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

Trainable Photonic Measurement for Physics-Informed PDE Learning

arXiv:2606.18713v1 Announce Type: new Abstract: Photonic quantum machine learning offers a route to trainable physical representations built from phase, interference and measurement. However, its role in scientific machine learning remains largely unexplored. Physics-informed neural fields provide a natural setting, because differential equations require trial spaces that preserve phase, frequency and derivative structure. Here we introduce a photonic quantum neural field in which coordinates become trainable optical phases, are mixed by multi-photon Fock-space interference and are decoded from photon-number measurements. The photonic circuit is optimized as the neural-field representation itself, not as a fixed feature map or hardware accelerator. Photonic measurement is therefore a trainable representation on which the physics-informed residual is minimized. Across seven elliptic, wave, nonlinear dispersive and inverse PDE benchmarks, we observe a phase-complexity transition: classical coordinate and Fourier-feature networks suffice in smooth regimes, whereas the photonic field is most accurate when residual derivatives amplify phase mismatch. In the hardest regimes it gives the lowest errors, with margins reaching an order of magnitude and about one quarter of the trainable parameters of classical baselines. Frozen and shuffled controls, together with noise stress tests, attribute this gain to learned interference and stable Fock-probability readout under compound perturbations. These results identify photonic quantum measurement as a representation-learning principle for scientific machine learning.

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

Text-Vision Co-Instructed Image Editing

Existing image editing methods can be generally categorized into textual instruction-based and visual prompt-based ones. Textual instructions are semantically expressive, but are limited by the coarse granularity of spatial control of the editing results. In contrast, visual prompts such as drag and point can provide precise spatial guidance, but are limited by the inherent ambiguity in semantic intent. To unify the strength of textual and visual prompts, we present Text-Vision Co-Instructed Image Editing, which jointly models textual instructions as semantic intent and sparse visual instructions as spatial guidance, aiming to achieve precise and intent-faithful image manipulation. To this end, we first construct a textual-visual instruction paired dataset with more than 23K samples derived from dynamic videos, enabling aligned supervision for cross-modal instruction. We then propose TV-Edit, a Textual-Visual instruction unified Editing framework to contextualize drag or point-based visual instructions with image-text semantics and lift them into semantic-aware control representations for pretrained editing backbones. By integrating semantic intent and spatial constraints, TV-Edit leads to more precise spatial control, less instruction ambiguity, and stronger structural consistency than text-only or drag-based alternatives. Finally, we establish TV-Edit-Bench, a deliberately designed benchmark to evaluate semantic faithfulness, spatial alignment, and visual consistency with ground-truth references and controlled textual-visual variations for reliable assessment. Our experiments across multiple editing backbones demonstrate that TV-Edit consistently yields more precise and intent-faithful edits, significantly outperforming state-of-the-art instruction-based and drag-based baselines.

03.
bioRxiv (Bioinfo) 2026-06-19

FeatureMSEA: Metabolic Feature-based Metabolite Set Enrichment Analysis

Liquid chromatography-mass spectrometry (LC-MS) untargeted metabolomics detects thousands of metabolic features, but converting these chemical signals into metabolite set-level biological knowledge remains challenging. This is because most features lack unambiguous metabolite identities. Conventional metabolite set enrichment analysis (MSEA) generally requires identified metabolites and metabolite-level ranked inputs, leaving much of the untargeted feature space unused. Here, we present FeatureMSEA, a feature rank-based framework for metabolite set enrichment directly from metabolic features with ambiguous annotations. FeatureMSEA integrates multi-evidence feature-to-metabolite annotation, feature rank-based enrichment scoring, permutation-based inference, and iterative leading-edge-guided annotation refinement, with an optional LLM-assisted module for post-enrichment interpretation. In null comparisons of randomly split healthy samples, FeatureMSEA detected no significant metabolite sets, whereas metabolite-set spike-in simulations showed recovery of implanted signals. In a cerebrospinal fluid metabolomics study of Huntington's disease, FeatureMSEA identified dysregulated metabolite sets related to amino acid metabolism, mitochondrial energy metabolism, and neuroactive signaling. MS/MS-based annotation analysis further showed that FeatureMSEA refinement reduced annotation ambiguity and prioritized chemically consistent candidate metabolites. In summary, FeatureMSEA provides a general framework for extracting metabolite set-level biological insights from LC-MS untargeted metabolomics in which confident metabolite identification remains incomplete.

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

Where, What, Why, and Importance: Structured Defect Grounding for Text-to-Image Feedback

Despite generating increasingly photorealistic images, text-to-image (T2I) models still exhibit localized, subtle, and structurally complex failures. Diagnosing these failures requires instance-level feedback that answers where a defect occurs, what type it is, why it is defective, and its importance to overall image quality. While recent dense-feedback methods move beyond scalar supervision, their heatmap-centric representations still formulate diagnosis as pixel-field regression, making it difficult to localize variable-cardinality defects and bind semantic reasons to individual failures. To address this representation bottleneck, we propose Structured Defect Grounding (SDG), which casts T2I diagnosis as structured set prediction by modeling each defect as a (location, type, reason, importance) tuple. To make this formulation trainable and measurable, we introduce SDG-30K, a 30K-image dataset with box-grounded annotations across four modern T2I generators, together with a dedicated evaluation protocol, SDG-Eval. Building on this structured representation, we further present a diagnosis-to-alignment framework in which a Vision-Language Model (VLM) serves as the SDG detector, and BoxFlow-GRPO converts predicted defect sets into box-derived, importance-weighted spatial rewards for diffusion model alignment. Extensive experiments show that our SDG detector outperforms leading proprietary VLMs on structured defect grounding, while SDG-guided rewards consistently improve T2I alignment and support localized image refinement. These results establish SDG as a unified, instance-level interface for diagnosing, evaluating, and enhancing modern generative models.

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

Variational Deep Unfolding with Mamba-Based Nonlocal Modeling for Underwater Image Enhancement

Underwater imaging plays a crucial role in ocean engineering, although captured data often suffer from poor visibility and color distortion. To address these challenges, we propose a model-based deep unfolding network for underwater image enhancement that integrates variational modeling into a learnable architecture. The framework is guided by a variational formulation based on a dehazing decomposition, incorporating a multiplicative residual component to absorb remaining artifacts and a nonlocal gradient-type constraint to preserve structural details and enhance edge sharpness. We provide a theoretical analysis establishing the existence of solution for the associated minimization problem. The proposed unfolding method incorporates Mamba layers to efficiently capture self-similarities in the scene. In addition, we introduce a proximal trajectory loss that enforces consistency between the unfolding stages and the iterations of an ideal restoration regularizer. Experimental results demonstrate that the proposed unfolding approach achieves improved visual quality and competitive quantitative performance compared with recent state-of-the-art methods. The source code will be available at https://github.com/MIA-UIB/Variational-Unfolding-Mamba-Underwater-Enhancement .

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

Mirage Probes: How Vision Models Fake Visual Understanding

Vision-language models (VLMs) can answer image-based questions confidently, and often correctly, even when no image is provided. This mirage behavior inflates benchmark scores without reflecting visual grounding. Prior work treats this as a single failure mode. We argue it is two. Using Mirage Probes, a contrastive probing framework that pairs paraphrased question variants with matched mirage and non-mirage labels on the same image, we show that mirage behavior is linearly decodable from internal activations across residual stream, MLP, post-attention, and attention-head sites in two open-source VLMs. We demonstrate that a Naive Bayes text baseline cannot recover this signal, ruling out surface lexical confounds. Cross-benchmark separability patterns, together with a novel Prior Harnessing Index (PHI) measuring how much a model can answer from text alone, expose two distinct regimes: textual biases, where the model answers from language priors without engaging visual representations, and spurious images, where it constructs false visual content in latent space and answers as if grounded. The distinction has direct mitigation consequences: text-distribution cleaning can address the first regime but cannot reach the second, since spurious-image mirages live in the model's visual representations rather than its text. Faithful visual grounding will require interventions at the representational level.

07.
arXiv (CS.AI) 2026-06-19

On the Limitations of Ray-Tracing for Learning-Based RF Tasks in Urban Environments

arXiv:2507.19653v2 Announce Type: replace-cross Abstract: We study the realism of Sionna v1.0.2 ray-tracing for outdoor cellular links in central Rome. We use a real measurement set of 1,664 user-equipments (UEs) and six nominal base-station (BS) sites. Using these fixed positions we systematically vary the main simulation parameters, including path depth, diffuse/specular/refraction flags, carrier frequency, as well as antenna's properties like its altitude, radiation pattern, and orientation. Simulator fidelity is scored for each base station via Spearman correlation between measured and simulated powers, and by a fingerprint-based k-nearest-neighbor localization algorithm using RSSI-based fingerprints. Across all experiments, solver hyper-parameters are having immaterial effect on the chosen metrics. On the contrary, antenna locations and orientations prove decisive. By simple greedy optimization we improve the Spearman correlation by 5% to 130% for various base stations, while kNN-based localization error using only simulated data as reference points is decreased by one-third on real-world samples, while staying twice higher than the error with purely real data. Precise geometry and credible antenna models are therefore necessary but not sufficient; faithfully capturing the residual urban noise remains an open challenge for transferable, high-fidelity outdoor RF simulation.

08.
medRxiv (Medicine) 2026-06-15

Diabetes and the Life-Course: Evidence from Panel Data and Electronic Health Records

Incidence of type 2 diabetes is increasing at ages when education, work, family, and financial transitions are taking place, yet we lack robust evidence of whether earlier treatment changes life-course outcomes and over which time span this takes place. This paper uses the medical cutoff for diabetes diagnosis (HbA1c of 6.5 percent) as a natural experiment to study the effects of diabetes treatment using electronic health records (EHR) and panel data. This paper has three main findings. First, using EHR data, we find that there is a sharp increase in the probability of both diagnosis of diabetes and prescription when the HbA1c equals 6.5 percent. Second, we find that treating diabetes reduces HbA1c levels, weight, BMI, and blood pressure and increases the amount of care received, proxied by the number of HbA1c tests. Both the diagnosis and a prescription are independently able to produce positive changes in metabolic health, although a prescription is more effective in this regard. Third, we conclude that treating diabetes does not have a significant effect on life-course outcomes for a cohort of young Americans aged 24-32, although it does result in a reduction in HbA1c levels that are seen even eight years after the intervention. Taken together, these findings suggest that receiving a diagnosis and prescription are both effective treatments for diabetes, but they do not translate to significant alterations in the lives of young adults in the medium-term.

09.
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.

10.
arXiv (math.PR) 2026-06-17

Extreme value theory for geometric Brownian motion and pricing of short maturity options

作者:

arXiv:2505.08036v2 Announce Type: replace Abstract: We investigate the limiting distribution of geometric Brownian motion conditional on its running maximum taking large values. The Freidlin-Wentzell large deviations theory predicts that the conditional distribution of the sample paths converge weakly to a deterministic exponential curve. We complement this result by showing that the conditional sample paths in fact converge in strong sense, and obtain quantitative bounds on the rate of convergence. As an application of our results to financial mathematics, we obtain new closed form asymptotic formulae for the fair price of barrier options with general path dependent payoff in the short maturity limit, with quantitative error estimates. We provide exact formulae for Asian and lookback style payoffs.

11.
arXiv (CS.AI) 2026-06-12

HD-Prot: A Protein Language Model for Joint Sequence-Structure Modeling with Continuous Structure Tokens

arXiv:2512.15133v3 Announce Type: replace-cross Abstract: Proteins inherently possess a consistent sequence-structure duality. The abundance of protein sequence data, which can be readily represented as discrete tokens, has driven fruitful developments in protein language models (pLMs). A key remaining challenge, however, is how to effectively integrate continuous structural knowledge into pLMs. Current methods often discretize protein structures to accommodate the language modeling framework, which inevitably results in the loss of fine-grained information and limits the performance potential of multimodal pLMs. In this paper, we argue that such concerns can be circumvented: a sequence-based pLM can be extended to incorporate the structure modality through continuous tokens, i.e., high-fidelity protein structure latents that avoid vector quantization. Specifically, we propose a hybrid diffusion protein language model, HD-Prot, which embeds a continuous-valued diffusion head atop a discrete pLM, enabling seamless operation with both discrete and continuous tokens for joint sequence-structure modeling. It captures inter-token dependencies across modalities through a unified absorbing diffusion process, and estimates per-token distributions via categorical prediction for sequences and continuous diffusion for structures. Extensive results demonstrate that HD-Prot achieves competitive performance in unconditional sequence-structure co-generation, motif-scaffolding, protein structure prediction, and inverse folding tasks. Furthermore, our method can perform on par with state-of-the-art multimodal pLMs, despite being developed under limited computational resources (i.e., less than one-tenth the budget for modality extension fine-tuning). It highlights the viability of simultaneously estimating categorical and continuous distributions within a unified language model architecture, offering a promising alternative direction for multimodal pLMs.

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

Learning from Own Solutions: Self-Conditioned Credit Assignment for Reinforcement Learning with Verifiable Rewards

arXiv:2606.18810v1 Announce Type: cross Abstract: Reinforcement learning with verifiable rewards (RLVR) has driven substantial progress in training LLMs for reasoning tasks, but representative methods such as GRPO assign uniform credit across all tokens, wasting gradient on routine tokens while under-crediting pivotal reasoning steps. Existing token-level credit assignment methods require resources beyond the model's own rollouts. GRPO variants rely on process reward models or ground-truth answers. Knowledge distillation assigns credit through per-token divergence but requires external teachers (On-Policy Distillation) or privileged information (On-Policy Self Distillation). However, these dependencies limit applicability in the pure RLVR setting. We observe that conditioning the model on its own verified trajectories induces a measurable per-token KL divergence between the original and conditioned distributions, and prove that distilling from a self-teacher constructed by verified trajectories leads to infeasible weighted-average solutions when multiple verified trajectories exist. We propose SC-GRPO (Self-Conditioned GRPO), which uses KL divergence mentioned before as a multiplicative weight on GRPO gradients. Across five benchmarks spanning math, code, and agentic tasks, SC-GRPO consistently outperforms 8.1% over GRPO and 5.9% over DAPO with stronger OOD performance. Moreover, SC-GRPO achieves higher performance than OPD.

13.
Nature (Science) 2026-06-22

C-glycoside synthesis via radical cross-coupling of glycohydrazides

作者:

Carbohydrates are among the most abundant and structurally diverse biomolecules in nature, playing central roles in energy storage, molecular recognition, and cell signaling. Within this domain, C-glycosides1-3, in which the oxygen atom of the glycosidic bond in O-glycosides is replaced by carbon, have emerged as valuable motifs in medicinal chemistry due to their resistance to enzymatic hydrolysis2,4. Of particular importance are C-aryl glycosides, exemplified by the SGLT2 inhibitors dapagliflozin, canagliflozin, and empagliflozin, which are frontline therapies for type 2 diabetes5-7. However, scalable syntheses of C-aryl glycosides have traditionally relied on protected sugar derivatives, lengthy sequences, or conventional cross-couplings that often suffer from poor selectivity, limited scope, and extensive protecting-group manipulation6. Herein, we report a practical approach to C-aryl glycosides using glycosyl sulfonyl hydrazides as redox-neutral radical precursors for cross-coupling. Prepared directly from unprotected native sugars, these reagents generate glycosyl radicals under mild conditions and enable efficient access to diverse C-aryl glycosides, including all approved SGLT2 inhibitors, natural products such as salmochelins and neopetrosins, and medicinally relevant probes. Beyond anomeric functionalization, this platform enables C–C bond formation at multiple positions on carbohydrate scaffolds and supports stereoretentive radical coupling that can override inherent stereochemical biases, expanding practical access to carbohydrate-derived therapeutics and chemical tools.

14.
arXiv (CS.LG) 2026-06-18

Everywhere Valid Bounds on False Discovery Proportions in Conformal Inference

arXiv:2605.20726v2 Announce Type: replace-cross Abstract: Modern applications of conformal inference to multiple testing problems, such as outlier detection and candidate selection, often involve selecting test samples whose conformal p-values fall below a threshold. The quality of such methods is often measured by the false discovery proportion (FDP), defined as the fraction of incorrect selections. Existing approaches typically control the expected value of the FDP, using methods such as the Benjamini-Hochberg procedure. This approach fails to provide high-probability bounds on the realized false discovery proportion and invalidates statistical guarantees if the rejection threshold is selected after inspecting the data. This paper establishes finite-sample, distribution-free upper bounds on the FDP that hold simultaneously over all possible rejection thresholds, enabling arbitrary post hoc selection of the threshold. Simultaneous validity is achieved by constructing a high-probability envelope for the empirical distribution function of null conformal p-values by sampling from their joint distribution. Furthermore, our framework allows practitioners to modulate the envelope's shape, thereby producing tight bounds in rejection regions of primary interest. We use this flexible approach to derive simultaneous FDP upper bounds for both outlier detection and conformal selection. We demonstrate through synthetic and real-data experiments that the resulting bounds are both valid and substantially less conservative than those derived from existing approaches.

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

UI2Code^N: UI-to-Code Generation as Interactive Visual Optimization

UI-to-code aims to translate UI screenshots into executable front-end code. Despite progress with vision-language models (VLMs), most existing methods formulate UI-to-code as a single-pass generation, which mismatches real-world UI development that is inherently iterative and feedback-driven. We reformulate UI-to-code as an interactive visual optimization problem, where code generation is embedded in a closed-loop process of execution, visual inspection, and iterative refinement driven by rendered visual feedback. To address the non-differentiability of visual objectives and the noise of absolute visual evaluators, we propose Relative Visual Policy Optimization (RVPO), a preference-based reinforcement learning method that optimizes relative visual rankings among rendered candidates under execution feedback. We instantiate this paradigm in UI2Code^N, an open-source 9B model trained via continual pre-training, supervised fine-tuning, and reinforcement learning. Experiments demonstrate state-of-the-art performance on UI drafting, UI polishing, and UI editing benchmarks, even outperforming larger models, with performance consistently improving through iterative visual optimization. Our code and models are available at https://github.com/zai-org/UI2Code_N.

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

Independent-Component-Based Encoding Models of Brain Activity During Story Comprehension

Encoding models provide a powerful framework for linking continuous stimulus features to neural activity; however, traditional voxelwise approaches are limited by measurement noise, inter-subject variability, and redundancy arising from spatially correlated voxels encoding overlapping neural signals. Here, we propose an independent component (IC)-based encoding framework that dissociates stimulus-driven and noise-driven signals in fMRI data. We decompose continuous fMRI data from naturalistic story listening into ICs using one subset of the data, and train encoding models on independent data to predict IC time series from large language model representations of linguistic input. Across subjects, a subset of ICs exhibited consistently high predictivity. These ICs were spatially and temporally consistent across subjects and included cognitive networks known to respond during story listening (auditory and language). Auditory component time series were strongly correlated with acoustic stimulus features, highlighting the interpretability of identified component time series. Components identified as noise or motion-related artifacts by ICA-AROMA showed uniformly poor predictive performance, confirming that highly predicted components reflect genuine stimulus-related neural signals rather than confounds. Overall, IC-based encoding models enable analyses at the level of functional networks, accommodating the variability in network locations across individuals and providing interpretable results that are easy to compare across subjects. Code provided at: https://github.com/kamyahari/IC-Encoding-Models.git

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

ForecastBench-Sim: A Simulated-World Forecasting Benchmark

Forecasting benchmarks for general-purpose AI systems usually inherit the constraints of the real world: outcomes resolve slowly, tail events are rare, and counterfactual questions are difficult to score. We introduce ForecastBench-Sim, a simulated-world forecasting benchmark built on game rollouts from Freeciv, a turn-based strategy game modelled on the Civilization series. Forecasters receive a fixed world report (a structured snapshot of the current game state) and answer questions about hidden future states; the benchmark then continues the simulation and scores forecasts. Because the world is simulated, the same setup can generate continuous or binary forecasting questions at arbitrary time horizons, paired intervention worlds for conditional or causal questions, and resolved examples of rare or disruptive outcomes. We describe the benchmark pipeline, question families, scoring protocol, and release artifacts, and report validation slices from model evaluations and an anonymized human pilot. ForecastBench-Sim is intended to complement real-world forecasting benchmarks by providing controlled, immediately resolvable tasks for studying probabilistic reasoning under dynamic world states.

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

A Text Recognition Dataset from Sahidic Coptic Ancient Manuscripts

In this work, we target Handwritten Text Recognition (HTR) in low-resource scenarios, which arise from underrepresented languages, rare scripts, and degraded visual conditions typical of historical documents. We introduce SCAM (Sahidic Coptic Ancient Manuscripts), a new line-level dataset built from digitized ancient manuscripts written in the extinct Sahidic Coptic dialect. The dataset reflects a realistic and challenging setting, as it combines heterogeneous acquisition conditions across libraries with typical manuscript degradations such as ink fading, bleed-through, and material deterioration. In addition to visual complexity, SCAM poses significant linguistic challenges due to the scarcity of resources for Sahidic Coptic, its uncommon alphabet, and dialect-specific diacritics. To support research in low-resource HTR, we benchmark several state-of-the-art approaches based on different paradigms, highlighting their limitations and strengths in this setting. Our results underline the gap between current HTR performance on well-resourced modern scripts and historically grounded, low-resource scenarios, thus providing a reference point for future developments.

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

Scaling Laws of Global Weather Models

arXiv:2602.22962v2 Announce Type: replace Abstract: Data-driven models are revolutionizing weather forecasting. To optimize training efficiency and model performance, this paper analyzes empirical scaling laws within this domain. We investigate the relationship between model performance (validation loss) and three key factors: model size ($N$), dataset size ($D$), and compute budget ($C$). Across a range of models, we find that Aurora exhibits the strongest data-scaling behavior: increasing the training dataset by 10x reduces validation loss by up to 3.2x. GraphCast demonstrates the highest parameter efficiency, yet suffers from limited hardware utilization. Our compute-optimal analysis indicates that, under fixed compute budgets, allocating resources to more total training data yields greater performance gains than increasing model size. Furthermore, we analyze model shape and uncover scaling behaviors that differ fundamentally from those observed in language models: weather forecasting models consistently favor increased width over depth. These findings suggest that future weather models should prioritize wider architectures and larger effective training datasets to maximize predictive performance.

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

G-Long: Graph-Enhanced Memory Management for Efficient Long-Term Dialogue Agents

While Large Language Models (LLMs) have advanced open-domain dialogue systems, maintaining long-term consistency remains a challenge due to inherent limitations in long-context reasoning and the inefficiency of processing extensive raw text. Existing approaches typically rely on either unstructured memory storage, which is prone to information loss, or computationally expensive LLMs that incur high latency. To address these limitations, we propose G-Long, a graph-enhanced framework that utilizes a fine-tuned small Language Model (sLM) for structured triplet extraction and associative retrieval, significantly reducing operational costs. Furthermore, we introduce the novel attention-aware importance scoring mechanism that leverages the intrinsic cross-attention signals of a T5 summarizer to identify salient memories. Extensive experiments across diverse benchmarks demonstrate that G-Long achieves state-of-the-art performance in both response generation and memory retrieval, yielding performance gains of up to 9.8% in response quality on MSC and 40.8% in retrieval recall on LME, while significantly minimizing computational overhead.

21.
medRxiv (Medicine) 2026-06-15

Validating Field-Feasible Measures of Recent Khat Use: A Diagnostic Accuracy Study Comparing Amphetamine Immunoassay and Assisted Self-Report Against HPLC in an Ethiopian Male Cohort

Background: Khat (Catha edulis) is a widely consumed natural amphetamine-analog used across East Africa and the Arabian Peninsula. Accurate field-feasible measurement of recent khat use is a prerequisite for large-scale epidemiological research; yet no validated alternatives to laboratory reference methods have been identified in the scientific literature. This nested validation study evaluated the diagnostic accuracy of two point-of-care measures, a commercial amphetamine immunoassay and a Timeline Followback (TLFB) Assisted Self-Report (ASR), against high-performance liquid chromatography (HPLC) quantification of urinary norephedrine (NE), while additionally assessing agreement between the two field measures. Methods: A prospective, random sub-sample of 119 male participants aged 18-40 years from the Gilgel Gibe Field Research Center (GGFRC) longitudinal cohort, Ethiopia (validation timepoint T2, 2015), was used. Three index-reference comparisons were conducted: (1) amphetamine immunoassay (nal von minden, Drug-Screen AMP test, 300 ng/mL cutoff) vs. HPLC; (2) binary ASR (past-week use) vs. HPLC; and (3) binary ASR vs. immunoassay. Sensitivity (positive percent agreement, PPA), specificity (negative percent agreement, NPA), positive predictive value (PPV), negative predictive value (NPV), overall accuracy (overall percent agreement, OPA), and Cohen's kappa were calculated with 95% confidence intervals. Pre-specified secondary analyses applied three pharmacokinetically-informed recall windows (0-2, 3-5, and 6-7 days prior to interview) to ASR. Results: Against HPLC (77 positive, 42 negative), the immunoassay showed perfect specificity (1.0 [0.916-1.0]) and PPV (1.0 [0.91-1.0]) but low sensitivity (0.52 [0.40-0.64]), NPV (0.53 [0.42-0.65]), overall accuracy (0.69 [0.60-0.77]), and weak kappa (0.43 [0.34-0.52]). Binary ASR showed high sensitivity (0.96 [0.89-0.99]), specificity of 0.60 [0.433-0.74], PPV (0.81 [0.72-0.89]), NPV (0.89 [0.72-0.98]), with overall accuracy 0.83 [0.75-0.89] and moderate kappa (0.60 [0.51,0.69]). Restricting ASR to use within 0-2 days improved specificity to 0.69 [0.52-0.84], PPV to 0.86 [0.77-0.93], overall accuracy to 0.87 [0.79-0.93], and kappa to 0.69 [0.61-0.78] (moderate), while sensitivity (0.96 [0.89-0.99]) and NPV (0.89 [0.72-0.98]) remained stable. Against the immunoassay, ASR achieved high PPA of (1.0 [0.91-1.0]), NPA of 0.35 [0.25-0.47], OPA of 0.57 [0.48-0.66], and minimal kappa (0.27 [0.19-0.35]). Conclusions: Time-stratified ASR (0-2 days) is a valid, scalable alternative to biological testing for recent khat use in resource-limited settings. The immunoassay's 300 ng/mL cutoff functions as a marker of heavy or recent high-dose khat use rather than any-use detection. Its perfect specificity and PPV make it valuable as a confirmatory test for substantial exposure, while its lower sensitivity reflects calibration to amphetamine rather than to khat-derived cathinone metabolite. Keywords: khat; Catha edulis; diagnostic accuracy; STARD; self-report; immunoassay; HPLC; Ethiopia; substance use measurement

22.
arXiv (CS.CV) 2026-06-19

Scaling Self-Play for End-to-End Driving

End-to-end autonomous driving models are typically trained on offline human-demonstration datasets that provide limited state coverage and often no closed-loop feedback, making them prone to compounding errors when deployed in closed-loop and brittle to long-tail agent interactions. To overcome these limitations, we propose an alternative strategy for training end-to-end driving models: large-scale self-play directly from pixels in simulation. While prior self-play approaches have shown promising transfer to real-world driving, they typically assume vectorized Bird's-Eye-View (BEV) observations that are incompatible with end-to-end policies operating directly on sensor observations. To this end, we introduce Gigapixel, a high-throughput batched driving simulator with perspective rendering, enabling scalable self-play directly from pixel observations. Rather than targeting compute-costly photorealistic sensor simulation, Gigapixel renders a simplified bounding-box world that preserves essential scene structure while achieving throughput at 50k agent steps per second. Since direct pixel-space self-play RL is prohibitively sample-inefficient at end-to-end model scale, we propose self-play DAgger training: we train pixel-based policies in self-play via on-policy distillation from a privileged RL teacher. To bridge the sim-to-real gap, we subsequently transfer the self-play trained policies to real-world sensor data through lightweight perception adaptation. Policies trained in Gigapixel and adapted to real-world sensor data achieve competitive performance on the HUGSIM and NAVSIM-v2 benchmarks without human trajectory supervision. Moreover, scaling self-play training yields proportional gains in policy performance, establishing self-play as a practical and scalable strategy for training end-to-end models.

23.
bioRxiv (Bioinfo) 2026-06-20

Seed variation impacts clustering stability in Single-Cell RNA-Seq and can be mitigated by StAbility-BasEd-Reassignment (SABER)

Single-cell RNA-seq clustering is commonly treated as reproducible once a random seed is fixed, yet the choice of seed itself may alter cell assignments and downstream interpretation. We systematically quantified seed-induced clustering variability by running Louvain and Leiden clustering across 100 seeds in Seurat and Scanpy on 28 single-cell RNA-seq datasets from the Human Cell Atlas and IMMUcan. Using Element-Centric Consistency, we found that seed choice affected a substantial fraction of cells, with Scanpy showing more unstable assignments than Seurat on average, 40.46% versus 26.78% unstable cells, respectively. This increased stability came at a marked computational cost: Seurat required approximately 19-fold higher median memory than Scanpy. Seed-dependent clustering variability also propagated to cell-type annotation, particularly among transcriptionally related populations including macrophage/monocyte, endothelial/epithelial and T/NK cell states. To mitigate this instability, we developed StAbility-BasEd Reassignment (SABER), a Scanpy-based framework that identifies seed-sensitive cells across repeated clusterings and reassigns them to stable cluster cores using cosine similarity. SABER improved clustering quality while preserving annotation concordance and reduced median memory usage 3.5-fold compared with Seurat-Louvain. Our results identify seed choice as an underappreciated source of variability in single-cell analysis and provide a scalable strategy to improve clustering robustness.

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

Mem-World: Memory-Augmented Action-Conditioned World Models for Persistent Robot Manipulation

Action-conditioned world models have emerged as a promising paradigm for robot learning, offering a scalable alternative to costly real-world experimentation by generating action-consistent video rollouts. However, persistent world modeling remains challenging in manipulation: frequent end-effector occlusions and rapid wrist-camera motion make the current observation insufficient for predicting future views, causing models to forget or hallucinate scene details seen in earlier frames. Existing memory retrieval strategies often fail to identify informative history in dynamic manipulation scenarios. To address this limitation, we propose Mem-World, a memory-augmented multi-view action-conditioned world model. At its core, we present W-VMem, a 4D wrist-view-centered surfel-indexed memory that anchors historical observations to temporally evolving surface elements. By explicitly modeling when and where scene elements are observed, W-VMem enables geometry-aware retrieval of relevant history frames conditioned on future actions. During generation, relevant history frames are selected via surfel-based rendering and scoring, providing informative and non-redundant context for prediction. Extensive experiments show that Mem-World generates persistent rollouts in complex manipulation scenarios, enables more reliable policy evaluation than Ctrl-World, improving the Pearson correlation with real-world performance by 14.5\%, and supports effective policy improvement through synthetic data generation, increasing success rates from 58\% to 72\% on long-horizon tasks.