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01.
arXiv (CS.CL) 2026-06-17

Top-Theta Attention: Sparsifying Transformers by Compensated Thresholding

We present Top-Theta (Top-$\theta$) Attention, a training-free method for sparsifying transformer attention during inference. Our key insight is that static, per-head thresholds can be calibrated to retain the desired constant number of significant elements per attention row. This approach enables content-based sparsity without retraining, and it remains robust across data domains. We further introduce compensation techniques to preserve accuracy under aggressive sparsification, establishing attention thresholding as a practical and principled alternative to top-k attention. We provide extensive evaluation on natural language processing tasks, showing that Top-$\theta$ achieves 3-10x reduction in V-cache usage and up to 10x fewer attention elements during inference while degrading no more than 1% in accuracy.

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

Imbalanced Classification under Capacity Constraints

arXiv:2605.03289v2 Announce Type: replace-cross Abstract: Detecting observations from a minority class under severe class imbalance is a central challenge in applications such as fraud detection, medical screening, and industrial quality control. In these settings, each positive prediction triggers a costly follow-up action, an MRI scan, a transaction audit, whose execution is subject to real operational constraints. This paper proposes a formal classification framework under capacity constraints: given a user-defined bound limit $b$ on the proportion of observations that can be labeled as belonging to the minority class, the goal is to find the classifier that maximizes sensitivity on that class. We characterize the optimal classifier under this constraint and establish its equivalence with the classical Bayes classifier under a reweighting of the prior probabilities. We also introduce a capacity-adjusted performance metric $M$ that accounts for the effective detection rate when the capacity constraint is binding. The framework is implemented on top of standard learning methods, k-NN, SVM, random forests, and neural networks, and statistical consistency is established for each. We further show that these methods reduce to post-hoc thresholding when no hyperparameters are oriented toward the capacity-constrained objective, and introduce a capacity-aware support vector machine that exploits the constraint during training and achieves the strongest empirical performance. Experiments on the Taiwanese credit card default dataset confirm that capacity-constrained classifiers substantially outperform both classical approaches and SMOTE under high imbalance regimes. The framework extends naturally to multiclass settings and online environments.

03.
arXiv (CS.AI) 2026-06-11

Inside the Latent Flow: Causal Deciphering of Attention Dynamics in Audio Separation Foundation Models

arXiv:2606.10046v2 Announce Type: replace-cross Abstract: Flow-matching transformers achieve strong audio separation, yet their attention dynamics are opaque. We adapt established causal-intervention principles into a deterministic, inference-time probing protocol for SAM Audio. Orthogonal probing uncovers a dual-pathway text-conditioning mechanism: additive injections control semantic identity, while cross-attention refines acoustic structure. We observe an asynchronous layerwise convergence: stable layers build temporal scaffolds early, whereas fast layers continue resolving artifacts during sampling. The model also attenuates temporal segmentation cues to maintain continuous-flow stability. Using these insights, we propose Layer-Selective Attention Caching (LSAC), a training-free acceleration method that caches attention in stable layers. Across acoustic complexities, LSAC cuts self-attention computation by about ~25% with negligible quality loss and yields up to 6.7x higher quality retention than naive step reduction.

04.
arXiv (quant-ph) 2026-06-12

Multiple Topological Haldane Phases for Symmetry-Protected Quantum Information Processing

arXiv:2606.12685v1 Announce Type: new Abstract: Symmetry-protected topological phases have attracted significant interest at the fundamental level and as a potential platform for quantum information processing, owing to their protected edge states and resilience to perturbations. Applying these features for practical and efficient quantum computation is highly desirable, but remains an open challenge. Here, we demonstrate the partitioning into multiple independent Haldane phase subsystems of a single spin-1/2 ladder system and propose this as a scalable architecture for gate-based quantum computation, which takes advantage of the symmetry-protected topological order. We encode qubits in the two topological states of the $S^{z}=0$ sector of each subsystem. Finite-size effects, typically viewed as detrimental, instead provide a controllable energy splitting that enables single-qubit rotations using only local magnetic fields. An Ising-type interaction between neighboring subsystem edges generates entangling gates, enabling universal quantum computation driven by two control parameters that are easily accessible experimentally. Our results demonstrate how symmetry-protected topological phases can be directly harnessed for circuit-model quantum computation in realistic systems.

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

How Far Can Machine Translation Quality Take You? Extrinsic Discourse Evaluation in Goal-Oriented Setups

Existing machine translation (MT) metrics and discourse-focused evaluations primarily assess translation quality intrinsically, without measuring the downstream consequences of translation errors. In this work, we focus on extrinsic discourse evaluation of machine translation under two distinct regimes: static and interactive. Under the static regime, we propose an entity counting task as a probe of referential consistency in discourse. We show that high intrinsic MT quality does not reliably predict downstream discourse success and strong MT systems still produce referential inconsistencies. For the interactive regime, we study the goal-oriented multi-agent Welfare Diplomacy game as a probe of long-horizon communication and coordination. We find that interaction-specific translation failures impact downstream coordination. Our results highlight goal-oriented environments as a viable framework for discourse-sensitive extrinsic MT evaluation.

06.
Nature Medicine 2026-06-15

Long-term independent use of an intracortical brain–computer interface for speech and cursor control

Brain–computer interfaces (BCIs) can provide naturalistic communication and digital access to people with severe paralysis by decoding neural activity associated with attempted speech and movement. Recent work has demonstrated highly accurate intracortical BCIs for speech and cursor control, but two critical capabilities needed for practical viability were unmet: independent at-home operation without researcher assistance and reliable long-term performance supporting accurate speech and cursor decoding. Here we demonstrate the independent and near-daily use of a multimodal BCI with novel brain-to-text speech and computer cursor decoders by a man with paralysis and severe dysarthria due to amyotrophic lateral sclerosis. Over nearly 2 years, the participant used the BCI for more than 3,800 h at home with no researchers present to maintain rich interpersonal communication with his family and friends, independently control his personal computer and sustain full-time employment—despite being paralyzed. He communicated 183,060 sentences—totaling 1,960,163 words—at an average rate of 56 words per minute. He labeled 92% of sentences as being decoded at least mostly correctly. In formal quantifications of performance where he was asked to say words presented on a screen, attempted speech was consistently decoded with more than 99% word accuracy (125,000 word vocabulary). The participant also used the speech BCI as keyboard input and the cursor BCI as mouse input to control his personal computer, enabling him to send text messages and emails and to browse the internet. These results demonstrate that intracortical BCIs have the potential to support independent use in the home, marking a critical step toward practical assistive technology for people with severe motor impairment. An automated intracortical brain–computer interface, used at home with no researcher intervention, provides long-term and accurate restoration of speech-based communication and cursor-based computer usage in a person with severe dysarthria due to amyotrophic lateral sclerosis.

07.
arXiv (CS.CL) 2026-06-11

LatticeBridge: Rare-Event Sequential Inference for Faithful Structured Sequence Synthesis

Structured sequence generation often requires a model to satisfy several input-derived constraints in a single output. Standard decoding methods may assign high probability to fluent continuations while placing low mass on continuations that realize all required anchors jointly. We study this regime as a rare-event sequential inference problem. LatticeBridge combines a compact prefix language model, instance-compiled surface automata, and a twisted sequential Monte Carlo (SMC) decoder with resampling, multilevel splitting, and a source-support proposal term derived from instance-provided phrases. The constraint representation is compiled from each input instance and does not rely on manually curated lexical classes. On 2,610 attainable validation tasks spanning CommonGen, E2E NLG, and WikiBio, the particle decoder improves exact anchor satisfaction and mean anchor coverage over greedy, beam-filtered, and best-of-k ancestral baselines under a shared proposal model. Since exact anchor satisfaction alone does not rule out unsupported attribute substitutions, the evaluation reports required-anchor coverage, source coverage, source-intrusion diagnostics, overlap, runtime, and particle statistics jointly. The benchmark characterizes the faithfulness-overlap-latency frontier under a fixed proposal model.

08.
arXiv (quant-ph) 2026-06-16

Study of the triangular-lattice Hubbard model with constrained-path quantum Monte Carlo

arXiv:2603.14808v2 Announce Type: replace-cross Abstract: We benchmark constrained-path Monte Carlo (CPMC) on the triangular-lattice Hubbard model for several fillings and $U$ values and show that symmetry-adapted trial wave functions substantially improve quantitative accuracy. Away from half-filling, simple free-electron-based trials that preserve the ground state symmetry yield energy deviations $\lesssim 1\%$ from exact diagonalization and density matrix renormalization group results. At half-filling, strong frustration in the intermediate to large $U$ regimes necessitates symmetry-projected trials to reach comparable accuracy, where both free-electron and symmetry-broken Hartree-Fock trials incur substantial constraint bias. Since the computational cost of CPMC with symmetry projection scales polynomially with system size, our results motivate its use as a practical route for studying competing ground states in strongly correlated, frustrated systems.

09.
arXiv (CS.CV) 2026-06-16

Metis: A Generalizable and Efficient World-Action Model for Autonomous Driving and Urban Navigation

World action models~(WAMs) have shown great promise for autonomous driving and urban navigation. Built upon Vision-Language-Action models or video generation models, existing approaches suffer key limitations: (1) High inference latency due to future observation prediction at test time, and (2) tightly coupled video and action modeling leading to representational mismatch and degraded generalization. To address both issues, we propose Metis, an end-to-end WAM framework that decouples video generation and action prediction. Specifically, Metis employs a Mixture-of-Transformers architecture with dedicated experts for video generation and action prediction, preserving the intrinsic distributional properties of each task. To enhance efficiency, we introduce an asymmetric attention mask that enables joint training of both experts while allowing the action model to bypass explicit video generation during inference. This design ensures training-inference consistency and significantly reduces computational costs without compromising planning performance. Extensive experiments demonstrate state-of-the-art performance on the NAVSIM navhard and navtest benchmarks and the CityWalker navigation benchmark, validating both the generalizability and efficiency across diverse tasks. Real-robot deployments further confirm the practical feasibility of our approach.

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

Not All Retrievals are Useful: Cross-Attention for Input-Aware RAG in Time Series Forecasting

arXiv:2603.14709v2 Announce Type: replace Abstract: Retrieval-augmented generation (RAG) enhances zero-shot time series (TS) forecasting by leveraging external knowledge bases, yet existing approaches overlook input-level relevance when fusing retrieved samples with the query. We argue that not all retrievals are equally useful, and irrelevant ones can degrade performance. To this end, we propose Cross-RAG, a zero-shot RAG-based forecasting framework that selectively attends to query-relevant retrieved samples via query–retrieval cross-attention. By modeling input-level relevance between the query and retrieved samples, Cross-RAG jointly incorporates three sources of information: 1) the query itself, 2) the retrieved samples, and 3) their relational interactions. In particular, this input-aware design enables Cross-RAG to remain stable as the number of retrieved samples $k$ grows, whereas prior methods without cross-attention require careful $k$ tuning to avoid degradation from irrelevant retrievals. Extensive experiments demonstrate that Cross-RAG consistently improves zero-shot forecasting performance across multiple TSFM backbones and various RAG methods, with additional analyses confirming its effectiveness across various retrieval scenarios. Code is available at https://github.com/seunghan96/cross-rag/.

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

Beyond Third-Person Audits: Situated Interaction Auditing for User-Centered LLM Bias Research

Research on bias in large language models (LLMs) has predominantly focused on third-person audits, which study how models represent or evaluate demographic groups as external subjects. However, this paradigm overlooks a structural blind spot because the user is absent from the audit. In practice, LLMs are used in open-ended, personal interactions, during which the model implicitly represents the user and adjusts its responses accordingly. When identical requests yield different responses depending on who is asking, bias manifests not in how the model describes others but in how it treats its interlocutor. We propose Situated Interaction Auditing (SIA), a user-centered framework for studying how user profile signals – implicit sociodemographic markers, writing style, and stated identity – systematically shape LLM response quality, content, and tone. We demonstrate the framework through a case study that intersects gender and socioeconomic status signals across multiple task domains and outline a research agenda for SIA as a new mission for natural language processing.

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

Self-Evolving Visual Questioner

Vision-language models (VLMs) are typically trained as passive answerers, while their ability to actively ask diverse, non-trivial, visual-centric and grounded questions remains underexplored. Existing visual questioners' performance is bottlenecked by the availability of high-quality training data or the cost of curating them. We show that a VLM can continuously improve itself as a visual questioner without any external supervision. We propose a self-evolving framework that uses a VLM itself as both a proposer and a filter to produce harder, more informative, and visual-centric questions, while maintaining their exploration diversity to avoid training collapse. These questions are then used to train the VLM in both questioner and answerer modes. To evaluate the questioner, we introduce an agentic protocol that assesses questions along perception, reasoning, and diversity dimensions. Experiments across various backbone VLMs show that our method substantially enhances the quality and substantially expands the difficulty boundary of autonomous question generation. Under the same budget, our self-supervision is more effective than training on the static source data. Moreover, the self-evolving questioner remains a competitive or even better answerer.

13.
arXiv (CS.LG) 2026-06-12

Disparate Impact in Synthetic Data Generation

arXiv:2606.13105v1 Announce Type: new Abstract: We revisit the fairness notion of disparate impact for synthetic data generation (SDG), that assesses whether the utility of generated records is the same across sensitive groups. Our approach departs from existing work on fair SDG, that address the problem of correcting for undue biases in the observed distribution, hence redefining SDG as learning a distribution that is not that of the real data. By contrast, non-disparate impact is notably achieved when the synthetic and real distributions are the same. We expose reasons why SDG may fail to reach that solution and discuss why approximation and estimation errors occur and can be disparate across groups. We notably look into the expressive power of SDG methods relative to distribution complexity, sampling errors due to group proportions, and estimation errors induced by differential privacy mechanisms. We illustrate cases of disparate impact on both artificial and real-world data, focusing on SDG methods that rely on probabilistic graphical models. We also introduce a strategy of learning group-wise SDG models and illustrate how it can improve both the overall utility and its parity in many settings.

14.
arXiv (CS.LG) 2026-06-19

Learning to Emulate Chaos: Adversarial Optimal Transport Regularization

arXiv:2604.21097v2 Announce Type: replace-cross Abstract: Chaos arises in many complex dynamical systems, from weather to power grids, but is difficult to accurately model with data-driven methods such as machine learning emulators. While emulators are promising tools for accelerating simulations and solving inverse problems, they still struggle to learn chaotic dynamics, where sensitivity to initial conditions renders exact long-term forecasts infeasible, especially given noisy data. Recent work instead trains emulators to match the statistical properties of chaotic attractors, but these approaches often rely on handcrafted summary statistics or large, diverse multi-environment datasets. In this work, we propose a family of adversarial optimal transport objectives that can jointly learn high-quality summary statistics and a physically consistent emulator from a single noisy trajectory. We theoretically analyze and experimentally validate a Sinkhorn divergence formulation (2-Wasserstein) and a WGAN-style dual formulation (1-Wasserstein) of our approach. Numerical experiments across a variety of chaotic systems, including ones with high-dimensional spatiotemporal chaos, show that emulators trained using our proposed objectives have significantly improved long-term statistical fidelity.

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

Generative Modeling of Bach-Style Symbolic Music: A Comparative Study of Autoregressive, Latent-Variable, and Adversarial Approaches

arXiv:2606.13626v1 Announce Type: cross Abstract: We study generative modeling of Bach-style symbolic piano music using a shared MIDI corpus and three model families: autoregressive LSTMs with attention, latent-variable models including recurrent VAEs and vector-quantized VAEs, and generative adversarial networks. We compare their ability to model polyphonic note sequences, learn useful latent representations, and generate stylistically coherent compositions. Our experiments show that the autoregressive LSTM with attention produces the most musically coherent samples, while vector quantization helps mitigate posterior collapse and yields more structured outputs than conventional recurrent VAEs. The adversarial approach captures local pitch patterns but remains difficult to train and generalizes less reliably to Bach's style. These results highlight the relative strengths and failure modes of autoregressive, latent-variable, and adversarial approaches for symbolic music generation.

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

FireRed-Image-Edit-1.0 Technical Report

We present FireRed-Image-Edit, a diffusion transformer for instruction-based image editing that achieves state-of-the-art performance through systematic optimization of data curation, training methodology, and evaluation design. We construct a 1.6B-sample training corpus, comprising 900M text-to-image and 700M image editing pairs from diverse sources. After rigorous cleaning, stratification, auto-labeling, and two-stage filtering, we retain over 100M high-quality samples balanced between generation and editing, ensuring strong semantic coverage and instruction alignment. Our multi-stage training pipeline progressively builds editing capability via pre-training, supervised fine-tuning, and reinforcement learning. To improve data efficiency, we introduce a Multi-Condition Aware Bucket Sampler for variable-resolution batching and Stochastic Instruction Alignment with dynamic prompt re-indexing. To stabilize optimization and enhance controllability, we propose Asymmetric Gradient Optimization for DPO, DiffusionNFT with layout-aware OCR rewards for text editing, and a differentiable Consistency Loss for identity preservation. We further establish REDEdit-Bench, a comprehensive benchmark spanning 15 editing categories, including newly introduced beautification and low-level enhancement tasks. Extensive experiments on REDEdit-Bench and public benchmarks (ImgEdit and GEdit) demonstrate competitive or superior performance against both open-source and proprietary systems. To support future research, our code, models, and benchmark suite are publicly available at https://github.com/FireRedTeam/FireRed-Image-Edit/ .

17.
arXiv (math.PR) 2026-06-12

Voronoi Percolation: Topological Stability and Giant Cycles

arXiv:2601.00793v2 Announce Type: replace Abstract: We study the topological stability of Voronoi percolation in higher dimensions. We show that slightly increasing p allows a discretization that preserves increasing topological properties with high probability. This strengthens a theorem of Bollobás and Riordan and generalizes it to higher dimensions. As a consequence, we prove a sharp phase transition for the emergence of i-dimensional giant cycles in Voronoi percolation on the 2i-dimensional torus.

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

Want Better Synthetic Data? Steer It: Activation Steering for Low-Resource Language Generation

Large language models (LLMs) have become an effective tool for synthetic data generation, including for low-resource languages, where generated data can improve downstream task performance. Current best-performing approaches typically rely on few-shot prompting with target-language examples, which increases inference costs and may reduce diversity through lexical anchoring. In this work, we investigate activation steering as an alternative for low-resource synthetic data generation. We study two steering strategies: Language Steering, which targets the linguistic identity of a language, and Quality Steering, which captures well-formedness by contrasting human-written and backtranslated text representations. We evaluate these methods across four open-source LLMs, multiple layers, and 11 typologically diverse languages by generating sentiment and topic classification data and finetuning smaller classifiers. Steering is applied in both zero-shot and few-shot prompting settings and compared against non-steered counterparts. Our results show that steering on early layers consistently improves the diversity of generated data while often yielding stronger downstream model performance, particularly for low-resource languages.

19.
Nature Medicine 2026-06-10

Dual-target gene therapy in Parkinson’s disease: a multicenter phase 1 trial

Authors:

Restoring striatal dopamine synthesis is a promising gene therapy strategy for Parkinson’s disease. Previous adeno-associated virus-mediated aromatic L-amino acid decarboxylase (AADC) monotherapies remain dependent on exogenous levodopa, whereas multigene delivery is constrained by strict adeno-associated virus packaging limits. A ‘dual approach’ targeting the two rate-limiting enzymes, tyrosine hydroxylase (TH) and AADC, offers the potential for autonomous dopamine synthesis. We report the 12-month primary safety and tolerability outcomes of a multicenter, open-label, dose-escalation, phase 1 trial evaluating BBM-P002, a new adeno-associated virus vector—AAVT42—codelivering constitutively active TH and AADC. Ten participants with moderate-to-advanced Parkinson’s disease were enrolled and received bilateral intraputaminal infusions across doses of 4.0 × 1011 vg (Cohort 1; n = 1), 6.0 × 1011 vg (Cohort 2; n = 2), 1.0 × 1012 vg (Cohort 3; n = 2) and 1.2 × 1012 vg (Cohort 4; n = 5). The trial achieved its primary outcome, as BBM-P002 demonstrated a favorable safety and tolerability profile within 12 months post-treatment. No dose-limiting toxicities or drug-related serious adverse events occurred. A total of 23 adverse events were reported, all judged unrelated to BBM-P002 and primarily mild and transient. Systemic toxicity and clinically meaningful immunogenicity were absent. In conclusion, intraputaminal delivery of BBM-P002 was safe and well tolerated in this phase 1 trial, supporting continued clinical development. ClinicalTrials.gov registration: NCT05822739 . Phase 1 results reveal that BBM-P002, a dual-target gene therapy co-delivering TH and DDC, is safe and well tolerated in Parkinson’s disease, with 12-month motor improvements signaling therapeutic potential.

20.
medRxiv (Medicine) 2026-06-17

Postoperative Cognitive Decline in Older Patients with Cardiovascular Disease and Preoperative Mild Cognitive Impairment

Objective. Older adults undergoing cardiac surgery may be vulnerable to postoperative cognitive decline. However, no studies have examined postoperative cognitive outcomes in older patients with cardiovascular disease (CVD) according to preoperative mild cognitive impairment (MCI). This study examined 12-month postoperative cognitive outcomes in older CVD patients according to preoperative MCI diagnosis and explored predictors of postoperative cognitive decline. Method. Twenty-two older CVD patients ([≥]65 years) and twenty-five controls were included. Neuropsychological assessment was conducted at baseline in both groups and repeated 12 months after surgery in the CVD group. MCI was diagnosed using current clinical criteria. Postoperative cognitive change was examined across preoperative MCI groups. Results. Fifty percent of patients met criteria for postoperative MCI, showing high diagnostic stability relative to preoperative frequency (45.5%). The preoperative CVD-MCI group showed a decline in working memory, executive functions, visual memory, and naming, whereas CVD-nMCI group declined only in verbal memory. Furthermore, CVD-MCI showed more heterogeneous postoperative cognitive trajectories of change than CVD-nMCI, who showed stability. Estimated IQ, APACHE-II score, and postoperative frailty were important variables in predicting the postoperative pattern. Conclusions. MCI frequency remained high and stable in older CVD patients across the preoperative and one-year postoperative period. However, this apparent diagnostic stability masks subclinical cognitive decline, particularly among patients with preoperative MCI, who showed greater susceptibility to further impairment. Estimated IQ, APACHE-II score, and postoperative frailty may be considered relevant predictors of outcome. These results highlight the value of preoperative neuropsychological assessment for characterizing postoperative cognitive risk in older CVD patients.

21.
arXiv (CS.CV) 2026-06-12

Contrast-Informed Augmentation and Domain-Adversarial Training for Adult-to-Neonatal MR Reconstruction Generalization

Purpose: To investigate whether contrast-informed data augmentation and domain-adversarial training improve the adult-to-neonatal generalization of the E2E-VarNet. Methods: Three training regimes were investigated: (1) adult-only training with unaugmented adult data, (2) mixed training with paired unaugmented and neonatal-informed augmented adult data, and (3) mixed training with a domain-adversarial objective. Models were trained on retrospectively undersampled multi-coil adult T2-weighted brain MR data and evaluated on neonatal and adult test data at acceleration factors $R=4$ and $R=8$ using quantitative metrics and qualitative evaluation. Feature analyses assessed whether domain-adversarial training altered the latent representations of unaugmented adult, augmented adult, and neonatal test samples. Results: Mixed training (Mixed) and mixed domain-adversarial training (Mixed-DAT) outperformed unaugmented adult-only training (Unaug-Only) when evaluated on neonatal data. At R=4, Mixed-DAT achieved the best performance (SSIM = 0.924 +/- 0.027, PSNR = 33.98 +/- 1.15 dB). At R=8, Mixed-DAT performed best when measured using SSIM (0.848 +/- 0.031 vs. 0.766 +/- 0.037 for Unaug-Only and 0.814 +/- 0.035 for Mixed) and Mixed performed best when measured using PSNR (29.56 +/- 0.83 dB vs. 26.26 +/- 0.78 dB for Unaug-Only and 29.43 +/- 0.83 dB for Mixed-DAT). Qualitative assessment of t-SNE plots suggested that Mixed-DAT increased the overlap among the latent representations of the unaugmented adult, augmented adult, and neonatal test data. Conclusion: Contrast-informed augmentation and domain-adversarial training improved adult-to-neonatal generalization of deep learning-based MR reconstruction. These findings suggest that contrast-informed data augmentation combined with adversarial training may improve robustness to domain shift in undersampled neonatal MR reconstruction.

22.
medRxiv (Medicine) 2026-06-22

Genetic and Shared Environmental Influences on Cancer Risk and Cross-Cancer Associations in Nordic Twins

The relative contributions of genetic and shared environmental influences to cancer risk and cross-cancer associations remain poorly understood. We analyzed data from 222,530 same-sex twins from Denmark, Finland, Norway, and Sweden in the Nordic Twin Study of Cancer, including 43,060 incident cancers over a median follow-up of 41.6 years. Using a target trial framework, biometric modeling, and competing-risk adjustment, we estimated familial risk, heritability, and shared environmental contributions across 35 cancer sites. Lifetime cancer risk was 36.5%, increasing to 51.4% in monozygotic (MZ) twins and 45.3% in dizygotic (DZ) twins with an affected co-twin. Overall cancer risk was explained by heritable (28%) and shared environmental (40%) influences. Heritability was highest for prostate (42%), non-melanoma skin (24%), and breast (18%) cancers. Cross-cancer analyses revealed extensive overlap in the genetic and shared environmental factors across sites, consistent with widespread pleiotropy and shared environmental susceptibility. Prostate cancer exhibited the strongest genetic overlap with rectum/anus (12%) and kidney (11%) cancers, whereas co-shared environmental influences were most pronounced for breast-lung (11%), prostate-bladder (11%), and prostate-lung (12%) cancers. These findings show pervasive genetic overlap across cancers at different sites and emphasize the importance of incorporating familial shared environmental exposures into cancer risk prediction and prevention strategies.

24.
PLOS Computational Biology 2026-06-01

Challenges and progress in RNA velocity: Comparative analysis across multiple biological contexts

Authors:

by Sarah Ancheta, Leah Dorman, Guillaume Le Treut, Abel Gurung, Greg Huber, Loïc A. Royer, Alejandro Granados, Merlin Lange Single-cell RNA sequencing is revolutionizing our understanding of cell state dynamics, allowing researchers to capture and quantify the transcriptomic profile of a single cell at a specific timepoint. Among the computational techniques used to predict cellular trajectories, RNA velocity has emerged as a predominant tool for modeling transcriptional dynamics. RNA velocity leverages the mRNA maturation process to generate velocity vectors that predict the likely future state of a cell, offering insights into cellular differentiation, aging, and disease progression. Although this technique has shown promise across biological fields, the performance accuracy varies depending on the RNA velocity method and dataset. We established a comparative pipeline and analyzed the performance of five RNA velocity methods on three datasets based on local consistency, method agreement, identification of driver genes, and robustness to sequencing depth. This benchmark provides a resource for scientists to understand the strengths and limitations of different RNA velocity methods.

25.
arXiv (CS.AI) 2026-06-18

The New Social Image: How AI Competency and AI Proactivity Influence Self- and Peer-Perceptions in the Workplace

arXiv:2606.00182v2 Announce Type: replace-cross Abstract: Human-AI collaboration is considered the most promising way to incorporate AI in the workplace. What remains unexplored are the experiential consequences of this teaming. More specifically, in a team with AI, how humans perceive themselves (self-perception) and how they are perceived by their coworkers (peer perception) in terms of work ownership and job meaningfulness. In a 2x2x2 vignette study (n=50), participants rated perceptions of ownership, affect, job meaningfulness and satisfaction, and role dynamics across two levels (low/high) of AI proactivity and AI competency as within-subject factors, with point-of-view (self perception/peer perception) as between-subjects. Our results showed that AI with low competency or low proactivity generally improved feelings related to ownership, meaningfulness, satisfaction, and role dynamics, and also increased positive affect while reducing negative affect. However, these effects were often influenced by point-of-view. For instance, low AI proactivity resulted in higher job satisfaction from self-perception rather than peer perception. Based on our findings, we argue that designing AI for the future of work solely around performance metrics may not be adequate. Highly competent and proactive AI-driven systems can have undesirable impacts on perceptions of ownership, job identity, social image and team dynamics, and consequently, job meaningfulness.