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01.

arXiv (CS.CL) 2026-06-12 DOI: arXiv:2606.12576

Helping Figures Tell their Story! Paper-Grounded Video Generation Explaining Complex Scientific Figures

作者:

Ishani Mondal↗Javad Baghirov↗Jordan Boyd-Graber↗

Scientific figures compress complex pipelines into a single canvas, yet understanding them requires paper-grounded, step-by-step narration aligned with visual highlights a capability missing from current video generation systems and benchmarks. To address this, we introduce paper-grounded figure-to-video generation: generating narrated, region-grounded walkthrough videos from a figure and its paper. We propose MINARD (Multimodal Interpretation of Narrated Architecture via Region Decomposition), a pipeline that generates paper-grounded narrations and sequentially grounds them to figure regions. We also release FigTalk, a benchmark with new sequential and component-level grounding metrics derived. On FigTalk, MINARD generates humanlike, paper-faithful narrations and outperforms narration-conditioned figure spatial grounding compared to existing approaches in both automatic and human evaluation

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02.

arXiv (CS.LG) 2026-06-16 DOI: arXiv:2606.15531

Greedy Coordinate Diffusion: Effective and Semantically Coherent Adversarial Attacks via Diffusion Guidance

作者:

Bohdan Turbal↗Blossom Metevier↗Max Springer↗Aleksandra Korolova↗

arXiv:2606.15531v1 Announce Type: new Abstract: Fine-tuning aligned language models on benign tasks (e.g. math tutoring) systematically breaks safety guardrails, even when training data contains no harmful content. While mechanistic approaches have shed light on where alignment resides in model weights, they do not by provide a general formal framework for deriving guarantees about when fine-tuning degrades it – leaving the field without principled tools for predicting or preventing alignment collapse. We develop a local geometric framework through geometric analysis of parameter-space trajectories and apply it to understand the fragility of alignment in fine-tuning. While first-order analysis suggests orthogonal updates are safe, we prove this is illusory: the curvature of the fine-tuning loss induces second-order acceleration that can induce second-order drift into alignment-sensitive regions. We formalize a construct of our framework as the Alignment Instability Condition (AIC), three geometric properties that, when present, are sufficient to guarantee degradation. Our main result proves quartic onset of alignment degradation along gradient-flow trajectories, determined by how sharply alignment depends on specific parameters and how strongly tasks couple to these parameters. These findings yield formal sufficient conditions under which static first-order protection can fail under gradient descent. We further empirically validate the framework's foundations, showing that the Fisher Information Matrix provides a proxy for the degree of safety degradation across diverse fine-tuning.

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03.

arXiv (CS.LG) 2026-06-12 DOI: arXiv:2606.13568

Adjusted Cup-Product Neural Layer

作者:

Snigdha Chandan Khilar↗

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.

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04.

arXiv (quant-ph) 2026-06-12 DOI: arXiv:2605.31544

More efficient Clifford+T synthesis for small-angle rotations and application to Trotterization

作者:

Marius Bothe↗Christoph S\"underhauf↗Michael J. Witham↗Earl T. Campbell↗Nick S. Blunt↗

arXiv:2605.31544v2 Announce Type: replace Abstract: Clifford+T synthesis of rotation gates is an important routine in fault-tolerant quantum compilation. While Clifford+T synthesis is scalable, it has a high overhead of tens of T gates per rotation in practice, translating to high resource estimates for many fault-tolerant algorithms. However, these well-known results, including those using probabilistic mixtures [Quantum 7, 1208 (2023)], are independent of the rotation angle $\theta$, requiring $O(\log 1/\delta)$ T gates. We show that it is possible to do much better for small angles, reducing the T cost to $\tilde{O}(\theta^2/\delta)$, and returning to existing $O(\log1/\delta)$ results in the worst case. This is particularly important since many algorithms, such as Trotterization, are dominated by small-angle rotations. Further, we perform a detailed theoretical and numerical study of quasi-probabilities, which can further reduce the total T cost of large circuits by orders of magnitude with only a small overhead in sample complexity. We also develop a scheme based on quasi-probability mixtures of Clifford+T fallback channels. We derive new $\theta$-dependent formulas that can be used for resource estimation of fault-tolerant quantum algorithms. As an application of our results, we show that the gate cost of Trotterization circuits compiled to a Clifford+T gate set is constant in the small Trotter step size limit, and can be reduced by orders of magnitude even for large step sizes. The cost of fault-tolerant Trotterization for a variety of applications should be re-examined in light of these results. Our work dispels the widely-stated claim that Clifford+T rotation synthesis has a high cost independent of $\theta$, and further develops a scalable quasi-probability method for rotation synthesis. We also expect our results to bring forward useful early fault-tolerant quantum computing by reducing required magic state resources.

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05.

arXiv (CS.AI) 2026-06-15 DOI: arXiv:2606.14629

When Good Verifiers Go Bad: Self-Improving VLMs Can Regress on New Tasks

作者:

Jianzhe Lin↗

arXiv:2606.14629v1 Announce Type: cross Abstract: Verifier-driven self-DPO is a common recipe for self-improving production visual-language models. In this setup, a frozen verifier scores candidate generations, the top- and bottom-scoring candidates form a preference example, and DPO updates the learner. The deployment-time assumption is monotone: a stronger verifier should yield a stronger student. We show that this assumption can fail because verifier quality is highly task-specific. On a four-rung open-source verifier ladder across MathVista, MMMU, and BLINK, the same verifiers that are above-threshold and improve a Qwen-3-VL-2B student on MathVista become sub-threshold on MMMU, where their task-rubric accuracy drops to 8% to 23%. In this regime, every verifier we tested silently regresses the student, producing drops of 3.4 to 10.9 percentage points below the frozen baseline while the DPO training loss continues to decrease. The regression replicates on a second student, Qwen-2.5-VL-3B. Moreover, within the failure regime, damage is confidence-inverted: the more accurate-but-still-wrong verifier causes larger regression than a near-random verifier, suggesting that progress-gated replay amplifies confidently wrong preference pairs. We give a compact mechanistic explanation via a variance theorem for progress-gated replay and its direction-mismatch failure mode. The deployment message is operational rather than purely diagnostic: before running any verifier-driven loop, teams should measure target-task rubric accuracy, rank verifiers by target-task rubric quality rather than parameter count, and treat diminishing returns in above-threshold regimes as a verifier-side compute budget cap.

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06.

arXiv (CS.AI) 2026-06-12 DOI: arXiv:2606.13355

Real-Time Execution with Autoregressive Policies

作者:

Sangkyu Lee↗Seohyeon Park↗Tackgeun You↗Avi Caciularu↗Idan Szpektor↗Hwasup Lim↗Youngjae Yu↗

arXiv:2606.13355v1 Announce Type: cross Abstract: Real-time execution, enabled by asynchronous inference that ensures both smooth action trajectories and fast reactivity, is critical for realistic deployments of large-scale Vision-Language-Action models. However, recent work on real-time execution primarily focuses on variants of diffusion policies, even though it is more critical for autoregressive policies given their slower rollout speed in synchronous inference. In contrast, we demonstrate that autoregressive policies can achieve real-time execution by adjusting the tokenization horizon and applying constrained decoding, thereby guaranteeing strict latency bounds that enable multi-trajectory decoding to maximize performance. Across simulated and real-world environments, we find that the autoregressive policy consistently outperforms its equivalent-level flow-matching policy counterpart while achieving significantly improved task completion speeds from synchronous inference. Coupled with the inherent advantages of autoregressive policies, such as faster convergence and better generalizability in instruction-following, these results confirm that autoregressive policies can remain a competitive policy type supporting real-time execution.

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07.

arXiv (CS.CV) 2026-06-19 DOI: arXiv:2606.20404

FlowBender: Feedback-Aware Training for Self-Correcting Conditional Flows

作者:

Daniel Gilo↗Sven Elflein↗Ido Sobol↗Or Litany↗

Conditional diffusion and flow models routinely fail to satisfy the very constraints that define their task. For instance, a depth-conditioned model often produces images whose re-extracted depth disagrees with the input, even though the forward operator–the depth predictor defining the constraint–is available during both training and inference. Existing approaches generally fall into two categories: supervised models that treat the conditioning signal as a static cue and ignore alignment information at inference, and guidance-based methods that consult it through hand-tuned linear updates, typically trading fidelity to the condition against the plausibility of the generated sample. We argue that the fundamental gap in both paradigms is that the model is never trained to utilize its own alignment error. We introduce FlowBender, a closed-loop framework that treats this error as a first-class input, training the network to learn a correction policy conditioned on inference-time feedback. At each step, an unguided look-ahead pass estimates the clean signal, a task-specific deviation is computed via the forward operator, and a refinement pass consumes this signal to produce a corrected velocity. We propose several variants of FlowBender, including a gradient-based formulation for differentiable operators and a zero-order variant for non-differentiable settings such as JPEG compression. For efficient sampling, we introduce a prior-step shortcut that enables closed-loop correction at a minimal additional computational cost. Across image-to-image translation, restoration, and 3D mesh texturing, FlowBender consistently outperforms standard supervised baselines, alignment-loss-augmented training, and state-of-the-art inference-time guidance, improving fidelity and plausibility simultaneously rather than trading them against each other. Project page: https://flow-bender.github.io/

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08.

bioRxiv (Bioinfo) 2026-06-11 DOI: HASH:f4d4106092322fb96fbad9f8a1c95e90

GermRL: Alleviating The Germline Bias In Autoregressive Antibody Language Models Through Reinforcement Learning

作者:

Ludwig↗Chungyoun↗Gray↗J. J↗

Antibodies are powerful therapeutics whose antigen specificity arises from sequence diversity shaped during development. Recently, language models trained on large antibody repertoire datasets have enabled the generation and screening of novel candidates, but these models retain a strong germline bias. As AI adoption increases in therapeutic workflows, it is crucial to develop models that harness the diversity of antibodies necessary for the discovery of mutations that encode desirable properties. Previous work explored the germline bias in masked antibody language models, yet the bias in generative autoregressive language models has not yet been addressed. Here, we present GermRL, a lightweight and modular reinforcement learning (RL) framework capable of alleviating the germline bias in pre-trained antibody autoregressive language models through group relative policy optimization (GRPO). GermRL achieves consistent one-shot generation of antibodies that satisfy specified mutation thresholds from germline while maintaining structural plausibility. Under the lowest and highest mutation thresholds tested (5 and 35 mutations from germline), GermRL scores 0.992 and 0.950 pass@1, respectively, compared to 0.398 and 0.034 for the pre-trained language model. Within GermRL, we introduce a key pair of modifications to GRPO that increase training efficiency by discouraging reward hacking under our antibody application. Furthermore, comparison of RL generated and natural antibody sequences reveals how RL based optimization can explore alternative evolutionary mutational patterns and residue compositional strategies while preserving key global properties of natural antibodies, including identifiable germline assignments, embedding-level similarity and comparable developability profiles. Thus, RL-trained generative models optimized to promote antibody mutations through diversity from germline provide a promising framework for navigating the antibody sequence landscape, enabling exploration of novel yet biologically plausible candidates for therapeutic design.

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09.

arXiv (CS.LG) 2026-06-17 DOI: arXiv:2606.17120

Noise-Driven Escape from Metastable Phases explains Grokking in Deep Neural Networks

作者:

Ibrahim Talha Ersoy↗Karoline Wiesner↗

arXiv:2606.17120v1 Announce Type: new Abstract: Deep neural networks (DNNs) exhibit first order phase transitions under variations of the L2 regularization strength, with each transition marking the onset of a new learnable feature. Below a critical regularization strength, all features are in principle learnable, but coexisting metastable states, separated by energy barriers, can trap the network and impede convergence. A strength of DNNs is their ability to generalize. But many open questions remain, among them the origin of so called grokking: the abrupt, delayed onset of generalization after prolonged apparent overfitting. We show for linear DNNs that grokking is consistent with hysteresis in first-order L2 phase transitions: using L2 regularization to engineer deliberate trapping, we demonstrate that a model in a low-accuracy metastable state escapes only when SGD noise drives it across an energy barrier, with escape times following Arrhenius scaling. We reproduce grokking-like delayed convergence across two orders of magnitude in escape time by deliberately trapping models in metastable phases. Using sparse sub-sampling we also reproduce the canonical grokking curve where test error eventually approaches the final training error. Our work suggests that the number of metastable states equals the number of learnable features – one per singular value of the data covariance – the potential for hysteresis grows naturally with task complexity. We provide evidence that the same mechanism likely operates in general nonlinear DNNs. Our results provide routes toward more efficient learning schemes.

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10.

arXiv (CS.LG) 2026-06-18 DOI: arXiv:2606.19039

Adaptive Speech-to-Spike Encoding for Spiking Neural Networks

作者:

Taharim Rahman Anon↗Jakaria Islam Emon↗

arXiv:2606.19039v1 Announce Type: cross Abstract: The mismatch between continuous acoustic signals and discrete event-driven processing remains a fundamental bottleneck for neuromorphic speech processing. Current systems typically rely on fixed spike encoders, forcing downstream Spiking Neural Networks (SNNs) to compensate for non-adaptive input representations. To address this, we present a learnable residual speech-to-spike encoder jointly trained end-to-end with a Recurrent Leaky Integrate-and-Fire (R-LIF) backbone. We validate this approach on the Google Speech Commands v2 (GSC-v2) benchmark, achieving up to 94.97% accuracy. Notably, the learned encoder remains highly parameter-efficient with a compact 35k-parameter variant that reaches 89.8%, matching or exceeding prior baselines that require an order of magnitude more parameters. Our encoder-focused analysis, including linear probing and gradient-residual inspection, indicates that the encoder does not target faithful signal reconstruction but instead learns task-aligned spike representations that enhance class separability. Finally, we benchmark bio-inspired, hardware-friendly credit assignment by comparing Direct Feedback Alignment (DFA) with surrogate-gradient BPTT under identical architectures and training conditions. We find that DFA reaches 91.5% accuracy, quantifying the performance trade-off of bio-inspired learning rules for modern neuromorphic audio.

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11.

arXiv (quant-ph) 2026-06-19 DOI: arXiv:2606.19628

Subsystem Quantum Error Correction for Noisy Quantum Metrology

作者:

Qiushi Liu↗Sisi Zhou↗

arXiv:2606.19628v1 Announce Type: new Abstract: Quantum error correction has been successfully applied to enhance the precision of parameter estimation in the presence of noise. Nonetheless, existing methods require a number of noiseless, controllable ancillae and lack efficient encoding and decoding procedures. In this Letter, we demonstrate that subsystem error correction provides a new direction that can substantially simplify the metrological protocol. We derive general conditions under which subsystem stabilizer codes achieve the Heisenberg limit and show that, for broad classes of noise, this can be realized by syndrome-free protocols using at most a single ancilla qubit. Furthermore, we extend this framework to dynamical error correction and show that Floquet codes can protect time-dependent metrological signals in reaching the Heisenberg limit.

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12.

arXiv (CS.AI) 2026-06-11 DOI: arXiv:2606.11264

OmniBioTwin: A System-of-Twinned-Systems Framework for Health Digital Twins

作者:

Zhaohui Wang↗Yu Huang↗Jiang Bian↗

arXiv:2606.11264v1 Announce Type: cross Abstract: Health digital twins (HDTs) promise patient-specific modeling and decision support but current approaches remain structurally fragmented: monolithic models that address a single organ or task lack cross-scale fidelity, while system-level twins lack generalizable architectural frameworks. We propose OmniBioTwin, a System-of-Twinned-Systems (SoTS) framework that organizes HDTs as modular computational entities coupled through explicit interaction operators within a multi-layer network architecture. The framework comprises seven coordinated layers - spanning data integration, autonomous twin modeling, cross-scale coupling, temporal synchronization, and human-in-the-loop decision support. We demonstrate OmniBioTwin by instantiating a multiscale twin for glucagon-like peptide-1 (GLP-1) signaling pathways in Alzheimer's disease, illustrating how molecular, cellular, and organ-level twins can be composed and coupled within a unified system.

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13.

arXiv (quant-ph) 2026-06-16 DOI: arXiv:2603.26039

Achieving double-logarithmic precision dependence in optimization-based quantum unstructured search

作者:

Zhijian Lai↗Dong An↗Jiang Hu↗Zaiwen Wen↗

arXiv:2603.26039v3 Announce Type: replace Abstract: Grover's algorithm is a fundamental quantum algorithm that achieves a quadratic speedup for unstructured search problems of size $N$. Recent studies have reformulated this task as a maximization problem on the unitary manifold and solved it via linearly convergent Riemannian gradient ascent (RGA) methods, resulting in a complexity of $O(\sqrt{N/M}\log (1/\varepsilon))$, where $M$ denotes the number of target items and $\varepsilon$ denotes the success probability error. In this work, we adopt the Riemannian modified Newton (RMN) method to solve the quantum search problem, under the assumption that the ratio $ M/N$ is known. We show that, in this setting, the Riemannian Newton direction is collinear with the Riemannian gradient in the sense that the Riemannian gradient is always an eigenvector of the corresponding Riemannian Hessian. This structure removes the overhead of Hessian inversion and allows the proposed RMN method to retain the local quadratic convergence in terms of the error $\varepsilon$. More precisely, we rigorously prove an overall complexity of $O(\sqrt{N/M}+\log\log(1/\varepsilon))$. Furthermore, our approach remains Grover-compatible, namely, it relies exclusively on the standard Grover diffusion and oracle operators to ensure algorithmic implementability, and its parameter update process can be efficiently precomputed on classical computers.

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14.

arXiv (CS.LG) 2026-06-16 DOI: arXiv:2606.16028

The Information-Theoretic Benefit of Shared Representations under Orthogonality Constraints

作者:

Thomas Dittrich↗Oliver Potocki↗Philipp Grohs↗

arXiv:2606.16028v1 Announce Type: new Abstract: Modern deep learning architectures are increasingly multi-task and multi-modal, using a pretrained foundation model combined with task-specific, fine-tuned models. Empirically, exploiting similarity across different problems, instead of solving them individually, can significantly improve overall performance. While the generalization and sample complexity properties of multitask learning have been widely studied, the parametric complexity of joint approximation in comparison to separate approximation remains less well understood. The question is particularly relevant in modern deep learning, where models are increasingly required to satisfy structural constraints such as equivariance, conservation laws, or orthogonality. We prove lower and upper bounds on the description-length for separate and joint approximation classes, respectively, in uniform norm. We build a class of orthogonal functions by composing a shared hard feature, realized by a Rademacher-Haar wavelet series, with Sawtooth-Walsh readouts to enforce orthogonality of output coordinates. The dyadic tree structure of the Rademacher-Haar wavelet concentrates the approximation hardness in the common feature component, while the readouts act as task-specific heads. Using an information-theoretic framework, we obtain a sharp gap between the optimal approximation rates achievable by joint and separate coding. Finally, we realize this separation in a neural network model using Heaviside activations via reduction to triangle-wave approximation. Our results show that even under an orthogonality constraint joint approximation requires strictly fewer bits in compositional architectures, provided the tasks share a latent hard feature. This provides theoretical insight into the description-length-efficiency of compositional multi-output architectures and clarifies how neural networks can retain expressivity under geometric constraints.

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15.

arXiv (CS.CL) 2026-06-18 DOI: arXiv:2606.18686

ForecastBench-Sim: A Simulated-World Forecasting Benchmark

作者:

Jaeho Lee↗Nick Merrill↗Ezra Karger↗

Forecasting benchmarks for general-purpose AI systems usually inherit the constraints of the real world: outcomes resolve slowly, tail events are rare, and counterfactual questions are difficult to score. We introduce ForecastBench-Sim, a simulated-world forecasting benchmark built on game rollouts from Freeciv, a turn-based strategy game modelled on the Civilization series. Forecasters receive a fixed world report (a structured snapshot of the current game state) and answer questions about hidden future states; the benchmark then continues the simulation and scores forecasts. Because the world is simulated, the same setup can generate continuous or binary forecasting questions at arbitrary time horizons, paired intervention worlds for conditional or causal questions, and resolved examples of rare or disruptive outcomes. We describe the benchmark pipeline, question families, scoring protocol, and release artifacts, and report validation slices from model evaluations and an anonymized human pilot. ForecastBench-Sim is intended to complement real-world forecasting benchmarks by providing controlled, immediately resolvable tasks for studying probabilistic reasoning under dynamic world states.

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16.

medRxiv (Medicine) 2026-06-18 DOI: HASH:978670384e849196db5d532e4702fbe7

Urinary Creatine Riboside Complements PSA to Improve Disease Detection in the Diagnostic Gray Zone of Prostate Cancer

作者:

Patel↗D. P↗Casiano↗A. S↗Toulabi↗Khan↗Dorsey↗T. H↗Mathe↗E. A↗Harris↗C. C↗…

Circulating prostate-specific antigen (PSA) discriminates poorly in the diagnostic gray zone (3.0-9.99 ng/mL), where ~75% of biopsies yield no clinically significant prostate cancer (PCa). We evaluated whether urinary creatine riboside (CR), a tumor-derived metabolite excreted through the prostatic urethra, complements PSA for gray-zone detection and independently predicts prostate-cancer-specific mortality (PCSM). In the NCI-Maryland PCa Case-Control Study (951 cases, 962 controls; 47.6% African American men; median follow-up 11.5 years), urinary CR was quantified by UPLC-MS/MS. Within the PSA gray zone (n = 668), urinary CR was complementary to PSA, with markedly higher single-marker discrimination than PSA (AUC 0.93, 95% CI 0.88-0.98 vs 0.77, 0.66-0.89) and additive when combined ({Delta}AUC +0.17, p < 0.001; 91.4% sensitivity at 80% specificity). After adjustment for 11 clinical and sociodemographic covariates, urinary CR independently predicted PCSM complementary to PSA (Fine-Gray SHR 1.72, 1.35-2.19 for CR; 1.35, 1.08-1.68 for PSA; Harrell's C 0.85 for CR + PSA vs 0.77 for PSA alone), with strongest signal in African American men (SHR 2.43, 1.57-3.75 for CR). We conclude that urinary CR is a candidate non-invasive biomarker complementary to PSA - improving gray-zone triage and predicting PCSM; prospective validation in biopsy-referred cohorts is warranted.

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17.

Nature Medicine 2026-06-08 DOI: HASH:7f47b16ecb7d5299a335dcb065d7f0a3

Post-adjuvant chemotherapy in ctDNA-positive patients with resected colorectal cancer: a randomized phase 3 trial

作者:

Hideaki Bando↗

Tumor-informed circulating tumor DNA (ctDNA) enables detection of molecular residual disease (MRD) after curative resection of colorectal cancer (CRC), but whether early intervention improves outcomes remains uncertain. ALTAIR was a randomized, double-blind, phase 3 trial embedded in the CIRCULATE-Japan platform evaluating a post-adjuvant ctDNA surveillance strategy with treatment initiation upon molecular recurrence. Patients with resected stage 0–IV CRC who became ctDNA positive after completion of standard-of-care therapy and had no radiological evidence of disease were randomly assigned (1:1) to receive trifluridine/tipiracil (FTD/TPI) or placebo for 6 months. The primary endpoint was investigator-assessed disease-free survival (DFS). Between July 2020 and June 2023, 243 patients were randomized to FTD/TPI (n = 122) or placebo (n = 121). Median DFS was 9.30 months with FTD/TPI and 5.55 months with placebo (hazard ratio = 0.79, 95% confidence interval: 0.60–1.05, P = 0.107), and the primary endpoint was not met. FTD/TPI increased grade 3 or higher hematologic adverse events (73.0% versus 3.3%) without new safety signals. These findings indicate that post-adjuvant intervention with FTD/TPI did not significantly improve DFS in ctDNA-positive patients without radiological disease. ClinicalTrials.gov identifier: NCT04457297 . In the randomized, double-blind phase 3 ALTAIR trial, patients with resected colorectal cancer who became positive for circulating tumor DNA during post-adjuvant surveillance received trifluridine/tipiracil hydrochloride therapy, which did not significantly prolong disease-free survival compared with placebo.

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18.

medRxiv (Medicine) 2026-06-15 DOI: HASH:a48ce293a7fd4e190e47329e4e2336b5

Differential DNA Methylation and Delirium After Anesthesia and Surgery

作者:

Hogan↗Berger↗Kolstad↗Madrid↗Hsia↗Wright↗Devinney↗Smith↗Aisch↗

Background: DNA methylation is an epigenetic modification that regulates gene expression in response to environmental exposures. We measured differential DNA methylation levels in blood before after general anesthesia and surgery in participants with and without postoperative delirium (POD) and postoperative neurocognitive disorder (PNCD). Methods: Blood sampling, delirium assessment and cognitive testing were prospectively performed at baseline before non-cardiac, non-neurologic surgery, and at 24 hours (24h) and 6 weeks (6wk) thereafter in 94 participants comprising 13 with POD and 81 without POD, and 40 with PNCD and 54 without PNCD 6wk after surgery who were matched for age and sex in the INTUIT and MADCO cohorts. DNA methylation was assessed using the Illumina Infinium MethylationEPIC Beadchip. Results: 132 differentially methylated positions (DMPs) annotated to 198 differentially methylated genes (DMGs) were identified in 94 participants 24h after surgery compared to baseline with a local false discovery rate (LFDR)

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19.

arXiv (CS.LG) 2026-06-11 DOI: arXiv:2606.11508

Probabilistic Contrastive Pretraining for Multi-task ADME Property Prediction

作者:

Yifan Xue↗Srimukh Prasad Veccham↗Saee Paliwal↗Tyler Shimko↗Micha Livne↗

arXiv:2606.11508v1 Announce Type: new Abstract: Accurate prediction of absorption, distribution, metabolism, and excretion (ADME) properties is critical to drug discovery, but remains challenging because ADME endpoints are noisy, interdependent, and often data-limited. We propose a molecular graph-transformer pretraining framework that combines chemistry-specific self-supervision with contrastive mutual information machine learning (cMIM). Our method encodes molecular graphs into latent variables, reconstructs SMILES strings from the graph-derived latent codes, and augments the contrastive objective with domain-specific self-supervised chemistry tasks. Rather than treating these tasks as auxiliary regularizers with separately tuned loss weights, we formulate reconstruction, contrastive discrimination, and chemistry-specific supervision as unit-weighted log-probability factors in a single probabilistic latent-variable objective. For fine-tuning, we propose a multi-task GNN readout architecture with task-specific multilayer perceptron heads, preserving shared representation learning while mitigating negative transfer and improving the modeling of heterogeneous, nonlinear task relationships. Across Biogen, ExpansionRX, and ChEMBL-MT, the resulting Contrastive KERMT pretraining improves over the KERMT baseline by 7.6%, 9.9%, and 9.5% respectively (averaged over significantly-improved endpoints). Adding ADME-adjacent molecules to the pretraining corpus further improves transfer, and the contrastive component sharpens chemically meaningful latent neighborhoods.

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20.

arXiv (quant-ph) 2026-06-11 DOI: arXiv:2501.02681

Quest for quantum advantage: Monte Carlo wave-function simulations of the Coherent Ising Machine

作者:

Manushan Thenabadu↗Run Yan Teh↗Jia Wang↗Simon Kiesewetter↗Margaret D Reid↗Peter D Drummond↗

arXiv:2501.02681v2 Announce Type: replace Abstract: The Coherent Ising Machine (CIM) is a quantum network of optical parametric oscillators (OPOs) intended to find ground states of the Ising model. This is an NP-hard problem, related to several important minimization problems, including the max-cut graph problem. In order to enhance its potential performance, we analyze the coherent coupling strategy for the CIM in a highly quantum regime. To explore this limit, without assuming gaussianity, we employ accurate numerical simulations. Due to the inherent complexity of the system, the maximum network size is limited. While master equation methods can be used, their scalability diminishes rapidly for larger systems. Instead, we use Monte Carlo wave-function methods, which scale as the wave-function dimension, and use large numbers of samples. These simulations involve Hilbert spaces exceeding $10^{7}$ dimensions. To evaluate success probabilities, we use quadrature probabilities. We demonstrate the potential for quantum computational advantage by reducing the time required to reach maximum success probability in a low-dissipation regime enabled by initial quantum superpositions and entanglement. Furthermore, we demonstrate that tailored time-dependent couplings can amplify these quantum effects. Comparisons with classical CIM models give evidence that quantum tunneling effects in this strong coupling limit can overcome trapping in false minima. This can greatly increase success rates, indicating a potential for quantum advantage. Finally, we perform a coherence analysis based on the state purity to examine the role of quantum coherence in CIM performance and to determine how state purity correlates with improved optimization outcomes.

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21.

arXiv (CS.AI) 2026-06-17 DOI: arXiv:2510.14807

Beyond the Sampled Token: Preserving Candidate Support in RLVR

作者:

Ruotian Peng↗Yi Ren↗Zhouliang Yu↗Weiyang Liu↗Yandong Wen↗

arXiv:2510.14807v3 Announce Type: replace Abstract: We revisit exploration collapse in reinforcement learning with verifiable rewards (RLVR), from the perspective of the candidate distribution for next-token prediction. We formally show that as probability concentrates on the top-$1$ candidate, the expected number of distinct responses collapses to one regardless of the sampling budget $K$. This theoretical implication is further verified by our empirical tracking of top-$N$ candidate probabilities during training, where the top-$1$ candidate progressively dominates while plausible alternatives are suppressed. These findings suggest a key desideratum for effective exploration: preserving non-negligible probability mass on the top-$N$ candidates. To this end, we propose Candidate-aware Support Preservation (CaSP), with two complementary designs. Specifically, CaSP redistributes positive gradients among top-$N$ candidates for correct responses, and applies a stronger penalty to the top-$1$ candidate for incorrect responses. Unlike many exploration-oriented methods that improve pass@$K$ at the cost of pass@1, CaSP improves pass@$K$ across the full $K$ spectrum. These gains generalize to 6 math, 2 logical-reasoning, and 2 coding benchmarks, and scales to 32B-parameter models and sampling budgets up to $K=1024$, positioning it as a principled, candidate-level approach for RLVR exploration.

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22.

arXiv (CS.CV) 2026-06-11 DOI: arXiv:2502.14894

FOCUS on Contamination: Hydrology-Informed Noise-Aware Learning for Geospatial PFAS Mapping

作者:

Jowaria Khan↗Alexa Friedman↗Sydney Evans↗Rachel Klein↗Runzi Wang↗Katherine E. Manz↗Kaley Beins↗David Q. Andrews↗Elizabeth Bondi-Kelly↗

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants with significant public health impacts, yet large-scale monitoring remains severely limited due to the high cost and logistical challenges of field sampling. The lack of samples leads to difficulty simulating their spread with physical models and limited scientific understanding of PFAS transport in surface waters. Yet, rich geospatial and satellite-derived data describing land cover, hydrology, and industrial activity are widely available. We introduce FOCUS, a geospatial deep learning framework for PFAS contamination mapping that integrates sparse PFAS observations with large-scale environmental context, including priors derived from hydrological connectivity, land cover, source proximity, and sampling distance. These priors are integrated into a principled, noise-aware loss, yielding a robust training objective under sparse labels. Across extensive ablations, robustness analyses, and real-world validation, FOCUS consistently outperforms baselines including sparse segmentation, Kriging, and pollutant transport simulations, while preserving spatial coherence and scalability over large regions. Our results demonstrate how AI can support environmental science by providing screening-level risk maps that prioritize follow-up sampling and help connect potential sources to surface-water contamination patterns in the absence of complete physical models.

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23.

arXiv (quant-ph) 2026-06-11 DOI: arXiv:2606.12383

The Simplified Stabilizer ZX-Calculus is Minimal

作者:

Harry K. Stoltz↗

arXiv:2606.12383v1 Announce Type: new Abstract: The stabilizer fragment of the ZX calculus is amongst the most important fragments of the theory. The closely related Clifford+T fragment is approximately universal (arXiv:1705.11151). Additionally, the stabilizer calculus can be described by a small collection of rewrites, most of which have been shown to be necessary (arXiv:1709.08903). However, two rules, describing the red/green compact-structure coincidence and the important bialgebra law, had not been shown to be necessary. We present a countermodel-style argument showing that both of these rules are individually necessary relative to the connectivity meta-rule of Backens–Perdrix–Wang (arXiv:1709.08903), and hence establish that the rule set presented in arXiv:1709.08903 has no redundant rewrite rule.

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24.

arXiv (quant-ph) 2026-06-17 DOI: arXiv:2606.17773

Quantum Routers: A Switching-Fabric Framework for Quantum-Native Forwarding

作者:

Jessica Illiano↗Caterina De Risi↗Angela Sara Cacciapuoti↗Marcello Caleffi↗

arXiv:2606.17773v1 Announce Type: new Abstract: Forwarding in quantum networks cannot be realized by directly transposing classical switching fabrics, since the no-cloning theorem and the quantum measurement postulate constrain the direct relay of quantum information while ruling out copy-based buffering and inspection. In this paper, we propose a switching-fabric framework for quantum routers based on multipartite entanglement. Specifically, we formalize the notion of an entanglement-based switching fabric, in which a graph state acts as the forwarding resource and entanglement forwarding is realized through local Pauli measurements. We translate the classical notions of blocking and non-blocking operation into structural conditions for entanglement-based fabrics, by deriving the edge-controlled (EC) design principle for non-blocking operation. We instantiate this principle through a monolithic EC crossbar and a modular Clos-type EC fabric, for which we characterize resource scaling and identify the regime where the modular design becomes more resource-efficient than the monolithic one. Finally, a forwarding-latency analysis establishes a fundamental distinction between matching-oblivious and matching-driven forwarding: the proposed EC fabrics realize all requested input-output entanglement links with constant forwarding depth under sufficient measurement parallelism, whereas matching-driven EPR-based fabrics exhibit latency that scales with the number of requested connections. The proposed framework provides a hardware-agnostic foundation for quantum-router switching fabrics.

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25.

Nature Medicine 2026-06-10 DOI: HASH:67c6d8ebe8dcc965606dad2629f3ad81

Dual-target gene therapy in Parkinson’s disease: a multicenter phase 1 trial

作者:

Mengyue Niu↗

Restoring striatal dopamine synthesis is a promising gene therapy strategy for Parkinson’s disease. Previous adeno-associated virus-mediated aromatic L-amino acid decarboxylase (AADC) monotherapies remain dependent on exogenous levodopa, whereas multigene delivery is constrained by strict adeno-associated virus packaging limits. A ‘dual approach’ targeting the two rate-limiting enzymes, tyrosine hydroxylase (TH) and AADC, offers the potential for autonomous dopamine synthesis. We report the 12-month primary safety and tolerability outcomes of a multicenter, open-label, dose-escalation, phase 1 trial evaluating BBM-P002, a new adeno-associated virus vector—AAVT42—codelivering constitutively active TH and AADC. Ten participants with moderate-to-advanced Parkinson’s disease were enrolled and received bilateral intraputaminal infusions across doses of 4.0 × 1011 vg (Cohort 1; n = 1), 6.0 × 1011 vg (Cohort 2; n = 2), 1.0 × 1012 vg (Cohort 3; n = 2) and 1.2 × 1012 vg (Cohort 4; n = 5). The trial achieved its primary outcome, as BBM-P002 demonstrated a favorable safety and tolerability profile within 12 months post-treatment. No dose-limiting toxicities or drug-related serious adverse events occurred. A total of 23 adverse events were reported, all judged unrelated to BBM-P002 and primarily mild and transient. Systemic toxicity and clinically meaningful immunogenicity were absent. In conclusion, intraputaminal delivery of BBM-P002 was safe and well tolerated in this phase 1 trial, supporting continued clinical development. ClinicalTrials.gov registration: NCT05822739 . Phase 1 results reveal that BBM-P002, a dual-target gene therapy co-delivering TH and DDC, is safe and well tolerated in Parkinson’s disease, with 12-month motor improvements signaling therapeutic potential.

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