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

Understanding Scam Trends and Rail Paths from Reddit Self-Disclosure Narratives

Online scam behavior is inherently multi-stage, and the lifecycle includes temporally ordered rails and events rather than isolated signals. Existing works analyze characteristics of scam types and rails, but they do not track scam trends across years. Moreover, the work on the relations between rails is hampered due to the lack of open-source datasets with annotations and coverage of different scam types. To address these gaps, we build a dataset to analyze the yearly trend of scam characteristics and rail paths using Reddit self-disclosure narratives from 2023 to 2025. We collect 21,304 posts from scam-related subreddits with at least one rail among identity, communication, platform, and payment for trend analysis by heuristic annotation. Then, we label 1,800 posts containing explicit or recoverable scam chains by an LLM-assisted method for scam path analysis. The method is evaluated with human annotation. Lastly, we run a topic model on the comments of the posts to analyze the community support behavior. The results reveal that scam processes are predominantly multi-rail. Across years, different scam types and rail components dominate. Different scam types vary systematically in path complexity. Reddit support behaviors have become more detailed over time. This work supports synthetic scam chain data simulation and AI-related scam risk assessment, though findings may not generalise to other platforms.

02.
arXiv (CS.AI) 2026-06-16

LatentGym: A Testbed For Cross-Task Experiential Learning With Controllable Latent Structure

arXiv:2606.15306v1 Announce Type: cross Abstract: We envision continually learning agentic systems that become more useful over time: as they encounter sequences of related tasks, they should infer the hidden structure shared across those tasks and use it to improve future decisions. This cross-task experiential learning capability is pivotal in domains such as personalization and interactive assistance, but existing training/evaluation frameworks do not provide shared, controllable latent structures and cannot measure whether or why agents improve. We introduce LatentGym: a controllable suite in which each environment is organized around a ground-truth latent variable governing the structure across tasks. Our construction yields metrics that separate exploration (whether the agent's actions gather information about the latent) from exploitation (whether the agent uses what it has gathered). We demonstrate our suite on empirical studies addressing three questions: how and why frontier models fail to adapt across related tasks; whether post-training on related task sequences improves general cross-task adaptation, and where those gains come from; and how design choices such as inter-task feedback shape training dynamics and generalization. Together, these results establish a controlled foundation for studying how LLM agents learn from experience across tasks, and for designing agents that adapt more reliably in sequential, personalized, and interactive settings.

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

Catastrophic Compositional Generation: Why Vanilla Diffusion Models Fail to Extrapolate

arXiv:2606.23920v1 Announce Type: cross Abstract: The task of compositional generation involves using a conditional generative model, trained only on a subset of the possible conditions, to produce samples from compositionally-defined target distributions such as a geometric combination of the source distributions. In this work, we argue that this task is often infeasible for vanilla conditional diffusion models: we conjecture that no inference-time technique can efficiently produce samples from the target distribution in certain well-motivated settings. This idea is supported by theory-guided generalization arguments and carefully-designed experiments on both synthetic and realistic data. In particular, while recent methods such as Feynman-Kac correction reduce inference-time approximation error, our results show that score estimation error has a more catastrophic effect on performance when the target distribution is out-of-distribution with respect to the sources, highlighting the need for a different approach to this task.

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

Advances in 4D Representation: Geometry, Motion, and Interaction

We present a survey on 4D generation and reconstruction, a fast-evolving subfield of computer graphics whose developments have been propelled by recent advances in neural fields, geometric and motion deep learning, as well as 3D generative artificial intelligence (GenAI). While our survey is not the first of its kind, we build our coverage of the domain from a unique and distinctive perspective of 4D representations, to model 3D geometry evolving over time while exhibiting motion and interaction. Specifically, instead of offering an exhaustive enumeration of many works, we take a more selective approach by focusing on representative works to highlight both the desirable properties and ensuing challenges of each representation under different computation, application, and data scenarios. The main take-away message we aim to convey to the readers is on how to select and then customize the appropriate 4D representations for their tasks. Organizationally, we separate the 4D representations based on three key pillars: geometry, motion, and interaction. Our discourse will not only encompass the most popular representations of today, such as neural radiance fields (NeRFs) and 3D Gaussian Splatting (3DGS), but also bring attention to relatively under-explored representations in the 4D context, such as structured models and long-range motions. Throughout our survey, we will reprise the role of large language models (LLMs) and video foundational models (VFMs) in a variety of 4D applications, while steering our discussion towards their current limitations and how they can be addressed. We also provide a dedicated coverage on what 4D datasets are currently available, as well as what is lacking, in driving the subfield forward. Project page:https://mingrui-zhao.github.io/4DRep-GMI/

05.
arXiv (CS.CV) 2026-06-15

CottonLeafVision: An Explainable and Robust Deep Learning Framework for Cotton Leaf Disease Classification

Globally, cotton is a highly economically beneficial crop, as the textile industry heavily depends on it. So, the precise identification and detection of cotton leaf disease is crucial for economic stability. The development goal of "CottonLeafVision" is to accurately classify and detect cotton leaf disease. With this goal, we have evaluated multiple pretrained Deep Convolutional Neural Networks, including DenseNet201, InceptionV3, and VGG19 on a publicly available cotton leaf disease image dataset. This image dataset includes seven classes, six disease classes, and one healthy class, collected under various field conditions reflecting real-world challenges. Among these pretrained models, with DenseNet201, we have achieved the highest classification accuracy of 98%. To enhance the model reliability and interpretability, we have implemented different techniques and methods such as Gradient-weighted Class Activation Mapping (Grad-CAM), occlusion sensitivity analysis and adversarial training to increase the noise resistance of the model. Finally, we have developed a prototype in order to utilize the model's capabilities on real life agriculture. This paper shows the deep learning model's capabilities to classify the disease in real-life cotton disease management situations.

06.
Nature (Science) 2026-06-22

C-glycoside synthesis via radical cross-coupling of glycohydrazides

Authors:

Carbohydrates are among the most abundant and structurally diverse biomolecules in nature, playing central roles in energy storage, molecular recognition, and cell signaling. Within this domain, C-glycosides1-3, in which the oxygen atom of the glycosidic bond in O-glycosides is replaced by carbon, have emerged as valuable motifs in medicinal chemistry due to their resistance to enzymatic hydrolysis2,4. Of particular importance are C-aryl glycosides, exemplified by the SGLT2 inhibitors dapagliflozin, canagliflozin, and empagliflozin, which are frontline therapies for type 2 diabetes5-7. However, scalable syntheses of C-aryl glycosides have traditionally relied on protected sugar derivatives, lengthy sequences, or conventional cross-couplings that often suffer from poor selectivity, limited scope, and extensive protecting-group manipulation6. Herein, we report a practical approach to C-aryl glycosides using glycosyl sulfonyl hydrazides as redox-neutral radical precursors for cross-coupling. Prepared directly from unprotected native sugars, these reagents generate glycosyl radicals under mild conditions and enable efficient access to diverse C-aryl glycosides, including all approved SGLT2 inhibitors, natural products such as salmochelins and neopetrosins, and medicinally relevant probes. Beyond anomeric functionalization, this platform enables C–C bond formation at multiple positions on carbohydrate scaffolds and supports stereoretentive radical coupling that can override inherent stereochemical biases, expanding practical access to carbohydrate-derived therapeutics and chemical tools.

07.
arXiv (quant-ph) 2026-06-17

Einstein-Podolsky-Rosen correlations between mechanical oscillators revealed through SU(1,1) interferometry

arXiv:2606.18202v1 Announce Type: new Abstract: Quantum correlations are essential for achieving quantum advantage in computing, communication and sensing. Moreover, their observation challenges and constrains our fundamental understanding of nature. Mechanical oscillators in the quantum regime provide an appealing platform for preparing and investigating quantum correlations at macroscopic scales. Despite substantial progress, however, continuous-variable quantum correlations stronger than entanglement have not yet been observed in this macroscopic regime. Here, we report the experimental observation of continuous-variable Einstein-Podolsky-Rosen correlations between two spatially-separated mechanical oscillators with an effective mass of $\sim 16 \,\mu g$ each. This is achieved by coupling them to a superconducting qubit which allows for engineering a two-mode squeezing interaction when parametrically driven. Crucially, we show that this interaction can be used to witness quantum correlations through the realization of a mechanical SU(1,1) interferometer. Our results expand the toolbox of operations in circuit quantum acoustodynamics and demonstrate that quantum correlations stronger than entanglement can also be observed in macroscopic systems, thereby shedding light on the boundary between quantum and classical regimes.

08.
arXiv (CS.CL) 2026-06-18

PEC-Home: Interpretation of Progressively Elliptical Commands in Smart Homes

Recent advancements in Large Language Models (LLMs) have empowered home assistants with natural language interaction capabilities. However, current assistants overlook the progressive omission that occurs in human dialogue as shared context accumulates, leading to more elliptical expressions for efficient communication. Thus, current assistants still struggle to interpret such elliptical expressions accurately, which limits their effectiveness in real-world applications. In practical smart home scenarios, assistants face two major challenges caused by elliptical commands: (1) referential ambiguity caused by different environmental expectations among multiple users; and (2) intention ambiguity resulting from user preferences that evolve over time or change with the environment. To address these challenges, we introduce PEC-Home, the first simulated home dataset specifically designed for interpreting progressively elliptical commands in smart homes. Extensive experiments on various LLMs, including GPT-4o, show that existing home assistants struggle to execute user-intended operations based solely on elliptical commands. Even when equipped with tools for storing and retrieving user dialogue history, execution accuracy remains below that achieved with complete commands.}.

09.
arXiv (CS.AI) 2026-06-15

SEVRA-BENCH: Social Engineering of Vulnerabilities in Review Agents

arXiv:2606.13757v1 Announce Type: cross Abstract: Large language model (LLM) reviewers are increasingly used in pull-request (PR) workflows, where their approvals help decide which code is merged into a repository. This raises a question that benchmarks for static vulnerability detection or code generation do not address: can an automated reviewer reject a malicious contribution when the attacker controls both the code change and the accompanying PR text? We introduce SEVRA-BENCH (Social Engineering of Vulnerabilities in Review Agents), a benchmark that measures how often an automated reviewer approves such adversarial pull requests. Each malicious PR in SEVRA-BENCH is built from a real project commit that previously fixed a vulnerability listed in the Common Vulnerabilities and Exposures (CVE) database. We automatically invert that fix to restore the original vulnerable code and submit it as a pull request wrapped in one of 15 social-engineering framings, which vary the claims made, the supporting evidence, the urgency conveyed, signals of prior approval, and appeals to authority. SEVRA-BENCH contains 1,062 malicious PRs drawn from Common Vulnerabilities and Exposures (CVE)-linked fixes across the top 10 entries of the 2025 Common Weakness Enumeration (CWE) Top 25. In a realistic setting, we evaluate 8 current LLMs as code review agents on PRs that introduce vulnerabilities previously reported in public disclosures. Our results reveal a sharp gap in security capabilities between closed- and open-source models. We hope SEVRA-BENCH will serve as a valuable resource for advancing open-source models and narrowing this gap.

10.
arXiv (CS.AI) 2026-06-11

An Ethical eValuation Agent (EeVA): Results of a Proof-of-Concept Test on a Prototype Agentic-like Workflow to Assist Ethical Deliberations

arXiv:2606.11218v1 Announce Type: cross Abstract: Ethical deliberation is often misunderstood as a search for single right or wrong answers, creating difficulties for non-ethically trained personnel who must address ethically laden challenges. We developed EeVA, an agentic-like LLM-based workflow designed to support comparative ethical reflection rather than deliver definitive ethical answers. EeVA was programmed in n8n using three interconnected workflows: starter, worker, and emitter. It evaluated uploaded use cases against 10 ethical frameworks through evaluator and synthesis prompts. Proof-of-concept testing used three published cases from urban mobility, peer-to-peer energy trading, and social-service resource allocation. Across all cases, EeVA produced consistently structured framework-specific evaluations and integrated syntheses. Outputs differentiated between frameworks, identified convergences and divergences, recommended modifications to increase alignment, and highlighted persistent ethical tensions. Syntheses were readable for non-specialists and shifted attention away from simplistic answers toward design conditions, safeguards, and areas where full cross-framework agreement was unlikely. The findings suggest that LLMs can be organised into usable workflows that preserve ethical plurality while helping bridge the communicative gap between ethicists and non-ethically trained personnel. EeVA's value lies not in replacing ethicists or resolving moral disagreement, but in scaffolding structured ethical deliberation. EeVA offers a promising proof of concept for supporting ethical reflection where access to ethics expertise is limited. Further work is needed on reproducibility, human evaluation, user testing, and efficiency before it can be considered a mature tool.

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

Model-Based and Data-Driven Hierarchical Control and Topology Co-Design for Robust Networked Systems

arXiv:2606.11596v1 Announce Type: cross Abstract: In this paper, we consider a class of networked systems comprising an interconnected set of linear subsystems, disturbance inputs, and performance outputs. Using dissipativity theory, we first propose a model-based hierarchical control design strategy to ensure the closed-loop networked system is dissipative from its disturbance inputs to performance outputs. This involves designing local controllers for each subsystem to enforce local dissipativity guarantees, which are then exploited to co-design distributed global controllers and the interconnection topology to enforce global dissipativity guarantees while optimizing interconnection topology costs. The overall design process requires only solving a sequence of linear matrix inequality (LMI) problems, thereby retaining compositionality and decentralizability while avoiding non-convex, iterative design processes that are inefficient and centralized. This model-based hierarchical control design strategy assumes the knowledge of the subsystem dynamics, which may not hold in many real-world networked systems. Motivated by this, we also propose a data-driven hierarchical control design strategy that assumes only the availability of rich input-state-output trajectory data from the subsystems. The proposed data-driven design process assumes that the unknown disturbances affecting the subsystem dynamics are bounded by a quadratic matrix inequality (relaxing conventional bounds) and accounts for this by using the matrix S-lemma. Finally, the effectiveness of the proposed model-based and data-driven hierarchical control designs is illustrated for a networked system representing a DC microgrid, with the aim of enforcing robust (dissipative) voltage regulation and current sharing.

12.
arXiv (quant-ph) 2026-06-24

Quantum mechanics over real numbers fully reproduces standard quantum theory

arXiv:2604.19482v3 Announce Type: replace Abstract: Standard quantum mechanics employs complex Hilbert spaces, but whether complex numbers are fundamental or merely convenient has long been debated. For decades, real-valued equivalents were considered mathematically possible but cumbersome. However, a highly cited 2021 result claimed that any quantum theory based on real numbers is experimentally falsifiable via network Bell experiments. Yet, it remains an open question whether this falsification applies to all real-valued theories. Here we show that this conclusion rests on an incomplete real formulation, and we present a rigorous real-valued framework that perfectly reproduces all predictions of standard quantum mechanics. We demonstrate that the standard real tensor product ($\otimes_{\mathbb{R}}$) used in previous no-go theorems is algebraically incompatible with the rich structure of conventional quantum mechanics. We present a real framework based on K\"{a}hler space and prove that it is exactly isomorphic to established quantum mechanics via an explicit bijection $\gamma$. The isomorphism extends to composite systems through a symplectic composition rule $\otimes^{\ks}$ that replaces the Kronecker product. Consequently, our formulation achieves the maximal $\mathrm{CHSH}_{3}$ violation of $6\sqrt{2}$ using purely real variables, demonstrating that the no-go theorem is specific to a particular real representation of states and operators and to the composition rule $\otimes_\mathbb{R}$ built upon it, neither of which extends to the present K\"{a}hler framework. These results demonstrate that complex numbers are not fundamentally required by nature; rather, they encode a deeper real geometric structure that governs quantum interference and entanglement, settling this long debate.

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

PACE-RAG: Patient-Aware Contextual and Evidence-Constrained RAG for Clinical Drug Recommendation

Drug recommendation requires a deep understanding of individual patient context, especially for complex conditions like Parkinson's disease. While LLMs possess broad medical knowledge, they fail to capture the subtle nuances of actual prescribing patterns. Existing RAG methods also struggle with these complexities because guideline-based retrieval remains too generic and similar-patient retrieval often replicates majority patterns without accounting for the unique clinical nuances of individual patients. To bridge this gap, we propose PACE-RAG (Patient-Aware Contextual and Evidence-Constrained RAG). Rather than directly copying frequent medications from retrieved patients, PACE-RAG personalizes recommendations by first extracting patient-specific clinical features, retrieving cases around these features, and then refining the final prescription using the patient's current symptoms, active medication history, and focus-specific prescribing tendencies. By analyzing treatment patterns tailored to specific clinical features, PACE-RAG generates patient-specific medication recommendations along with an explainable clinical summary. Evaluated on a Parkinson's cohort and the MIMIC-IV benchmark using Llama-3.1-8B and Qwen3-8B, PACE-RAG achieved state-of-the-art performance, reaching F1 scores of 80.84% and 47.22%, respectively. These results suggest that PACE-RAG is a robust and clinically grounded framework for personalized decision support. Our code is available at: https://github.com/ChaeYoungHuh/PACE-RAG.

14.
Nature Medicine 2026-06-16

<b>Engineered heart muscle passes early clinical milestone</b>

Engineered heart muscle allografts derived from induced pluripotent stem cells show promising early outcomes in patients with treatment-refractory advanced heart failure with reduced left ventricular ejection fraction, in support of further clinical investigation. Engineered heart muscle allografts derived from induced pluripotent stem cells show promising early outcomes in patients with treatment-refractory advanced heart failure with reduced left ventricular ejection fraction, in support of further clinical investigation.

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

EDoF-NeRF: extended depth-of-field neural radiance fields using a coded aperture camera

We propose a method for extending the depth-of-field (DoF) to construct high-fidelity neural radiance fields (NeRF) – an emerging technique for rendering photorealistic novel views from a dataset of images captured at different viewpoints, based on implicit neural representations. The trade-off between DoF and light quantity is inherent not only in conventional cameras but also in NeRF, since the datasets used by NeRF are captured by these cameras. To address this issue, we introduce a coded aperture placed at the camera pupil, preserving spatial frequency components under defocused conditions. We develop a camera model incorporating coded apertures into NeRF, allowing direct input of coded images and enabling the generation of novel views with an extended DoF. We validate the proposed method, termed extended DoF-NeRF (EDoF-NeRF), through simulations and experiments, demonstrating its superior performance compared to conventional aperture cameras.

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

ShowFlow: From Robust Single Concept to Condition-Free Multi-Concept Generation

Customizing image generation remains a core challenge in controllable image synthesis. For single-concept generation, maintaining both identity preservation and prompt alignment is challenging. In multi-concept scenarios, relying solely on a prompt without additional conditions like layout boxes or semantic masks, often leads to identity loss and concept omission. In this paper, we introduce ShowFlow, a comprehensive framework designed to tackle these challenges. We propose ShowFlow-S for single-concept image generation, and ShowFlow-M for handling multiple concepts. ShowFlow-S introduces a KronA-WED adapter, which integrates a Kronecker adapter with weight and embedding decomposition, and together with a novel Semantic-Aware Attention Regularization (SAR) training objective to enhance single-concept generation. Building on this foundation, ShowFlow-M directly reuses robust models learned by ShowFlow-S to support multi-concept generation without extra conditions, incorporating a Subject-Adaptive Matching Attention (SAMA) and a Layout Consistency guidance as the plug-and-play module. Extensive experiments and user studies validate ShowFlow's effectiveness, highlighting its potential in real-world applications like advertising and virtual dressing. Our source code will be publicly available at: https://htrvu.github.io/showflow.

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

Adaptable Method for Crystal Design across Diverse Constraints and Objectives with Pretrained Property Predictors

arXiv:2410.08562v5 Announce Type: replace-cross Abstract: Advanced crystal design can accelerate materials discovery across applications from photovoltaics to spintronics. Practical design must satisfy multiple properties and physical constraints, yet existing machine-learning-based approaches to such design often depend on large datasets, retraining, or task-specific generators. Here, we show that direct predictor-guided gradient optimization enables data-efficient, constraint-rich crystal design by combining off-the-shelf predictors with site-wise element masks, template initialization, and task-specific losses. In perovskites, it outperformed generative and Bayesian baselines under three targets – band gap, formation energy, and tolerance factor – and two hard constraints. DFT assessment further showed band-gap targeting competitive with a leading generative model despite using predictors trained on roughly one-tenth of the data. By flexibly combining pretrained predictors with application-oriented masks and custom losses, the same framework supported half-metal design. Such modularity could help researchers and engineers translate diverse application requirements directly into optimized candidate crystals with minimal computational cost.

18.
arXiv (quant-ph) 2026-06-19

Transfer-matrix functions for algebraically decaying interactions in variational infinite matrix product states

Authors:

arXiv:2606.20522v1 Announce Type: cross Abstract: Variational infinite matrix product state (iMPS) calculations usually make Hamiltonians with algebraically decaying interactions compatible with standard MPO algorithms by first replacing the target Hamiltonian with a finite-pole sum-of-exponentials surrogate, thereby introducing a Hamiltonian-representation residual. We formulate the fixed-$D$ variational energy without introducing such a surrogate. For a fixed finite-$D$ MPS, the algebraic tail can be summed directly through the connected transfer matrix: the tail $e^{\mathrm{i} Qr}/r^\alpha$ is represented by the matrix function $F_{\alpha,Q}(\widetilde{T}_A)$, with $F_{\alpha,Q}(z)=\operatorname{Li}_\alpha(e^{\mathrm{i} Q}\,z)/z$. We evaluate the resulting matrix-function action using a Krylov method and obtain stable gradients by combining a Fréchet adjoint with implicit fixed-point differentiation. Benchmarks on long-range free fermions and the inverse-square Heisenberg family, including the Haldane–Shastry point, validate the transfer-matrix-function formulation. A long-range Ising-chain calculation illustrates a practical consequence of avoiding a finite-pole Hamiltonian representation. At a fixed, independently known critical field, finite-pole surrogate Hamiltonians can bias a critical diagnostic away from criticality, whereas the matrix-function calculation retains the expected critical signatures of the target algebraic Hamiltonian.

19.
arXiv (quant-ph) 2026-06-11

Tensor-Network Algorithm for Many-Body Trace Norms

arXiv:2606.11882v1 Announce Type: new Abstract: Trace norms are fundamental to quantum information theory, yet in many-body systems their evaluation remains a major computational bottleneck, as it generally requires diagonalizing exponentially large operators. Here, we overcome this bottleneck by introducing a controlled tensor-network algorithm for estimating the trace norm of matrix product operators without full diagonalization. The key idea is to combine Zolotarev's rational approximation to the sign function with a variational formulation solved using a density-matrix-renormalization-group-like algorithm. The resulting approximation is systematically improvable, with its accuracy controlled by the rational approximation parameters and the spectral weight near zero. Beyond the reach of exact diagonalization, we demonstrate controlled trace-norm calculations for entanglement negativity, quantum fidelity and quantum Fisher information, achieving substantially improved accuracy over polynomial-based Lanczos approaches. Our results establish trace-norm-based quantities as practical tensor-network observables, opening a route toward tensor-network studies of quantum information in mixed states.

20.
arXiv (CS.AI) 2026-06-16

TERMS-Bench: Diagnosing LLM Negotiation Agents Beyond Deal Rate

arXiv:2605.13909v2 Announce Type: replace-cross Abstract: Negotiation is a central mechanism of economic exchange, shaping markets, procurement, labor agreements, and resource allocation. It is also a canonical testbed for agentic language models, requiring multi-turn interaction under hidden preferences, strategic communication, and binding constraints. These properties make negotiation hard to evaluate: unlike math or code, it has no intrinsic verifier. Existing LLM negotiation evaluations rely on LLM-vs.-LLM interaction or aggregate outcomes such as deal rate, leaving failures opaque. We introduce Terms-Bench, short for Testbed for Economic Reasoning in Multi-turn Strategy, a Bayesian-game framework that makes the environment itself the verifier by specifying the counterpart's latent type, policy, and payoff structure. We instantiate it in bilateral price negotiation, where the counterpart's private state and simulator policy are hidden from the agent but observable to the evaluator. This turns the counterpart from a black-box opponent into a diagnostic instrument, enabling agent-attributable failure analysis and oracle-reference optimality gaps. Evaluating 13 LLM agents spanning frontier systems from major providers, Terms-Bench turns negotiation evaluation from aggregate ranking into actionable diagnosis: where agents fail, why they fail, and what to strengthen. Empirically, frontier models saturate deal rate yet diverge in surplus extraction, cue use, belief calibration, and compliance, revealing agent-specific bargaining bottlenecks masked by prior benchmarks.

21.
medRxiv (Medicine) 2026-06-24

Allostatic load modifies neuropsychiatric risk following traumatic brain injury

Importance: Outcomes following traumatic brain injury (TBI) vary substantially, with a subset of individuals experiencing neuropsychiatric morbidity and worse prognosis. Exposure to psychosocial and environmental stressors may be an important, yet understudied, modifier of TBI trajectory. Allostatic load (AL) represents the cumulative physiological burden of chronic stress and provides a useful framework for evaluating pre-injury vulnerability. Objective: To assess the relationship between pre-injury AL burden and risk of mortality and incident neuropsychiatric diagnosis following TBI. Design, Setting, and Participants: This cohort study leveraged electronic health record, survey, and laboratory data from the All of Us Research Program, version 8. Participants aged 18 years or older enrolled between May 6, 2018, and October 1, 2023, were queried for TBI diagnosis using clinical diagnostic codes. Data were analyzed between November 11, 2024, and January 7, 2026. Exposure: The physiological burden of pre-injury chronic stress exposure was estimated using an AL index (pALI) derived from anthropometric and laboratory biomarkers collected before index TBI. Main Outcomes and Measures: Post-TBI mortality and incident neuropsychiatric diagnosis clusters. Mortality risk was assessed using Cox proportional hazards models (hazard ratio [HR] with 95% CI), and risk of incident neuropsychiatric diagnosis was modeled using competing-risk regression with death as a competing event (sub-distribution HR with 95% CI). Results: The primary cohort included 4,552 individuals with an established TBI diagnosis and sufficient biomarker data to estimate pALI. The pALI measure differed across sociodemographic groups and was positively correlated with perceived stress (r=.08, p=.002). Higher pALI was associated with increased post-TBI mortality risk (adjusted HR=1.71; 95%CI, 1.36-2.14). Elevated pALI was also associated with greater risk of incident post-traumatic stress disorder (PTSD; adjusted HR=1.28; 95%CI, 1.10-1.50) and sleep disorder (adjusted HR=1.42 95%CI, 1.29-1.57) diagnoses. Conclusions and Relevance: Higher pre-injury ALI was associated with increased risk of mortality and select neuropsychiatric outcomes following TBI, suggesting that AL burden may shape post-injury trajectories. Pre-injury chronic stress exposure and underlying stress biology may represent underrecognized determinants of vulnerability and resilience in brain injury recovery.

22.
arXiv (CS.CL) 2026-06-15

CacheRL:Multi-Turn Tool-Calling Agents via Cached Rollouts and Hybrid Reward

We present CacheRL, a system for training small agent foundation models that achieves 92 percent process accuracy on multi-step tool-calling tasks, approaching GPT-5's 94 percent while requiring 100 times less compute. Our approach addresses three challenges in practical agent training: transferring tool-calling knowledge from large models at scale, enabling reinforcement learning without costly live tool execution, and learning robustly from noisy cached environments. CacheRL introduces three key innovations. First, a hybrid thinking trajectory pipeline augments agent trajectories with LLM-generated reasoning traces, producing training examples that teach models not only what tools to call but also why. Second, the CacheAgentLoop eliminates live execution costs through a three-tier fuzzy cache while preserving trajectory fidelity using token-level masking. Third, a cache-tier-aware reward dynamically adjusts answer-quality weights to avoid penalizing models for cache-induced limitations. Through iterative supervised fine-tuning (SFT) and Group Relative Policy Optimization (GRPO), CacheRL improves Qwen3-4B-Thinking's validation reward from 0.43 to 0.78. On public agentic tool-calling benchmarks, our model achieves competitive performance against frontier models such as GPT-5. Ablation studies show that removing knowledge transfer reduces performance by 41 percent, while cache-aware rewards contribute a 17 percent improvement. Interestingly, reinforcement learning improves training stability but yields limited gains beyond strong supervised fine-tuning, suggesting that data quality and reward design play a more important role than complex optimization methods in building practical small agent models.

23.
Nature (Science) 2026-06-24

Chiral laser gyroscopes breaking the lock-in limit

Authors:

Ring laser gyroscopes (RLGs) measure rotation via the Sagnac effect: a slight difference in the frequency of the two counter-propagating beams within the resonator. However, at low rotation rates, an intrinsic limitation in RLGs, known as the lock-in phenomenon, counteracts this effect, precluding the widespread adoption of RLGs as motion sensors. Past efforts to avoid this phenomenon include mechanical dithering1 and magneto-optic non-reciprocity techniques2. Such techniques require external components that limit the miniaturization of RLGs. Here we present a self-biased method that overcomes this limitation through chiral spontaneous symmetry breaking and nonlinear frequency pulling in a He–20Ne RLG without inserted elements. Supported by a theoretical model that reveals phase transition conditions with spontaneous symmetry breaking and the dynamics of bistable chiral states, our experiments demonstrate deterministic chirality switching synchronized with rotation direction. Remarkably, the chiral RLG has a linear frequency response at near-zero rotation rates, achieving an open-loop bias instability of 2.2 × 10−2 degrees per hour at a 10 s integration time. Our work presents a strategy for the development of all-solid-state, high-precision and miniaturized laser gyroscopes, which could be used for the exploration of the interplay of nonlinear dynamics and spontaneous symmetry breaking in photonic systems. Ring laser gyroscope lock-in has been&nbsp;eliminated&nbsp;using spontaneous symmetry breaking in a He–Ne laser, enabling accurate near-zero rotation sensing without external components, improving miniaturization and precision.

24.
bioRxiv (Bioinfo) 2026-06-11

Machine Learning-Guided Discovery of Bacterial-Selective Membrane-Active Compounds Reveals Mechanistic Bias in Antibiotic Training Datasets

The rise of antibiotic resistance necessitates the discovery of antibacterial compounds with novel mechanisms of action (MoAs). Recent machine learning approaches have shown promise in antibacterial compound discovery, but often identify derivatives of known antibiotic classes rather than mechanistically novel compounds. Previous approaches applied Tanimoto similarity filters at the end of screening pipelines, but this method has substantial drawbacks: Tanimoto similarity can be misleading in chemical space, and post-hoc filtering does not influence what activity models learn to prioritize. Here, we present a machine learning pipeline that addresses chemical novelty upfront by employing an XGBoost-based MoA classifier to explicitly prioritize compounds predicted to have mechanisms distinct from known antibiotic classes, combined with graph neural networks for antibacterial activity and toxicity prediction. Applied to the Zinc20 database, our approach successfully identified non-toxic antibacterial compounds structurally distinct from known antibiotics. Notably, the majority of these hits exhibited membrane-targeting activity with selectivity for bacterial cells over mammalian cells, suggesting potential for next-generation membrane-active antibiotics. However, we did not identify compounds with novel protein targets. Systematic analysis revealed that this limitation stems from mechanistic bias in training data rather than model architecture. Specifically, our activity model learned to preferentially score compounds similar to specific groups in the training data, thus overrepresenting certain MoA classes including membrane-active compounds. Even substantial model architecture and training data enhancements did not overcome this constraint. Our findings demonstrate that the primary bottleneck for discovering mechanistically novel antibiotics is the scarcity of diverse, mechanistically-annotated training data. This work provides both a methodological framework for mechanism-aware screening and critical insights into data requirements for genuinely novel antibiotic discovery.

25.
Nature Biotechnology 2026-06-08

Single-cell spatial pharmacobiology for imaging antibody-based therapies in solid tumors

Authors: Unknown Author

We have developed single-cell spatial pharmacobiology (SSP), which combines in situ imaging of a systemically infused fluorescent therapeutic antibody with high-plex spatial proteomics. Applied to head and neck and pancreatic tumors from patients treated in phase 1 trials, SSP revealed marked spatial heterogeneity in antibody delivery and target engagement, which was shaped by conserved stromal barriers.