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01.
arXiv (CS.AI) 2026-06-18

SafeClawBench: Separating Semantic, Audit-Evidence, and Sandbox Harm in Tool-Using LLM Agents

arXiv:2606.18356v1 Announce Type: cross Abstract: Tool-using language-model agents introduce security failures that go beyond unsafe text: they can disclose protected objects, write persistent memory, send messages, modify databases, or trigger harmful code and tool effects. Existing evaluations often collapse these stages into a single attack success rate, making it difficult to tell whether a model merely agreed with an attacker or actually produced observable harm. We introduce SafeClawBench, a staged benchmark for tool-using agent security with 600 controlled adversarial tasks across six attack families: direct and indirect prompt injection, tool-return injection, memory poisoning, memory extraction, and ambiguity-driven unsafe inference. SafeClawBench reports three separate endpoints: semantic attack acceptance, audit-visible harm evidence, and sandbox-observed tool/state harm. Evaluating five agent endpoints under four prompt-level policies, we find that these endpoints capture different failure modes. Without additional prompt protection, semantic failure rates vary widely across models, from 9.0% to 44.2%. Audited harm evidence is narrower than semantic failure, and under a separate executable protocol some matched task identities produce sandbox harm despite passing the Semantic Core call: in a 12,000-row matched analysis, 291 of 347 observed sandbox harms occur in rows that pass the semantic check. Prompt policies change endpoint outcomes, but their effects depend on both model and protocol. SafeClawBench provides a reproducible framework for comparing agent models and prompt-policy conditions without conflating textual compliance, evidence-supported harm, and executable state changes. The open-source dataset is available at https://huggingface.co/datasets/sairights/safeclawbench.

02.
arXiv (CS.CV) 2026-06-17

Impact of Hand Impairment and Occlusions on Hand Pose Estimation Accuracy in Augmented Reality Applications

Mixed reality applications can be designed for hand rehabilitation. Augmented reality (AR) head mounted displays (HMDs) specifically allow for ecologically valid tasks because individuals can see their real environment and interact with real objects while receiving additional cues on the HMD. While these applications rely on accurate hand pose estimation, there is a gap in investigating the influence of hand impairment or occlusion from real-object interactions on pose estimation accuracy. Further, comparisons between AR HMD predictions and state-of-the-art pose estimation methods have not been established. The current study assessed pose estimation accuracy of the HoloLens 2 HMD and state-of-the-art pose estimation algorithms (WiLoR, HaMeR, WildHands, and MediaPipe) while individuals with cervical spinal cord injury (cSCI; n = 13, Neurological Level of Injury: C3-C6; American Spinal Injury Association Impairment Scale: A-D) and 15 uninjured controls interacted with clear and opaque objects. Ground truth estimates of 3D joint positions were generated via triangulation from a multi-camera setup. Pose estimation accuracy did not differ between the cSCI and uninjured control groups suggesting that 3D joint predictions from the HoloLens 2 and pose estimation algorithms can generalize to populations with hand impairment. Further, clear objects provided a small accuracy advantage over opaque objects (0.1 mm) and predictions from both WiLoR and HaMeR were slightly more accurate than the HoloLens 2 (2 mm). Overall, these results suggest that the HoloLens 2 may be viable for hand rehabilitation applications and the dataset generated can be used to refine pose estimation methods for hand-impaired populations.

03.
arXiv (CS.CL) 2026-06-17

ART: Attention Run-time Termination for Efficient Large Language Model Decoding

Long-context decoding in Large Language Models (LLMs) is constrained by the cost of accessing and processing the Key-Value (KV) cache. Despite evidence that attention outputs depend jointly on keys and values, most existing KV management methods rely on key-only pruning, since incorporating values incurs prohibitive overhead. In this paper, we propose Attention Run-time Termination (ART), a lightweight run-time mechanism that tracks accumulated attention outputs during kernel execution and terminates subsequent KV block accesses once further contributions become negligible. Rather than replacing KV selection, ART dynamically terminates redundant KV traversal on top of existing dense or sparse attention policies. We introduce a stability-based criterion that monitors both magnitude and directional changes of intermediate attention outputs and provideds a theoretical characterization of the resulting truncation error. Experiments on the LongBench and RULER Needle-in-a-Haystack tasks show that ART increases the generation throughput of existing KV-cache methods by up to 20%, without compromising the result quality.

04.
arXiv (CS.LG) 2026-06-16

Schattor: Schatten-family methods for deep learning optimization

arXiv:2606.15702v1 Announce Type: cross Abstract: Modern deep learning optimization features heterogeneous parameter structures, noisy gradients, and highly nonconvex landscapes, posing significant challenges for both algorithm design and theoretical analysis. Motivated by the limitations of SGD and the success of adaptive optimizers, we propose {\it Schattor}, a family of adaptive first-order methods based on Schatten norms. Schattor unifies SGD and the recently proposed matrix-variate adaptive optimizer Muon within a single Schatten-norm-based framework. We establish dimension-free stationarity guarantees for methods in the Schattor family for stochastic matrix optimization problems via a novel matrix martingale moment bound. We also develop multi-block extensions that adaptively balance block-wise optimization progress and prove dimension-free stationarity guarantees in this more general setting.

05.
arXiv (CS.CL) 2026-06-11

Scenario-based Probing and Steering Cultural Values in Large Language Models–Extended Version

Large Language Models (LLMs) are deployed across cultural contexts but often reflect homogenized values inherited from training data. Evaluations of cultural alignment typically rely on direct prompting with survey-style questions, which frequently elicit neutral or safety-aligned responses and fail to capture underlying model preferences. We propose a framework for probing and steering latent cultural representations in LLMs along the two Inglehart–Welzel axes of the World Values Survey (WVS). By translating social value questions into scenario-based behavioral dilemmas, we extract token-level probabilities to measure implicit values and apply activation steering, optionally combined with country-conditioned prompting, to shift model behavior without retraining. Across three open-source LLMs and four target cultures, we find substantial variation in steerability and identify latent entanglement, where interventions along one cultural dimension induce shifts along another. This coupling mirrors correlations in human WVS data and persists across activation, prompt, and hybrid steering. It constrains axis-independent alignment, though general task performance is largely preserved.

06.
medRxiv (Medicine) 2026-06-11

Dissecting the functional landscape of rare diseases through genomic variation in a heterogeneous cohort of 11,000 patients

Rare diseases (RDs) remain a major diagnostic challenge. Genetic and phenotypic heterogeneity, incomplete knowledge of disease mechanisms, and limitations in variant clinical interpretation leave many patients without a molecular diagnosis. Meanwhile, the growing volume of genomic data generated in clinical practice offers an opportunity to develop data-driven methodologies for exploring disease mechanisms and improving the reanalysis of unsolved cases. We aggregated real-world genomic data from 11,084 unrelated patients with suspected RD. Patients were clinically classified into 122 diseases. We built a multi-disease genomic variant frequency database (FJD-DB), which enabled the development of variant and gene-disease association scores by means of case-control subcohort comparisons across 32 disease groups. Functional enrichment analyses were then used to highlight disease-associated protein domains, pathways, biological processes, and phenotypes. Finally, the resulting knowledge was integrated into a data-driven framework for the guided reanalysis of unsolved RD patients applied to Inherited Retinal Dystrophies (IRD) patients as first use case. FJD-DB contained more than 45 million unique variants, including ~185,000 potentially pathogenic variants. Disease-specific analyses identified disease-associated pathogenic variants and highlighted both established and candidate disease genes. We detected 179 significantly enriched protein domains across 23 diseases, 124 Human Phenotype Ontology terms across 13 diseases, 79 Reactome pathways across 10 diseases, and 72 Gene Ontology biological processes across 8 diseases, revealing highly disease-specific functional signatures. Integration of disease-specific variant, gene, and functional association signals enabled the development of a data-driven framework for guided reanalysis of unsolved RD cases. Applied to more than 1,100 unsolved IRD cases, the framework generated clinically relevant findings in 26 patients, including four molecular diagnoses, seven candidate diagnoses, and 15 cases upgraded from non-informative findings to variants of uncertain significance. Aggregated real-world genomic data can be leveraged to identify disease-associated molecular signals generating novel biological hypotheses. A unified analytical framework provides a scalable strategy for knowledge discovery and guided reanalysis, facilitating the identification of overlooked and potentially novel genetic causes of RDs.

07.
arXiv (CS.LG) 2026-06-16

M-CTX: Exact and Scalable Spatial Context Retrieval for Trajectory Analytics

arXiv:2606.15244v1 Announce Type: new Abstract: Modern trajectory predictors increasingly condition on external spatial context, such as map geometry, signed distance fields (SDFs), and nearby moving agents. While this context improves prediction quality, constructing it for every training anchor has become a hidden systems bottleneck. In a representative maritime AIS pipeline, spatial context construction requires roughly 17 CPU-days for a 5.48M-anchor corpus, dominating the cost of the downstream predictor. We present M-CTX, an exact and scalable spatial context-retrieval framework for trajectory analytics. M-CTX recasts context construction as an ingest-once, query-many spatial database workload and replaces three brute-force stages – OSM range retrieval, SDF computation, and moving-vessel neighbour lookup – with composable, index-backed operators. Its learned range-index backend, BR-LZ, provides recall-complete MBR-overlap range retrieval and reduces candidate amplification by 1.1x–2.7x relative to global-expansion one-curve baselines. Across four maritime regions, eight baseline systems, synthetic workloads with up to 40M spatial features, and 10^7-record AIS streams, M-CTX reproduces the reference context exactly. On the 5.48M-anchor corpus, it reduces context construction from about 17 CPU-days to 1.8 hours, a measured 226x end-to-end speed-up. An optional storage mode further compresses SDF context by 64x with only a 0.04 m ADE change. These results establish exact spatial context retrieval as a first-class database problem in modern trajectory analytics. Code and datasets are publicly available at https://github.com/mark000071/M-CTX-Traj.

08.
PLOS Computational Biology 2026-06-01

On real-time calibrated prediction for complex model-based decision support in pandemics: Part 2

by Trevelyan J. McKinley, Daniel B. Williamson, Xiaoyu Xiong, James M. Salter, Robert Challen, Leon Danon, Ben Youngman, Doug McNeall Calibration of complex stochastic infectious disease models is challenging. These often have high-dimensional input and output spaces, with the models exhibiting complex, non-linear dynamics. Coupled with a paucity of necessary data, this results in a large number of non-ignorable hidden states that must be handled by the inference routine. Likelihood-based approaches to this missing data problem are very flexible, but challenging to scale, due to having to monitor and update these hidden states. Methods based on simulating the hidden states directly from the model-of-interest have an advantage that they are often more straightforward to code, and thus are easier to implement and adapt in real-time. However, these often require evaluating very large numbers of simulations, rendering them infeasible for many large-scale problems. We present a framework for using emulation-based methods to calibrate a large-scale, stochastic, age-structured, spatial meta-population model of COVID-19 transmission in England and Wales. By embedding a model discrepancy process into the simulation model, and combining this with particle filtering, we show that it is possible to calibrate complex models to high-dimensional data by emulating the log-likelihood surface instead of individual data points. The use of embedded model discrepancy also helps to alleviate other key challenges, such as the introduction of infection across space and time. We conclude with a discussion of major challenges remaining and key areas for future work.

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

Efficient Multinomial Logistic Bandit via Frequent Directions

arXiv:2606.11968v1 Announce Type: new Abstract: This paper studies efficient online algorithms for multinomial logistic bandits (MLogB), where the feedback distribution over $K+1$ outcomes follows a multinomial logistic model of $d$-dimensional action vectors. A representative UCB-type algorithm, OFUL-MLogB, achieves a regret bound of $\tilde{\mathcal{O}}(Kd\sqrt{T})$, but still requires $\mathcal{O}(K^3d^3)$ time and $\mathcal{O}(K^2d^2)$ space per round due to parameter estimation and optimistic reward construction, which is prohibitive in high-dimensional settings. To address this limitation, we propose EOFD-MLogB, which integrates frequent directions matrix sketching into OFUL-MLogB. By maintaining a low-rank SVD sketch of the accumulated Hessian, constrained online Newton updates in parameter estimation and $Kd \times K$ spectral-norm computations in the reward bonus are reduced to one-dimensional root-finding tasks and $K \times K$ eigenvalue computations, respectively. This yields dominant per-round time complexity $\mathcal{O}(Kd(m+K)^2)$ and space complexity $\mathcal{O}(Kd(m+K))$, where $m \ll d$ is the sketch size. We further prove a regret bound of $\tilde{\mathcal{O}}(\Delta_T(Kd\ln\Delta_T+m)\sqrt{T})$, where the sketching error factor $\Delta_T$ is controlled by the $m$-truncated spectral tail of the Hessian. Thus, when the Hessian is approximately low-rank, the regret is close to that of OFUL-MLogB. Experiments validate the computational efficiency and competitive performance.

10.
arXiv (quant-ph) 2026-06-11

Invariants of Sequential Circuits and Generalized Non-Abelian Statistics

arXiv:2606.11527v1 Announce Type: cross Abstract: Non-invertible symmetries in quantum many-body systems generally give rise to sequential unitary circuits that move symmetry defects. In this paper, we investigate invariants defined by sequences of such circuits, which move non-invertible defects and generate a Berry phase evaluated on quantum states with defects. We show that this Berry phase generally defines an invariant under local deformations, provided that the sequential circuits preserve the locality of those deformations. This invariant also rules out a short-range-entangled state that preserves the non-invertible symmetry, thereby signaling the 't Hooft anomaly of a non-invertible symmetry purely in terms of unitary operators acting on a state. We then apply this framework to loop excitations in three spatial dimensions and identify a new loop excitation in the (3+1)D $\mathbb{D}_4$ topological order, which we dub a non-Abelian fermionic loop. Using the invariant of sequential circuits, we characterize the statistics of non-Abelian fermionic loops. In addition, we find a new (3+1)D mixed topological order with a single non-Abelian fermionic loop, whose long-range entanglement is protected by an invariant of sequential circuits.

11.
arXiv (quant-ph) 2026-06-16

Quantum Fisher Information and the Speed of Entanglement

arXiv:2606.15484v1 Announce Type: new Abstract: We investigate the speed at which entanglement can be generated by an interaction parameter encoded in a two-qubit Hamiltonian, quantified by the derivative of concurrence with respect to the coupling parameter. For arbitrary pure two-qubit states evolving under a general nonlocal interaction, we derive a bound relating this entanglement speed to the quantum Fisher information (QFI). Specifically, we show that $|\partial_g C| \le \sqrt{F_Q^{(g)}}$, where $F_Q^{(g)}$ is the QFI associated with estimation of the parameter. This establishes $\sqrt{F_Q}$ as a an upper bound on the speed of entanglement generation in parameter space. We further derive the saturation conditions and identify the states and dynamical regimes for which equality is attained. At saturation, concurrence evolves at the maximum rate permitted by the distinguishability of the underlying quantum state. These results reveal a direct connection between quantum metrology and entanglement generation, showing that the same information-theoretic quantity that governs parameter-estimation precision also limits the speed at which entanglement resources can be created.

12.
arXiv (CS.AI) 2026-06-16

Why Low-Precision Transformer Training Fails: An Analysis on Flash Attention

arXiv:2510.04212v4 Announce Type: replace-cross Abstract: The pursuit of computational efficiency has driven the adoption of low-precision formats for training transformer models. However, this progress is often hindered by notorious training instabilities. This paper provides the first mechanistic explanation for a long-standing and unresolved failure case where training with flash attention in low-precision settings leads to catastrophic loss explosion. Our in-depth analysis reveals that the failure is not a random artifact but caused by two intertwined phenomena: the emergence of similar low-rank representations within the attention mechanism and the compounding effect of biased rounding errors inherent in low-precision arithmetic. We demonstrate how these factors create a vicious cycle of error accumulation that corrupts weight updates, ultimately derailing the training dynamics. To validate our findings, we introduce a minimal modification to the flash attention that mitigates the bias in rounding errors. This simple change stabilizes the training process, confirming our analysis and offering a practical solution to this persistent problem. Code is available at https://github.com/ucker/why-low-precision-training-fails.

13.
arXiv (CS.AI) 2026-06-17

Trust-Aware Multi-Agent Traceability: Confidence-Calibrated Knowledge Graphs for Consistent Software Artifact Management

arXiv:2606.17203v1 Announce Type: cross Abstract: Multi-agent AI systems are increasingly used to automate software engineering tasks including requirements analysis, architecture design, test generation, and traceability linking. When these agents operate as a sequential pipeline over shared software artifacts, errors and low-confidence decisions made by upstream agents propagate to downstream stages, producing orphaned requirements, contradictory links, and compliance gaps that pose significant risks in safety-critical domains. We propose a trust-aware coordination framework where a shared knowledge graph serves as both centralized semantic memory and a coordination surface through which agents assess and build upon each other's contributions using calibrated confidence scores. Our approach introduces a two-stage traceability link prediction pipeline combining embedding-based retrieval with LLM-based multi-criteria analysis, a traceability seeding mechanism that enables comparison between derivation-time and validation-time confidence, and a consistency protocol governing pipeline interactions through confidence threshold gating, confidence divergence detection, and conflict resolution. We evaluate on an automotive software engineering case study measuring link prediction calibration, protocol effectiveness, threshold sensitivity, and the impact of traceability seeding. Ablation studies confirm that confidence calibration is essential for effective pipeline coordination.

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

FairGen: Preference-Aligned Diffusion for Demographically Equitable Medical Image Synthesis

Medical imaging is central to modern diagnostics, and artificial intelligence (AI) systems are increasingly used to support image-based analysis by improving efficiency, accuracy, and access to care. However, inequities in healthcare access and differential disease prevalence create severe demographic imbalances in clinical image data. Such imbalances are compounded by the fact that diseases can manifest with distinct features across demographic groups, rendering certain phenotypic presentations naturally rare. AI models trained on such imbalanced data risk perpetuating diagnostic bias and widening healthcare disparities. Here we introduce FairGen, a fairness-aware diffusion framework that synthesizes demographically balanced medical images while preserving pathology-relevant visual features. By embedding physician-aligned preferences into the generation process, FairGen improves subgroup coverage during synthesis and downstream classification. Applied to dermatology, radiology, and neuroimaging benchmark tasks, FairGen achieves fairness improvements of 95.9% for skin images, 80.0% for chest radiography, and 35.2% for brain MRI, while maintaining competitive diagnostic accuracy relative to models trained on original clinical data. Clinician-facing expert review and external validation on independent cohorts further support that these gains extend beyond standard fidelity metrics and are not confined to the original in-distribution datasets.

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

SpatioTemporal Causal Network Diagnostics for Geographic Tipping Point Early Warning

arXiv:2606.17553v1 Announce Type: new Abstract: Geographic tipping points in ecosystems, climate subsystems, or ice sheets pose severe challenges for localized early warning. Classical spatial indicators such as Moran's I summarize global spatial structure, but they struggle with three issues: spatial dilution, Euclidean assumptions, and correlated noise. This paper introduces SpatioTemporal Causal Network Diagnostics (ST-CND), a framework that addresses these three issues by representing the geographic field as a time-evolving directed causal network. The core workflow is as follows: (1) infer which spatial nodes help predict other nodes via transfer entropy, replacing fixed Euclidean neighborhoods with data-driven information-flow topology; (2) estimate local recovery rates within each candidate subnetwork via dynamic mode decomposition; and (3) identify the most vulnerable subnetwork by combining three signals, namely high internal fluctuation, high internal synchronization, and low external coupling, thereby suppressing false alarms from spatially correlated noise. Validated on synthetic bifurcations and two observational sea-surface temperature benchmarks, namely Indo-Pacific SST and North Atlantic AMOC, ST-CND delivers localized and interpretable warnings. On the AMOC task, it achieves an AUROC of 0.783 and a critical-subnetwork IoU of 0.378, outperforming recurrence-network and lambda-AR1 baselines. The framework provides an interpretable and scalable pipeline for spatial early warning in Earth system science.

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

Heteroskedastic Signals in Budgeted LLM Verification: Structural Heterogeneity Limits Optimization Gains

作者:

arXiv:2606.15841v1 Announce Type: new Abstract: Large language model (LLM) systems increasingly use uncertainty signals to allocate limited computation across verification, test-time scaling, tool execution, and other selective-compute decisions. Such policies rely on a global signal comparability assumption: equal scores should carry comparable decision value across inputs. Using budgeted verification as a controlled diagnostic setting, we identify a failure mode of this assumption: uncertainty quality is heteroskedastic across cost strata, with some regions exhibiting near-random discriminability despite concentrating many errors. Under an explicit local model, we characterize the resulting distortion of global allocation and show that its upper bound scales with cross-stratum signal-quality dispersion. We separate weak signals, optimization instability, and structural heterogeneity through a controlled intervention hierarchy: Threshold, MP-Adapt, MP-Strat, and a deliberately simple cost-stratified thresholding intervention (CST). Across MBPP and MATH using Qwen3-8B, LLaMA3-8B, and GPT-4o-mini, global online adaptation yields inconsistent gains over static thresholding; MP-Strat partially recovers performance, while CST improves hit rate by up to 17 percentage points in strongly heterogeneous settings without gradient updates. These results identify structural heterogeneity, rather than optimizer weakness alone, as the primary bottleneck in the observed settings. More broadly, misaligned feedback structure cannot always be repaired by stronger optimization.

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

Steering the Noise: Turning Random Perturbations into Effective Descent for Memory-Efficient LLM Fine-Tuning

Fine-tuning large language models (LLMs) achieves strong performance but is often limited by the memory overhead of backpropagation. Zeroth-order (ZO) optimization avoids this overhead by estimating gradients through forward passes alone, yet it typically converges slowly because random Gaussian perturbations yield high-variance gradient estimates in high-dimensional parameter spaces. In this paper, we propose a plug-and-play framework that turns random perturbations into more effective descent directions. The key idea is to draw a small pool of candidate perturbations, evaluate their loss values, and then select or combine those that are best aligned with the optimization objective. We develop two instantiations of this idea: MeZO-GV, which forms a guiding vector from the contrast between low-loss and high-loss perturbation groups, and MeZO-Greedy, which keeps the single best perturbation within a fixed evaluation budget. We theoretically show that both strategies yield a larger per-step reduction in the objective than standard ZO estimation, leading to improved convergence rates. Experiments on LLMs of different scales and architectures confirm that the proposed methods integrate naturally with existing ZO optimizers and consistently improve convergence speed and task accuracy. On OPT-13B, our approach outperforms all ZO baselines across 11 benchmarks and exceeds gradient-based methods on 9 of them, while retaining the memory efficiency of forward-only optimization.

19.
arXiv (CS.CV) 2026-06-19

SAM3 Self-Distillation for Fine-Grained GOOSE 2D Semantic Segmentation

作者:

We describe our 4th-place entry to the ICRA 2026 GOOSE 2D Fine-Grained Semantic Segmentation Challenge, which reached a composite mean Intersection-over-Union (mIoU) of 69.73% on the official 1,815-image test set. Our model adapts the image encoder of a recent visual foundation model, Segment Anything Model 3 (SAM3), with a lightweight decoder. Beyond this, we contribute two techniques and one empirical finding: (i) a self-distillation scheme that re-uses SAM3 itself, prompted with ground-truth boxes, as a teacher on the classes where it outperforms our own model; (ii) an image-level multi-scale test-time augmentation scheme that restores multi-scale inference for a fixed-input-size model by rescaling the image rather than the model input; and (iii) the finding that an aggressive photometric distortion from a winning 2025 GOOSE 2D entry, transplanted onto our pipeline, is its single largest source of improvement.

20.
arXiv (CS.CL) 2026-06-12

EurekAgent: Agent Environment Engineering is All You Need For Autonomous Scientific Discovery

LLM-based agents have shown increasing potential in automating scientific discovery. Given an optimizable metric and an execution environment, they can propose, validate, and iterate scientific solutions, and have produced results that outperform human-designed approaches. As model capabilities continue to improve, we argue that the bottleneck for autonomous scientific discovery is shifting from prescribing agent workflows to designing agent environments: the resources, constraints, and interfaces that shape agent behavior. We frame this as environment engineering: building environments that amplify productive behaviors, such as open-ended exploration, systematic artifact management, and inter-agent collaboration, while suppressing harmful behaviors, such as reward hacking and high-friction human oversight. We present EurekAgent, an environment-engineered agent system for metric-driven autonomous scientific discovery. EurekAgent engineers the environment along four dimensions: permissions engineering for bounded agent execution and isolated evaluation; artifact engineering for filesystem and Git-based collaboration; budget engineering for budget-aware exploration; and human-in-the-loop engineering for easy human supervision and intervention. EurekAgent sets new state-of-the-art results on multiple mathematics, kernel engineering, and machine learning tasks, including new state-of-the-art 26-circle packing results discovered with less than $11 in total API cost. We open-source our code and results, and call for environment engineering as a core research direction for developing reliable autonomous research agents.

21.
PLOS Medicine 2026-05-27

Sequential chemo-immunotherapy followed by standard versus reduced thoracic radiotherapy for older and/or frail stage III non-small-cell lung cancer: A randomized open-label cohort trial

作者:

by Wei-Xiang Qi, Shuyan Li, Mengdi Wang, Huan Li, Feifei Xu, Lei Yao, Biao Yu, Linlin Chen, Gang Cai, Cheng Xu, Xianwen Sun, Zhiyao Bao, Jiayi Chen, Yi Xiang, Shengguang Zhao Background The appropriateness of concurrent chemoradiotherapy (cCRT) for older or clinically vulnerable stage III unresectable non-small-cell lung cancer (NSCLC) patients remains contentious. Furthermore, the survival implications of de-escalating thoracic radiotherapy (RT) intensity in this population have not been conclusively elucidated. Methods and findings We conducted a phase II randomized, open-label, two-cohort (non-comparative) trial at a tertiary hospital in China (NCT05557552). Between September 30, 2022 and April 30, 2024, we enrolled 56 older and/or frail patients with stage III NSCLC who were ineligible for cCRT. The primary endpoint was the 1-year progression-free survival (PFS) rate estimated using the Kaplan–Meier method. Secondary endpoints included objective response rate (ORR), overall survival (OS), and safety. In the intention-to-treat (ITT) set, which included all 56 randomized patients who received at least one dose of study treatment, the 1-year PFS was 84.3% (95% confidence interval [CI] [70.3%, 98.3%]) in the standard RT group and 70.7% (95% CI [54.3%, 87.1%]) in the reduced RT group. In the per-protocol set (53 patients), the 1-year PFS was 82.9% (95% CI [68.9%, 98.8%]) in the standard RT group and 73.4% (95% CI [58.3%, 92.4%]), with a median follow-up of 24 months. Among 56 patients in the safety analysis set, 71.4% of patients experienced grade 3/4 adverse events (AEs) in the standard RT group and 53.6% in the reduced RT group. One patient (3.6%) in the reduced RT and three patients (10.7%) in the standardized RT experienced grade 5 AEs. The main limitations are the non-comparative design, small sample size, and lack of power to establish non-inferiority or superiority. Conclusion The current study suggested that reduced RT combined with sequential chemo-immunotherapy might be feasible for older/frail patients intolerant to cCRT, showing numerically similar survival outcomes. These exploratory findings warrant confirmation in larger, adequately powered randomized trials. Trial registration The trial had been registered on ClinicalTrials.gov on Sep 30, 2022.ClinicalTrials.gov NCT05557552

22.
arXiv (CS.AI) 2026-06-19

SleepMaMi: A Universal Sleep Foundation Model for Integrating Macro- and Micro-structures

arXiv:2602.07628v2 Announce Type: replace Abstract: While the shift toward unified foundation models has revolutionized many deep learning domains, sleep medicine remains largely restricted to task-specific models that focus on localized micro-structure features. These approaches often neglect the rich, multi-modal context of Polysomnography (PSG) and fail to capture the global macro-structure of a full night's sleep. To address this, we introduce SleepMaMi , a Sleep Foundation Model engineered to master both hour-long sleep architectures and fine-grained signal morphologies. Our framework utilizes a hierarchical dual-encoder design: a Macro-Encoder to model full-night temporal dependencies and a Micro-Encoder to capture short-term characteristics from biosignals. Macro-Encoder is trained via Demographic-Guided Contrastive Learning, which aligns overnight sleep patterns with objective subject metadata, such as age, sex and BMI to refine global representations. Micro-Encoder is optimized via a hybrid Masked Autoencoder (MAE) and multi-modal contrastive objective. Pre-trained on a massive corpus of $>$20,000 PSG recordings (158K hours),SleepMaMi outperforms or matches state-of-the-art existing foundation models across a diverse suite of downstream tasks, demonstrating superior generalizability and label-efficient adaptation for clinical sleep analysis.

23.
Science (Express) 2026-06-11

Laser phase plate improves structure determination of small proteins by cryo-EM | Science

作者: 未知作者

Phase plates can in principle overcome the poor image contrast in electron cryo–microscopy (cryo-EM) and the resulting limits on the structural reconstruction of small proteins. However, previous designs have been unstable and compromised the high-resolution signal. They have thus been unable to surpass results achieved by standard cryo-EM. Here, we show that the laser phase plate (LPP), installed in a custom, modern Titan Krios microscope, enhances the resolution in single-particle reconstruction of small proteins by improving specimen-motion correction, recovery of information from the early frames, as well as particle visualization, 3D classification, and alignment. These advances use standard defocus ranges and reconstruction procedures, but open the door to LPP-tailored protocols offering further improvements by leveraging the LPP demonstrated here.

24.
arXiv (CS.CV) 2026-06-17

Not Truly Multilingual: Script Consistency as a Missing Dimension in VLM Evaluation

Current multilingual evaluations for Vision-Language Models (VLMs) assume a one-to-one mapping between language and orthography, overlooking billions of users of multi-script languages. We introduce PuMVR (Punjabi Multimodal Visual Reasoning), a benchmark of 1,000 strictly parallel image-text instances across Punjabi's three active scripts: Gurmukhi, Shahmukhi, and Roman. Evaluating 10 state-of-the-art VLMs, we expose a substantial and systematic Script Gap. Models frequently solve visual tasks in one script while failing identical tasks in another, with accuracy deltas reaching 16%. Crucially, visual input boosts absolute performance uniformly yet does not close the orthographic gap. Furthermore, cross-script in-context transfer is highly brittle, exposing script-locked knowledge representation. Supported by McNemar tests across all script pairs, our findings demonstrate that current "multilingual" VLMs are not truly multi-script. We propose the Script Consistency Rate (SCR), which falls as low as 24.8% on our benchmark, as a mandatory metric for script-agnostic evaluation to ensure equitable AI access. Data and code are available at: https://github.com/prabhjotschugh/Not-Truly-Multilingual-PuMVR.

25.
medRxiv (Medicine) 2026-06-23

Sex-Specific Hemostatic Responses and Diagnostic Potential of Platelet Distribution Width (PDW) and D-Dimer in Mild COVID-19, Malaria, and Co-Infection in a Tropical Setting: A Case-Control Study in Port Harcourt, Nigeria

Background: In malaria-endemic tropical regions, the overlapping coagulopathy in COVID-19 and malaria poses diagnostic and prognostic challenges, particularly with potential sex differences. This study evaluated sex-specific variations in platelet indices and fibrinolytic markers and assessed the utility of Platelet Distribution Width (PDW) and D-dimer in mild/asymptomatic cases. Methods: A case-control study was conducted with 220 participants (55 each in healthy controls, malaria-positive, COVID-19-positive, and COVID-19+malaria co-infected groups), aged 20-65 years, in Port Harcourt, Nigeria. Platelet indices were analysed using Sysmex XP-300 haematology analyser, while D-dimer and fibrinogen were measured by ELISA. Data were analysed using SAS 9.4 with ANOVA, Tukey's HSD, Pearson correlation, and sex-stratified comparisons. Results: PDW was significantly elevated in all infected groups compared to controls (malaria: 15.21 +/- 0.22 fL; COVID-19: 15.21 +/- 0.22 fL; co-infection: 15.61 +/- 0.21 fL vs. control: 13.26 +/- 0.17 fL; F=25.850, p < 0.001). D-dimer levels were highest in the co-infected group (553.42 +/- 59.74 ng/ml, F=2.816, p = 0.040). No significant changes were observed in other platelet indices or fibrinogen across groups. No significant correlation existed between platelet indices and the fibrinolytic markers. Males exhibited significantly higher D-dimer levels across all infected groups (p < 0.05) and higher fibrinogen in COVID-19 subjects (p = 0.036). Sex exerted a stronger influence on parameters than age. Conclusion: Males show heightened fibrinolytic activation in COVID-19 and malaria co-infection. PDW and D-dimer are promising, cost-effective biomarkers for screening mild infections in resource-limited tropical settings.