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01.
arXiv (CS.CL) 2026-06-16

Spokes: Optimizing for Diverse Pretraining Data Selection

Diversity plays a critical role in data selection, improving performance under fixed data budgets by reducing redundancy and repetition. However, optimizing for diversity is inherently challenging, as it is a set-level property that depends on interactions between data points rather than individual examples. As a result, existing approaches typically rely on proxies or approximations, which often fail to ensure sufficiently diverse subsets. In this work, we directly optimize diversity by introducing a probabilistic diversification framework based on the G-Vendi score, optimized via exponentiated gradient descent. Our method produces subsets that are substantially more diverse than those obtained via random sampling, achieving a +489 increase in G-Vendi score on a 500k-sample subset. We evaluate our approach on FineWeb and DCLM, where it consistently outperforms existing methods. Notably, SPOKES (diversity-only) improves average downstream performance by +0.4 and +0.5 points over random sampling on DCLM and FineWeb, respectively. More importantly, jointly optimizing for both quality and diversity yields the strongest results: SPOKES achieves gains of +1.5 and +1.4 points on DCLM and FineWeb, outperforming all baselines, including semantic deduplication and quality filtering.

02.
arXiv (CS.CV) 2026-06-24

MorVess: Morphology-Aware Pulmonary Vessel Segmentation Network

Accurate pulmonary vessel segmentation remains challenging due to the sparse, tortuous, and multi-scale nature of vascular structures, where small branches are easily lost and topology integrity is difficult to preserve under voxel-wise supervision. Existing deep segmentation models primarily optimize binary masks, lacking explicit geometric constraints, thus struggling to recover continuous tubular morphology and fine vascular connectivity. In this study, we introduce MorVess, a morphology-aware segmentation framework that integrates differentiable geometric priors with large-scale foundation model adaptation to achieve fine-grained vascular parsing. MorVess jointly predicts vessel masks, distance maps, and thickness maps, providing explicit supervision for vascular boundaries, centerline consistency, and smooth diameter transitions. A lightweight 2.5D adapter bridges 3D spatial context and 2D SAM representations, while a global-local fusion block aggregates multi-level semantics and geometric cues for high-fidelity topology reconstruction. Across two challenging pulmonary CT benchmarks, MorVess delivers superior Dice, clDice, and HD95 scores, substantially improving small-vessel recovery and global connectivity. These results demonstrate that embedding geometric intelligence into pretrained vision models offers a principled and scalable pathway toward precise vessel analysis and clinically reliable structural quantification. Our source code is available at https://github.com/MaoFuyou/MorVess.

03.
PLOS Medicine 2026-06-23

Comparisons of core component delivery in cardiac rehabilitation programs by country income classification and decade based on the 2025 Global Audit Update: A survey study

by Gabriela Lima de Melo Ghisi, Rachael P. Carson, Karam Turk Adawi, Rongjing Ding, Warner M. Mampuya, Mariya P. Jiandani, Jimena Martinez, Monserrat Cruz Rivero, Claudia V. Anchique, Dinah L. van Schalkwijk, Jonathan Gallagher, Buket Akinci, Dion Candelaria, Jirapa Champaiboon, Daniel F. Quesada-Chaves, Tone M. Norekvål, Iwona Szadkowska, Borut Jug, Evangelia Kouidi, Marta Supervia, Won-Seok Kim, Chamila Mettananda, Lilian Mbau, Gulsim T. Aimakova, Sherry L. Grace, on behalf of the ICCPR Global Cardiac Rehabilitation Audit Update Investigators Background Cardiovascular disease (CVD) remains a leading global health burden. Cardiac rehabilitation (CR) is essential to reducing morbidity and improving patient outcomes. Since the COVID-19 pandemic, CR delivery worldwide has evolved, yet these changes have not been systematically charactemkjrized. The objective of this study was to characterize globally: (1) the delivery of core CR components, including risk factors assessed, patient education practices, and program resources; (2) differences in these elements by country income classification and relative to the initial 2016 Global CR Audit. Methods and findings A cross-sectional Audit update was conducted. Program-level data were collected from May 1st to September 1st 2025 using a REDCap survey adapted from previous Audits. Eligible respondents were leads of phase II/post-discharge CR programs providing at least an initial assessment, structured aerobic exercise, and ≥1 additional core component. ICCPR associations and local leaders supported program identification. Main outcomes were core components delivered (10 assessed), risk factors assessed (14 assessed), patient education dose (hours/patient/program), and program resources (17 assessed). Generalized linear mixed models (GLMM) tested differences by income classification and (when applicable) changes since 2016. Of 7,025 programs identified globally, 1,505 (62% median country response rate) initiated a survey from 90/113 (80%) countries with CR. The median number of core components offered was 8/program (p25, p75 = 6, 10), with upper-middle income countries offering significantly more components overall (median = 9), and also high-income countries offering more than low-income countries (8 versus 6, p 

04.
arXiv (CS.LG) 2026-06-17

Tight $L_\infty$ Sample Complexity for Low-Degree and Sparse Boolean Polynomials

arXiv:2606.17319v1 Announce Type: cross Abstract: Motivated by the optimization of bounded binary black-box functions, we study the problem of learning polynomial surrogates over the Boolean hypercube. To ensure that optimizing the surrogate yields good solutions for the underlying objective, we require uniform $L_\infty$-error guarantees rather than the usual $L_2$-type guarantees. We characterize the minimax sample complexity of uniform estimation under subgaussian noise for two classes of bounded polynomials. First, for polynomials of degree at most $d$ on $n$ variables, the sample complexity scales as $n^{d+1}$. Second, for $s$-sparse Fourier-Walsh polynomials with $s \leq n$, it scales as $ns^2$. These rates differ structurally from the noiseless setting, where uniform exact recovery scales as $n^d$ and $ns$, respectively. Our lower bounds hold even for arbitrary adaptive learners, showing that the additional factors are intrinsic to the noisy cases. Standard Fourier-analysis tools for the $L_2$-norm do not naturally extend to the $L_\infty$-setting in a way that yields uniform guarantees. Our proofs overcome this difficulty by relying on suitably chosen auxiliary norms that serve as proxies for controlling the $L_\infty$-error. Together, our results provide a tight characterization of the sample complexity of learning optimization-safe polynomial surrogates.

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

Near–Real-Time Conflict-Related Fire Detection in Sudan Using Unsupervised Deep Learning

Ongoing armed conflict in Sudan highlights the need for rapid monitoring of conflict-related fire-affected areas. Recent advances in deep learning and high-frequency satellite imagery enable near–real-time assessment of active fires and burn scars in war zones. This study presents a near–real-time monitoring approach using a lightweight Variational Auto-Encoder (VAE)–based model integrated with 4-band Planet Labs imagery at 3 m spatial resolution. We demonstrate that these impacted regions can be detected within approximately 24 to 30 hours under favorable observational conditions using accessible, commercially available satellite data. To achieve this, we adapt a VAE–based model, originally designed for 10-band imagery, to operate effectively on high-resolution 4-band inputs. The model is trained in an unsupervised manner to learn compact latent representations of nominal land-surface conditions and identify burn signatures by quantifying changes between temporally paired latent embeddings. Performance is evaluated across five case studies in Sudan and compared against cosine distance, CVA, and IR-MAD using precision, recall, F1-score, and the area under the precision-recall curve (AUPRC) computed between temporally paired image tiles. Results show that the proposed approach consistently outperforms the other methods, achieving higher recall and F1-scores while maintaining viable precision in highly imbalanced fire-detection scenarios. Experiments with 8-band imagery and temporal image sequences yield only marginal performance gains over single 4-band inputs, underscoring the effectiveness of the proposed lightweight approach for scalable, near–real-time conflict monitoring.

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

Fast and high-fidelity transfer of edge states via dynamical control of topological phases and effects of dissipation

arXiv:2505.16606v2 Announce Type: replace-cross Abstract: Topological edge states are robust against symmetry-preserving perturbations and noise, making them promising for quantum information and computation, particularly in topological quantum computation through the braiding operations of Majorana quasiparticles. Realizing these applications requires fast and high-fidelity dynamic control of edge states. In this work, we theoretically propose a high-fidelity protocol for transferring topological edge states by dynamically moving a domain wall between two regions with different topological numbers in one dimension. This protocol fundamentally relies on Lorentz invariance and relativistic effects, because moving the domain wall at a constant speed is described by a mass term with the uniform linear motion in the Dirac equation. We demonstrate the effectiveness of our protocol in transferring edge states with high fidelity using a one-dimensional quantum walk with two internal states, which is feasible with current experimental technology. We also investigate how bit-flip and dephasing dissipation to the environment affect transfer efficiency. Remarkably, bit (dephasing) dissipation does not affect the fidelity at the slow (fast) transfer limit, which can be explained by the relativistic effects on the edge states.

07.
arXiv (CS.LG) 2026-06-17

Resource-Efficient Variational Quantum Classifier

arXiv:2511.09204v3 Announce Type: replace-cross Abstract: We introduce the unambiguous quantum classifier based on Hamming distance measurements combined with classical post-processing. The proposed approach improves classification performance through a more effective use of ansatz expressivity, while requiring significantly fewer circuit evaluations. Moreover, the method demonstrates enhanced robustness to noise, which is crucial for near-term quantum devices. We evaluate the proposed method on a breast cancer classification dataset. The unambiguous classifier achieves an average accuracy of 90%, corresponding to an improvement of 6.9 percentage points over the baseline, while requiring eight times fewer circuit executions per prediction. In the presence of noise, the improvement is reduced to approximately 3.1 percentage points, with the same reduction in execution cost. We substantiate our experimental results with theoretical evidence supporting the practical performance of the approach.

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

UltraSketchLLM: Sub-1-Bit LLM Compression via Sketch and Hardware-Friendly Operators

arXiv:2506.17255v2 Announce Type: replace-cross Abstract: Large language models (LLMs) require larger GPU memory size these days, necessitating efficient and extreme weight compression methods. Existing compression methods are either theoretically limited by 1 bit per weight or face severe performance degradation and inefficiency. To deploy LLMs in resource-constrained scenarios, we introduce UltraSketchLLM, compressing LLMs with data sketch. It reduces peak GPU memory footprint with a high compression rate down to 0.5 bit per weight. Combined with hardware-friendly implementation, UltraSketchLLM keeps tolerable performance degradation and extremely low latency overhead with 14.9x speedup compared to naive sketch solution.

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

CaReTS: A Multi-Task Framework Unifying Classification and Regression for Time Series Forecasting

arXiv:2511.09789v2 Announce Type: replace Abstract: Recent advances in deep forecasting models have achieved remarkable performance, yet most approaches still struggle to provide both accurate predictions and interpretable insights into temporal dynamics. This paper proposes CaReTS, a novel multi-task learning framework that combines classification and regression tasks for multi-step time series forecasting problems. The framework adopts a dual-stream architecture, where a classification branch learns the stepwise trend into the future, while a regression branch estimates the corresponding deviations from the latest observation of the target variable. The dual-stream design provides more interpretable predictions by disentangling macro-level trends from micro-level deviations in the target variable. To enable effective learning in output prediction, deviation estimation, and trend classification, we design a multi-task loss with uncertainty-aware weighting to adaptively balance the contribution of each task. Furthermore, four variants (CaReTS1–4) are instantiated under this framework to incorporate mainstream temporal modelling encoders, including convolutional neural networks (CNNs), long short-term memory networks (LSTMs), and Transformers. Experiments on real-world datasets demonstrate that CaReTS outperforms state-of-the-art (SOTA) algorithms in forecasting accuracy, while achieving higher trend classification performance.

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

Incentives and Evidence in Learned Service Orchestration

arXiv:2606.16555v1 Announce Type: cross Abstract: Reinforcement learning for service orchestration has been the subject of sustained research for over a decade, yet it is not used in production at scale. The usual explanation is that learned controllers degrade under delayed and noisy telemetry, workload shifts, and uncontrolled tenants. We test whether existing evidence supports that explanation. We evaluate three highly influential RL-based orchestration systems spanning resource allocation, DAG scheduling, and autoscaling, using pre-registered predictions about comparative degradation under production-relevant perturbations and paired inference with family-wise error correction. Across the tests, most predicted performance reversals do not occur. Diagnostic analyses show that these outcomes often reflect comparator collapse, artefact limitations, or evaluation choices rather than evidence that learned controllers tolerate the perturbations. One apparent advantage under observation lag is roughly fortyfold compared to a Kubernetes HPA-equivalent controller. Another widely cited result cannot be reconstructed from its released artefact, and the strongest reproducible margin is far smaller than the published results. Conclusions also reverse under changes in perturbation magnitude and evaluation mode. Based on these results and broader patterns in the literature, we identify an institutional problem. Publication and review incentives favour benchmark gains against convenient comparators, even when those gains provide little evidence of deployment performance. We argue that the problem is not solely technical. Rather, it is institutional, so learned orchestration needs production-grade comparators, registered perturbation models, separate operational metrics, and publication criteria that reward reproducible operational evidence. Without these changes, the literature can grow without establishing whether learning improves orchestration.

11.
arXiv (CS.LG) 2026-06-12

Disentangling Dynamical Systems: Causal Representation Learning Meets Local Sparse Attention

arXiv:2603.14483v2 Announce Type: replace Abstract: Parametric system identification methods estimate the parameters of explicitly defined physical systems from data. Yet, they remain constrained by the need to provide an explicit function space, typically through a predefined library of candidate functions chosen via available domain knowledge. In contrast, deep learning can demonstrably model systems of broad complexity with high fidelity, but black-box function approximation typically fails to yield explicit descriptive or disentangled representations revealing the structure of a system. We develop a novel identifiability theorem, leveraging causal representation learning, to uncover disentangled representations of system parameters without structural assumptions. We derive a graphical criterion specifying when system parameters can be uniquely disentangled from raw trajectory data, up to permutation and diffeomorphism. Crucially, our analysis demonstrates that global causal structures provide a lower bound on the disentanglement guarantees achievable when considering local state-dependent causal structures. We instantiate system parameter identification as a variational inference problem, leveraging a sparsity-regularised transformer to uncover state-dependent causal structures. We empirically validate our approach across four synthetic domains, demonstrating its ability to recover highly disentangled representations that baselines fail to recover. Corroborating our theoretical analysis, our results confirm that enforcing local causal structure is often necessary for full identifiability.

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

Mitigating Disparate Impact of Differentially Private Learning through Bounded Adaptive Clipping

arXiv:2506.01396v2 Announce Type: replace Abstract: Differential privacy (DP) has become an essential framework for privacy-preserving machine learning. Existing DP learning methods, however, often have disparate impacts on model predictions, e.g., for minority groups. Gradient clipping, which is often used in DP learning, can suppress larger gradients from challenging samples. We show that this problem is amplified by adaptive clipping, which will often shrink the clipping bound to tiny values to match a well-fitting majority, while significantly reducing the accuracy for others. We propose bounded adaptive clipping, which introduces a tunable lower bound to prevent excessive gradient suppression. Our method improves worst-class accuracy by over 10 percentage points on Skewed and Fashion MNIST compared to unbounded adaptive clipping, 7 points compared to Automatic clipping, and 5 points compared to constant clipping. The code is available at https://github.com/TrustworthyMLHelsinki/adaptive-clipping-fairness.

14.
arXiv (CS.LG) 2026-06-15

Denoising Score Matching with Random Features: Insights on Diffusion Models from Precise Learning Curves

arXiv:2502.00336v3 Announce Type: replace Abstract: We theoretically investigate the phenomena of generalization and memorization in diffusion models. Empirical studies suggest that these phenomena are influenced by model complexity and the size of the training dataset. In our experiments, we further observe that the number of noise samples per data sample ($m$) used during Denoising Score Matching (DSM) plays a significant and non-trivial role. We capture these behaviors and shed insights into their mechanisms by deriving asymptotically precise expressions for test and train errors of DSM under a simple theoretical setting. The score function is parameterized by random features neural networks, with the target distribution being $d$-dimensional Gaussian. We operate in a regime where the dimension $d$, number of data samples $n$, and number of features $p$ tend to infinity while keeping the ratios $\psi_n=\frac{n}{d}$ and $\psi_p=\frac{p}{d}$ fixed. By characterizing the test and train errors, we identify regimes of generalization and memorization as a function of $\psi_n,\psi_p$, and $m$. Our theoretical findings are consistent with the empirical observations.

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

Latent space mapping of interpretable structural coordinates from stochastic single-molecule signals

arXiv:2606.16950v1 Announce Type: cross Abstract: Nanopores are versatile single-molecular sensors, but their utility is fundamentally constrained by stochastic translocation dynamics warping any encoded information. We resolve it by shifting from time-domain analysis to a learned latent-space mapping via a contrastive encoder trained exclusively on simulated signals from a physics-informed model. This encoder maps solid-state nanopore signals of engineered DNA barcodes into an interpretable molecular coordinate system. The learned representation is responsive to structural barcode parameters while remaining invariant to acquisition conditions and translocation conformation, allowing data pooling across devices. Molecule identification requires a single pass through the encoder, reducing computational cost by three orders of magnitude relative to alignment-based methods. We experimentally validate through mixture quantification, rare-variant detection, consensus barcode reconstruction, and real-time signal acquisition. This shift from temporal analysis to mapping structural coordinates into a latent space changes the paradigm behind analyzing stochastic sensor signals by linking classification to interpretable encoded molecular information.

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

Spectrally engineered collinear type-0 SPDC source with enhanced spectral brightness for entanglement distribution

arXiv:2606.24036v1 Announce Type: new Abstract: Entangled photon sources with high spectral brightness are important resources for photonic quantum information processing, particularly in quantum communication and quantum networking where usable photon flux of entangled photons is often constrained by channel loss and source inefficiency. Here, we demonstrate a spectrally engineered type-0 spontaneous parametric down-conversion (SPDC) source with enhanced spectral brightness for entanglement distribution. By pumping a 30-mm ppKTP crystal with an ultra-narrowband laser slightly detuned from degeneracy, photon-pair generation is concentrated into a narrow spectral bandwidth while retaining the strong nonlinear interaction of type-0 phase matching. The source produces a coincidence rate of 44.6 kHz corresponding to a detected spectral brightness of 0.507 MHz/mW/nm. We further integrate the source into a Sagnac interferometer to generate polarization-entangled photon pairs and demonstrate entanglement distribution through a 2.56 km free-space round-trip channel. Our results show that spectral engineering provides a practical route to compact, spectrally bright entangled-photon sources for quantum communication applications.

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

C2-Faith: Benchmarking LLM Judges for Causal and Coverage Faithfulness in Chain-of-Thought Reasoning

Large language models (LLMs) are increasingly used as judges of chain-of-thought (CoT) reasoning, yet it remains unclear whether they can reliably assess process faithfulness rather than merely answer plausibility. We introduce C2-Faith, a benchmark built from PRM800K that explicitly decomposes faithfulness into two complementary dimensions: causality (whether each step logically follows from prior context) and coverage (whether essential intermediate inferences are present). Using controlled perturbations, we construct examples with known causal error positions by replacing a single step with a logically inconsistent variant, and with controlled coverage deletions at varying rates, enabling direct measurement against reference labels. We evaluate three frontier LLM judges across three tasks: binary causal detection, causal step localization, and coverage scoring. Our results reveal that judge reliability is highly task-dependent, with no single model dominating across settings. While models often detect that an error exists, they struggle to accurately localize it, indicating a substantial gap between detection and attribution. Moreover, all judges systematically overestimate reasoning completeness, assigning high coverage scores even when substantial portions of intermediate reasoning are missing. These findings expose fundamental limitations of LLM judges in process-level evaluation and highlight the need for more reliable and calibrated methods when using LLMs to assess reasoning quality.

18.
arXiv (quant-ph) 2026-06-16

Optimal learning of quantum channels in diamond distance

arXiv:2512.10214v3 Announce Type: replace Abstract: Quantum process tomography, the task of estimating an unknown quantum channel, is a central problem in quantum information theory. A long-standing open question is how many uses of an unknown channel are required to learn it in diamond distance, the standard metric for distinguishing quantum processes. While quantum state tomography is well understood, for general channels the problem remained open beyond the unitary case. Here we establish the query complexity of channel tomography with optimal dependence on the dimension parameters, at any fixed constant accuracy. We design an algorithm showing that any channel with input/output dimensions $d_{\mathrm{in}},d_{\mathrm{out}}$ and Kraus rank at most $k$ can be learned to accuracy $\varepsilon$ using $O(d_{\mathrm{in}}d_{\mathrm{out}}k/\varepsilon^{2})$ channel uses. Conversely, we prove that $\Omega(d_{\mathrm{in}}d_{\mathrm{out}}k)$ uses are necessary at constant accuracy and that, for non-minimal Kraus rank, a separate $\Omega(1/\varepsilon^{2})$ contribution is unavoidable. Since channels subsume states, unitaries, isometries, and measurements as special cases, our protocol provides a unified framework for these tomography tasks, yielding new guarantees for isometry and measurement tomography while recovering known optimal scalings for state and unitary tomography. Our algorithm follows the natural strategy of performing optimal tomography on the Choi state. The main technical contribution is to show that this suffices to control the induced diamond-distance error, avoiding the dimension loss incurred by a naive conversion from Choi-state trace distance to channel diamond distance. The protocol uses the channel non-adaptively to prepare Choi-state copies, purifies them in parallel, and performs optimal pure-state tomography on the resulting purifications. Hence, we reduce channel tomography to pure-state tomography.

19.
arXiv (CS.LG) 2026-06-18

Learning to Annotate Delayed and False AEB Events: A Practical System for Extreme Class Imbalance and Asymmetric Label Noise

arXiv:2606.19186v1 Announce Type: cross Abstract: Autonomous Emergency Braking (AEB) optimization relies on accurately annotated real-world trigger events, particularly rare but critical delayed and false AEB triggers that expose system deficiencies. However, these minority samples comprise less than 5% of thousands of daily triggers, making manual annotation prohibitively expensive at scale. We present the first automated AEB annotation framework to address this problem. During development, we identified two fundamental challenges that severely impair delayed/false trigger annotation accuracy: (1) Extreme class imbalance where delayed/false triggers are overwhelmed by true triggers; (2) Asymmetric label noise where mislabeled majority samples (true triggers) suppress minority samples (delayed/false triggers) learning. To overcome these challenges, we propose two key innovations: (1) Specific data augmentation that synthesizes realistic samples by manipulating focal target attributes, transplanting ego-vehicle dynamics, and masking non-focal agents; (2) noise suppression using stable hardness estimation and probe-guided adaptive threshold to clean mislabeled true trigger samples. Crucially, we deploy our model as a practical annotation system with full-stack architecture, efficiently identifying critical delayed/false triggers from thousands of daily AEB events. Production results demonstrate 80% improvement in recall of delayed/false triggers and 50% reduction in manual workload. Beyond immediate gains, the system enables continuous self-improvement through accumulated high-quality annotations, establishing a necessary data foundation for on-vehicle AEB system optimization

20.
medRxiv (Medicine) 2026-06-24

Genetically Proxied Interleukin-6 Inhibition and Cancer Risk: A Multi-Ancestry Drug-Target Mendelian Randomization Study of Hepatocellular Carcinoma and Colorectal Cancer

Background: Interleukin-6 (IL-6) signalling drives chronic inflammation and is therapeutically targeted by tocilizumab, an approved IL-6 receptor inhibitor. Whether genetically proxied lifelong IL-6 inhibition causally influences the risk of hepatocellular carcinoma (HCC) or colorectal cancer (CRC) remains unanswered. Prior single-variant estimates from pooled observational data are methodologically limited and may reflect confounding. Methods: A two-sample drug-target Mendelian randomization (MR) study was conducted. Four independent cis-acting protein quantitative trait loci (pQTL) variants within the IL6 and IL6R gene loci (rs2228145, rs4129267, rs7529229, rs1800795) were selected as genetic instruments , with F-statistics ranging from 32.3 to 120.5, confirming instrument strength. Outcome data were obtained from four independent genome-wide association studies: HCC from BioBank Japan (BBJ; 1,866 cases, 195,745 controls), HCC from FinnGen Release 10 (674 cases, 218,118 controls), CRC from a European meta-analysis (19,948 cases, 12,124 controls), and CRC from BBJ (7,062 cases, 195,745 controls). Causal estimates were derived using inverse variance weighted (IVW) regression as the primary method, with MR-Egger and weighted median analyses as sensitivity methods. Cochran Q statistics assessed heterogeneity and MR-Egger intercept testing assessed directional pleiotropy. Results: Genetically proxied IL-6 inhibition showed no significant causal effect on HCC risk in East Asian populations (IVW odds ratio [OR] 0.997, 95% confidence interval [CI] 0.903 to 1.101, p=0.953) or European populations (IVW OR 0.984, 95% CI 0.802 to 1.208, p=0.880). Similarly, no causal effect was observed on CRC risk in European populations (IVW OR 1.015, 95% CI 0.957 to 1.075, p=0.623) or East Asian populations (IVW OR 0.999, 95% CI 0.948 to 1.052, p=0.971). Sensitivity analyses confirmed the absence of directional pleiotropy and heterogeneity across all four analyses. Leave-one-out analyses demonstrated that no single instrument drove the null findings. Conclusions: Genetically proxied IL-6 receptor inhibition, modelling the therapeutic effect of tocilizumab, showed no causal effect on HCC or CRC risk across four independent cohorts and two ancestries. These findings do not support a role for IL-6 pathway inhibition in the prevention of these cancers and provide reassuring genetic safety evidence regarding cancer risk in patients receiving tocilizumab. Larger HCC-specific GWAS are needed to definitively evaluate modest effects in this cancer type.

21.
arXiv (CS.AI) 2026-06-18

An In-depth Study of LLM Contributions to the Bin Packing Problem

arXiv:2510.27353v2 Announce Type: replace Abstract: Recent studies have suggested that Large Language Models (LLMs) could provide interesting ideas contributing to mathematical discovery. This claim was motivated by reports that LLM-based genetic algorithms produced heuristics offering new insights into the online bin packing problem under uniform and Weibull distributions. In this work, we reassess this claim through a detailed analysis of the heuristics produced by LLMs, examining both their behavior and interpretability. Despite being human-readable, these heuristics remain largely opaque even to domain experts. Building on this analysis, we propose a new class of algorithms tailored to these specific bin packing instances. The derived algorithms are significantly simpler, more efficient, more interpretable, and more generalizable, suggesting that the considered instances are themselves relatively simple. We then discuss the limitations of the claim regarding LLMs' contribution to this problem, which appears to rest on the mistaken assumption that the instances had previously been studied. Our findings instead emphasize the need for rigorous validation and contextualization when assessing the scientific value of LLM-generated outputs.

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

A Judge-Aware Ranking Framework for Evaluating Large Language Models without Ground Truth

arXiv:2601.21817v3 Announce Type: replace-cross Abstract: Evaluating large language models (LLMs) on open-ended tasks without ground-truth labels is increasingly done via the LLM-as-a-judge paradigm. A critical but under-modeled issue is that judge LLMs differ substantially in reliability; treating all judges equally can yield biased leaderboards and misleading uncertainty estimates. More data can make evaluation more confidently wrong under misspecified aggregation. We propose a judge-aware ranking framework that extends the Bradley-Terry-Luce model by introducing judge-specific discrimination parameters, jointly estimating latent model quality and judge reliability from pairwise comparisons without reference labels. We establish identifiability up to natural normalizations and prove consistency and asymptotic normality of the maximum likelihood estimator, enabling confidence intervals for score differences and rank comparisons. Across multiple public benchmarks and a newly collected dataset, our method improves agreement with human preferences, achieves higher data efficiency than unweighted baselines, and produces calibrated uncertainty quantification for LLM rankings.

23.
arXiv (CS.CL) 2026-06-11

FlowBank: Query-Adaptive Agentic Workflows Optimization through Precompute-and-Reuse

Large Language Model (LLM)-based multi-agent systems are increasingly powerful, but current agentic workflow optimization paradigms make an unsatisfying trade-off. Task-level methods spend substantial offline compute yet deploy only a single workflow, leaving complementary candidates unused, while query-level methods synthesize a new workflow per query at substantial inference cost. Our motivating analysis shows these paradigms are more complementary than competing: workflows discovered during offline search often solve different subsets of queries, and many queries handled by expensive query-level generation can already be solved by cheaper precomputed workflows. This suggests a different objective: rather than searching for one universally best workflow or regenerating one per instance, we should build a compact bank of reusable, complementary workflows and select among them adaptively at inference time. Doing so requires solving three coupled problems: generating complementary rather than redundant candidates, compressing them into a small deployable portfolio, and assigning each query to the right workflow under a performance-cost trade-off. To this end, we present FlowBank, a three-stage framework for portfolio-based agentic workflow optimization. Diversifying proposes DiverseFlow to steer search toward under-covered queries and produce a high-coverage candidate pool. Curating proposes CuraFlow to compress this pool into a compact portfolio with minimal redundancy. Matching casts deployment as edge-value prediction on a query-workflow bipartite graph and routes each incoming query to the portfolio member with the best predicted utility. Across five benchmarks, FlowBank achieves the highest average score among the evaluated methods while remaining cost-competitive, improving over the strongest automated and handcrafted baselines by 4.26% and 14.92% relative, respectively.

24.
Nature Medicine 2026-06-22

Biological aging and generational shifts in early-onset cancer risk

作者:

Incidence of early-onset cancer is rising globally in recent generations, which underscores the need to elucidate the influence of emerging generational risk factors. Systemic and organ-specific aging reflects the cumulative impact of exposures and may provide an integrative and complementary approach to understand early-onset cancer risk. Here among 154,169 young adults from the United Kingdom Biobank, systemic aging measured by PhenoAge increased across birth cohorts, with 23% s.d. increase for those born 1965–1974 versus 1950–1954, and was associated with early-onset solid cancer risk (hazard ratio (HR)per s.d. 1.08; 95% confidence interval (CI), 1.03–1.13), driven by lung, gastrointestinal and uterine cancers, independent of genetic risks of aging and cancer. Patterns were consistent using alternative systemic aging measures, including the Klemera–Doubal method-defined age gap and metabolomic-based age gap. These findings were validated partially among 10,262 participants in the United States All of Us Research Program. Proteomics-based organ-specific aging analyses linked immune aging with early-onset lung cancer (HRper s.d. 1.89; CI, 1.20–2.97) and adipose tissue aging to early-onset colorectal cancer (HR 1.60; CI, 1.11–2.32). Greater age gap, reflecting more advanced biological aging relative to chronological age, may serve as a driver associated with risk of early-onset solid cancers, highlighting the importance of uncovering underlying mechanisms to guide effective prevention strategies. Analyses of population cohorts found that young adults exhibited earlier systemic and organ-specific aging, which was associated with increased risk of early-onset cancer compared with older adults born decades earlier.

25.
arXiv (CS.CL) 2026-06-15

Multi-component Causal Tracing in Large Language Models

Causal tracing systematically intervenes on a large language model's (LLM's) internal representations to uncover and quantify the causal pathways linking specific inputs or computations to specific metrics of interest, quantifying the LLM's behavior. Building on previous single-component or single-layer studies, this paper presents a unified framework for causally tracing multiple components simultaneously. This framework systematically identifies the subsets of components (e.g., attention heads and multi-layer perceptron neurons) most critical to a desired target performance metric (e.g., accuracy and fairness). This is achieved by incorporating flexible interventions applied to a wide range of desired metrics. To address the combinatorial complexity of the multi-component problem, an efficient algorithm is designed that leverages soft interventions and a carefully designed metric transformation, converting the combinatorial search problem into a continuous one that can be solved efficiently under proper constraints, thereby generating proper binary decisions for selecting components. Experimental results demonstrate that the proposed method efficiently identifies subsets of the model's components that have a high impact on the target metric, outperforming existing baseline approaches. Our code is available at https://github.com/ZiruiYan/multi-component-causal-tracing.