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

Attention as Frustrated Synchronization

A network of oscillators that synchronizes perfectly computes nothing further, so an attention architecture built from synchronization must locate its computation in structured departures from agreement. We introduce the Frustrated Synchronization Network (FSN), whose token states are phases on a torus and whose entire value pathway is one learned complex coupling kernel over harmonics and a one-step delay. Each component of the kernel is a frustration in the sense of the synchronization literature. The complex phases are static Kuramoto-Sakaguchi frustration angles, the signed harmonics are repulsive Daido components, and the delay term, which couples each token to the successors of the tokens it attends to, is algebraically identical to Kuramoto-Sakaguchi coupling whose frustration angle is the data's own transition, so next-token prediction is implemented as synchronization frustrated by the data. At matched one-million-parameter and training budgets on character-level text and code, the FSN's validation loss is below a tuned RoPE-SwiGLU transformer's at every epoch measured, and the comparison survives training the baseline to convergence: every thirty-epoch enwik8 seed finishes below the transformer's converged fifty-epoch loss of 1.611, and the FSN's completed fifty-epoch runs converge to 1.5953 +/- 0.0014. A variant with every feed-forward block replaced by mean-field coupling to learned collective modes, leaving no multilayer perceptron in the stack, tracks the transformer. On natural text the unfrustrated base layer falls behind the converged transformer at every copy depth, worst on long-range copy events; the kernel reverses the deficit at every depth of four and beyond. Headline comparisons are at the one-million-parameter scale; a scale ladder is complete through four million parameters with the advantage persisting, and remaining arms are marked as in progress.

02.
arXiv (CS.AI) 2026-06-19

Flickering Multi-Armed Bandits

arXiv:2602.17315v3 Announce Type: replace-cross Abstract: We introduce Flickering Multi-Armed Bandits (FMAB) to model sequential decision-making in environments with changing action availability, where accessibility of the next action is restricted to a subset dependent on the agent's current choice. We formalize these constraints through stochastically evolving graphs where actions are limited to local neighborhoods. This mobility-constrained structure imposes a dual challenge: the statistical requirement of information acquisition and the physical overhead of navigation. We analyze FMAB under i.i.d. Erdős–R'enyi and Edge-Markovian process, proposing a two-phase lazy random walk algorithm for robust exploration. We establish high-probability sublinear regret bounds and prove near-optimality via a matching information-theoretic lower bound. Our results characterize the intrinsic cost of learning under local-move constraints, complemented by a robotic disaster-response simulation.

03.
arXiv (CS.LG) 2026-06-15

Neural Variability Enhances Artificial Network Robustness

arXiv:2606.13801v1 Announce Type: new Abstract: Neural responses in cortex exhibit substantial trial-to-trial variability in response to repeated stimuli, while peripheral sensory neurons respond far more consistently, leading many to wonder whether stochasticity may carry meaning. Existing work has argued that noise and signal correlations may be optimized for discrimination in animals, whereas artificial neural network (ANN) studies have shown similar benefits of noise in machine learning tasks, although most ANN work has neglected the effects of correlations. Here we investigate whether correlated noise improves the robustness of artificial neural networks to adversarial attacks and naturalistic image modifications. Using the covariance of activations under modified versus clean inputs, we find that structured noise may significantly improve network robustness. Robustness to naturalistic image modifications benefits most from structure, but this structure transfers poorly across modification types. In contrast, noise structure from adversarial attacks can generalize to other kinds of attacks. These results suggest that structured noise in ANN activations generally improves robustness, establishing a biologically plausible strategy for creating robust artificial neural networks that only relies on local information.

04.
arXiv (CS.AI) 2026-06-11

Feature-Aligned Speech Watermarking for Robustness to Reconstruction Distortions

arXiv:2606.11828v1 Announce Type: cross Abstract: Audio watermarking aims to embed identifiable information into audio while remaining imperceptible. Existing methods adopt high-fidelity, low-energy designs to preserve perceptual quality, but the resulting watermarks lack robustness under suppression by speech reconstruction models. Improving robustness is challenging due to the inherent robustness-fidelity trade-off in existing designs, where increasing watermark energy improves robustness but reduces fidelity. To address this problem, we propose a feature-aligned watermarking method that aligns the watermark with the original speech feature distribution, allowing higher watermark energy to improve robustness while preserving imperceptibility. We use a pretrained speech codec to generate a pseudo-speech watermark and fuse it into the spectrogram of the input audio, with VAD loss and perceptual losses guiding embedding within voiced regions. Experiments show that our method maintains imperceptibility comparable to existing approaches while substantially improving robustness under both seen and unseen speech reconstruction models.

05.
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/

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

A Judge-Aware Ranking Framework for Evaluating Large Language Models without Ground Truth

arXiv:2601.21817v3 Announce Type: replace-cross Abstract: Evaluating large language models (LLMs) on open-ended tasks without ground-truth labels is increasingly done via the LLM-as-a-judge paradigm. A critical but under-modeled issue is that judge LLMs differ substantially in reliability; treating all judges equally can yield biased leaderboards and misleading uncertainty estimates. More data can make evaluation more confidently wrong under misspecified aggregation. We propose a judge-aware ranking framework that extends the Bradley-Terry-Luce model by introducing judge-specific discrimination parameters, jointly estimating latent model quality and judge reliability from pairwise comparisons without reference labels. We establish identifiability up to natural normalizations and prove consistency and asymptotic normality of the maximum likelihood estimator, enabling confidence intervals for score differences and rank comparisons. Across multiple public benchmarks and a newly collected dataset, our method improves agreement with human preferences, achieves higher data efficiency than unweighted baselines, and produces calibrated uncertainty quantification for LLM rankings.

07.
arXiv (CS.CV) 2026-06-17

Structured Adversarial Camouflage via Voronoi Diagrams

Pixel-wise adversarial patches are computationally heavy and often visually detectable, limiting utility in security-critical systems. We present adversarial Voronoi camouflage that optimizes only seed-point locations under fixed, printable palettes using a soft assignment, producing structured, splinter camouflage-like patterns without additional regularization. Evaluated on person detection with COCO-style AP@[.5:.95], naive placement (Inria -> COCO) performs comparably bad, while garment-level application via segmentation mask (3DPeople) results in a significant AP drop. The attack transfers to out-of-domain backgrounds and across detector families (YOLOv9/10/11/12), indicating robustness in black-box settings. Repainting with different palettes largely nullifies the effect, and single-color tweaks show limited tolerance (

08.
arXiv (math.PR) 2026-06-16

Geometry of critical discrete structures: long-range percolation on the hierarchical lattice and the discrete torus

arXiv:2509.09589v2 Announce Type: replace Abstract: Consider (a) balls $\Lambda_n$ of growing volumes in the $d$-dimensional hierarchical lattice, and (b) the $d$-dimensional discrete torus $\mathbb{T}_n^d$ on $n^d$ vertices. Place edges independently between each pair of vertices $x\neq y\in\Lambda_n$ or $\mathbb{T}_n^d$ with probability $1-\exp(-\beta J(x, y) )$ where $J(x, y) \asymp \| x-y \|^{-\alpha}$ for some $0

09.
arXiv (CS.CL) 2026-06-17

Evaluating Second-Order Bias of LLMs Through Epistemic Entitlement

Evaluations of social bias in LLMs largely focus on whether models generate or imply biased content. However, as LLMs are increasingly used as judges of bias, they may exhibit social biases in subtler ways in how they evaluate biased content, which current methods do not systematically capture. We call this second-order bias: social bias in an LLM's judgment about social bias, which we evaluate through a novel, philosophically grounded reasoning task. Drawing on entitlement epistemology, we conceptualize bias as misplaced foundational knowledge that shapes an agent's rational inquiry, and derive a logical reasoning task for LLMs to judge to whom a biased text is acceptable or non-acceptable. We develop two simple metrics to measure how biased LLM judges are in inferring demographics for acceptability without sufficient support, and how these inferences vary across groups targeted by biased texts. Evaluating open and closed models, we find that our task evades safety guardrails by surfacing bias in model judgment. It varies systematically across target groups, reflects implicit social maps, and shows how models are still triggered by demographic labels. Our work points to the need for LLM bias evaluation in judgment tasks and broadly, for more theoretically grounded approaches to bias evaluation in NLP. We release our code and model responses at https://github.com/uofthcdslab/second-order-bias.

10.
Nature (Science) 2026-06-10

Gen Z scepticism towards AI is a wake-up call — universities must take it seriously

作者:

The challenge for universities is not adopting artificial intelligence, but doing so in ways that the current generation of students can trust. The challenge for universities is not adopting artificial intelligence, but doing so in ways that the current generation of students can trust.

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

Robust Transformer-Based One-Step Stock Index Forecasting via Shifted Data Augmentation

arXiv:2606.15701v1 Announce Type: new Abstract: Transformers have shown remarkable success in sequence modeling, yet their direct application to financial time series remains challenging due to noisy signals, short-memory dynamics, and distributional shifts. This paper proposes a modified Transformer architecture for one-step stock index forecasting, combined with advanced learning-rate scheduling and a novel Shifted Data Augmentation (SDA) technique. We evaluate the proposed framework on two benchmark stock index datasets, VN30 and S&P 500. Experimental results demonstrate that cosine annealing with warmup consistently improves forecasting accuracy over the generalized inverse-power scheduler. Furthermore, SDA substantially reduces forecasting errors and run-to-run variability while improving robustness to hyperparameter selection. The combination of cosine annealing scheduling and SDA achieved the best performance on both datasets, indicating that data augmentation can play a more important role than increasing model complexity in Transformer-based financial forecasting. These findings provide a practical and computationally efficient approach for robust stock index forecasting in noisy financial environments.

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

Facial Affect Analysis for Service-Oriented Systems: Advances, Challenges, and Future Visions

Facial Affect Analysis (FAA) is evolving from a stand-alone recognition task into a reusable perception capability for Service-Oriented Software Ecosystems (SoSE). This paper preserves the FAA methodological core while reframing recent advances through systems-engineering requirements for composable and dependable services. We review representative progress in static and dynamic expression analysis, action-unit and micro-expression modeling, and modern CNN, Transformer, graph, and hybrid architectures, then interpret these advances by their operational fit in edge, cloud, and hybrid service pipelines. The synthesis emphasizes SoSE concerns that determine deployability: service contracts for uncertainty-aware outputs, latency and availability envelopes, lifecycle monitoring and recalibration, governance-aware integration, and interoperability across independently evolving components. Our analysis shows that benchmark gains alone are insufficient for SoSE readiness; robustness under shift, intervention stability, fairness, privacy posture, and runtime guarantees are equally critical. We conclude with a roadmap for treating FAA as an operational service component with explicit interfaces, measurable quality attributes, and accountable lifecycle management.

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

LLM-ODDR: A Large Language Model Framework for Joint Order Dispatching and Driver Repositioning

arXiv:2505.22695v2 Announce Type: replace Abstract: Ride-hailing platforms face significant challenges in optimizing order dispatching and driver repositioning operations in dynamic urban environments. Traditional approaches based on combinatorial optimization, rule-based heuristics, and reinforcement learning often overlook driver income fairness, interpretability, and adaptability to real-world dynamics. To address these gaps, we propose LLM-ODDR, a novel framework leveraging Large Language Models (LLMs) for joint Order Dispatching and Driver Repositioning (ODDR) in ride-hailing services. LLM-ODDR framework comprises three key components: (1) Multi-objective-guided Order Value Refinement, which evaluates orders by considering multiple objectives to determine their overall value; (2) Fairness-aware Order Dispatching, which balances platform revenue with driver income fairness; and (3) Spatiotemporal Demand-Aware Driver Repositioning, which optimizes idle vehicle placement based on historical patterns and projected supply. We also develop JointDR-GPT, a fine-tuned model optimized for ODDR tasks with domain knowledge. Extensive experiments on real-world datasets from Manhattan taxi operations demonstrate that our framework significantly outperforms traditional methods in terms of effectiveness, adaptability to anomalous conditions, and decision interpretability. To our knowledge, this is the first exploration of LLMs as decision-making agents in ride-hailing ODDR tasks, establishing foundational insights for integrating advanced language models within intelligent transportation systems. While the current framework incurs higher computational costs than traditional methods, we show that parallel decomposition and model distillation can reduce latency to production-viable levels for deployment.

14.
arXiv (quant-ph) 2026-06-11

Q-DICE: Quantum Distributed Interconnect Compiler and Emulator

arXiv:2606.11340v1 Announce Type: new Abstract: As distributed quantum computing (DQC) offers a leading path towards scalable quantum computation, the ability to benchmark distributed algorithms under realistic conditions becomes critical for system co-design. However, without access to physical systems, researchers lack tools to evaluate distribution protocols. We introduce Q-DICE (Quantum Distributed Interconnect Compiler and Emulator), a hardware-aware emulation environment for benchmarking distributed quantum circuits on classical simulators and on NISQ-era monolithic hardware. This work provides three core contributions: (1) a programmatic scheme to construct distributed QPU backends, utilizing two novel techniques - QPU slicing and stitching - to facilitate distributed circuit mapping, (2) a methodology for modeling nonlocal link noise using physically motivated Kraus operators and stochastic error channels, and (3) a boundary-aware circuit mapping algorithm enforcing distributed QPU topology constraints during transpilation. Together, these components constitute a distribution-aware compiler and noise-modeling engine that faithfully enforces the physical limitations of distributed quantum hardware within existing execution environments. We validate Q-DICE against a multitude of experimentally demonstrated quantum circuits, including a distributed Grover's search on optically linked trapped-ion hardware, achieving a worst-case fidelity deviation of 4% between simulated and experimental results. These findings demonstrate Q-DICE's capacity to accurately reproduce real distributed quantum system behavior across platforms, streamlining experimentation with distributed quantum algorithms and architectures.

15.
PLOS Computational Biology 2026-06-22

GrassSV – hybrid method to detect structural variants in high throughput DNA-seq data

by Dominik Witczak, Krzysztof Sychla, Julia Wysocka, Artur Laskowski, Wojciech Frohmberg, Marta Glowacka, Alicja Dzik, Piotr Lukasiak, Jacek Blazewicz, Aleksandra Swiercz Genetic diversity is crucial for populations to adapt and survive in dynamic environments. This diversity arises from genetic mutations, which manifest in the genome as structural variants (SVs). Several types of SVs exist, but not all are equally easy to detect. Current SV detection tools tend to specialize in certain SV types or require the use of multiple tools to obtain a comprehensive variant profile, which increases computational cost and complexity. While some methods excel at identifying breakpoints, they often struggle with accurately classifying variant types, and their precision depends strongly on data quality and sequencing technology. At present, the majority of available genomic data originates from high-quality short reads, which remain the most affordable sequencing technology. In this manuscript, we introduce GrassSV, a novel and computationally efficient method that employs a hybrid pattern-matching approach to detect all major classes of structural variants using short-read sequencing data. GrassSV integrates depth-of-coverage analysis with contig-based pattern recognition to ensure both sensitivity and precision while minimizing false positives and runtime. Its robustness was demonstrated on the human Genome in a Bottle dataset, as well as on synthetic data derived from the yeast genome, where it achieved high accuracy across all SV types at a lower computational cost compared to existing methods. This makes GrassSV a practical alternative to multi-tool pipelines typically required for comprehensive SV detection. GrassSV is available at https://github.com/Domomod/GrassSV under GPL-3.0 license and the benchmark at: https://github.com/Domomod/GrassBenchmark.

16.
arXiv (CS.CL) 2026-06-15

When Plausible Is Not Realistic: Evaluating Human Mobility in LLM-Based Urban Simulation

LLM-based generative agents are increasingly used in urban simulators, yet it remains unclear whether they reproduce empirically realistic human mobility patterns or merely generate plausible mobility narratives. We introduce a validation framework for evaluating the mobility of generative agents of LLM-based urban simulators against real-world mobility data. For this, we use mobility laws, temporal rhythms, network motifs, semantic activity transitions, and behavioral mobility profiles. Using datasets from the Greater Paris region and Shanghai, we evaluate AgentSociety and CitySim across multiple dimensions of mobility realism. Our analysis reveals a substantial gap between narrative plausibility and empirical mobility realism. Although the simulators capture some high-level semantic activity distributions, they struggle to reproduce core spatial and temporal constraints, including realistic trip-length distributions, origin-destination flows, dwell times, and transition dynamics. We further observe that realistic mobility diversity is unstable across default prompting configurations and may require explicit profile-aware initialization. To support reproducible evaluation, we also contribute scalable and open LLM-driven infrastructure for regional-scale map generation, observability-enhanced simulation, mobility-metric computation, and traffic simulation. Our findings highlight the need for rigorous empirical validation of LLM-based urban simulators and provide practical tools for building more realistic and reproducible urban simulation systems.

17.
PLOS Computational Biology 2026-06-11

Robust discovery of mutational signatures using power posteriors

by Catherine Xue, Jeffrey W. Miller, Scott L. Carter, Jonathan H. Huggins Mutational processes, such as the molecular effects of carcinogenic agents or defective DNA repair mechanisms, produce different mutation types with characteristic frequency profiles, known as mutational signatures. Non-negative matrix factorization (NMF) has been successfully used to discover many mutational signatures, yielding novel insights into cancer etiology and informing targeted therapies. However, the NMF model is only a rough approximation to reality, and even small departures from this assumed model can have large negative effects on the accuracy and reliability of the results. We propose BayesPowerNMF, a Bayesian NMF method that provides nonparametric robustness to model misspecification, principled automated selection of the number of latent processes, and uncertainty quantification of model parameters. In extensive simulation studies, we find that our proposed approach recovers more true signatures with greater accuracy than current leading methods. On whole-genome sequencing data for six cancer types from the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium, we find that our method is able to accurately recover more signatures than the current state-of-the-art.

18.
arXiv (CS.CV) 2026-06-19

DiT-JSCC: Rethinking Deep JSCC with Diffusion Transformers and Semantic Representations

Generative joint source-channel coding (GJSCC) has emerged as a new Deep JSCC paradigm for achieving high-fidelity and robust image transmission under extreme wireless channel conditions, such as ultra-low bandwidth and low signal-to-noise ratio. Recent studies commonly adopt diffusion models as generative decoders, but they frequently produce visually realistic results with limited semantic consistency. This limitation stems from a fundamental mismatch between reconstruction-oriented JSCC encoders and generative decoders, as the former lack explicit semantic discriminability and fail to provide reliable conditional cues. In this paper, we propose DiT-JSCC, a novel GJSCC backbone that can jointly learn a semantics-prioritized representation encoder and a diffusion transformer (DiT) based generative decoder, our open-source project aims to promote the future research in GJSCC. Specifically, we design a semantics-detail dual-branch encoder that aligns naturally with a coarse-to-fine conditional DiT decoder, prioritizing semantic consistency under extreme channel conditions. Moreover, a training-free adaptive bandwidth allocation strategy inspired by Kolmogorov complexity is introduced to further improve the transmission efficiency, thereby indeed redefining the notion of information value in the era of generative decoding. Extensive experiments demonstrate that DiT-JSCC consistently outperforms existing JSCC methods in both semantic consistency and visual quality, particularly in extreme regimes.

19.
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.

20.
arXiv (math.PR) 2026-06-17

Poisson approximation by coupling

arXiv:2605.01894v2 Announce Type: replace Abstract: It is well known that a binomial $(n,p)$ can be approximated by a Poisson distribution with parameter $np$. The typical approach in undergraduate probability texts is to show a convergence result for the distribution of the binomial as $n$ goes to infinity and $np$ converges to some $\lambda$. In this note we use instead the coupling technique to show a much more general result. Moreover, we only use elementary results from probability.

21.
arXiv (CS.LG) 2026-06-16

One-Step Generalization Ratio Guided Optimization for Domain Generalization

arXiv:2606.16301v1 Announce Type: new Abstract: Domain Generalization (DG) aims to train models that generalize to unseen target domains but often overfit to domain-specific features, known as undesired correlations. Gradient-based DG methods typically guide gradients in a dominant direction but often inadvertently reinforce spurious correlations. Recent work has employed dropout to regularize overconfident parameters, but has not explicitly adjusted gradient alignment or ensured balanced parameter updates. We propose GENIE (Generalization-ENhancing Iterative Equalizer), a novel optimizer that leverages the One-Step Generalization Ratio (OSGR) to quantify each parameter's contribution to loss reduction and assess gradient alignment. By dynamically equalizing OSGR via a preconditioning factor, GENIE prevents a small subset of parameters from dominating optimization, thereby promoting domain-invariant feature learning. Theoretically, GENIE balances convergence contribution and gradient alignment among parameters, achieving higher OSGR while retaining SGD's convergence rate. Empirically, it outperforms existing optimizers and enhances performance when integrated with various DG and single-DG methods.

22.
bioRxiv (Bioinfo) 2026-06-15

Biological meaning in protein embedding space is resolution-dependent

Protein language model embeddings are increasingly used to organise biological sequences, yet how biological meaning is encoded within embedding neighbourhoods remains poorly understood. Using two independent hierarchical enzyme systems, carbohydrate-active enzymes and peptidases, we investigated how biological interpretation changes across embedding organisations aligned to different levels of biological hierarchy. Different embedding organisations give rise to distinct neighbourhood semantics. When aligned to membership-boundary resolution, embeddings robustly separated artefacts and unrelated proteins from members of the target category. However, embeddings aligned to functional-grouping resolution maintained compositional neighbourhood structure for multi-domain proteins spanning more than one functional or catalytic group. Finally, embeddings aligned to local-family resolution recovered compact family-like neighbourhoods, including families withheld from training, while weakening broader membership-boundary and functional-grouping relationships. Moreover, embeddings optimised toward the same level of biological organisation retain different biological relationships depending on optimisation trajectory employed. Together, our results show that proximity in protein embedding space has no fixed biological interpretation. Instead, biological meaning emerges across embedding resolutions through selective preservation of different forms of biological organisation.

23.
Nature Medicine 2026-06-12

Efficacy and target engagement of dopamine agonist pramipexole for anhedonic depression: a randomized placebo-controlled trial

Anhedonia is a core and disabling symptom of mood disorders with limited treatment options. We evaluated the efficacy and safety of the dopamine agonist pramipexole in patients with mood disorders characterized by clinically significant anhedonia. In this single-center, randomized, double-blind, placebo-controlled trial, adults with major depressive disorder, dysthymia or bipolar depression and elevated Snaith−Hamilton Pleasure Scale (SHAPS) scores were assigned (1:1) to flexible dose, once-daily oral pramipexole as add-on treatment or placebo for 9 weeks. The primary outcome was change in SHAPS score from baseline to week 9. Analyses were conducted in the modified intention-to-treat population. Eighty-five participants were randomized, and 82 were included in the analysis. The primary outcome was met: pramipexole was associated with a greater reduction in SHAPS scores compared to placebo (mean difference: −4.04, 95% confidence interval: −6.89 to −1.18, P = 0.006, Hedges’ g = 0.62). Exploratory analyses indicated that pramipexole was associated with increased light physical activity and relative preservation of reward-related ventral striatal activation. Improvements in anhedonia were sustained during a 6-month open-label extension. Pramipexole was generally well tolerated compared to placebo. Pramipexole significantly improved anhedonia and showed a favorable safety profile, supporting its potential as an augmentation strategy in mood disorders. ClinicalTrials.gov identifiers: NCT05355337 and NCT05825235 . Pramipexole, in patients with major depressive disorder, dysthymia or bipolar depression, reduced Snaith−Hamilton Pleasure Scale scores significantly compared to placebo.

24.
arXiv (quant-ph) 2026-06-19

Quantum-Accelerated Self-Consistent Field: A Hybrid Algorithm

arXiv:2606.20176v1 Announce Type: new Abstract: We present the Grover adaptive search self-consistent field (GAS-SCF) algorithm. GAS-SCF leverages quantum arithmetic to construct an efficient oracle that marks target states (Fock states) which improve upon some initial classical energy estimate. Amplitude amplification then increases the probability of measuring these states. This approach offers a theoretical quadratic speed-up for the optimization problem encountered in SCF quantum chemistry and establishes a baseline against which structured optimization algorithms, such as QAOA and DQI may be compared. In this work, we classically simulate three examples as proofs of concept of the algorithm, the largest consisting of 26 qubits. We then extend our analysis to two larger systems, with O3 representing the largest case at 330 qubits. These examples are chosen to probe classically challenging SCF regimes. Achieving chemically relevant applications of GAS-SCF will require large-scale, fault-tolerant quantum hardware.

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

GENIE: A Fine-Grained Measure for Novelty

Large Language Models have consistently demonstrated a lack of creativity and diversity across tasks. Prior work has focused on addressing whether models are capable of generating creative outputs. Here, we aim to consider novelty and investigate what makes model-generated content novel or not novel in a task-specific manner. We propose a fine-grained evaluation metric GENIE to measure the novelty of responses along task-specific features with respect to a population of responses. We show that unlike GENIE, holistic metrics struggle to capture the high-dimensionality of novelty and do not provide insight on which properties they target. Finally, we use GENIE to measure the effectiveness of mitigation methods that address creativity to better understand where these methods can improve novelty.