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01.
arXiv (CS.AI) 2026-06-15

Position: AI Must Become Planet-Centered, Not Just Human-Centered

arXiv:2606.13704v1 Announce Type: cross Abstract: This position paper argues that contemporary AI paradigms are insufficient for supporting complex global goals and introduces Planet-Centered AI (PCAI) as a design philosophy and research agenda that reorients AI toward planetary-scale socio-ecological systems and their long-term trajectories. A planet-centered approach is grounded in systems thinking, treating Earth as an interconnected whole of which humans are part. We diagnose recurring limitations across AI frameworks, many of which remain human-centered, and show why these become especially consequential under current planetary conditions characterized by systemic risk, non-stationarity, and deep uncertainty. We then articulate how PCAI reshapes the AI lifecycle, from problem formulation and model design to evaluation and deployment, by emphasizing alignment with global agendas, developing system-aware AI foundations, trajectory-oriented evaluation, and monitorability. Finally, we advance a falsifiable claim: AI systems optimized without explicit consideration of systemic consequences are more likely to exacerbate systemic instability than to mitigate it.

02.
bioRxiv (Bioinfo) 2026-06-20

Evaluation of Trypanosoma brucei Phosphofructokinase Allosteric Inhibition: An In-Silico Study

Human African trypanosomiasis, caused by a protozoan parasite Trypanosoma brucei, is a neglected tropical disease for which well-tolerated, conveniently administered, and highly efficacious medicines are still missing. Previously, T. brucei Phosphofructokinase was targeted by small-molecule inhibitor development efforts. This approach has shown promise both in vitro and in vivo. In this study, we have used these wet-lab results, evaluated the compounds already characterised by Molecular Dynamics simulations, found relationships between in silico and wet-lab data and used these observations to evaluate compounds that we selected through several different approaches of virtual screens. We observed that inhibitor-ATP interactions are highly predictive of the inhibitory activity. Several compounds selected through virtual screens have outperformed previously characterised compounds.

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

Detect Before You Leap: Mirage Detection in Vision-Language Models

Vision-language models (VLMs) can produce confident visual answers even when the required visual evidence is missing, blank, or unrelated to the question. This failure mode, recently described as mirage (mirage2026), is especially concerning in medical and document VQA, where a plausible but visually ungrounded answer may be mistaken for image-based evidence. We study the complementary problem of pre-release mirage detection: given an image-question pair, determine whether the VLM should answer or abstain before generation. To that end, we propose a novel model-agnostic Text-Conditioned Layer-wise Internal Alignment (TC-LIA) method that probes patch-token representations across the layers of a CLIP ViT-H/14 vision encoder. The key idea is to project layer-wise image patch tokens into the final CLIP embedding space and measure their similarity with the question embedding, thereby tracking whether question-relevant visual evidence emerges across vision layers. TC-LIA summarizes this alignment trajectory using final image-text cosine similarity, late-layer top-k patch-text alignment, early-to-late gain, and layer-wise slope. These features are combined with pixel-statistic based blank/noise detection, zero-shot domain routing, and structured VLM self-assessment in an ensemble. Across five VQA domains with related, unrelated-real, and blank/noise inputs, and across twelve VLM backbones, Qwen2.5-VL-32B achieves the highest three-class detection accuracy of 94.7% with a 3.0% mirage rate, while Qwen2.5-VL-72B achieves 94.6% accuracy with a lower 2.8% mirage rate. Baseline mirage rates span 21.7-66.6%.

04.
arXiv (CS.AI) 2026-06-12

Two-Layer Linear Auto-Regressive Models Estimate Latent States

arXiv:2606.12691v1 Announce Type: cross Abstract: Auto-regressive models have emerged as powerful tools for sequential data, from language to video. Understanding how and why these models learn latent representations remains an open theoretical question. In this work, we demonstrate that when trained by empirical risk minimization on data from partially observed linear dynamical systems, two-layer linear auto-regressive models naturally learn to approximate Kalman filtering. In particular, we show that the learned hidden representation coincides, up to a similarity transformation, with the state estimates produced by the optimal (Kalman) filter, even though the model has no explicit knowledge of the underlying dynamics or state. The result follows from three main insights. First, we establish that the Kalman filter is well approximated by an auto-regressive model with bounded truncation error. Second, we show that despite non-convexity, the two-layer optimization landscape is benign, i.e., all stationary points are either strict saddles or global minima. Finally, as our main contributions, we provide finite-sample guarantees on prediction error, parameter estimation error, and latent state recovery. Numerical simulations support the theoretical results and demonstrate that the latent representations of auto-regressive models recover state estimates.

05.
arXiv (CS.CV) 2026-06-12

DiskChunGS: Large-Scale 3D Gaussian SLAM Through Chunk-Based Memory Management

Recent advances in 3D Gaussian Splatting (3DGS) have demonstrated impressive results for novel view synthesis with real-time rendering capabilities. However, integrating 3DGS with SLAM systems faces a fundamental scalability limitation: methods are constrained by GPU memory capacity, restricting reconstruction to small-scale environments. We present DiskChunGS, a scalable 3DGS SLAM system that overcomes this bottleneck through an out-of-core approach that partitions scenes into spatial chunks and maintains only active regions in GPU memory while storing inactive areas on disk. Our architecture integrates seamlessly with existing SLAM frameworks for pose estimation and loop closure, enabling globally consistent reconstruction at scale. We validate DiskChunGS on indoor scenes (Replica, TUM-RGBD), urban driving scenarios (KITTI), and resource-constrained Nvidia Jetson platforms. Our method uniquely completes all 11 KITTI sequences without memory failures while achieving superior visual quality, demonstrating that algorithmic innovation can overcome the memory constraints that have limited previous 3DGS SLAM methods.

06.
medRxiv (Medicine) 2026-06-11

A Global Health Quality Improvement Project: Enhancing Cervical Cancer Awareness and screening in Nigeria

Background Cervical cancer remains a significant global public health challenge, ranking as the fourth most common cancer among women worldwide. According to The World Health Organization (WHO) 604,000 women were diagnosed with cervical cancer globally in 2020, with over 342,000 deaths amongst this group [1]. Despite its high mortality, cervical cancer is largely preventable through early detection and vaccination against human papillomavirus (HPV), which causes nearly all cases of cervical cancer [1,2] In Nigeria, it is the second most common cancer among women in Nigeria and a leading cause of cancer-related deaths, with low screening rates exacerbating late diagnoses and poor outcomes [1]. Despite global commitments to elimination with Pap smear screening and HPV vaccination, less than 10% of women in Nigeria have undergone screening due to misconceptions, stigma, and limited awareness. Educational interventions may improve awareness and promote screening behaviors. This global health quality improvement (QI) project aimed to enhance cervical cancer awareness and increase Pap smear uptake at the Central Bank of Nigeria (CBN) Clinic in Abuja, Nigeria. Methods In November 2024, we conducted a health education intervention at the Central Bank of Nigeria (CBN) through a structured educational session for male and female CBN staff members. The session focused on cervical cancer prevention, risk factors, and screening guidelines. Additionally, cervical cancer awareness was raised via email, social media, and electronic bulletin board. Participants completed pre and post-interventions surveys assessing cervical cancer knowledge across 10 key items and demographic characteristics. Pap smear uptake was assessed using the CBN clinic records for three months before and after the intervention. Institutional approval was obtained from CBN and external institutional review board approval was not required. Results 188 participants attended the health education session with 124 survey responses (70 pre-event, 54 post-event). Participants were mostly women aged 30-39. Post-intervention, eight of ten survey questions showed improved knowledge, with five demonstrating statistically significant gains: understanding Pap smear frequency (p

07.
arXiv (CS.LG) 2026-06-18

Hierarchical Attention via Domain Decomposition

arXiv:2606.18525v1 Announce Type: new Abstract: We propose a hierarchical attention mechanism based on two-level overlapping Schwarz domain decomposition. The method is motivated by the observation that two-level Schwarz domain decomposition methods combine local subdomain corrections with a coarse level that communicates global, long-range information. We test its usefulness in the context of finite-dimensional operator learning using a simple, one-dimensional diffusion problem with homogeneous Dirichlet boundary conditions. Although elementary, this problem provides a controlled sequence-to-sequence setting in which the exact nonlocal solution operator is known. After discretization, learning the solution operator amounts to approximating the inverse of a symmetric positive definite matrix. As a baseline, we use a global softmax-free low-rank attention operator of the form $QK^T$. The proposed construction replaces this dense global factorization by a two-level additive structure: local low-rank attention blocks on overlapping subdomains are combined with a coarse attention block. The resulting operator has the form $$M_{\theta}^{-1} = \Phi Q_0 K_0^T \Phi^T + \sum_{i=1}^{N} R_i^T D_i^{1/2} Q_i K_i^T D_i^{1/2} R_i.$$ Here $R_i$ restricts to an overlapping subdomain, $D_i$ is a partition-of-unity weight, and $\Phi$ is a coarse interpolation (or prolongation) matrix. Numerical experiments for synthetic Fourier right-hand sides indicate that the domain-decomposition attention operator is able to train faster and can give more accurate approximations than a global low-rank attention baseline while using significantly fewer parameters.

08.
arXiv (CS.CV) 2026-06-16

The Importance of Phase in Neural Representations: An Internal Oppenheim-Lim Test of Image Classifiers

Oppenheim and Lim (1981) showed that natural images stay recognizable when reconstructed from their Fourier phase alone, while the magnitude carries little of their identity. We ask whether trained image classifiers reproduce this asymmetry inside their hidden layers, and we test it causally: given two images, we transplant the phase of one onto the magnitude of the other at a chosen layer and record which image the prediction follows. In PRISM2D, GFNet, and ViT-B/16 the prediction follows the phase or sign donor, and deleting all image-specific magnitude barely moves accuracy, so identity rides on phase while image-specific magnitude is largely dispensable to the readout. ResNet-50 at first seems to break the pattern, because transplanting sign after its ReLUs does nothing; a fair intervention before the ReLU reveals a strong latent sign code in the late blocks, and a DC-only control shows the readout consumes a channel-wise spatial average. Controls rule out the trivial case in which magnitude simply stops depending on the image. The architectures therefore share a phase/sign identity code but expose it in different bases, set by rectification and readout geometry, which gives a mechanistic account of the texture–shape gap between CNNs and attention models.

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

ToolMenuBench: Benchmarking Tool-Menu Filtering Strategies for Reliable and Efficient LLM Agents

arXiv:2606.15508v1 Announce Type: new Abstract: Tool-augmented large language model agents increasingly operate over large tool libraries, but existing evaluations often focus on whether a model can call a tool correctly rather than how the visible tool menu shapes reliability, efficiency, and safety-relevant risk exposure. We introduce ToolMenuBench, a benchmark for evaluating tool-menu construction in multi-step LLM agents. ToolMenuBench varies tool-menu size, distractor type, state-dependent task structure, and risk exposure, and reports both filter-level and downstream agent metrics, including visible-tool count, risky-tool exposure, task success, wrong-tool calls, premature actions, and token usage. In a controlled evaluation across seven model backends, three tool-menu sizes, six filtering methods, and seven evaluation settings, CMTF improves task success from 32.1% under all-tools exposure to 85.7%, while reducing average token usage by roughly 98%. Causal minimal tool filtering achieves the strongest overall tradeoff, reducing visible tools, wrong-tool calls, premature actions, and risky-tool exposure relative to unfiltered exposure, lexical filtering, state-aware filtering, and broader causal-path baselines. ToolMenuBench provides a reusable evaluation framework for studying the agent-interface problem: which tools should be visible, when they should be visible, and under what cost or risk constraints.

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

CRC-Screen: Certified DNA-Synthesis Hazard Screening Under Taxonomic Shift

Authors:

arXiv:2605.00074v2 Announce Type: replace-cross Abstract: DNA-synthesis providers screen incoming orders by searching the requested sequence against curated hazard lists. We show that this baseline collapses to a 100% false-flag rate when the hazardous sequence comes from a taxonomic family absent from the reference set: under Conformal Risk Control's certified miss-rate constraint, a low-discrimination signal forces the threshold below the entire test-benign mass. We compose three signals derived from a synthesis order's public annotation: $k$-mer Jaccard similarity to known toxins, the trimmed-mean score of a five-LLM judge panel, and cosine similarity to clustered embedding centroids. Fused under a monotone logistic aggregator and calibrated by Conformal Risk Control, the resulting screener certifies $\mathbb{E}[\mathrm{FNR}] \le \alpha + \mathrm{TV}$, where the additive term is the calibration-to-test distribution shift under family holdout (a certified ceiling of 24-49% across folds). Across ten leave-one-taxonomic-family-out folds at $\alpha=0.05$ on UniProt KW-0800 reviewed toxins, the calibrated screener achieves 0% empirical test miss rate on every fold and 0% test false-flag rate on nine of ten folds. The bound's finite-sample slack $1/(n_{\mathrm{cal}}+1)$ caps the certifiable miss rate at 1.77% on our 200-hazard subsample; reaching procurement-grade $\alpha=10^{-3}$ requires an $18\times$ larger calibration set, which the full reviewed UniProt KW-0800 corpus is large enough to deliver. The binding constraint on certifiable DNA-synthesis screening is calibration data, not algorithms. Code: https://github.com/najmulhasan-code/crc-screen

11.
arXiv (CS.AI) 2026-06-18

MIDS: Detecting Stealthy Masquerade and Tampering Attacks on CAN Bus via Bidirectional Mamba

arXiv:2606.18599v1 Announce Type: cross Abstract: The Controller Area Network (CAN) protocol is the primary communication standard for Electronic Control Units (ECUs) in modern vehicles, but its lack of encryption and authentication exposes it to a range of security threats. Existing intrusion detection systems are largely tuned to fabrication-style attacks (DoS, fuzzing, ID spoofing realised by frame injection), in which detection signals such as per-ID inter-arrival statistics are readily available. We instead address the harder masquerade setting[b37], in which an internal adversary substitutes a legitimate frame in-situ at its original transmission slot, preserving traffic periodicity and rendering traffic-statistic defences ineffective. We propose the Mamba Intrusion Detection System (MIDS), an innovative dual-stream framework that processes CAN identifiers and payloads in parallel and reconstructs their joint temporal semantics through bidirectional selective state-space modelling. To evaluate MIDS, we collected over 100 million CAN frames from a physical Tesla Model 3 across three driving regimes and synthesised 54 masquerade attack variants spanning ID-only, data-only, and combined modifications. MIDS attains an F1 of 96.94\% on this dataset, exceeding the strongest reproducible baseline by more than 8 percentage points, while sustaining a 1.147~ms single-window inference latency – ample headroom for real-time onboard deployment. To verify generalisation, we further evaluate MIDS on four public benchmarks (ROAD, CrySyS, OTIDS, CT\&T) covering both masquerade and injection scenarios; MIDS attains F1 from 93.70\% to 99.61\%, outperforming the strongest of eight reproduced baselines by up to 13.94 percentage points under a unified 5-fold protocol.

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

Out-of-Distribution (OOD) Detectors for Open-Set RF Fingerprinting

arXiv:2606.12718v1 Announce Type: new Abstract: Radio-frequency (RF) fingerprinting systems must operate in open-world environments where signals from unknown transmitters and temporal drift introduce distribution shift at test time. Out-of-distribution (OOD) detection provides a natural framework for this problem, yet its application to RF fingerprinting (RFF) remains limited. A key barrier to their adoption is that most OOD detectors require auxiliary OOD data for parameter tuning, an assumption that is difficult to satisfy in RF environments where representative OOD data is impractical to collect. In this work, we introduce a promising set of OOD detection methods from the machine learning literature to open-set RFF domain. We present these methods within a unified mathematical framework based on information theory, which is a natural framework for communication systems. Our framework allows for the systematic analysis of methods and development of new methods. We further demonstrate the applicability of recent work on tuning OOD detectors without given OOD tuning data for open-set RFF. We evaluate on the POWDER RF fingerprinting dataset, showing that detectors tuned without any given OOD data achieve performance comparable to baselines with access to true OOD tuning data and greatly out-perform baseline approaches without access to true OOD tuning data, showcasing the practical viability for the RFF problem.

13.
medRxiv (Medicine) 2026-06-15

Artificial Intelligence-Based Detection of Airway Mucus Plugs on CT and Associations With Clinical Outcomes in COPDGene

RATIONALE: Airway mucus plugging is a clinically relevant manifestation of airway pathology in chronic obstructive pulmonary disease (COPD) and is associated with increased mortality even in early disease; however, visual computed tomography (CT) assessment is subjective and labor intensive. OBJECTIVES: To develop an AI-based quantitative CT method for automated detection of airway mucus plugging and evaluate associations with physiologic impairment and clinical outcomes. METHODS: Inspiratory CT scans from 8,971 COPDGene Phase 1 (GOLD 0-4 and PRISm) participants were analyzed. An AI-based framework combining 3D airway segmentation discontinuities and convolutional neural network classification identified mucus plug obstructions, yielding mucus plug burden (total plug count). Associations with outcomes were evaluated using covariate-adjusted models. MEASUREMENTS AND MAIN RESULTS : Higher mucus plug burden was associated with lower post-bronchodilator FEV % predicted ({rho} = -0.41; P < 0.001), greater air trapping (LAA < -856 HU; {rho} = 0.33; P < 0.001), worse health status (SGRQ; {rho} = 0.31; P < 0.001), and shorter 6-minute walk distance ({rho} = -0.26; P < 0.001). Among GOLD 1-4 participants, mucus plug presence was independently associated with increased all-cause mortality (adjusted hazard ratio, 1.28; P < 0.005) and exacerbation frequency (adjusted incidence rate ratio, 1.32; P < 0.005). Plug presence was also associated with increased respiratory mortality across GOLD categories and cardiovascular mortality in GOLD 1-2. CONCLUSIONS: AI-based quantitative CT assessment of airway mucus plugging provides a scalable, reproducible measure associated with physiologic impairment and adverse outcomes in COPD, supporting its role in risk stratification and future therapeutic studies.

14.
medRxiv (Medicine) 2026-06-12

Does the method matter? Evaluating the effectiveness, efficiency and ease of hearing-aid gain self-adjustment

In conventional hearing-aid personalisation, clinicians cannot hear what their patients hear, and patients cannot often reliably detect or describe what they hear. Self-adjustment avoids this issue but requires user controls that adjust hearing-aid signal processing parameters to be effective, efficient and easy. In this study, we explored (a) the roles of interface complexity and stimulus type in the self-adjustment of hearing-aid gain, and (b) how well individuals can adjust one sound to match another to assess the same interfaces and stimuli. Adult hearing-aid users with mild to moderate symmetrical sensorineural hearing loss repeatedly adjusted the gain (a) to their preference from individual prescription (n = 41) and (b) to match their previous preferences from a random starting point (n = 32) using three interfaces representing different bass/mid/treble configurations and three stimuli (music, speech and speech-in-noise). The large interindividual variability in self-adjusted gains clustered into three patterns of deviation from initial prescription: increased relative bass, overall gain reduction, and close to initial prescription. There were no substantial effects of interface nor stimulus on self-adjustment reliability (median {sigma} = 2.8 dB), whereas absolute sound-matching error increased with increasing interface complexity and centre frequency. Neither individual matching accuracy nor questionnaire responses predicted either self-adjusted gains or reliability. Overall, these results show that many - but not all - hearing-aid users can adjust gains with reasonable reliability, and while it can be difficult to predict the behaviour from the individual, the individual applies a similar self-adjustment behaviour across different interfaces and stimuli.

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

CogGen: Cognitive-Load-Inspired Fully Unsupervised Deep Generative Modeling for Compressively Sampled MRI Reconstruction

arXiv:2603.04438v3 Announce Type: replace-cross Abstract: Fully unsupervised deep generative modeling (FU-DGM) offers significant potential for compressively sampled magnetic resonance imaging (CS-MRI) reconstruction. Representative FU-DGM formulations, such as deep image prior (DIP) and implicit neural representation (INR), employ architectural bias to induce a low-dimensional manifold in the image space that aligns with the forward observation. However, as the underlying inverse system is highly ill-posed, prolonged iterative fitting in FU-DGM typically leads to poor efficiency and noise amplification. In this paper, guided by the cognitive principle of easy-to-hard learning, we propose CogGen, an FU-DGM framework that reformulates CS-MRI reconstruction as a staged inversion problem. Specifically, CogGen implements an self-paced curriculum learning (SPCL)-driven progressive scheduling strategy through an MRI-aware dual-threshold weighting criterion, which adaptively regulates k-space measurement participation. The data-consistency residual thresholding evaluates the fitting reliability of the current generator, while the k-space radius thresholding controls stage-wise measurement exposure, thereby avoiding uniform fitting throughout optimization. Theoretically, our analysis shows that, when early stages favor easy-to-fit measurements, CogGen yields a reduced local sufficient-iteration bound and a smaller cumulative noise-amplification bound, explaining the improved convergence behavior and reconstruction fidelity of CogGen within a finite iteration budget. Numerical experiments demonstrate that both CogGen instantiations, CogGen-DIP and CogGen-INR, achieve superior performance over prevailing CS-MRI reconstruction techniques, including unsupervised and supervised pipelines.

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

From 2D Grids to 1D Tokens: Reforming Shared Representations for Multimodal Image Fusion

Multimodal image fusion aims to integrate complementary information from different modalities into a fused image that preserves rich local details while maintaining globally consistent appearance. Existing approaches build shared representations on 2D feature grids, which excel at modeling local structures but offer limited leverage over image-level global appearance factors. To balance these objectives, we introduce a compact 1D token interface based on a frozen pretrained image tokenizer for modeling non-local appearance/base factors. Rather than using the tokenizer as a reconstruction backbone, our design uses the 1D token space as a global carrier while retaining the 2D spatial pathway for local structure restoration. Specifically, we introduce Selective Token Editing (STE), which sparsely updates/replaces a small set of critical tokens, providing a lightweight mechanism to steer global appearance coherence while keeping the fusion backbone unchanged and avoiding extra losses. Experiments on four commonly used benchmarks show that our method achieves the best overall performance, with consistent, multi-metric improvements in both global coherence and local fidelity. Project page: https://zju-xyc.github.io/1D-Fusion-Project-Page/

17.
arXiv (CS.CV) 2026-06-18

Forged Calamity: Benchmark for Cross-Domain Synthetic Disaster Detection in the Age of Diffusion

The rapid advancement of text-to-image diffusion models has enabled the creation of highly photorealistic synthetic images that closely resemble real photographs, making it increasingly difficult to distinguish authentic content from AI-generated fabrications. This poses challenges for cybersecurity, digital forensics, and disaster response, where fake imagery of floods, fires, or earthquakes can spread misinformation or disrupt emergency operations. To address this, we introduce Forged Calamity, a benchmark dataset for synthetic disaster detection containing 30,000 images, including 6,000 real and 24,000 synthetic samples generated by four diffusion models. Comprehensive experiments across fine-tuned and zero-shot settings reveal consistent weaknesses in current forensic approaches. Fine-tuned detectors perform well in-distribution but lose up to 50\% accuracy on unseen generators or disaster types, showing overfitting to model-specific artifacts. Zero-shot generalized detectors also struggle to maintain stable accuracy, with only limited resilience in a few representation-robust models. These findings highlight persistent generalization gaps and the urgent need for domain- and model-agnostic detection methods to ensure visual authenticity in the diffusion era.

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

RUB: Evaluating Residual Knowledge in Unlearned Models

Machine Unlearning (MUL) has emerged as a key mechanism for privacy protection and content regulation, yet current techniques often fail to guarantee the complete removal of sensitive information. While most existing works focus on verifying the execution of unlearning, they overlook the critical question of whether models remain robust against adversarial attempts to recover forgotten knowledge. In this work, we advocate for the principle of Robust Unlearning, which requires models to be both indistinguishable from retrained counterparts and resilient against diverse adversarial threats. To instantiate this principle, we propose a unified benchmark, RUB (Robust Unlearning Benchmark), that systematically evaluates the robustness of unlearning algorithms across classification, image-to-image reconstruction, and text-to-image synthesis. Within this framework, we introduce the Unlearning Mapping Attack (UMA) as a generalizable method to detect residual information, and demonstrate how existing attack strategies can be adapted into this framework as long as they conform to the generic UMA framework. Our experiments across discriminative and generative tasks reveal that state-of-the-art unlearning methods remain vulnerable under these evaluations, even when passing standard verification metrics. By positioning robustness as the central criterion and providing a benchmark for adversarial evaluation, we hope RUB paves the way toward more reliable and secure unlearning practices. The codebase and model checkpoints in RUB will be published.

19.
Nature Medicine 2026-06-12

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

Authors:

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.

20.
arXiv (CS.LG) 2026-06-12

The Geometry of Phase Transitions in Generative Dynamics via Projection Caustics

arXiv:2606.13191v1 Announce Type: new Abstract: Continuous-state generative samplers, including diffusion and flow-matching models, evolve through continuous reverse-time dynamics, yet their samples often undergo abrupt qualitative changes: trajectories commit to modes, semantic alternatives collapse, and small perturbations in narrow time windows can produce large downstream effects. This paper develops a geometric account of such phase-transition-like behaviour. We view denoising as gradient descent on a free energy landscape and show that sharp transitions arise near projection caustics, where the nearest-point projection onto the data support ceases to be unique. Motivated by this perspective, we introduce the Critical Boundary Detector (CBD), as practical diagnostics for score-direction instability. Across toy models, standard diffusion models, and latent text-to-image diffusion models, CBD localises mode commitment, predicts intervention-sensitive windows, and supports targeted control in geometrically sensitive regions. Our results connect geometry of data and dynamics of diffusion generation.

21.
medRxiv (Medicine) 2026-06-11

Malaria Risk among Internally Mobile Individuals and Heterogeneous Mobility Patterns in Two Hypoendemic Communities: Implications for Malaria Elimination in the Peruvian Amazon.

Background: Human mobility is increasingly recognized as a key factor influencing malaria transmission dynamics, particularly in low-transmission settings approaching elimination. This study aimed to assess mobility patterns and their association with malaria risk in two hypoendemic communities in the Peruvian Amazon. Method: A longitudinal study was conducted in the communities of Libertad and Urcomirano (Mazan River basin). Monthly population screenings were combined with weekly active and passive case detection. A total of 678 individuals were enrolled. Mobility patterns were assessed through structured questionnaires, and social network analysis was used to characterize travel connections. Log-binomial regression analysis was applied to identify risk factors associated with malaria infection. Result: Internally, mobile individuals in Libertad showed a higher malaria incidence (>32.47 cases per 1,000 person-months) than those in Urcomirano (

22.
arXiv (math.PR) 2026-06-15

Mixing Times for the Facilitated Exclusion Process

arXiv:2402.18999v2 Announce Type: replace Abstract: The facilitated simple exclusion process (FEP) is a one-dimensional exclusion process with a dynamical constraint. We establish bounds on the mixing time of the FEP on the segment, with closed boundaries, and the circle. The FEP on these spaces exhibits transient states that, if the macroscopic density of particles is at least $1/2$, the process will eventually exit to reach an ergodic component. If the macroscopic density is less than $1/2$ the process will hit an absorbing state. We show that the symmetric FEP (SFEP) on the segment $\{1,\ldots,N\}$, with $k>N/2$ particles, has mixing time of order $N^{2}\log(N-k)$ and exhibits the pre-cutoff phenomenon. For the asymmetric FEP (AFEP) on the segment, we show that there exists initial conditions for which the hitting time of the ergodic component is exponentially slow in the number of holes $N-k$. In particular, when $N-k$ is large enough, the hitting time of the ergodic component determines the mixing time. For the SFEP on the circle of size $N$, and macroscopic particle density $\rho \in(1/2,1)$, we establish bounds on the mixing time of order $N^{2}\log N$ for the process restricted to its ergodic component. We also give an upper bound on the hitting time of the ergodic component of order $N^{2}\log N$ for a large class of initial conditions. The proofs rely on couplings with exclusion processes (both open and closed boundaries) via a novel lattice path (height function) construction of the FEP.

23.
arXiv (CS.CV) 2026-06-16

MMLongEmbed: Benchmarking Multimodal Embedding Models in Long-Context Scenarios

Recent advancements have significantly expanded the theoretical context windows of Multimodal Embedding Models (MEMs). However, larger context windows do not necessarily translate into effective comprehension and representation of long-context multimodal inputs, which remains a critical bottleneck for real-world deployment. To address the lack of systematic evaluation in this setting, we introduce MMLongEmbed, the first comprehensive benchmark for evaluating MEMs in long-context scenarios. MMLongEmbed comprises four retrieval tasks spanning multiple context-length ranges, covering text, document, and video modalities. Through extensive evaluation of state-of-the-art models, we find that current architectures rely heavily on superficial feature matching and struggle to capture deep semantic and structural dependencies. We further observe that performance degradation varies systematically with context length and key information placement. Moreover, models exhibit substantially different robustness to redundant contextual information across modalities. For reproducibility, the benchmark and code are publicly available.

24.
Nature (Science) 2026-06-10

Deep learning four decades of human migration

Authors:

Human migration is a fundamental driver of global demographic change, shaping population structure, labour markets and social policy across countries1–3. Although long-term migration patterns are often linked to economic development4, they can shift rapidly in response to shocks such as conflict, environmental crises and political change5. Despite its importance, migration remains difficult to measure consistently: existing data are sparse, concentrated in high-income settings and are fragmented across incompatible definitions, temporal resolutions and data types6–8. Past efforts have relied on partial datasets, including flow records, stock estimates and model-based reconstructions with limited coverage9–14. A central challenge is therefore to construct a globally consistent, high-resolution account of migration flows over time. Here we present a new dataset of annual origin-destination migration across 230 countries and regions from 1990 to the present, integrating diverse data sources into a unified modelling framework. By combining official statistics, census-based stocks, net migration estimates and past flow reconstructions, our approach produces temporally detailed and spatially comprehensive estimates that substantially extend existing resources. Using an ensemble of deep recurrent neural networks informed by geographic, economic, cultural and political covariates, we capture both persistent trends and short-term responses to changing conditions—all while propagating uncertainty to generate confidence bounds. Our results outperform existing five-year flow estimates on held-out data and provide finer temporal resolution, revealing previously obscured dynamics in global migration patterns. This framework highlights regions in which uncertainty remains high and data collection is most urgently needed. By releasing all data, code and trained models, we provide a transparent and reproducible foundation for future work. These advances enable a more timely and detailed understanding of human mobility, with implications for research and policy in an increasingly dynamic global system. A global annual migration-flow dataset (1990–2024) is produced using deep-learning models and diverse sources to estimate movements across 230 countries with improved temporal resolution, coverage and uncertainty estimates.

25.
bioRxiv (Bioinfo) 2026-06-11

DyMoTree decodes early cell state transitions and drivers from single-cell transcriptomes using a tree-structured neural network

Inferring early cell fate from single-cell RNA-sequencing data is essential for identifying cellular origins and fate plasticity in development and disease. However, existing methods often fail to exploit tree-structured lineage trajectories, limiting the accuracy and interpretability of fate mapping. Here we present DyMoTree, a computational framework that models cell fate decisions as nonlinear mappings between progenitor and terminal cell states under explicit lineage constraints. By integrating lineage graphs with a tree-structured neural architecture, DyMoTree learns lineage-resolved cell-state transition maps from single-cell transcriptomes, enabling robust inference of early fate bias and identification of fate-specific progenitor substates and driver genes. Across simulations, lineage-tracing experiments, and in vivo systems, DyMoTree outperformed existing methods in resolving early fate biases. Applications to mouse embryogenesis, lung adenocarcinoma progression, and CAR-T immunotherapy revealed regulatory programs underlying developmental and disease-associated transitions. DyMoTree provides a general framework for modeling lineage-resolved cell-state dynamics underlying development and disease progression.