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

Attention is Just Another Name for Coupling?: A Fast-Slow ODE Perspective on Hierarchical Pretraining

arXiv:2606.16730v1 Announce Type: cross Abstract: Causal self-attention is a coupling mechanism: each token's hidden state is updated by a learned mixture of preceding tokens at the same timescale. This paper asks whether a second, temporally slower coupling-a slow sub-system operating on a temporally-downsampled view of the sequence and fed back into the fast path through a zero-initialised gate-complements it. The question is framed in the language of singularly perturbed ordinary differential equations (ODEs), where the fast variable $x$ evolves at the token rate, the slow variable $y$ evolves at one update per $P$ tokens, and the timescale ratio $\varepsilon = 1/P$ is enforced structurally by causal block-mean pooling. The paper instantiates the fast-slow ODE formalism as a concrete neural network: a fast path of standard causal attention over $T$ tokens, a slow path of full attention over $T/P$ pooled tokens ($P^2 \times$ cheaper per layer), and a zero-initialised additive gate. In addition, under a linear-generator assumption on the fast dynamics, we prove that the equilibrium manifold $x = \phi(y)$ is exactly the master-equation (ME) stationary distribution $p_{\mathrm{st}}(y)$; in that regime a learned MLP $\phi_\theta(y)$ is a variational approximation of it (the trained block is not a generator, so this identity is the structured limit, not a claim about the network as trained). Empirically, at $500$k tokens the coupling is neutral – the gate stays closed and the coupled and frozen ablations are within run-to-run noise – at a wall-clock cost comparable to a dense baseline. The contribution is the precise, gap-marked mapping itself, not a performance gain.

02.
bioRxiv (Bioinfo) 2026-06-11

Hyper3D-lite: count-preserving representation auditing for long-read multi-contact genome data

作者:

Long-read and single-molecule sequencing technologies are rapidly increasing molecule-level data, with platforms such as Oxford Nanopore, PacBio HiFi, and Roche sequencing-by-expansion advancing at different technology readiness levels. In the specific context of Pore-C and HiPore-C multi-contact chromatin-conformation assays, long-read multi-contact 3D genome assays preserve molecule-level contact context, but common downstream pairwise projections can expand one multi-contact molecule into many pair records. This creates a representation problem: apparent contact evidence can increase through the counting frame before biological interpretation begins. Hyper3D-lite addresses this problem as a representation-first audit tool for read-to-fragment-style long-read multi-contact inputs. It compares all-pair projection with CPB, a count-preserving statistical accounting reference point, and separates broad software outputs from conservative higher-order candidate calls.

03.
PLOS Computational Biology 2026-06-01

BeetleAtlas 2: An enhanced <i>Tribolium castaneum</i> web resource for tissue and developmental transcriptomics allowing refinement of gene predictions

by David P. Leader, Muhammad T. Naseem, Janina L. Rinke, Kenneth Veland Halberg BeetleAtlas is an online resource for tissue- and stage-specific transcriptomics in the red flour beetle, Tribolium castaneum. On updating from the original Tcas5.2 genome assembly to the more recent improved icTriCast1.1 genome assembly it became evident that there were major discrepancies between the gene models of the two genome annotations in use: the OGS3 and the NCBI gene sets. As neither was clearly superior we implemented a new design in BeetleAtlas 2 (beetleatlas.org) comprising two parallel ‘modes’ — one incorporating results using the NCBI gene models and a second incorporating those using the OGS3 gene models. This allows direct comparison where equivalent gene models exist: 50–57% of cases. To aid resolution of discrepancies between the two gene model sets and verification of results, gene models are linked to a custom visualization of RNA-seq read coverage of the genome in the UCSC Genome Browser. This displays reads from 22 tissues and life stages superimposed on the icTriCast1.1 genome assembly. Reference tracks show the NCBI gene models, the OGS3 gene models after translation of their coordinates from the Tcas5.2 assembly, and 1050 discontinued NCBI gene models from the previous assembly after a similar transfer of coordinates. We document various situations in which distinct patterns of expression of the tissues can be used to confirm and extend correlations between the two gene sets, resolve discrepancies between them, make corrections and identify putative genes or exons absent from the current gene sets. BeetleAtlas 2 allows those involved in Tribolium research to avoid the pitfalls inherent in incorrect gene models when planning experiments on specific genes and interpreting the results. It also demonstrates how BeetleAtlas 2 might play an important role in establishing a revised gene set for Tribolium castaneum in the future.

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

Robust Dual-Signal Fusion: Hybrid Neuro-Symbolic Gating with Compressed Chain-of-Thought Refinement for Irony Detection in Social Media Texts

Large Language Models (LLMs) natively default to literal semantic interpretations, making zero-shot irony detection a persistent challenge. We introduce the Robust Dual-Signal (RDS) Fusion framework, a hybrid neuro-symbolic architecture that compresses Chain-of-Thought (CoT) reasoning trajectories without Supervised Fine-Tuning (SFT). Evaluated on a strictly held-out TweetEval test set (N=734), RDS achieves 78.1% accuracy and a Macro F1 of 0.777, matching the absolute performance ceiling of the fine-tuned BERTweet. On the heavily imbalanced iSarcasm dataset, the frozen CoT pipeline filters 22.5% of out-of-distribution hallucinations, yielding a zero-shot Macro F1 of 0.6726 and Ironic F1 of 0.4821, outperforming multiple heavily supervised SemEval transformer ensembles. A statistical ablation confirms this structural synergy: adding the symbolic prior to the neural baseline yields no significant gain (p = 0.242), and the marginal benefit of adding the CoT pipeline to that prior is heavily compressed (p = 0.149). Only the complete, concurrent fusion of all three signals achieves a statistically validated improvement over the baseline (p = 0.005).

05.
Science (Express) 2026-05-21

Observation of quantum vortex core fractionalization and skyrmion formation in a superconductor | Science

作者: 未知作者

Magnetic fields can penetrate a superconductor in the form of quantum vortices, which consist of a core singularity with circulating currents. London’s quantization implies that there is one core singularity per quantum of magnetic flux in single-component superconductors. Here, we report signatures of quantum vortex core fractionalization on the potassium-terminated surface of a multiband superconductor KFe 2 As 2 . The observed splitting of single integer-flux vortices into several fractional vortices results in a disparity between the numbers of flux quanta and vortex cores. These fractional vortices often arrange in chains, which calculations show are characterized by a ℂP 2 skyrmionic topological invariant; this constitutes a different type of topological defect: the chiral skyrmion. The disparate natures of integer and fractional vortices comprising skyrmions lead to distinct spectroscopic signatures.

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

TextHOI-3D: Text-to-3D Hand-Object Interaction via Discrete Multi-View Generation and Joint Mesh Optimization

Text-conditioned 3D generation has progressed rapidly for images and isolated objects, but producing a hand-object mesh remains challenging: the output must preserve language semantics, cross-view consistency, object geometry, articulated hand shape, and physically plausible contact. We present TextHOI-3D, a staged framework that uses generated multi-view observations as an explicit interface between text-conditioned visual generation and geometry-aware hand-object recovery. TextHOI-3D learns a compact VQ token space for fixed-camera hand-object observations, predicts multi-view visual tokens from text with a CLIP-conditioned visual autoregressive model, and recovers a unified hand-object mesh through prior initialization, multi-view joint optimization, and anti-penetration refinement. The design separates semantic generation from geometric recovery while keeping both stages connected by a discrete multi-view representation. On HO3D-derived evaluations, the multi-view setting reduces object CD from 17.26 mm to 4.92 mm and penetration volume from 5.3721 cm^3 to 0.2193 cm^3 compared with a single-view counterpart, while improving hand errors and surface F-scores. These results support multi-view visual tokens as an effective intermediate representation for text-driven 3D hand-object mesh creation.

07.
arXiv (math.PR) 2026-06-11

Construction of ergodic IDLA forests in $\mathbb{Z}^d$

arXiv:2506.10476v2 Announce Type: replace Abstract: We prove the existence of infinite-volume IDLA forests in $\mathbb{Z}^d$ , with $d \geq 2$, based on a multi-source IDLA protocol. Unlike IDLA aggregates, the laws of the IDLA forests studied here depend on the trajectories of particles, and then do not satisfy the famous Abelian property. Their existence is due to a stabilization result (Theorem 1.1, our main result) that we establish using percolation tools. Although the sources are infinitely many, we also prove that each of them play the same role in the building procedure, which results in an ergodicity property for the IDLA forests (Theorem 1.2).

08.
arXiv (CS.CL) 2026-06-17

Rethinking Groups in Critic-Free RLVR

Reinforcement learning (RL) has become a central paradigm for post-training large language models. Existing critic-free RL methods typically generate a group of rollouts for the same question to estimate value baselines for advantage computation. However, this design suffers from data inefficiency, group synchronization barriers, and inflexibility with structured rollouts. In this work, we revisit the role of the ``group'' and show that its underlying function is not merely to estimate baselines but to prevent false penalties on negative samples. Building on this insight, we propose negative token filtering, a simple and effective strategy that enables stable single-rollout training. We apply it to two batch-level advantage methods, achieving comparable performance on reasoning tasks and stronger performance on agentic tasks relative to group-based RL techniques.

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

Mood-Aware Music Recommendation: Integrating User Affective Signals into Ranking Systems

arXiv:2606.13858v1 Announce Type: cross Abstract: Recommendation systems are essential in modern music streaming platforms due to the vast amount of available content. While collaborative filtering is widely used to suggest items based on the preferences of others with similar patterns, it performs poorly in domains where user-item interactions are sparse, such as music. Content-based filtering is an alternative approach that examines the qualities of the items themselves. Genre, instrumentation, and lyrics have been explored; however, relatively little attention has been given to emotion recognition. Since a user's emotional state strongly influences their music choice, incorporating mood signals offers a promising direction for personalization. In this work, we propose a mood-conditioned ranking framework that integrates user affective signals into the recommendation process via softmax-based sampling in the energy-valence space. We evaluate the approach via single-blind experiments in which participants compare recommendations from the proposed system against a baseline. The results indicate improved perceived recommendation quality, providing preliminary evidence for the effectiveness of incorporating mood-based inputs into music recommendations.

10.
arXiv (quant-ph) 2026-06-16

Scalable Graph State Generation with O(1) Local Feedforward in Quantum Networks

arXiv:2606.16375v1 Announce Type: new Abstract: The development of quantum networks faces a key challenge: the contradiction between probabilistic long-range entanglement generation and finite coherence time. Existing routing protocols typically focus on global state computation or path optimization. As the network scales up, classical delays accumulate and exacerbate decoherence, leading to a decrease in entanglement fidelity. To reduce routing decision delays to levels far below the coherence time of qubits, we propose a protocol based on local measurement and classical feedforward. This protocol reduces the local decision complexity to amortized O(1) level, ensuring that the decision delay is always much smaller than the coherence time of qubits. We map this protocol onto a dual-species trapped-ion platform and perform hybrid simulations. The results show that the proposed protocol performs well in terms of both resource efficiency and time feasibility. Noise analysis indicates that readout fidelity is the main bottleneck of this protocol, but noise suppression can be achieved by employing an erasure transformation in the dual-species architecture, combined with spatial multiplexing and branch independence, thereby ensuring the generation of high-fidelity star subgraphs. This protocol provides a clear path to achieving high-fidelity star subgraphs. These subgraphs can serve as general modules, merging to construct arbitrary subgraphs, providing a feasible solution for future fault-tolerant distributed quantum computing.

11.
arXiv (quant-ph) 2026-06-17

Quantum-inspired Ising machine using sparsified spin connectivity

arXiv:2604.04606v2 Announce Type: replace-cross Abstract: Combinatorial optimization problems become computationally intractable as these NP-hard problems scale. We previously proposed extraction-type majority voting logic (E-MVL), a quantum-inspired algorithm using digital logic circuits. E-MVL mimics the thermal spin dynamics of simulated annealing (SA) through controlled sparsification of spin interactions for efficient ground-state search. This study investigates the performance potential of E-MVL through systematic optimization and comprehensive benchmarking against SA. The target problem is the Sherrington-Kirkpatrick (SK) model with bimodal and Gaussian coupling distributions. Through equilibrium state analysis, we demonstrate that the sparsity control mechanism provides a consistent search of the solution space regardless of the problem's coupling distribution (bimodal, Gaussian) or size. E-MVL not only achieves the best performance among all tested algorithms–solving exact solutions up to 1600 spins where the best SA baseline is limited to 400 spins–but also provides insights that significantly improve SA's own temperature scheduling. These results establish E-MVL's dual contribution as both an efficient optimizer and a practical methodology for enhancing SA performance. Moreover, FPGA implementation achieved an approximately 6-fold faster solution speed than SA.

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

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

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

13.
arXiv (CS.LG) 2026-06-15

On the Influence of the Feature Computation Budget on Per-Instance Algorithm Selection for Black-Box Optimization

arXiv:2605.04954v2 Announce Type: replace-cross Abstract: Per-instance algorithm selection (PIAS) takes advantage of complementarity between a set of algorithms by deciding which algorithm to run on a given instance. This decision is based on features of the instances, which, in the context of black-box optimization (BBO), require a part of the optimization budget to be computed. This raises two questions: (a) from which fraction of the budget spent on feature computation does PIAS become worth it for BBO, and (b) which fraction of the budget optimizes the tradeoff between feature accuracy and PIAS performance. To this end, we perform a broad study where PIAS with varying sampling budgets for feature computation is compared to the single best algorithm on a broad range of algorithm selection scenarios. These scenarios consist of two portfolio sizes, three problem sets, 4 dimensionalities, and 10 target budgets. We find that PIAS is viable for the majority of tested scenarios, even when as much as a quarter of the total budget is spent on feature computation. The tradeoff for the fraction of the budget spent on feature computation to maximize the benefit of PIAS is highly dependent on the specific AS scenario. Further, on average 20 percent of PIAS loss to the virtual best solver is explained by the budget spent on feature computation, highlighting the importance of properly accounting for the feature budget.

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

Fast Autoregressive Video Diffusion and World Models with Temporal Cache Compression and Sparse Attention

Autoregressive video diffusion models enable streaming generation, opening the door to long-form synthesis, video world models, and interactive neural game engines. However, their core attention layers become a major bottleneck at inference time: as generation progresses, the KV cache grows, causing both increasing latency and escalating GPU memory, which in turn restricts usable temporal context and harms long-range consistency. In this work, we study redundancy in autoregressive video diffusion and identify three persistent sources: near-duplicate cached keys across frames, slowly evolving (largely semantic) queries/keys that make many attention computations redundant, and cross-attention over long prompts where only a small subset of tokens matters per frame. Building on these observations, we propose a unified, training-free attention framework (FAST-AR) for FAST-AutoRegressive diffusion, consisting of three components: TempCache compresses the KV cache via temporal correspondence to bound cache growth; AnnCA accelerates cross-attention by selecting frame-relevant prompt tokens using fast approximate nearest neighbor (ANN) matching; and AnnSA sparsifies self-attention by restricting each query to semantically matched keys, also using a lightweight ANN. Together, these modules reduce attention, compute, and memory and are compatible with existing autoregressive diffusion backbones and world models. Experiments demonstrate up to x5 - x10 end-to-end speedups while preserving near-identical visual quality and, crucially, maintaining stable throughput and nearly constant peak GPU memory usage over long rollouts, where prior methods progressively slow down and suffer from increasing memory usage.

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

Identifiable Markov Switching Models with Instantaneous Effects and Exponential Families

arXiv:2606.02231v2 Announce Type: replace-cross Abstract: Temporal systems often exhibit non-stationary behaviour, such as seasonal climate variation or glucose fluctuations in patients with type-1 diabetes. One way to model non-stationarity is through discrete latent regimes, i.e., stationary segments of time. Such systems induce a Markov Switching Model (MSM), a class of Hidden Markov Models with autoregressive dependencies among latent regimes and observed variables. Identifying latent regimes is challenging in the presence of frequent regime switches and nonlinear and non-Gaussian dynamics, particularly when there are instantaneous effects between the variables, e.g., due to slow rates of measurements. In this work, we establish the identifiability of both latent regimes and regime-dependent causal structures under temporal regime dependencies, nonlinear lagged and instantaneous effects, and independent noise from the exponential family. Our identifiability theory subsumes non-temporal mixtures of causal models. Furthermore, we introduce FlowMSM, a regime detection framework that can be paired with any stationary causal discovery method to recover regime-dependent causal structures. Experiments on synthetic benchmarks and a financial economics dataset demonstrate the effectiveness of our approach to detect latent regimes and discover causal structures from non-stationary time series.

18.
arXiv (CS.AI) 2026-06-16

Agentic Framework for Deep Learning workload migration via In-Context Learning

arXiv:2606.15994v1 Announce Type: new Abstract: Translating deep learning models from PyTorch's flexible, object-oriented design to JAX's functional, stateless setup is usually a manual and error-prone task. Automated migration is challenging because Large Language Models (LLMs) struggle with strict and dynamic API alignment and are prone to mistakes for exacting operations. We propose a fully autonomous system that combines In-Context Learning (ICL) with oracle-driven self-debugging. First, we curated an ICL context that serves as a strict reference for idiomatic JAX styling and test case generation. Second, instead of depending on the LLM to deduce mathematical outputs, we run the source PyTorch modules to get their actual dynamic tensor states. This creates an unchangeable execution oracle. We then use an autonomous agentic loop to synthesize tests based on the oracle data. The test cases are executed repeatedly, and the traceback is sent back to the LLM for self-correction. Ablations show that combining ICL references with oracle grounding and self-debugging greatly outperforms pure instructional and basic agentic baselines. This improvement does not add an excessive computational overhead. Our lightweight pipeline achieves 91% numerical equivalence (compared to baseline: 9%, instruction + self-debugging: 27%) on neural modules, providing a highly reliable, scalable blueprint for cross-framework migration. This has been validated across several state-of-the-art models including SAM (segment anything), T5, Code Whisper amongst others showing high numerical equivalency. Code: https://github.com/AI-Hypercomputer/accelerator-agents/tree/main/MaxCode

19.
arXiv (CS.CL) 2026-06-11

Mapping Scientific Literature with Large Language Models and Topic Modeling

Scientific literature is increasingly fragmented by disciplinary boundaries, specialized terminology, and potentially sparse keyword systems, making it difficult to capture the evolving structure of modern science. This study introduces a large language model (LLM)-driven framework for mapping scientific literature from a topic modeling perspective. The approach is demonstrated on a 20-year corpus of more than 1,500 engineering-related articles published in the Proceedings of the National Academy of Sciences (PNAS). A two-stage classification pipeline first assigns a primary thematic category to each article based on its abstract, followed by full-text analysis to identify secondary classifications that reveal latent cross-topic connections within the corpus. Unlike conventional topic models, the LLM-based framework produces semantically interpretable topics while maintaining strong quantitative performance. Comparative evaluation against established topic modeling methods shows higher topic diversity and lower overlap with competitive coherence metrics. Manual validation on a randomly sampled subset of abstracts yields an accuracy of 75.9%. Additional traditional natural language processing analyses confirm that the generated topics correspond to meaningful linguistic patterns in the corpus. A bipartite network linking primary and secondary classifications further reveals implicit thematic relationships that are not readily observable through abstracts or keyword systems alone. The findings indicate that the framework independently recovers much of the journal's editorial dual-classification structure without prior knowledge of its schema. Overall, the proposed approach offers a powerful tool for mapping science and identifying emerging cross-topic connections in research.

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

Hierarchical Modeling of ICD Codes in EHR Foundation Models

arXiv:2606.15447v1 Announce Type: new Abstract: Electronic health record foundation models typically treat ICD diagnosis codes as flat tokens, overlooking the clinically meaningful hierarchical structure that captures disease families, subcategories, and fine-grained diagnostic detail. As a result, existing EHR representation learning methods do not explicitly exploit the hierarchical structure already present in the coding system. In this work, we study ICD-10-CM hierarchy as a general inductive bias for clinical representation learning. We investigate two complementary mechanisms for incorporating hierarchy: first, by augmenting diagnosis sequences in a BERT-style transformer with tokens corresponding to different levels of the ICD hierarchy, and second, by injecting hierarchy into graph-based code representations through hierarchy-aware edges combined with diagnosis co-occurrence structure. Across these settings, we evaluate whether explicit hierarchy improves downstream prediction, which levels of the hierarchy are most useful, whether hierarchy encoding improves transfer across datasets, and how hierarchy reshapes embedding similarity structure. We conduct experiments on two large-scale real-world clinical datasets: MIMIC-IV, used for pretraining and in-domain evaluation, and eICU, used to assess cross-dataset transfer via frozen encoder probing. Our findings show that explicitly encoding ICD hierarchy improves over flat code representations in both in-domain and cross-dataset settings, while revealing that the most useful level of hierarchy depends on both the task and the modeling approach. More broadly, we focus on hierarchy-aware EHR representation learning and show that the benefits of encoding hierarchy are generalizable across modeling settings and hierarchy levels.

21.
arXiv (CS.CL) 2026-06-19

NRITYAM: Language Models Meet Art and Heritage of Dance

Language models have become essential tools in shaping modern workflows. However, their global effectiveness hinges on a nuanced understanding of local socio-cultural contexts. To address this gap, we present NRITYAM, a comprehensive benchmark for evaluating the cultural comprehension capabilities of language models in the context of global dance traditions. NRITYAM comprises 9,260 carefully curated question-answer pairs spanning 12 languages, making it the largest dataset dedicated to evaluating cultural knowledge in dance. The dataset has been developed from the ground up through close collaboration with native dance artists and native speakers of the languages, who authored and validated culturally relevant questions specific to their regions. We evaluate a broad set of models, including large language models, small language models, multimodal large language models, and small multimodal language models. As a multilingual and multicultural benchmark, NRITYAM sets a new standard for evaluating the ability of AI systems to understand and reason about traditional performing arts. Detailed dataset samples are available at~\url{https://github.com/niladrighosh03/NRITYAM}.

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

IterCAD: An Iterative Multimodal Agent for Visually-Grounded CAD Generation and Editing

Computer-Aided Design is pivotal in modern manufacturing, yet existing automated methods predominantly rely on open-loop, one-shot generation, creating a mismatch with iterative real-world practices. In this paper, we present IterCAD, a unified multimodal agent framework for closed-loop, interactive CAD generation and editing. We formulate the task as a multi-turn interaction between a multimodal agent and an executable CAD sandbox, covering three tasks: Drawing-to-Code, Text-to-Code, and Interactive Editing. To support this, we develop a data synthesis pipeline incorporating advanced industrial manufacturing features to generate standard-compliant multi-view engineering drawings, complex code-editing tasks, and high-fidelity interaction trajectories. We optimize the agent via progressive SFT followed by geometry-aware reinforcement learning with viable-prefix masking to enhance code executability and geometric fidelity. Finally, we introduce the IterCAD-Bench evaluation suite and propose the Chamfer Distance Tolerance-Recall (CD-TR) curve alongside its AUC-TR metric, establishing a survivor-bias-free standard that unifies code validity and geometric precision. Extensive experiments demonstrate that IterCAD achieves highly competitive performance across multiple benchmarks, significantly outperforming existing approaches in both code executability and geometric precision, while exhibiting superior capabilities in closed-loop iterative refinement.

23.
medRxiv (Medicine) 2026-06-22

Sex-specific multimorbidity clusters and all-cause mortality in relatively healthy older adults: findings from the ASPREE cohort

Background: Multimorbidity is common in older adults, but sex differences in chronic condition clustering remain unclear. This study explored multimorbidity clusters and their associations with all-cause mortality among community-dwelling adults aged 70 years and over. Methods: This was a secondary analysis of data from 16,095 Australian ASPREE participants aged at least 70 years without prior dementia or cardiovascular disease. Fifteen baseline chronic conditions were grouped using latent class analysis (LCA). Observed-to-expected (O/E) ratios characterised conditions over-represented within clusters, and Cox proportional hazards models assessed associations with all-cause mortality. Results: Among 16,095 participants (mean age 74 years), 88.3% had multimorbidity at baseline; 4,217 deaths occurred over a median follow-up of 10.85 years. Five clusters were identified overall: hypertension and dyslipidemia (52.1%), gout and metabolic (14.4%), depressive symptoms, osteoporosis and frailty (10.0%), anaemia and kidney disease (10.2%), and hypotension, thyroid disorder and past cancer (13.3%). Sex-stratified analyses revealed three clusters in males and four in females. The frailty, depressive symptoms and osteoporosis cluster was associated with higher mortality in both sexes (aHR 1.56 [95% CI 1.40-1.73] in males; 1.68 [1.49-1.89] in females). Higher mortality was also observed for the metabolic, gout and kidney disease cluster in males (aHR 1.63 [1.47-1.81]) and the gout, anaemia and kidney disease cluster in females (aHR 1.96 [1.74-2.21]). Conclusions: Distinct multimorbidity clusters differed by sex and were associated with increased all-cause mortality. These findings may support risk stratification, targeted screening, and more person-centred management of older adults with multimorbidity.

24.
Nature Biotechnology 2026-06-11

Large-scale, spatially resolved panoramic CRISPR screening in native tissue environments using Perturb-DBiT

作者:

Spatially resolved CRISPR screening in vivo has been limited to small perturbation panels and subsets of protein-coding RNAs. We present Perturb-DBiT, a method for co-sequencing of spatial total RNA whole transcriptomes and single guide RNAs (sgRNAs) on the same tissue section in situ. In a human cancer metastatic colonization model, we applied large (80,000+) sgRNA panels across tumor colonies in multiple consecutive tissue sections alongside their corresponding total RNA transcriptomes. We linked perturbations affecting long noncoding RNA covariation, microRNA–mRNA interactions and distinct amino acid-specific tRNA alterations to tumor migration and growth. By integrating transcriptional pseudotime trajectories, we further observed the impact of perturbations on clonal dynamics and cooperation. In an immune-competent syngeneic mouse model, investigation of the tumor immune microenvironment indicated distinct, synergistic effects on immune infiltration and suppression. Perturb-DBiT provides a spatially resolved comprehensive view of perturbation responses in complex tissues, including small and large RNA regulation, tumor proliferation, migration, metastasis and immune interactions. In vivo CRISPR genetic perturbations are spatially mapped at scale.

25.
arXiv (CS.AI) 2026-06-16

How to Detect and Measure the AI Dangers to Democracy

arXiv:2606.16054v1 Announce Type: cross Abstract: Research on artificial intelligence and democracy has grown quickly over the last decade. A shared conclusion in this literature is that AI does not create new democratic problems so much as it makes old ones worse. We now see this across information ecosystems, in elections, and in public administration. However, despite growing evidence, we lack a clear way to prioritize risks in this area, compare them across domains, and identify where democratic control is most likely to break down. So, our problem is: How can we systematize the problems that AI systems pose to democratic processes? This paper argues that principal agent theory may fit the task. In many phases of democratic systems, principals delegate key functions to AI systems and their providers without really being able to monitor how these systems operate or the outputs they produce. Treating AI as a delegation problem helps identify accountability gaps and other governance failures. Most importantly, as we shall illustrate, it provides metrics for empirical assessments of AI impact on democracy. As a second analytical element, we draw on the NIST AI Risk Management Framework and its seven characteristics of trustworthy AI, which supply substantive criteria for evaluating delegated tasks. Operationalized across the three domains through measurable indicators and domain specific trustworthiness criteria, we propose an analytical framework that centers on institutional assessability as the central condition for democratic control over AI. However, we stress that how severe a harm is, and how much risk is acceptable, are evaluative judgments that current methodologies neither acknowledge nor operationalize. This becomes acute when such evaluative judgments are (silently) delegated to private vendors. We identify this as a strong limitation left for future work.