as a weighted token graph, we extract four diagnostics: Fiedler value, High-Frequency Energy Ratio (HFER), spectral entropy, and smoothness, that require no learned parameters. Experiments across seven models from four architectural families yield effect sizes up to Cohen's $d = 3.30$ ($p < 10^{-116}$), enabling $85$–$96\%$ single-threshold classification accuracy. Two findings sharpen the interpretation. First, Platonic validity: the spectral signal tracks logical coherence rather than compiler acceptance, proofs rejected for timeouts or missing imports are correctly classified as valid, a distinction confirmed by a manual audit ($\kappa = 0.82$, $n = 51$). Second, architectural determinism: Sliding Window Attention shifts the discriminative feature from HFER to smoothness ($d = 2.09$, $p < 10^{-48}$), showing that attention design governs which spectral channel encodes reasoning quality. Causal ablation confirms the signature traces induction-head circuits. The method generalises to informal chain-of-thought ($d = 0.78$, $p < 10^{-3}$), and in proof search, HFER reranking improves Best-of-16 Pass@1 by $+4.4$–$6.6$\%, matching $98\%$ of the AUC of fully supervised probes with zero labels. Spectral graph analysis is a principled, architecture-aware primitive for reasoning verification.

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

Training-Free Adversarial Robustness in Computational MRI

Deep learning (DL) methods have become the state-of-the-art for reconstructing sub-sampled magnetic resonance imaging (MRI) data. However, studies have shown that these methods are susceptible to small adversarial input perturbations, resulting in major distortions in the output images. Various strategies have been proposed to reduce the effects of these attacks, but they require retraining. In this work, we propose a novel approach for mitigating adversarial attacks on MRI reconstruction models without any retraining. Based on the idea of cyclic measurement consistency, we devise a novel mitigation objective that is minimized in a small ball around the attack input. Results show that our method substantially reduces the impact of adversarial perturbations across different datasets, attack types/strengths and PD-DL networks, and qualitatively and quantitatively outperforms conventional mitigation methods. We also introduce a practically relevant scenario for small adversarial perturbations that models impulse noise in raw data, which relates to herringbone artifacts, and show the applicability of our approach in this setting. Finally, we show our mitigation approach remains effective in two realistic extension scenarios: a blind setup, where the attack strength or algorithm is not known to the user; and an adaptive attack setup, where the attacker has full knowledge of the defense strategy.

06.
bioRxiv (Bioinfo) 2026-06-13

PertDiffBench: Benchmarking Diffusion Models for Single-Cell Perturbation Response Prediction

Diffusion models are increasingly used to predict transcriptional responses to perturbations, but whether they improve on simpler generative and representation-based baselines remains unclear. Existing evaluations often do not separate the effects of model architecture, input representation, biological context and metric choice, making it difficult to determine where diffusion-based methods are useful. Here we introduce PertDiffBench, a standardized benchmark for diffusion-based transcriptomic perturbation prediction across single-cell and bulk RNA-seq datasets. PertDiffBench evaluates diffusion-based models across three complementary evaluation settings: standard prediction in known single-cell contexts and bulk perturbation conditions, generalization to unseen cell types, species, drugs and intermediate time points, and stress tests of feature dimensionality, input representation, noise type and gene ordering. Across these settings, diffusion models did not show a consistent advantage. scGen remained a strong baseline in common prediction tasks, whereas scDiffusion was the most competitive diffusion-based method in several generalization settings. Temporal imputation showed a different pattern, with a simple DDPM operating directly in expression space outperforming more specialized models. Stress tests showed that performance was model dependent and sensitive to feature dimensionality, encoder choice, noise type and gene ordering. Pretrained encoders did not consistently improve performance, with the classical scVI representation slightly exceeding STATE in seen-condition and unseen-cell-type settings. These results indicate that diffusion-model performance in perturbation response prediction depends strongly on task design and representation choice. PertDiffBench provides a practical framework for evaluating these models under biologically varied and stress-tested conditions.

07.
arXiv (quant-ph) 2026-06-11

Fast Adiabatic Quantum Gates via Hyperfine Intermediate States

arXiv:2606.11655v1 Announce Type: new Abstract: The appeal of adiabatic quantum computing lies in its intrinsic robustness against various technical imperfections, making it attractive for many quantum information applications. However, it faces a fundamental challenge: accelerating the adiabatic operations while preserving adiabaticity within the qubit coherence time. In this article, we propose an electromagnetically induced transparency-based adiabatic CNOT gate protocol which harnesses atomic hyperfine intermediate states (HISs) to speed up the adiabatic evolution. The HISs, naturally-existed in two-photon transitions, often need to be suppressed due to their significant decay errors. In contrast, this paper introduces a novel method that utilizes appropriately chosen HISs not only to enhance the adiabaticity in STAY pathway but also to accelerate the population transfer in TRANSFER pathway. Through pulse optimization, we achieve adiabatic gate fidelities exceeding 0.9991 within 0.3903 {\mu}s in realistic Cs atomic setups. To demonstrate the generality of protocol we further assess the impact of decays from multiple HIS and extend our model to arbitrary number of states, providing a practical route toward fast and robust adiabatic quantum gates in Rydberg-atom platforms.

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

Position: AI Must Become Planet-Centered, Not Just Human-Centered

arXiv:2606.13704v1 Announce Type: cross Abstract: This position paper argues that contemporary AI paradigms are insufficient for supporting complex global goals and introduces Planet-Centered AI (PCAI) as a design philosophy and research agenda that reorients AI toward planetary-scale socio-ecological systems and their long-term trajectories. A planet-centered approach is grounded in systems thinking, treating Earth as an interconnected whole of which humans are part. We diagnose recurring limitations across AI frameworks, many of which remain human-centered, and show why these become especially consequential under current planetary conditions characterized by systemic risk, non-stationarity, and deep uncertainty. We then articulate how PCAI reshapes the AI lifecycle, from problem formulation and model design to evaluation and deployment, by emphasizing alignment with global agendas, developing system-aware AI foundations, trajectory-oriented evaluation, and monitorability. Finally, we advance a falsifiable claim: AI systems optimized without explicit consideration of systemic consequences are more likely to exacerbate systemic instability than to mitigate it.

09.
arXiv (CS.AI) 2026-06-11

Noise-Guided Transport for Imitation Learning

arXiv:2509.26294v2 Announce Type: replace-cross Abstract: We consider imitation learning in the low-data regime, where only a limited number of expert demonstrations are available. In this setting, methods that rely on large-scale pretraining or high-capacity architectures can be difficult to apply, and efficiency with respect to demonstration data becomes critical. We introduce Noise-Guided Transport (NGT), a lightweight off-policy method that casts imitation as an optimal transport problem solved via adversarial training. NGT requires no pretraining or specialized architectures, incorporates uncertainty estimation by design, and is easy to implement and tune. Despite its simplicity, NGT achieves strong performance on challenging continuous control tasks, including high-dimensional Humanoid tasks, under ultra-low data regimes with as few as 20 transitions.

10.
bioRxiv (Bioinfo) 2026-06-14

Virtual phenotypic screening discovers novel scaffolds inhibiting the PI3K/mTOR pathway

Phenotypic drug discovery has yielded many first-in-class small-molecule drugs by discovering modulators of disease phenotypes in physiologically relevant cellular systems. However, high-content phenotypic assays lack the ultra-high-throughput scalability of target-based screens. Recent advances in virtual screening present an opportunity to address this bottleneck, but have been limited to simple phenotypes like viability, restricted to small repurposing libraries, or lack in-depth biological validation. Here, we present PhenoCompass, a multimodal co-embedding model that aligns compound structures and high-content phenotypic imaging to enable virtual phenotypic screening over billion-compound libraries. Following training on the Joint Undertaking in Morphology dataset with more than 100,000 Cell Painting compound profiles, retrospective validation with historical biochemical high-throughput screening data demonstrates that PhenoCompass ranks compounds according to their biochemical target engagement. Leveraging PhenoCompass, we performed a prospective screen of 3.8 billion Enamine REAL compounds for inhibitors of PI3K/mTOR pathway, a critical signaling cascade whose aberrant activation is a common tumor driver. This search identified 11 novel compounds with pathway-consistent Cell Painting readout and diverse scaffolds, a 54-fold enrichment over the training set. Orthogonal validation experiments using a FOXO3A reporter assay and direct kinase inhibition confirmed seven structurally novel inhibitors with distinct mechanisms of action. These results highlight the convergence of diverse molecular target profiles onto a shared morphological pathway signature and establish PhenoCompass as a robust framework for high-content phenotypic virtual screening.

11.
arXiv (quant-ph) 2026-06-17

Tungsten Germanide Superconducting Nanowire Single-Photon Detectors with Saturated Internal Detection Efficiency at Wavelengths up to 29 {\mu}m

arXiv:2511.20868v2 Announce Type: replace-cross Abstract: Superconducting nanowire single-photon detectors (SNSPDs) are among the most sensitive single-photon detectors available and have the potential to transform fields ranging from infrared astrophysics to molecular spectroscopy. However, extending their performance into the mid-infrared spectral region - crucial for applications such as exoplanet transit spectroscopy and vibrational fingerprinting of molecules - has remained a major challenge, primarily due to material limitations and scalability constraints. Here, we report on the development of SNSPDs based on tungsten germanide, a novel material system that combines high mid-infrared sensitivity with compatibility for large-scale fabrication. Our detectors exhibit saturated internal detection efficiency at wavelengths up to 29 {\mu}m, while using 2.7x thicker films (8 nm vs 3 nm) and up to 4.5x wider nanowires (360 nm vs 80 nm) compared to mid-infrared-optimized SNSPDs fabricated from tungsten silicide. This advance will enable scalable, high-performance single-photon detection in a spectral region that was previously inaccessible, opening new frontiers in remote sensing, thermal imaging, environmental monitoring, molecular physics, and astronomy.

12.
arXiv (CS.LG) 2026-06-18

Online Distributional Prediction via Latent Cluster Geometry Under Drift and Corruption

arXiv:2606.18778v1 Announce Type: new Abstract: Online learning in non-stationary streams is often formulated as tracking a point estimate, but many applications require predicting the full data-generating distribution. We study online distributional prediction under drift and adversarial corruption. Our approach represents each candidate law through a latent cluster geometry: a variable-size configuration of centers that organizes probability mass and induces a predictive distribution. A Gibbs quasi-posterior over these configurations yields an online predictor by posterior averaging, and the resulting variable-dimensional posterior can be sampled with reversible-jump MCMC. The method therefore avoids specifying a parametric streaming law while retaining a structured latent space for uncertainty, regularization, and comparison. We evaluate performance by cumulative Wasserstein-1 regret against the time-varying true law. The analysis separates two effects: corruption perturbs the loss-based posterior update, whereas drift makes long-horizon posterior memory stale. We address the latter with a restarted variant that temporally localizes the same quasi-Bayesian update. The resulting high-probability bounds decompose into a PAC-Bayesian complexity term, a corruption-sensitive posterior perturbation term, and a dynamic optimal-transport term driven by \(A_T^{\mathrm{OT}}=\sum_{t=2}^T W_2^2(p_{t-1}^*,p_t^*)\). Under bounded support, stable latent geometry, predictive-map regularity, oracle realizability, localized restart windows, sublinear transport action, and sublinear corruption budget, the restarted predictor achieves sublinear cumulative Wasserstein regret. These guarantees require no parametric model for the stream, drift mechanism, or corruption process.

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

One Token to Fool LLM-as-a-Judge

Large language models (LLMs) are increasingly trusted as automated judges, assisting evaluation and providing reward signals for training other models, particularly in reference-based settings like Reinforcement Learning with Verifiable Rewards (RLVR). However, we uncover a critical vulnerability even in this reference-based paradigm: generative reward models are systematically susceptible to reward hacking. We find that superficial inputs, which we term ''master keys'' such as non-word symbols (e.g., '':'' or ''.'') or generic reasoning openers (e.g., ''Thought process:'' or ''Let's solve this problem step by step.''), can consistently elicit false positive rewards without any substantive reasoning. Our systematic evaluation demonstrates this is a widespread failure affecting a diverse range of models, including leading proprietary systems such as GPT-o1 and Claude-4. These results challenge the assumed robustness of LLM judges and pose a significant threat to their reliability. To address this, we propose a simple yet effective data augmentation strategy using truncated model outputs as adversarial negative examples. The resulting Master Reward Models (Master-RMs) demonstrate state-of-the-art robustness against these ''master key'' attacks while maintaining high performance in standard evaluation settings. We supplement these findings with a comprehensive analysis of the vulnerability across model scales, prompt variations, and common inference-time strategies, offering insights to guide future research on robust LLM evaluation. We release our robust, general-domain reward models and the synthetic training data at https://huggingface.co/sarosavo/Master-RM and https://huggingface.co/datasets/sarosavo/Master-RM.

14.
arXiv (CS.LG) 2026-06-16

Neural Bayesian Anomaly Mitigation: A Robust Loss that Doubles as an Unsupervised Contamination Classifier

arXiv:2606.16524v1 Announce Type: new Abstract: Engineered robust losses such as Huber, Student-$t$, and generalised cross-entropy make supervised models tolerant of contamination but cannot answer which observations are corrupted. We introduce Neural Bayesian Anomaly Mitigation (NBAM), a general-purpose drop-in loss derived from a Bayesian latent-switch mixture model: the marginal likelihood defines a robust supervised loss, and the associated posterior defines an unsupervised contamination classifier. Like Huber or Student-$t$, NBAM can replace the standard training loss in any supervised pipeline; unlike them, it additionally learns a structured contamination model and returns a calibrated per-sample contamination posterior. A learned input-dependent prior $\pi_\phi(x)$ captures the spatial locality of contamination, so that samples near known corruptions are more likely to be flagged, while an Occam penalty emerges automatically and regularises against over-flagging. On CIFAR-10 with asymmetric label contamination, NBAM recovers the structure of the corruption process without supervision: the contamination posterior separates clean from corrupted samples, and the learned anomaly head identifies the direction of every label-flip pair. Alongside these capabilities, NBAM outperforms the four robust-loss baselines considered here at contamination rates 0.2-0.6.

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

Binary Black Hole Parameter Estimation with Hybrid CNN-Transformer Neural Networks

arXiv:2606.13941v1 Announce Type: cross Abstract: The detection of gravitational waves has revolutionized our ability to explore fundamental aspects of the Universe. Traditionally, modeled gravitational-wave signals have been identified using template-based matched filtering, followed by coincidence analysis across multiple detectors in the signal-to-noise ratio time series. Recent advances in Machine Learning and Deep Learning have sparked growing interest in their application to both signal detection and parameter estimation. In this study, a hybrid Deep Learning strategy is proposed that leverages the effectiveness of Transformer encoders alongside well-established Convolutional Neural Network architectures in an attempt to estimate the intrinsic and extrinsic parameters of non-precessing binary black hole systems. The primary focus of this work is point estimation, producing single best-fit values for each parameter rather than full posterior distributions. This method is evaluated on both simulated signals embedded in Gaussian noise and real gravitational-wave events, and it demonstrates strong predictive performance and robustness across key astrophysical parameters.

16.
PLOS Computational Biology 2026-06-22

TCRBinder: Unified pre-trained language model with paired-chain synergy for predicting T-cell receptor binding specificity

Authors:

by Weihe Dong, Qiang Yang, Long Xu, Xiaokun Li, Kuanquan Wang, Suyu Dong, Gongning Luo, Xianyu Zhang, Tiansong Yang, Xin Gao, Guohua Wang Deciphering how human T cells recognise peptide-HLA (pHLA) complexes underpins next-generation vaccines and personalised immunotherapies, yet extreme sequence diversity and paired-chains interdependence still hamper reliable in silico prediction of T-cell receptor (TCR) specificity. To overcome these hurdles, we built TCRBinder, a paired-chain-aware deep model with a multi-branch encoder that routes each molecular component through dedicated transformer-based modules to capture contextual signals in both HLA pseudo-sequences and antigenic peptides while simultaneously processing the TCR α and β chains. This design captures the synergistic interaction between paired chains to emulate peptide-HLA-TCR (PHT) interactions and expose residue-level contact motifs. Across PHT and peptide-TCR (pTCR) benchmarks, the model delivered state-of-the-art performance (AUC-ROC = 0.911, AUPR = 0.791 for the PHT task) and remained superior on multiple independent datasets. We tracked the dynamics of clonal expansion and, in a large SARS-CoV-2 repertoire containing completely unseen peptides, improved the AUC-ROC by up to 16.3% over the leading alternatives. Moreover, TCRBinder provided mechanistic insights by pinpointing contact hotspots and quantifying residue contributions to binding probability. These capabilities position TCRBinder as a versatile tool for rational antigen discovery, immunotherapy stratification, and neoantigen vaccine design.

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

In-Context Learning Is Provably Bayesian Inference: A Generalization Theory for Meta-Learning

arXiv:2510.10981v3 Announce Type: replace-cross Abstract: This paper develops a finite-sample statistical theory for in-context learning (ICL), analyzed within a meta-learning framework that accommodates mixtures of diverse task types. We introduce a principled risk decomposition that separates the total ICL risk into two orthogonal components: Bayes Gap and Posterior Variance. The Bayes Gap quantifies how well the trained model approximates the Bayes-optimal in-context predictor. For a uniform-attention Transformer, we derive a non-asymptotic upper bound on this gap, which explicitly clarifies the dependence on the number of pretraining prompts and their context length. The Posterior Variance is a model-independent risk representing the intrinsic task uncertainty. Our key finding is that this term is determined solely by the difficulty of the true underlying task, while the uncertainty arising from the task mixture vanishes exponentially fast with only a few in-context examples. Together, these results provide a unified view of ICL: the Transformer selects the optimal meta-algorithm during pretraining and rapidly converges to the optimal algorithm for the true task at test time.

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

Edge Flow: A Tractable and Predictive Continuous-Time Model for Gradient Descent at the Edge of Stability

Authors:

arXiv:2606.18080v1 Announce Type: new Abstract: Gradient descent in deep learning may operate at the edge of stability (EoS), a regime in which the largest eigenvalue of the loss Hessian hovers near the stability threshold $2/\eta$, where $\eta$ is the learning rate. Classical analysis tools such as gradient flow and the descent lemma do not apply here, motivating the search for a continuous-time model valid at EoS. We propose Edge Flow, a system of three coupled ordinary differential equations that provides a tractable, faithful, and predictive model of gradient descent dynamics at EoS. Edge Flow decomposes the dynamics into a center, an oscillation direction, and an oscillation magnitude. The center follows a modified gradient flow on a symmetrized loss; the direction tracks a top eigenvector of the Hessian via Rayleigh quotient dynamics; and the magnitude grows or decays exponentially depending on whether the sharpness exceeds or falls below the threshold $2/\eta$. Crucially, sharpness stabilization emerges from the coupled dynamics via a self-stabilization feedback loop. Discretizing Edge Flow only requires two gradient evaluations and one Hessian–vector product at each iteration. We demonstrate empirically that Edge Flow tracks the dynamics of gradient descent at least as faithfully as previously proposed continuous-time EoS models, while in addition resolving the oscillation of the sharpness at the onset of EoS, and that it provides a principled framework for understanding and mitigating instabilities in this regime.

19.
arXiv (quant-ph) 2026-06-12

Coulomb crystallization of xenon highly charged ions in a laser-cooled Ca+ matrix

arXiv:2512.12266v2 Announce Type: replace-cross Abstract: We report on the sympathetic cooling and Coulomb crystallization of xenon highly charged ions (HCIs) with laser-cooled Ca$^+$ ions. The HCIs are produced in a compact electron beam ion trap, then charge selected, decelerated, and finally injected into a cryogenic linear Paul trap. There, they are captured into $^{40}$Ca$^+$ Coulomb crystals, and co-crystallized within them, causing dark voids in their fluorescence images. Fine control over the number of trapped ions and HCIs allows us to realize mixed-species crystals with arbitrary ordering patterns. By investigating Xe$^{q+}$–Ca$^+$ strings, we confirm the HCI charge states, measure their lifetime and characterize the mixed-species motional modes. Our system effectively combines the established quantum control toolbox for Ca$^+$ with the rich set of atomic properties of Xe highly charged ions, providing a resourceful platform for optical frequency metrology, searches for signatures of new physics, and quantum information science.

20.
arXiv (CS.AI) 2026-06-15

Expert-Driven Survival Machines: Improving Stratification and Interpretability in Multiple Clinical Cohorts

arXiv:2606.14608v1 Announce Type: cross Abstract: Survival prediction plays a central role for healthcare providers and clinical researchers. Accurate risk stratification enables early intervention and improved patient management. Most existing deep survival models learn one common feature representation for all patients, which may hide important differences between patient subgroups. In contrast, a Mixture-of-Experts (MoE) framework allows different parts of the model to focus on different patient patterns, leading to more individualized representations. Therefore, in this work, we propose a mixture-of-experts enhanced adaptive deep clustering survival framework (AdaCSM) for modeling such heterogeneous survival patterns. We introduce a routing-based expert mechanism that enables conditional specialization within a parametric survival modeling framework. The proposed architecture allocates patients to specialized risk predictors dynamically while preserving the patient survival and subtype clustering objectives. We compare our method with state-of-the-art survival and deep clustering models on multiple real-world longitudinal clinical cohorts spanning diverse disease domains. The proposed method demonstrates improved predictive performance and leads to interpretable results in survival analysis.

21.
bioRxiv (Bioinfo) 2026-06-14

Systematic AI-Driven Drug Repurposing via Clinical Trial Data Mining: A Framework and Six Cross-Therapeutic Case Studies.

Authors:

Drug repurposing, the application of approved or shelved compounds to new therapeutic indications, offers a cost- and time-efficient alternative to de novo drug discovery. However, the systematic identification of repurposing candidates from the rapidly expanding body of clinical trial data remains a significant challenge. Here we present a publicly accessible AI-powered tool that mines the ClinicalTrials.gov registry to identify approved drugs with under-explored therapeutic potential in high-value disease areas. The tool integrates natural language processing, mechanism-of-action pathway analysis, and trial density scoring to surface candidates where biological plausibility is high and clinical trial coverage is sparse. We demonstrate the tool's utility across six cross-therapeutic case studies spanning oncology, cardiology, neurology, rare diseases, immunology, and infectious disease. Key findings include: the identification of Zonisamide as an under-explored combination candidate for obesity alongside GLP-1 receptor agonists; mechanistic validation of SGLT2 inhibitors in heart failure with preserved ejection fraction (HFpEF); and a novel cross-domain mapping of anti-TNF biologics to early-stage neurodegeneration via shared neuroinflammatory pathways. The tool is freely accessible and designed to lower the barrier for academic and industry researchers to systematically pursue repurposing opportunities.

22.
arXiv (CS.AI) 2026-06-12

Is It You or Your Environment? A Bayesian Inference Framework for Genomically-Anchored Personalized Physiological Interpretation

arXiv:2606.13556v1 Announce Type: new Abstract: Personalized health AI systems face a fundamental cold-start problem: machine learning models for physiological interpretation require weeks of individual behavioral data before they can distinguish constitutional variation from environmentally driven deviation. We propose a solution grounded in causal inference and Bayesian prior design. An individual's genomic profile serves as an exogenous genetic anchor – a domain-informed, personalized prior that is fixed at conception, immune to reverse causation, and available before a single behavioral observation is collected. The anchor initializes a Bayesian belief state over an individual's physiological set point G-hat = mu + sum(beta_i * g_i), where beta_i are GWAS-derived effect sizes and g_i are risk-allele counts. Each incoming physiological measurement P produces a non-constitutional deviation delta = P - G-hat that separates the signal attributable to environment and state from the constitutionally fixed baseline. As behavioral data accrue, the prior decays according to G-hat_t = w(t)*G-hat_genomic + [1-w(t)]*P-bar_t, transitioning from genome-dominated to empirical-baseline-dominated inference. The same observed HRV of 55 ms generates a suppression hypothesis for a person whose prior predicts 80 ms, and an enhancement hypothesis for a person whose prior predicts 30 ms – a reversal impossible without a personalized anchor. We develop this architecture across six physiological domains, grading genomic priors by evidence strength, distinguishing robustly replicated anchors (FTO, FADS1/2, FKBP5) from contested candidate genes (SLC6A4, MAOA, DRD2). We address the inference boundary between association, Mendelian randomization, and individual token causation, and define four constraints for deployment: evidence-graded priors, dynamic decay, ancestry-matched effect sizes, and attribution rather than deterministic output.

23.
arXiv (CS.LG) 2026-06-12

Physics-Informed Neural Networks for Chemotherapy Pharmacokinetics: Benchmarking the Clinical Estimator and Exposing Parameter Identifiability

arXiv:2606.12658v1 Announce Type: new Abstract: Physics-Informed Neural Networks (PINNs) are an attractive tool for partial-observation problems in biology, where the governing dynamics are known but some compartments cannot be measured. Chemotherapy pharmacokinetics (PK) is a clean instance: drug concentration in plasma is routinely measured, but concentration in tissue – which determines tumour kill and off-target toxicity – is not. We benchmark a PINN against the standard clinical baseline (nonlinear least-squares on the analytical biexponential plasma solution, hereafter NLS) and a physics-agnostic neural baseline (a data-only MLP) on two PK problems. On the linear two-compartment problem, NLS is near-optimal; the PINN matches it to within a small constant factor while also producing the tissue curve in a single training pass, whereas the data-only MLP fails on tissue by roughly 10x. On a Michaelis-Menten extension (saturable elimination), the biexponential closed form no longer exists, so NLS is mis-specified and silently returns meaningless rate constants. The PINN instead exposes a deeper fact: the Michaelis-Menten two-compartment model is non-identifiable from plasma alone, and the PINN reports this honestly by converging to a basin with k12 -> 0. Adding two sparse tissue observations largely resolves identifiability: across five seeds the PINN recovers k21 to within 1% of truth and Vmax, Km to within one standard-deviation bar, while k12 moves in the correct direction (0.02 -> 0.82) but remains ~2 sigma below truth – a recovery the closed-form NLS estimator cannot attempt at all, because its biexponential ansatz describes only plasma. Our claim is not that PINNs beat NLS. It is that PINNs offer a uniform recipe that ties the textbook estimator on the textbook problem, exposes structural identifiability that the textbook estimator hides, and absorbs heterogeneous measurements within a single loss.

24.
arXiv (quant-ph) 2026-06-15

Experimental violation of a Bell-like inequality for causal order

arXiv:2506.20516v2 Announce Type: replace Abstract: Quantum mechanics is compatible with scenarios where physical processes happen in an indefinite order. In theory, this feature could be detected through violations of inequalities on the observed correlations, analogous to Bell inequalities. However, experimental demonstrations of such violations have been missing until recently due to the complexity of the required setup. Here we report an experimental violation of a Bell-like inequality involving the correlations of four parties, one of which is spacelike separated from the others. Our demonstration employs 3 km fiber spools to simulate spacelike separation, and achieves high-speed operations in photonic time-bin encoding, nanosecond synchronization, and accurate temperature stabilization. These experimental advances enable a violation by 5.7 standard deviations and open a path towards a certification of indefinite order in conditions that guarantee spacelike separation with existing state-of-the-art devices. However, the certification is not device-independent, as it relies on knowledge about the setup to exclude bidirectional signaling–a loophole inherent to implementations in classical acyclic spacetimes, which may be resolved in future quantum-spacetime tests.

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

Interpretable and Verifiable Hardware Generation with LLM-Driven Stepwise Refinement

arXiv:2606.19387v1 Announce Type: cross Abstract: Large language models (LLMs) have achieved remarkable success in software development. However, they are susceptible to hallucinations, meaning that they can introduce subtle semantic and logical errors. Due to the high stakes in chip design and manufacturing, hardware engineers are still reluctant to rely on LLMs for register-transfer level (RTL) generation. In this paper, we propose a hardware generation framework that combines the creativity and broad knowledge of LLMs with the explainability and mathematical rigor of formal methods. Specifically, we devise a set of transformation rules that cover various design decisions and hardware features. By iteratively applying these rules, an LLM agent can convert a design specification into an RTL program with guaranteed correctness. Experimental results demonstrate the effectiveness and efficiency of the framework.