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

Improving End-to-End Speech Recognition for Dysarthric Speech through In-Domain Data Augmentation

arXiv:2606.19797v1 Announce Type: cross Abstract: Dysarthric speech recognition is crucial for facilitating effective communication among individuals with dysarthria. However, accurately recognizing dysarthric speech poses significant challenges due to varying severity levels and limited data availability. In this paper, we explore data augmentation techniques for dysarthric automatic speech recognition (ASR) systems by fine-tuning the End-to-End pre-trained Wav2Vec2 model, with a specific focus on severity levels. To address the challenges of data scarcity and the need for extensive data in fine-tuning pre-trained ASR systems for dysarthric speech, we investigate four prominent data augmentation methods: Speaking-Rate Modification (SRM), Pitch Modification (PM), Formant Modification (FM), and vocal tract Length Perturbation (VTLP), tailored to different aspects of dysarthria. The study uses individually fine-tuned Wav2Vec2 models for each severity class as baseline systems. Additionally, we conducted severity-specific fine-tuning of the ASR model using augmented data. Results demonstrate distinct efficacy patterns for each augmentation technique across severity levels. The best WERs were achieved with SRM ($s$=0.8) for low (9.02\%) and medium (38.11\%) severities, and with PM ($\tau$=0.8) for high severity (55.15\%), reflecting relative improvements of 30.02\%, 16.64\%, and 15.47\%, respectively. These results confirm the effectiveness of the augmentation methods in improving dysarthric ASR performance.

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

Beyond Bayer: Task-Optimal Sensor Co-Design for Robust Autonomous-Driving Segmentation

arXiv:2606.24096v1 Announce Type: cross Abstract: Robust perception underpins autonomous driving, and most recent progress comes from scaling the model-larger backbones, foundation models, and cooperative multi-agent fusion. We pursue a complementary, upstream question: what should the camera itself measure? Using a differentiable RAW-to-task pipeline, we decompose which sensor degrees of freedom benefit dense prediction. Learning the spectral colour-filter-array (CFA) weights is the dominant lever, improving mIoU by +0.017 (KITTI-360) and +0.023 (ACDC) over a fixed camera. In contrast, point-spread-function (optics) co-design is net-negative (-0.020 mIoU on KITTI-360) - a consequence of the data-processing inequality, which also bounds the task information that any downstream model, however large or cooperative, can recover. Noise co-optimisation is marginal, and counter to intuition enlarging the CFA tile beyond 2x2 consistently hurts, as the filters are confined to the rank three sRGB input. Because the intervention is at the sensor, the gains are model-agnostic; we validate robustness on ACDC's fog, night, rain, and snow, and conclude with a simple recipe: learn the 2x2 CFA weights and keep an identity PSF.

04.
medRxiv (Medicine) 2026-06-11

A global cross-sectional survey of health professionals' interest-confidence gaps in value-based health care implementation: a learning needs assessment

Abstract Objectives Value-Based Health Care (VBHC) increasingly guides health system redesign internationally. Despite the increasing availability of VBHC education, gaps remain between health professionals' conceptual understanding of VBHC and their confidence to implement it in practice. This study assessed perceived learning needs and preferences of healthcare professionals across foundational topics essential to VBHC implementation. Design Cross-sectional online survey study Setting and participants The survey was distributed to the global VBHC community and yielded 518 responses. Most respondents were based in the UK and Ireland (51%) and 65% had more than 10 years of experience in the health sector. Participants represented a variety of professional backgrounds, including clinicians (34%), operational or executive managers and leaders (22%), and life sciences or procurement professionals (13%). Primary and secondary outcome measures Primary outcome measures included self-reported interest and confidence across 15 VBHC domains and the magnitude of the gap between them. Secondary outcomes included perceived implementation challenges and preferred VBHC learning approaches, including prior engagement with VBHC-related learning. Results Respondents identified substantial VBHC implementation challenges, including implementing outcome measurement (62.4%), conflicting priorities (57.7%), and resistance to change (56.8%). Interest in all VBHC domains was high (median >= 80/10), while confidence to implement remained substantially lower across most domains (median

05.
medRxiv (Medicine) 2026-06-22

Effect of Lowering the Drink-Driving Blood Alcohol Limit in Scotland on Road Traffic Crashes: a Synthetic Difference-in-Differences Study

Objective: To evaluate the road safety impact arising from Scotlands 2014 reduction in the legal blood alcohol concentration (BAC) limit for drivers, and to assess whether the effect of the reform varied across different spatial contexts. Design: A quasi-experimental statistical longitudinal study using a Synthetic Difference-in-Differences (SDID) approach. Setting: Small-area panel data for Great Britain, with areas (Middle-layer Super Output Areas, MSOAs, in England and Wales and Intermediate Zones, IZs, in Scotland) classed into control and treatment groups according to whether they were exposed to Scotlands BAC reform. The control and treatment groups comprise 7088 spatial units in England and Wales and 852 spatial units in Scotland, respectively, observed over the period 2008-2019. Participants: The study primarily analyses police-reported road traffic collision data from the UK Department for Transports STATS19 system. Data were analysed at the MSOA/IZ level. This is a secondary dataset, and we therefore did not involve patients or the public in formulating the research question, determining outcome measures, or designing and conducting the study. Main Outcome Measures: The main outcome measures were log-transformed rates of total road traffic crashes, and (weekend) night-time crashes (22:00-04:00) per 100,000 population. The latter is used as a proxy measure for drunk driving. Results: Our results indicate that the reduction in the legal BAC limit led to statistically significant declines in road traffic crash rates. Aggregate estimates suggest reductions of 12.0% (95% confidence interval (CI): [-13.7%, -10.3%]) in total crashes, 15.6% (95% CI: [-20.7%, -10.2%]) in night-time crashes, and 12.4% (95% CI: [-16.7%, -7.9%]) in weekend night-time crashes. We also find substantial heterogeneity in treatment effects across spatial contexts. Effects were strongest in rural and less densely populated areas, where reductions exceeded 16% (95% CI: [-18.7%, -13.9%]) for total crashes and reached up to 29.6% (95% CI: [-35.8%, -22.8%]) for night-time and 21.4% (95% CI: [-28.3%, -13.9%]) for weekend night-time crashes. Moderate but statistically significant effects were also observed in dense urban areas, whereas effects in suburban and transitional areas were smaller and not statistically significant. Conclusions: Our analysis suggests that lowering the legal BAC limit in Scotland led to meaningful reductions in road traffic crashes, particularly during higher-risk periods and in rural areas. The findings further suggest that the effectiveness of BAC regulation may vary across local contexts, highlighting the importance of accounting for spatial heterogeneity when evaluating road safety policies.

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

Indirect Computing Model with Indirect Formal Method

Authors:

This paper,from the perspective of a collaborative intelligent computing system formed by combining human-computer interface and collaborative computing programs, discusses the principles of optimized cloud computing technology supported by the combination of an indirect computing model and an indirect formal method. On the basis of systematically reviewing the influence of previous theoretical achievements Turing's computability theory,Kleene's formal theory of small strings,von Neumann's digital computer architecture and Turing's hypothesis on AI judgment on the mainstream general-purpose digital computer paradigm,the author focuses on introducing an indirect computing model and an indirect formal theory compatible with both large and small strings. Using Chinese information data as an example,the design concept of a collaborative intelligent computing system prototype is presented. The significance is that this achievement facilitates optimization of cloud computing from data centers to knowledge centers.

07.
arXiv (CS.AI) 2026-06-15

Quantized Evolution Strategies: High-precision Fine-tuning of Quantized LLMs at Low-precision Cost

arXiv:2602.03120v2 Announce Type: replace-cross Abstract: Post-Training Quantization (PTQ) is essential for deploying Large Language Models (LLMs) on memory-constrained devices, yet it renders models static and difficult to fine-tune. Standard fine-tuning paradigms, including Reinforcement Learning (RL), fundamentally rely on backpropagation and continuous weights to compute gradients. Thus they cannot be used on quantized models, where the parameter space is discrete and non-differentiable. While Evolution Strategies (ES) offer a backpropagation-free alternative, optimization of the quantized parameters can still fail due to vanishing or inaccurate gradient estimation. This paper introduces Quantized Evolution Strategies (QES), an optimization paradigm that performs full-parameter fine-tuning directly in the quantized space. QES is based on two innovations: (1) it integrates accumulated error feedback to preserve high-precision weight updating signals, and (2) it utilizes a stateless seed replay to reduce memory usage to low-precision inference levels. QES significantly outperforms the state-of-the-art zeroth-order fine-tuning methods on a variety of tasks, making direct fine-tuning for quantized models possible. It therefore opens up the possibility for scaling up LLMs entirely in the quantized space. The source code is available at https://github.com/dibbla/Quantized-Evolution-Strategies .

08.
medRxiv (Medicine) 2026-06-24

Pembrolizumab, Temozolomide and HSPPC-96 Vaccine in Newly Diagnosed Glioblastoma Post-Chemoradiation: Results from a Multi-institutional, Phase 2, Randomized, Placebo-Controlled Trial

Background: GBM is one of the most common and most aggressive brain tumors in adults, and upfront standard of care treatment has limited efficacy. Immune checkpoint inhibitor strategies have significantly improved outcomes in various solid tumors but have not proven effective in GBM, suggesting other strategies may be needed to realize their full potential. Methods: GBM patients were treated with upfront standard of care chemoradiation with temozolomide and pembrolizumab, followed by adjuvant temozolomide and pembrolizumab for six nine-week cycles. Depending on production of sufficient vaccine, patients were randomized into HSPPC-96 vaccine or placebo group (q4 weeks) while those with failed vaccine production continued on study unblinded as an ancillary group. The primary objective was overall survival at one year, and secondary endpoints were progression-free survival at six months, overall and progression-free survival, radiographic response, and tolerability by patient-reported outcomes and adverse event documentation. Results: 90 patients were screened, 32 were treated (8 vaccine, 9 placebo, 15 ancillary), and 26 were evaluable for radiographic responses prior to accrual termination. The study did not meet its primary endpoint of overall survival at one year (65.5% in vaccine group, 75% in placebo). Progression-free endpoints were mildly improved in the vaccine group but were not significant, and response rates were not significantly different. The regimen was well-tolerated and safe. Conclusions: Though limited by early discontinuation, these findings do not support the combination of pembrolizumab and HSPPC-96 vaccine with standard of care therapy. Trials Registration: ClinicalTrials.gov identifier: NCT03018288

09.
medRxiv (Medicine) 2026-06-24

Cortisol Stress Response is Associated with Iron Status in Pregnancy

Background: Iron deficiency (ID) affects up to 40% of pregnant women in the third trimester, even in highly resourced and iron-supplemented populations, with adverse consequences for maternal health and long-term offspring development. Psychological stress may compromise iron status through hypothalamic-pituitary-adrenocortical (HPA) axis dysregulation and inflammation, but no study has directly examined cortisol in relation to iron status across human pregnancy. Objective: This longitudinal study examined associations between HPA function and maternal iron status across pregnancy and tested whether IL-6 and CRP mediated the relationship between cortisol and ferritin across gestation. Methods: One hundred sixty-eight pregnant Black women with Medicaid insurance completed up to four laboratory assessments across pregnancy. Salivary cortisol was measured before and in response to the Trier Social Stress Test, yielding basal and reactive cortisol indices. Serum ferritin, IL-6, and CRP were collected at each visit. Trimester-specific regression models examined cortisol reactivity in relation to ferritin; linear mixed-effects models with moderated mediation tested whether basal cortisol predicted ferritin via inflammation. Results: Higher cortisol reactivity was associated with lower ferritin specifically in the third trimester (std. {beta} = -0.197, p = .004). Higher basal cortisol predicted a steeper IL-6 rise across gestation (p = .002), and IL-6 was positively associated with ferritin (b = 0.236, p = .006), consistent with inflammatory iron sequestration. The indirect effect of basal cortisol on ferritin via IL-6 was statistically significant, and higher basal cortisol was negatively associated with cortisol reactivity in the third trimester. No pathway was observed through CRP. Conclusion: Greater cortisol reactivity predicted lower third-trimester ferritin, a pattern that suggests cumulative iron depletion, atypically sustained HPA reactivity in late pregnancy, or both. To our knowledge, this is the first prospective study linking cortisol reactivity to iron status across human pregnancy, identifying maternal stress physiology as a novel target for understanding and addressing gestational iron deficiency.

10.
arXiv (quant-ph) 2026-06-15

Optimal Decoding of Small Codes by Density Matrix Propagation

arXiv:2606.14455v1 Announce Type: new Abstract: Accurate and efficient decoding is a crucial component for achieving fault-tolerant quantum computing. Realistic circuit-level noise introduces temporal correlations and degeneracy, making optimal (maximum-likelihood) decoding computationally intractable in general. As a result, practical decoders rely on heuristic approximations, and it is generally difficult to quantify how suboptimal they are, as this strongly depends on the code and noise model considered. In this work, we study the accuracy of practical decoding algorithms under circuit-level noise by comparing them against a maximum likelihood decoding benchmark. Our approach propagates the density matrix through the full memory experiment and computes the optimal decoding decision for each syndrome history. We introduce pruning techniques with rigorous bounds, allowing us to access larger numbers of syndrome-extraction rounds. We apply this framework to small instances of the repetition code and a cellular automaton code, and benchmark minimum-weight perfect matching (MWPM), belief propagation with ordered statistics decoding (BP+OSD), Tesseract, and Planar decoders against optimal decoding. While standard decoders remain close to optimal for the repetition code, we find significant deviations for the cellular automaton code, with BP+OSD deteriorating already in experimentally relevant noise regimes. Moreover, the pruning method developed here highlights that, at low physical error rates, only a narrow fraction of syndrome histories contributes significantly to the logical error rate.

11.
arXiv (CS.AI) 2026-06-18

PSyGenTAB: A Privacy-Preserving Framework for Synthetic Clinical Tabular Data Generation via Constrained Optimization

arXiv:2606.18518v1 Announce Type: cross Abstract: The development of medical AI is constrained by limited access to high-quality clinical data due to institutional silos and strict privacy regulations such as HIPAA and GDPR. Synthetic data generation offers a potential solution, but existing methods lack principled mechanisms to explicitly manage the privacy-utility trade-off, often degrading clinically meaningful patterns or risking patient re-identification. We present PSyGenTAB, a privacy-preserving generative framework that formulates synthetic healthcare data generation as a constrained optimization problem solved using the Augmented Lagrangian Method. By embedding configurable privacy constraints directly into model training, PSyGenTAB enforces minimum privacy thresholds while maximizing clinical data utility. Across multiple clinically motivated benchmarks, PSyGenTAB preserves inter-feature clinical relationships and minority-class diagnostic patterns essential for reliable health AI. Downstream evaluation using Train-on-Synthetic, Test-on-Real and Train-on-Real, Test-on-Synthetic protocols shows that models trained on synthetic data achieve performance comparable to those trained on real patient records. Privacy auditing further demonstrates reduced exact record reproduction and strong resilience to membership inference attacks. These results establish PSyGenTAB as a principled framework for balancing privacy protection and clinical utility in synthetic healthcare data, supporting secure cross-institutional AI development.

12.
arXiv (quant-ph) 2026-06-16

Adaptively secure unitary designs with constant non-Clifford cost

arXiv:2510.08129v2 Announce Type: replace Abstract: Randomness is a fundamental resource in quantum information, with crucial applications in cryptography, algorithms, and error correction. A central challenge is to construct unitary $k$-designs that closely approximate Haar-random unitaries while minimizing the costly use of non-Clifford operations. In this work, we present a protocol able to generate unitary $k$-designs on $n$ qubits, secure against any adversarial quantum measurement, with a system-size-independent number of non-Clifford gates. Our construction applies a $k$-design only to a subsystem of size $\Theta(k)$, independent of $n$. This ``seed'' design is then ``diluted'' across the entire $n$-qubit system by sandwiching it between two random Clifford operators. The resulting ensemble forms an $\varepsilon$-approximate unitary $k$-design on $n$ qubits. We prove that this construction achieves full quantum security against adaptive adversaries using only $\tilde{O}(k^2 \log\varepsilon^{-1})$ non-Clifford gates. If one requires security only against polynomial-time adaptive adversaries, the non-Clifford cost decreases to $\tilde{O}(k + \log^{1+c} \varepsilon^{-1})$. This is optimal, since we show that at least $\Omega(k)$ non-Clifford gates are required in this setting. Compared to existing approaches, our method significantly reduces non-Clifford overhead while strengthening security guarantees to adaptive security as well as removing artificial assumptions between $n$ and $k$. These results make high-order unitary designs practically attainable in near-term fault-tolerant quantum architectures.

13.
arXiv (CS.CV) 2026-06-16

Mask Proposal Voting Based on Geodesic Framework for Robust Image Segmentation

Despite great advances, finding accurate segmentation remains a challenging task, especially in scenarios with cluttered backgrounds, complex intensity variations and topology appearance. Minimal path models have exhibited their strong ability in addressing image segmentation tasks. However, the performance of minimal paths-based segmentation approaches is heavily influenced by model initialization, hence limiting their application scope in practice. In this work, we propose a novel mask proposal voting framework that overcomes the major drawback of classical approaches, allowing robust segmentation even in complicated scenarios. Firstly, we introduce an efficient method for constructing adaptive domain cuts as a constraint for initializing the region-based min-cut evolution, by which diverse and reliable mask proposal candidates can be generated, substantially increasing the possibility of accurately covering the objective region by these proposals. Secondly, we propose a new mask voting scheme to build a voting score map encoding the final segmentation information. In contrast to classical path voting methods, our model allows incorporating priors to assign different importance to each individual mask. As a consequence, the proposed segmentation model is capable of accurately delineating object boundaries under complex scenarios, and is insensitive to initialization. Experiments demonstrate that our method consistently outperforms state-of-the-art minimal path-based approaches in both accuracy and robustness.

14.
arXiv (CS.LG) 2026-06-24

A Time-Reparameterized Cumulative Intensity Extrapolation Sampler for Discrete Flow Matching

arXiv:2606.24140v1 Announce Type: new Abstract: Discrete flow matching (DFM) provides a principled framework for generative modeling on discrete state spaces via continuous-time Markov chain dynamics. In practice, sampling for DFM commonly employs discretizations such as $\tau$-leaping, yet efficient sampling methods under a limited number of function evaluations (NFE) remain less studied. To address this gap, we propose the Time-Reparameterized Cumulative Intensity Extrapolation (TR-CIE) sampler, which aims to improve sampling quality when function evaluations are restricted. TR-CIE consists of two components. First, a schedule-based time reparameterization rescales the time grid according to the noise schedule. Under standard factorized DFM rate parameterizations, this transformation of variables absorbs the schedule-dependent growth term and mitigates stiffness near the terminal sampling stage. Second, we introduce a cumulative-intensity extrapolation updating rule. By reusing cached model outputs from the previous step as a history term, this improves the approximation of stepwise cumulative intensities on the resulting non-uniform time grid. We provide a theoretical analysis that bounds the local approximation error of cumulative intensities and establishes convergence results. The resulting sampler requires one NFE per step and introduces no additional model evaluations compared to the standard $\tau$-leaping sampler. Extensive experiments on synthetic tasks, text generation, and text-to-image benchmarks demonstrate that our method improves sampling quality under limited NFE.

15.
arXiv (CS.AI) 2026-06-18

Target-confidence Recourse Using tSeTlin machines: TRUST

arXiv:2606.18832v1 Announce Type: cross Abstract: Counterfactual explanations are widely used to provide algorithmic recourse in high-stakes decision-making systems. Most existing methods seek the smallest change to an input that flips a model's decision. However, decision-makers often rely not only on predicted labels but also on confidence thresholds and risk margins. Counterfactuals that barely cross a decision boundary can be fragile and unstable under noise or model variation. In this paper, we propose Target-confidence Recourse Using tSeTlin machines (TRUST), a framework in which users explicitly specify the desired prediction confidence for recourse. Rather than generating counterfactuals and evaluating confidence afterward, TRUST directly searches for minimal changes that satisfy a user-defined confidence target, enabling comparison of recourse options in terms of cost, confidence, and robustness. We instantiate TRUST using a Probabilistic Tsetlin Machine (PTM) combined with Bayesian optimization. The probabilistic clause-based structure of PTM links prediction confidence to the stability of decision rules. We show that counterfactuals satisfying the same rules can still differ substantially in reliability depending on how securely they satisfy those rules, revealing whether decisions are supported by robust or fragile clause activations. Experiments on synthetic and real-world datasets demonstrate that target-confidence counterfactuals produce more robust and interpretable recourse than conventional boundary-based approaches. Across multiple benchmarks, TRUST achieves perfect robustness while maintaining low recourse cost, including an L2 distance of 0.10 on the Haberman dataset at 0.92 confidence. By explicitly controlling confidence and exposing rule-level stability, TRUST provides actionable recourse for high-stakes decision support.

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

Entanglement in the Dicke subspace

arXiv:2602.15800v2 Announce Type: replace Abstract: We provide a complete mathematical theory for the entanglement of mixtures of Dicke states. These quantum states form an important subclass of bosonic states arising in the study of indistinguishable particles. We introduce a tensor-based parametrization where the diagonal entries of these states are encoded as a symmetric tensor, enabling a direct translation between entanglement properties and well-studied convex cones of tensors. Our results bridge multipartite entanglement theory with semialgebraic geometry and the theory of completely positive and copositive tensors. This dictionary maps separability to completely positive tensors, the PPT property to moment tensors, entanglement witnesses to copositive tensors, and decomposable witnesses to sum of squares tensors. Using this framework, we construct explicit PPT entangled states in three or more qutrits, disproving a recent conjecture. We establish that PPT entanglement exists for all multipartite systems with local dimension d >= 3 and n >= 3 parties. We also show that, for mixtures of Dicke states, the PPT condition with respect to the most balanced bipartition implies all other PPT conditions. We further connect bosonic extendibility of mixtures of Dicke states to the duals of known hierarchies for non-negative polynomials, such as the ones by Reznick and Polya. We thus provide semidefinite programming relaxations for separability and entanglement testing in the Dicke subspace.

17.
arXiv (quant-ph) 2026-06-16

High-performance gates on trapped ion qubits using counterpropagating pulse-shaped laser beams

arXiv:2606.15672v1 Announce Type: new Abstract: Highly-localized light-matter interactions are necessary for scaling trapped-ion architectures. In hyperfine qubits, counterpropagating beams generate entangling gates by coupling with motion, but this effect is undesirable during single-qubit operations. For that reason, single-qubit gates are traditionally implemented with copropagating beams, and the coexistence of two beam geometries adds hardware and computational overhead. In an effort towards collective performance improvement with minimal overhead, we design and implement pulse-amplitude and dephasing robust dynamically corrected gates using Space Curve Quantum Control (SCQC) and compare them against the constant-amplitude gate implementation. We perform gate set tomography on a four-qubit trapped-ion register, and we discover more than 50% error reduction when robust pulses are used. We find that counterpropagating robust gates often outperform their copropagating counterparts and reach error rates as low as $(3.59 \pm 1.25)\cdot 10^{-3}$, using diamond distance as a metric. This value establishes a laser-driven-gate error reference and is merely an order of magnitude higher than the best reported $microwave$ gate on a $single$ ion. Additional experiments reveal that robust pulses can effectively suppress non-Markovian errors that grow during runtime. Our work challenges the widely accepted belief that copropagating gates should be preferred for their weak motional coupling and invites the adoption of high-performance robust pulses that suppress multiple noise sources of the trapped-ion error budget.

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

Adjusted Cup-Product Neural Layer

arXiv:2606.13568v1 Announce Type: new Abstract: Many important observables in physics and geometry are cup products of cochains. The adjusted cup product neural layer has been introduced in this paper. It is a neural primitive that hard wires the cup product with an adjustment term from higher gauge theory. This creates a readout that is gauge invariant by design. Their main theoretical result shows that on a closed cycle the output relies entirely on the adjustment coefficient. Setting this coefficient to zero removes the output completely regardless of other parameters. Thus the adjustment is the only source of gauge invariant signal. They prove this observable is a nonzero quadratic form and is exactly invariant under one and two gauge transformations.

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

Contextual Invertible World Models: A Neuro-Symbolic Agentic Framework for Colorectal Cancer Drug Response

arXiv:2603.02274v3 Announce Type: replace-cross Abstract: Precision oncology is currently limited by the small-N, large-P paradox, where high-dimensional genomic data is abundant but pharmacological response samples are sparse. While deep learning achieves predictive accuracy, it frequently fails to provide the mechanistic clarity required for clinical adoption. We present the Contextual Invertible World Model (CIWM), a Neuro-Symbolic Agentic Framework that bridges this gap by integrating a quantitative machine learning emulator with a Large Language Model reasoning layer. Utilising a stringently curated, high-fidelity data engineering pipeline on the Sanger GDSC dataset (\( N=83 \)), we isolate true biological signals from in vitro artifacts to establish a rigorous baseline predictive correlation for complex transcriptomics (\( r=0.268 \)). Through Inverse Reasoning, we perform in silico CRISPR perturbations across the colorectal landscape. The framework autonomously overturns classical mechanistic assumptions, identifying a hierarchical dominance of mutant KRAS over the APC/Wnt-axis in driving 5-fluorouracil resistance (\( \Delta=-0.0469 \)) via a "KRAS Shield" mapped to MAPK/PI3K networks. Furthermore, the agentic layer identified a "PIK3CA Paradox", revealing that repairing PIK3CA inadvertently increases chemoresistance (\( \Delta=+0.0085 \)) by triggering a compensatory feedback loop that hyperactivates the dominant MAPK survival pathway.

20.
Nature (Science) 2026-06-10

A first-in-class pulsatile FXR agonist for bile-acid-related liver diseases

Authors:

Nuclear receptors are central regulators of metabolism1, yet therapeutic strategies that enforce continuous receptor activation frequently lead to reduced efficacy and unacceptable toxicity. Here we report a first-principles drug design strategy that aligns pharmacokinetics with physiological signalling cycles. We developed linafexor, a potent non-bile-acid agonist of the farnesoid X receptor (FXR)2; it is engineered for rapid systemic clearance, which enables pulsatile receptor activation that mirrors endogenous bile acid dynamics3–5. Linafexor has robust efficacy across multiple preclinical models of metabolic dysfunction-associated steatohepatitis6, liver fibrosis7, primary biliary cholangitis and primary sclerosing cholangitis8,9. Transcriptomic analyses reveal that, unlike long-acting FXR agonists10,11, linafexor preserves cyclic FXR signalling, avoids receptor downregulation and prevents broad transcriptional dysregulation. Direct manipulation of delivery patterns demonstrates that sustained FXR activation—independent of compound identity—induces severe toxicity, establishing activation duration as a determinant of therapeutic index. In phase 1 clinical studies (ClinicalTrials.gov; NCT05082779), linafexor administered once daily produces transient FXR pathway engagement, marked by (1) induction of FGF1912–14, a key endocrine mediator of bile acid feedback regulation; and (2) suppression of C415, an intermediate reflecting hepatic bile acid synthesis, with no treatment-related adverse events. Together, these findings identify pulsatile FXR activation as a mechanistically grounded and clinically translatable strategy, and establish linafexor as a first-in-class therapeutic for bile acid–related liver diseases. Linafexor is a rapidly cleared FXR agonist designed to mimic natural bile acid signalling, achieving transient receptor activation with strong efficacy and reduced toxicity in preclinical and early clinical studies.

21.
arXiv (CS.CL) 2026-06-24

MMed-Bench-IR: A Heterogeneous Benchmark for Multilingual Medical Information Retrieval

Retrieval-augmented generation (RAG) in clinical settings increasingly requires multilingual retrieval against predominantly English evidence corpora. Multilingual medical retrieval demands three capabilities: cross-lingual alignment, concept discrimination, and evidence retrieval. However, existing benchmarks evaluate these only in isolation, leaving the interaction between biomedical expertise and multilingual coverage unmeasured. We introduce MMed-Bench-IR, a benchmark designed to disentangle these axes across 6 languages and three structurally heterogeneous tasks: (1) cross-lingual medical QA retrieval with 6,127 queries grounded in the Unified Medical Language System (UMLS), (2) concept discrimination over 4,975 confusion sets at three difficulty tiers, and (3) multilingual evidence retrieval for RAG with 2,040 quality-assured queries. The three tasks share zero concept and query overlap by design, ensuring that aggregate scores reflect genuine capability breadth. Evaluation of ten systems across six paradigm families reveals severe cross-lingual failure: biomedical encoders that score 0.818 nDCG@10 in English drop to 0.056 in Japanese, a gap that English-only benchmarks cannot detect.

22.
arXiv (quant-ph) 2026-06-24

Offline Channel-Independent QAOA Angles for RIS Power Aggregation: Unit-Circle Phase Dictionaries and Infinite-Size Spin-Glass Limits

arXiv:2606.24540v1 Announce Type: new Abstract: Reconfigurable intelligent surfaces (RIS) maximize received power by setting per-element phases. Discrete-phase optimization is NP-hard in the worst case, while the quantum approximate optimization algorithm (QAOA) applied to RIS faces limited phase alphabets, either per-problem angle optimization or uncharacterized training cost exposed to barren plateaus, and no scalable performance benchmark. We introduce a $2^{M}$-phase $\theta$ dictionary for optimizing power $\|\mathbf{A} \, e^{j\theta}\|^{2}$ having $K \times N$ channel matrix $\mathbf{A}$ and QAOA angle offline optimization with instance and size-independent infinite-size limit of the mixed-$q$ Gaussian ensemble of Basso et al. Our design bounds the spin-Hamiltonian interaction order to at most quartic for any $M$, and the deployed order-2 reduction lies below the even-$q\!\ge\!4$ regime in which constant-level QAOA limitations are proved. We perform analytical, state-vector, matrix-product-state and Pauli-path-simulation numerical studies for $N=K \leq 100$ and QAOA depth $p=9$, verifying offline angle transfer to Rayleigh, Rician/line-of-sight, cascaded double-fading and spatially-correlated RIS channels at $N\!\in\!\{5,12\}$. We observe performance reaching a near-optimal multi-start single-flip local-search reference for $N\!\le\!16$ under order-2 modeling with $2^{5}{=}32$-phase dictionary while the order-4 model shows a performance ceiling below the classical reference. The approach suggests a route to near-optimal large-$N$ performance on future fault-tolerant (FTQ) quantum computers, which enable the higher-depth QAOA circuits.

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

MoVerse: Real-Time Video World Modeling with Panoramic Gaussian Scaffold

We present MoVerse, a real-time video world model that creates an interactively navigable scene from a single narrow-field-of-view image. This setting is challenging because the input observes only a small fraction of the environment, while interactive roaming requires a complete surrounding world, persistent geometry, controllable camera motion, and temporally coherent high-fidelity observations. MoVerse addresses this problem by separating world construction from observation rendering. It first expands the input into a gravity-aligned 360$^\circ$ panorama with topology-aware diffusion, closing the missing field of view before 3D reasoning. It then lifts the panorama into a persistent 3D Gaussian scaffold using panoramic geometry-aware residual prediction, yielding a dense and directly renderable spatial memory. Finally, a Gaussian-conditioned video renderer translates scaffold renderings along user-specified camera trajectories into photorealistic video. To make this renderer practical for interaction, we train a bidirectional diffusion teacher for high-quality conditional rendering and distill it into a causal autoregressive student for bounded-latency streaming. This design combines the controllability and long-range consistency of explicit 3D representations with the perceptual quality of generative video models. MoVerse supports real-time scene roaming at 8~FPS on a single NVIDIA RTX~4090 GPU, demonstrating a practical path toward single-image world creation with interactive video output.

24.
medRxiv (Medicine) 2026-06-16

AI-assisted continuous-time modelling of metastatic breast cancer reveals subtype-specific spatiotemporal organ interactions

Metastatic breast cancer is one of the leading causes of premature mortality among women worldwide. A major barrier to optimal care is the marked heterogeneity in both the temporal dynamics of metastatic spread and the organ-specific spatial distribution of metastases. Existing analyses do not adequately capture this complexity, as they either neglect temporal dependencies or assume independence between metastasic sites. As a result, it remains unclear how established metastases influence subsequent organ-specific dissemination. We address this question using patient-level longitudinal trajectories from a large multicentre real-world metastatic breast cancer registry, combined with an AI-assisted disease-progression modelling framework based on continuous-time Markov chains that represent combinations of metastatic sites and the non-uniform and practice-driven timing of radiologic response assessments, as encountered in routine clinical care. We present a stochastic model determined by progression rates, which are parameterised to capture baseline organ-specific transition risks, patient-level covariates, and pairwise inter-organ interaction effects. High-dimensional treatment information is incorporated using an large language model based encoding. We find that metastatic spread follows non-independent, subtype-specific spatiotemporal patterns, with subtype-specific inter-organ interaction patterns that shape progression. Visceral metastases, particularly lung and liver metastasis, are associated with an increased hazard of subsequent brain metastasis, with effects varying across hormone receptor-positive, HER2-positive, and triple-negative subtypes. Together, these findings define a clinically relevant spatiotemporal architecture of metastatic progression in breast cancer. This framework enables refined mechanism-informed risk stratification and provides a data-driven rationale for targeted and risk-adapted – rather than symptom-triggered – surveillance strategies.

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arXiv (CS.CV) 2026-06-18

Toward Training-Free Zero-Shot Anomaly Detection in 3D Medical Images: A Batch-Based Approach Using 2D Foundation Models

Authors:

Zero-shot anomaly detection (ZSAD) is attractive for medical imaging because clinical systems must handle heterogeneous acquisition protocols, changing patient populations, and pathologies for which annotated training data may be unavailable. Most existing zero-shot anomaly detection methods are designed for 2D images, and their direct extension to 3D medical volumes is limited by the scarcity of large-scale volumetric foundation models or by the difficulty of utilizing volumetric context. We propose CS3F, a training-free batch-based framework for ZSAD in 3D medical images using 2D foundation models. Each volume is decomposed along multiple anatomical axes and encoded slice-wise by a 2D vision transformer. These are then converted into localized volumetric tokens by pooling neighboring slice features. Anomaly scores are obtained from cross-subject mutual similarity: tokens that lack close analogues in other subjects are assigned higher anomaly scores. To reduce the attenuation of focal lesion signals caused by depth pooling, we introduce a coarse-to-fine tokenization strategy that enables fine-resolution volumetric scoring without exhaustive matching. CS3F is evaluated on brain MRI across metastases, glioma, and stroke, as well as validated on lung CT to test generalizability beyond atlas-aligned brain MRI. The results show that frozen 2D foundation models can support anomaly localization in 3D medical images, and that the benefit of fine tokenization depends strongly on lesion contrast and imaging modality.