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01.
PLOS Computational Biology 2026-06-22

Adhesion and polarity-driven morphogenesis: Mechanisms and constraints in tissue formation

by Yoshiyuki T. Nakamura, Chikara Furusawa, Kunihiko Kaneko Embryonic development in multicellular organisms exhibits diverse morphogenetic patterns, which can generally be categorized into fundamental types such as monolayer and multilayer spheres, as well as cell masses. Furthermore, we identify two distinct processes for the formation of spherical structures. These basic patterns are thought to be governed by the microscopic properties of intercellular adhesion. However, the specific mechanisms linking the microscopic factors to the emergence of distinct macroscopic morphogenetic patterns remain poorly understood. In this study, we explore how different morphogenetic patterns arise by employing a computational model that incorporates intercellular adhesion and polarity. Our results demonstrate that all fundamental morphogenetic patterns can be generated through the interplay of two key parameters: the polarity strength of the cell and the regulation of polarity via mechanical signals. Furthermore, analytical considerations reveal key mechanisms underlying the formation of these patterns. These findings highlight the critical role of physical constraints in morphogenesis and suggest potential applications to the design of artificial tissues and organoids.

02.
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.

03.
arXiv (CS.AI) 2026-06-16

VGPT-RSI for RH-Adjacent Formal Progress: Boundary Certificates, Verified Finite Lagarias Inequalities, and Explicit Failure Localization

arXiv:2606.15096v1 Announce Type: new Abstract: The Riemann Hypothesis remains one of the central unsolved problems in mathematics. Rather than claiming proof, we investigate whether a verifiable AI-assisted reasoning system can produce reliable, formally checked partial progress while explicitly identifying the remaining mathematical obstructions. We apply the Verifiable Growing Physical Transformer with Recursive Self-Improvement (VGPT-RSI) to two RH-adjacent certification tasks. First, we construct and verify a finite RH-boundary certificate for inequality on a parameterized safe lower curve over a region. The numerical boundary curve is converted into a certificate-backed lower curve, audited using outward-rounded interval arithmetic and Arb/FLINT ball arithmetic, and then checked in Rocq/CoqInterval for the parameterized theorem. Second, we initiate a formal Lagarias-route certificate. Lagarias criterion states that RH is equivalent to the global inequality. We formalize the finite quantity and produce a Coq-checked finite certificate. The final system identifies the exact unresolved mathematical bottlenecks: formalizing the Lagarias equivalence, proving the global tail theorem beyond any finite cutoff, and potentially reducing counterexamples to colossally abundant or related extremal integers. These results demonstrate that VGPT-RSI can produce certified RH-adjacent formal progress, organize proof dependencies, and avoid overclaiming when the remaining obstruction is genuinely mathematical.

04.
arXiv (CS.CL) 2026-06-18

G-IdiomAlign: A Gloss-Pivoted Benchmark for Cross-Lingual Idiom Alignment

Idioms are difficult to transfer across languages due to their non-compositionality and weak surface-form grounding, making literal mappings unreliable. We present G-IdiomAlign, a gloss-pivoted benchmark where each idiom is anchored by an English gloss from Wiktionary. We further construct a high-confidence reference alignment set for reproducible evaluation. G-IdiomAlign supports two protocols: (1) a controlled Multiple-Choice Idiom Equivalence with typed distractors for error attribution; and (2) a Gloss-Contrastive Generation contrasting No-gloss and With-gloss inputs to isolate the effect of an explicit semantic pivot. Across diverse LLMs, a bias to literal translation is a dominant failure mode, especially when the target is a low-resource language. Glosses consistently improve Gloss-Contrastive Generation under an embedding-based semantic proxy, but performance remains modest, indicating substantial headroom in the open output space. Subsequent analysis on Qwen3-8B further suggests that cross-condition differences are concentrated more in attention heads than in layers, while better With-gloss generations coincide with stronger gloss anchoring.

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

StreamMemBench: Streaming Evaluation of Agent Memory for Future-Oriented Assistance

arXiv:2606.14571v1 Announce Type: new Abstract: A central role of personal-agent memory is to turn stored information and prior interactions into future-oriented assistance. In daily use, useful cues come from what the agent observes and how the user interacts with the agent, and the agent must carry them forward from the current request to similar future tasks. Existing memory benchmarks usually test dialogue recall or task improvement in isolation, leaving the trajectory from streaming observations to later assistance largely untested. We introduce StreamMemBench, a streaming benchmark that constructs a two-step task sequence around each evidence anchor from EgoLife egocentric streams. The initial task tests evidence use, while the follow-up task tests whether feedback and interaction experience are reused. Four metrics diagnose evidence recall, initial evidence use, feedback incorporation, and follow-up reuse. Experiments with eight memory systems across two backbones show that current systems often fail to use observed evidence or turn feedback into reliable follow-up behavior, even when evidence is stored or feedback is incorporated locally. StreamMemBench is publicly available at https://github.com/landian60/StreamMemBench.

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

ShoppingBench: A Real-World Intent-Grounded Shopping Benchmark for LLM-based Agents

Existing benchmarks in e-commerce primarily focus on basic user intents, such as finding or purchasing products. However, real-world users often pursue more complex goals, such as applying vouchers, managing budgets, and finding multi-products seller. To bridge this gap, we propose ShoppingBench, a novel end-to-end shopping benchmark designed to encompass increasingly challenging levels of grounded intent. Specifically, we propose a scalable framework to simulate user instructions based on various intents derived from sampled real-world products. To facilitate consistent and reliable evaluations, we provide a large-scale shopping sandbox that serves as an interactive simulated environment, incorporating over 2.5 million real-world products. Experimental results demonstrate that even state-of-the-art language agents (such as GPT-4.1) achieve absolute success rates under 50% on our benchmark tasks, highlighting the significant challenges posed by our ShoppingBench. In addition, we propose a trajectory distillation strategy and leverage supervised fine-tuning, along with reinforcement learning on synthetic trajectories, to distill the capabilities of a large language agent into a smaller one. As a result, our trained agent achieves competitive performance compared to GPT-4.1.

07.
arXiv (CS.CL) 2026-06-12

MDForge: Agentic Molecular Dynamics Pipeline Design under Sparse Simulator Feedback

Molecular dynamics (MD) is the canonical in-silico method for atomistic molecular science, simulating molecular behavior from first-principle physics. Designing an MD pipeline for a new system requires substantial expert knowledge: running it on even one molecule is expensive, ruling out trial-and-error. We automate this expert pipeline-design process with an LLM agent. Unlike existing MD agents that orchestrate a predefined tool set, we treat pipeline design as open-ended code generation in which the agent's behavior is reshaped online by verbal reward. Specifically, we build MDForge, an LLM agent whose in-context update rule densifies the sparse reward via a multi-agent debate among physics experts. On three SAMPL host-guest binding free-energy benchmarks, MDForge automatically designs MD pipelines competitive with human experts. Deployed on a library of unseen candidate guests, its CB[7] pipeline discovers a novel binder that wet-lab competition NMR confirms is a high-affinity, picomolar CB[7] binder. Our data and code are available at https://github.com/Zehong-Wang/MDForge.

08.
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.

09.
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/

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

Discovering Symmetry Groups with Flow Matching

arXiv:2512.20043v3 Announce Type: replace Abstract: Symmetry is fundamental to understanding physical systems and can improve performance and sample efficiency in machine learning. Both pursuits require knowledge of the underlying symmetries in data, yet discovering these symmetries automatically is challenging. We propose LieFlow, a novel framework that reframes symmetry discovery as a distribution learning problem on Lie groups. Instead of searching for the symmetry generators, our approach operates directly in group space, modeling a symmetry distribution over a large hypothesis group $G$. The support of the learned distribution reveals the underlying symmetry group $H \subseteq G$. Unlike previous works, LieFlow can discover both continuous and discrete symmetries within a unified framework, without assuming a fixed Lie algebra basis or a specific distribution over the group elements. Experiments on synthetic 2D and 3D point clouds, ModelNet10 and a real-world MI-Motion dataset show that LieFlow accurately discovers continuous and discrete subgroups, significantly outperforming a state-of-the-art baseline, LieGAN, in identifying discrete symmetries.

11.
arXiv (CS.LG) 2026-06-15

Conformal calibration and look-elsewhere effect in anomaly detection for new-physics searches

arXiv:2606.13780v1 Announce Type: cross Abstract: Machine-learned anomaly detection is reshaping searches for new physics, but it has outrun the statistics used to interpret it. A raw anomaly score has no calibrated meaning, a model that scans many regions inflates the look-elsewhere effect, and the asymptotic significances the field relies on are blind to the background mismodelling that anomaly detectors are especially prone to. We propose a calibration layer, built on conformal prediction, that turns any anomaly score into a defensible significance with distribution-free, finite-sample guarantees. Conformal prediction converts scores into valid local p-values, weighted and Mondrian variants repair the sideband-to-signal-region exchangeability failures that resonant searches suffer, and a Gross-Vitells step carries the result through to a look-elsewhere-aware global significance. The layer does two things at once. It exposes miscalibration that the standard pipeline cannot see, and it corrects it without retraining the detector. On public LHC Olympics data, a classifier develops a substructure-mass correlation that makes sideband-calibrated background p-values anti-conservative. Taken at face value, this manufactures a $\sim 46\sigma$ excess from background sculpting alone, which the label-free weighted correction removes, restoring an honest null. When run as a blind wide-mass bump hunt, the standard asymptotic and unweighted procedures fabricate $\gtrsim10\sigma$ excesses and $\approx5\sigma$ excesses even in signal-free windows, while the conformal layer raises no false alarms and its global false-positive rate is verified on background-only pseudoexperiments. The result is an auditable, detector-agnostic path from an uncalibrated score to a trials-factor-aware significance, ready to be folded into experimental anomaly searches.

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

SAGE: Stochastic Prompt Optimization via Agent-Guided Exploration

Context engineering has emerged as a primary lever for improving AI systems without parameter updates. Recent work showing that textual gradients do not function as real gradients motivates treating automatic prompt optimization (APO) as black-box search. We introduce SPO (Stochastic Prompt Optimization), a framework for stochastic search over prompt space, and compare three strategies of increasing sophistication: error-informed random search, a genetic algorithm with evolutionary operators, and SAGE (SPO via Agent-Guided Exploration), a multi-agent pipeline with diagnostic code execution. Across three benchmarks, no single strategy dominates; effectiveness depends on the interaction of landscape structure with error type. We further deploy SAGE on a mental-health chatbot under a continuous optimization paradigm, where it compounds eight cycles of individually-noisy A/B tests into a statistically robust gain in next-day retention. We argue that coupling qualitative diagnosis with quantitative validation is what makes agentic optimization effective for open-ended task-oriented dialogue.

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

A Benchmark for Omni-Modal Reasoning in Long Videos

Long-form omni-modal video understanding requires integrating vision, speech, and ambient audio with coherent long-context reasoning. Existing video benchmarks often trade off temporal scale, modality coverage, open-ended interaction, and interpretable scoring. To address this gap, we introduce LongShOTBench, a long video understanding benchmark designed around three coupled goals: holistic omni-modal integration, intent-driven open-ended interaction, and rubric-level diagnosis. It builds single- and multi-turn questions from real viewing scenarios, with systematic tasks probing visual, speech, ambient-audio, temporal, and cross-modal reasoning. Each item includes a reference answer and a weighted criterion-level rubric, letting evaluation identify which perceptual facts, temporal links, modality-grounding requirements, and reasoning steps are satisfied or missed. All samples are manually verified to improve grounding, clarity, and rubric reliability. We also introduce LongShOTAgent, a training-free omni-modal evidence-seeking agent coupling full-video preprocessing with targeted retrieval, query-adaptive segment refinement, and explicit claim verification over visual, speech, and non-speech audio evidence. Its iterative search-refine-verify loop exposes intermediate evidence and lets modality-specific specialists re-analyze relevant moments before answering. We evaluate 105 video-capable models spanning open-source omni-modal models, vision-language systems, audio LLMs, agentic pipelines and closed-source APIs. Current MLLMs remain far from saturating LongShOTBench, while our LongShOTAgent is the strongest training-free system, reaching 66.64% overall. By releasing the benchmark, leaderboard, and method, we provide a shared, interpretable testbed for advancing long-form omni-modal video reasoning. Code, data, and the leaderboard are available at https://longshot.cvmbzuai.com/.

14.
arXiv (quant-ph) 2026-06-16

Minimum measurements quantum protocol for band structure calculation

arXiv:2511.04389v2 Announce Type: replace Abstract: Protocols for quantum measurement are an essential part of quantum computing. Measurements are no longer confined to the final step of computation but are increasingly embedded within quantum circuits as integral components of noise-resilient algorithms. However, each observable typically requires a distinct measurement basis, often demanding a different circuit configuration. As the number of such configurations typically grows with the number of qubits, measurements constitute a major bottleneck. Focusing on electronic structure calculations in crystalline systems, we propose a measurement protocol that restricts the required measurement configurations to an absolute minimum of just three, independent of the number of qubits. This makes it one of the few known protocols that do not scale with qubit number. In particular, we derive the measurement protocol from the symmetries of tight-binding (TB) Hamiltonians and implement it within the Orthogonal-Ansatz Variational Quantum Eigensolver (OA-VQE) algorithm. We demonstrate its performance on three systems, namely a two-dimensional CuO$_2$ square lattice (3 qubits), bilayer graphene with hexagonal (Honeycomb) lattice (4 qubits) and three-dimensional diamond lattice (10 qubits). Beyond tight-binding systems, the protocol can be extended to enable efficient initial state preparation for many-body Hamiltonians, such as multi-orbital Hubbard models in a momentum space.

15.
arXiv (CS.AI) 2026-06-12

Real-Time Execution with Autoregressive Policies

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

16.
arXiv (CS.CL) 2026-06-11

Building Social World Models with Large Language Models

Understanding and predicting how social beliefs evolve in response to events – from policy changes to scientific breakthroughs – remains a fundamental challenge in social science. Given LLMs' commonsense knowledge and social intelligence, we ask: Can LLMs model the dynamics of social beliefs following social events? In this work, we introduce the concept of the Social World Model (SWM), a general framework designed to capture how social beliefs evolve in response to major events. SWM learns state-transition functions for social beliefs by mining temporal patterns in social data and optimizing the evidence lower bound, without the need for explicit human annotations linking events to belief shifts, or for expensive census data. To evaluate SWM, we introduce a benchmark, SWM-bench, derived from real-world prediction markets, specifically Kalshi and Polymarket. SWM-bench includes over 12k data points for social belief prediction tasks spanning diverse domains such as politics, finance, and cryptocurrency. Our experimental results show that SWM significantly outperforms time-series foundation models, achieving state-of-the-art results on Kalshi data and demonstrating competitive performance on Polymarket data, while offering interpretable insights into the underlying mechanisms of social belief dynamics.

17.
arXiv (CS.AI) 2026-06-12

A Minimal Model of Bounded Trade-Off Screening in Multi-Attribute Choice

arXiv:2606.13201v1 Announce Type: new Abstract: Human decision-making often involves choosing between multi-attribute alternatives, yet classical models assume fully compensatory utility aggregation despite evidence that people reject options with poor performance on critical attributes. We propose a bounded trade-off reasoning framework in which decisions are governed by a screening process that evaluates the balance between gains and losses across attributes. The model introduces a trade-off tolerance parameter that controls acceptable imbalance and can vary across contexts. Through simulation, we show that this mechanism produces preference patterns that differ from standard utility-based models and captures context-dependent variation in trade-off behavior. These results establish bounded trade-off screening as a plausible computational mechanism for multi-attribute choice and generate testable predictions for future behavioral studies.

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

"Did you lie?" Evaluating Lie Detectors across Model Scale and Belief-Verified Model Organisms

arXiv:2606.12618v1 Announce Type: new Abstract: Robust lie detectors for language models could enable powerful techniques for auditing, monitoring, and post-hoc investigation of model behaviour, but evaluating them requires testbeds where models verifiably believe the opposite of what they say. We show that existing trained model organisms often fail this requirement, leaving prior positive and negative detection results difficult to interpret. We address this with 13 reasoning model organisms whose hidden beliefs are verified in chain-of-thought and shown to generalise to held-out tasks, alongside Varied Deception, a prompted-lying testbed covering a broad range of lie-inducing motivations. On these testbeds we evaluate four detectors: a chain-of-thought judge, a logprob classifier, and two activation probes, including Did-You-Lie (DYL), a new method for training follow-up probes. On prompted lying, across 31 open-weight models spanning 2B to 1T parameters, all four detectors show positive scaling with model capability. However, every activation- and logprob-based detector drops sharply on our trained model organisms, with DYL retaining the most signal; only the chain-of-thought judge remains strong, with 0.82 balanced accuracy, partly as an artefact of our verification process favouring CoT-readable beliefs. Current lie detectors therefore cannot support high-confidence claims about model beliefs, and we suggest research directions that may address some of their current limitations. We release our datasets, model organisms, and trained detectors.

19.
arXiv (CS.AI) 2026-06-17

From Democracies to Autocracies: How AI Systems Enable Authoritarianism by Design

arXiv:2606.17286v1 Announce Type: cross Abstract: AI-enabled authoritarianism is not confined to autocracies. In this paper, we provide greater transparency by investigating and mapping the lifecycles of six AI systems deployed in different political regimes, ranging from the US to China. By drawing on an extensive range of sources (academic publications, investigative research reports, third-party evaluations, media interviews, government procurement notices), we conduct a systematic, qualitative comparison across systems to identify the critical technical and operational features that enable authoritarianism within their respective political contexts. We find that enabling features include the centralization and co-optation of administrative data for law enforcement and political punishment, regulatory gaps that fail to deter misuse, weak user compliance that nullifies human oversight mechanisms, and the encoding of protected group traits that identify members of vulnerable populations. We find that these features are present across systems deployed in autocratic and democratic regimes, albeit in varying configurations. We also find that both centralized and fragmented AI systems can contribute to authoritarianism by exploiting governance gaps: centralized systems directed by executive authorities, particularly within security and military institutions, are often not subjected to formal oversight mechanisms, while fragmented systems diffuse accountability between stakeholders, paving the way for entrenchment. These findings reveal that AI-enabled authoritarianism is distributed, resulting from design and operational choices made by developers, administrators, and users alike. We conclude with recommendations for developers and policymakers to mitigate these risks.

20.
bioRxiv (Bioinfo) 2026-06-11

HoloCell: A Generative Foundation Model for Holistic Cellular Modeling

Single-cell multi-omics technologies have recently advanced to enable the profiling of epigenomic, transcriptomic, and proteomic layers within individual cells, offering new opportunities to characterize cellular states as integrated biological systems. However, developing a unified framework that can seamlessly integrate diverse omics modalities and remain robust to heterogeneous modality missingness remains challenging. Here we present HoloCell, to our knowledge the first generative foundation model for joint representation learning and generative modeling across all three major single-cell omics modalities, i.e., epigenomics, transcriptomics, and proteomics. HoloCell contains over 860 million parameters and is pretrained on the Human-Multi-Omics-Corpus, which comprises approximately 468 million single-cell profiles across these three omics layers, corresponding to over 425 billion tokens. HoloCell introduces a simple yet biologically grounded hierarchical tokenization strategy that encodes cis-regulatory elements, genes, and proteins as structured tokens within a shared modeling framework. We evaluated HoloCell across single-omics representation learning, paired multi-omics integration, unpaired multi-omics alignment, and cross-modal generation via iterative diffusion and remasking, demonstrating its superior performance and flexibility across diverse omics tasks. From a representation perspective, HoloCell provides a unified digital mapping of cellular states across multiple omics layers, capturing cell heterogeneity as an integrated system. From a generation perspective, its iterative diffusion and remasking framework accounts for the inherently unordered nature of biological features, enabling in silico simulation of multi-omics information flow. Together, these capabilities position HoloCell as a versatile foundation model toward the emerging concept of a virtual cell, offering both systematic characterization and generative simulation of cellular systems within a unified framework.

21.
medRxiv (Medicine) 2026-06-22

Evidence-guided AI regularization for suicidal ideation prediction in pediatric bipolar disorder

Background: Suicide prediction models in psychiatry often rely on purely data-driven feature selection, which can produce unstable and clinically opaque predictor sets in modest-sized samples. We developed Evidence-Based AI LASSO (EBAL), an evidence-guided regularization framework that incorporates curated clinical evidence into feature-specific penalty factors for interpretable prediction. Methods: Baseline data from 136 youth with confirmed bipolar spectrum disorder in the Greater Houston Area Bipolar Registry were analyzed using 20 candidate clinical predictors. Forty higher-level evidence documents on suicidality and related predictor domains were curated through a structured evidence synthesis workflow and indexed as an auditable evidence corpus. An open-weight large language model assigned feature-specific penalty factors using a prespecified scoring rubric, and these penalties were used to fit a weighted LASSO model. EBAL was compared with a standard evidence-agnostic LASSO using nested leave-one-out cross-validation. Results: For suicidal ideation, EBAL achieved an AUROC of 0.768, balanced accuracy of 0.757, sensitivity of 0.758, and specificity of 0.757. The standard LASSO achieved an AUROC of 0.760 and balanced accuracy of 0.715. EBAL improved balanced accuracy (+0.042, p=0.010) and Matthews correlation coefficient (+0.079, p=0.010), while retaining fewer stable predictors than standard LASSO (11/20 vs 18/20). The strongest positive predictors were current depressed mood, duration of mood disorder illness, and comorbid generalized anxiety disorder. For suicidal behavior, both models performed near chance and retained all candidate predictors. Limitations: The study was cross-sectional, single-site, and modest in sample size, with no external validation cohort. Conclusions: EBAL produced a sparser and more clinically coherent model for suicidal ideation in pediatric bipolar disorder, but did not improve prediction of suicidal behavior. These findings support evidence-guided regularization as a transparent strategy for aligning psychiatric prediction models with prior clinical knowledge while preserving interpretability.

22.
arXiv (CS.AI) 2026-06-12

Iterating Toward Better Search: A Two-Agent Simulation Framework for Evaluating Agentic Search Architectures in E-Commerce

arXiv:2606.12924v1 Announce Type: new Abstract: We present a modular two-agent simulation framework for evaluating conversational shopping assistant architectures. An independent buyer agent, configured with personas, missions, and patience levels, is paired with an interchangeable responder that integrates with a real e-commerce search API. Holding the buyer constant across experiments enables controlled comparison of responder designs on identical scenarios. Using 2011 conversations across 14 persona buckets, we establish four empirical findings. First, rolling-window memory outperforms intent-extraction memory on all quality metrics while being 35% faster per query. Second, illustrating rapid evidence-driven iteration, a systematic failure analysis of a responder version enables targeted fixes that reduce failure and near-failure rates by 62% across the full dataset. Third, swapping the responder LLM backbone from Gemini~2.5 to Llama~3.3~70B costs 0.16–0.45 points despite identical architecture. Finally, we document systematic philosophical disagreement between frontier LLM judges: Gemini rewards process correctness while Claude demands concrete outcomes, despite using the same evaluation prompt.

23.
Nature (Science) 2026-06-10

Amplified Arctic iceberg traffic reshapes benthic biodiversity

The Arctic is undergoing rapid warming, resulting in retreating sea ice and glaciers1, yet how cryospheric changes propagate into the deep ocean remains poorly understood2. Here we identify a climate-driven mechanism linking accelerating glacier disintegration to an increase in deep-sea hard-bottom habitats far beyond calving fronts. Seafloor observations in Fram Strait show a localized increase in the density and patchiness of dropstones delivered by debris-laden icebergs. At the same time, four decades of shipboard records show that the occurrence of icebergs increased abruptly in the early 2000s. Backtracking links these icebergs to the main outlet glaciers in northeast Greenland and the Russian High Arctic. In northeast Greenland, the timing of glacier destabilization coincides with this rise, whereas sparse satellite coverage in the Russian sector limits temporal attribution despite indications of enhanced glacier activity. A model sensitivity study shows that, apart from intensified calving, a more dynamic sea ice cover enhances downstream transport of glacial ice. Along these pathways, increased iceberg activity could reshape deep-sea habitats through enhanced melt and associated lithogenic input, and elevate navigational hazards as maritime traffic expands in the Arctic. Although modest compared with the iceberg discharges of Pleistocene Heinrich events, this mechanism provides a modern analogue of long-range cryospheric influence on the seafloor in a warming climate. Accelerated Arctic glacier disintegration and a more dynamic sea ice cover are increasing iceberg-delivered dropstones in the deep ocean, reshaping seafloor habitats and extending cryospheric impacts far beyond glaciers.

24.
medRxiv (Medicine) 2026-06-15

International Consensus Guideline on Management of Genitourinary Adverse Events Associated with Prostate Cancer Radiotherapy

Purpose/Objective: Genitourinary (GU) adverse events (AEs) are common during and after pelvic radiation therapy (RT) for prostate cancer and can substantially impact quality of life. We convened an international committee to establish consensus in the prevention, mitigation, and management of radiation-related acute and late GU AEs, as there are no relevant evidence-based consensus guidelines to inform treating providers. Materials/Methods: A systematic evidence review focused on mitigation and management of radiation-related acute and late GU AEs was performed in PubMed, Embase and Cochrane. The following topics were addressed: management of acute GU AEs in the intact and post-operative settings; RT techniques; bladder outlet obstruction procedures; and indications for urology referral or hyperbaric oxygen therapy (HBO). Evidence-based consensus recommendations were developed using a Delphi process. We highlight the current state of evidence and evidence gaps worthy of future study. Results: Consensus was reached for 31 key questions. For management of lower urinary tract symptoms (LUTS), most evidence comes from trials in patients without cancer and not undergoing RT. A consensus algorithm for medical management of acute GU AEs was developed with the following highlights: (a) alpha blockers as 1st-line for obstructive symptoms in the intact setting, (b) anti-spasmodics as 1st -line for irritative symptoms in the intact setting, and (c) anti-spasmodics as 1st -line in the post-operative setting. The consensus algorithm provides an ordered list of medications to offer if 1st -line options afford inadequate relief. For RT fractionation, randomized clinical trial (RCT) data are available. 40% of panelists rarely or never use standard fractionation over moderate hypofractionation for patients with baseline LUTS, but most consider moderate hypofractionation over SBRT for AUA IPSS > 15. For patients with severe obstructive LUTS (most commonly AUA IPSS >20), the panel recommends a prophylactic bladder outlet obstruction procedure and, if obstructive symptoms improve, consideration of moderate hypofractionation or SBRT, based on retrospective data. There is one RCT supporting use of HBO for late radiation cystitis. Conclusions: The consensus guideline synthesizes available evidence and expert opinion across key clinical decision points to provide practical guidance in the prevention, mitigation, and management of radiation-related acute and late GU AEs in prostate cancer RT. Envisioned as a living document with periodic updates, this guideline serves as a resource for practicing radiation oncologists by outlining expert-derived consensus recommendations of evidence-based care in areas where high-quality data is limited.

25.
arXiv (CS.CL) 2026-06-12

ArogyaSutra: A Multi-Agent Framework for Multimodal Medical Reasoning in Indic Languages

Multimodal Large Language Models (MLLMs) have shown promising reasoning capabilities in general domains, yet their performance remains limited in specialized settings such as healthcare, especially in multilingual and low-resource scenarios. This gap is critical in regions like rural India, where patients often express complex medical queries in native Indic languages and rely on multimodal inputs such as medical images. Existing English-centric MLLMs struggle to support such use cases, limiting equitable access to AI-driven healthcare assistance. To address this challenge, we introduce ArogyaBodha, a large-scale multilingual multimodal medical question-answer dataset constructed from eight heterogeneous sources, covering 31 body systems, six imaging modalities, and 21 clinical domains across English and seven major Indian languages. We further propose ArogyaSutra, an actor-critic-based multi-agent framework that integrates tool grounding with dual-memory mechanisms for step-wise, reasoning-aware decision making, and uses stored actor-critic simulation trajectories for distillation. Experiments show that our dataset and framework improve multilingual medical reasoning accuracy across all Indic languages, with ablations validating the contribution of each component. The source code and dataset are available at: https://iitp-cse.github.io/ ArogyaSutra/