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01.
arXiv (CS.AI) 2026-06-19

Variable-Length Tokenization via Learnable Global Merging for Diffusion Transformers

arXiv:2606.20076v1 Announce Type: cross Abstract: Latent Diffusion Models (LDMs) have become dominant in visual synthesis, but their quality-compute trade-off is largely constrained by the tokenizer's fixed compression ratio. Variable-length tokenizers (VLTs) promise adaptive compression by varying token counts, allowing diffusion models to flexibly balance quality and compute. However, conventional VLTs modulate length by truncating ordered token sequences, which makes token semantics depend on token position and breaks representational alignment across lengths. This leads to a cross-length shift in the latent distribution that hinders a single variable-length diffusion model from operating effectively. To address this, we propose a novel variable-length tokenizer that modulates length by merging tokens. We show that encouraging similar tokens to merge enables direct cross-length representation alignment when the diffusion transformer operates according to the merging pattern. Since conventional merging methods are data-dependent, making the merging pattern inaccessible during generation, we introduce learnable global merging, which is data-independent, to ensure compatibility with diffusion transformers. On ImageNet 256$\times$256 generation, our merging-based variable-length tokenizer integrated with a diffusion transformer achieves a superior gFID-compute trade-off compared to prior VLT methods. Code is available at [this https URL](https://github.com/movinghoon/lgm)

02.
arXiv (CS.AI) 2026-06-15

LEPO: Latent Reasoning Policy Optimization for Large Language Models

arXiv:2604.17892v4 Announce Type: replace-cross Abstract: Recently, latent reasoning has been introduced into large language models (LLMs) to leverage rich information within a continuous space. However, without stochastic sampling, these methods inevitably collapse to deterministic inference, failing to discover diverse reasoning paths. To bridge the gap, we inject controllable stochasticity into latent reasoning via Gumbel-Softmax, restoring LLMs' exploratory capacity and enhancing their compatibility with Reinforcement Learning (RL). Building on this, we propose \underline{L}atent R\underline{e}asoning \underline{P}olicy \underline{O}ptimization~(LEPO), a novel framework that applies RL directly to continuous latent representations. Specifically, in rollout stage, LEPO maintains stochasticity to enable diverse trajectory sampling, while in optimization stage, LEPO constructs a unified gradient estimation for both latent representations and discrete tokens. Extensive experiments show that LEPO significantly outperforms existing RL methods for discrete and latent reasoning.

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

Mapping Geopolitical Bias in 11 Large Language Models: A Bilingual, Dual-Framing Analysis of U.S.-China Tensions

Large language models are how hundreds of millions of people now encounter contested political questions, raising a subtle measurement problem: a model that simply agrees with whatever it is told can masquerade as biased, contaminating any claim that models hold political opinions. We address this by importing balanced keying from survey psychometrics, posing each proposition and its swapped reverse and signing the response so acquiescence cancels and genuine conviction accumulates. The result is a reproducible, quantitative instrument that maps geopolitical stance across 11 models and 2 languages (19,712 responses). Developer origin, query language and issue domain emerge as three near-equal, additive factors; every model, including those built in the United States, leans more Pro-China in Mandarin; and two models with identical agreement bias are told apart, one neutral, one biased. We release it as an open, interactive tool that extends to any contested-opinion domain.

04.
PLOS Computational Biology 2026-06-01

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

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

05.
arXiv (CS.CV) 2026-06-19

VideoSketcher: Sequential Sketch Generation Using Video Model Priors

Sketching is inherently sequential: strokes are drawn progressively to explore and refine ideas. Yet most generative approaches treat sketches as static images, ignoring the temporal process underlying creative exploration. Modeling this sequential structure remains challenging: prior methods either rely on large-scale human-drawn datasets with limited diversity, or use large language models (LLMs) to produce drawing instructions, often at the cost of visual fidelity. We present VideoSketcher, a method for generating high-quality sketching processes by adapting pretrained text-to-video diffusion models to the sparse, continuous nature of sketch formation. Our key insight is that LLMs and video diffusion models offer complementary strengths: LLMs act as semantic planners that decompose concepts into step-by-step instructions, while video diffusion models serve as powerful "renderers" that translate them into temporally coherent sketch sequences. We introduce a two-stage fine-tuning strategy that decouples temporal structure from visual appearance: stroke ordering is learned from synthetic shape compositions, while style is distilled from as few as seven hand-drawn examples. Despite minimal supervision, our method can generate diverse, high-quality sequential sketches that faithfully follow specified drawing orders. Our framework naturally extends to brush style control and autoregressive generation, supporting artistic applications.

06.
bioRxiv (Bioinfo) 2026-06-11

A multi-agent system for spine MRI report generation from multi-sequence imaging

Spinal pathology is a leading cause of pain and disability worldwide. Spine magnetic resonance imaging (MRI) is central to clinical evaluation, yet its interpretation remains complex and time-consuming, requiring integration of information across multiple imaging sequences and anatomical regions. Despite recent advances in automated MRI analysis, effectively combining multi-sequence data while preserving sequence-specific diagnostic information remains an open challenge. Here we present SpineAgent, a multi-agent framework for spine MRI report generation built upon a multi-sequence foundation model trained on routine clinical data from 32,047 patients and 453,683 MRI series, comprising a total of 13,441,191 MRI slices. To accommodate diverse modalities of sequences, we first pre-train two DINOv3-based encoders separately on T1- and T2-weighted sequences. We then introduce a continual training strategy that learns a synthesizer to embed images of other sequences using the T1 and T2 encoders, producing patient-level embedding that integrates various signals across MRI sequences. Using these embeddings, SpineAgent achieves state-of-the-art performance, with mean 10.8% AUROC improvement across 17 spinal condition-prediction tasks compared to the best competing method, and demonstrates strong generalizability under cross-manufacturer and cross-cohort evaluation. Beyond classification, SpineAgent enables pathology localization by identifying findings-relevant slices and segmenting pathological regions. It also supports multimodal image-report retrieval, providing a solid foundation for scalable and explainable MRI report generation. We further integrate these validated capabilities of SpineAgent into 37 specialized agents for condition diagnosis, pathological-region localization, and clinically-similar-cases retrieval. Finally, we incorporate their outputs as structured tokens within a Medical Report Agent trained end-to-end for report generation. Through both automated metrics and expert evaluation by five radiologists, SpineAgent achieves leading performance in spine MRI report generation. Together, SpineAgent introduces a continual training approach for multi-sequence spine MRI understanding. By decomposing report generation into clinically grounded subtasks addressed by specialized agents, the SpineAgent framework enables accurate, interpretable and generalizable spine MRI reporting across diverse imaging sequences and anatomical regions.

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

Beyond Accuracy: Measuring Logical Compliance of Predictive Models

arXiv:2606.20208v1 Announce Type: new Abstract: Machine learning models are predominantly evaluated through predictive performance metrics such as ranking quality, prediction error, or classification accuracy. While these metrics effectively quantify how closely predictions match the ground truth, they do not assess whether model outputs respect predefined logical or domain-specific constraints. In high-stakes applications, including healthcare, finance, and autonomous systems, logical consistency can be as critical as predictive accuracy, yet no standard metric captures this dimension. We introduce the Rule Violation Score (RVS), a complementary evaluation metric that quantifies the extent to which a predictive model respects a given set of logical rules, independently of predictive accuracy. RVS treats hard rules (strict constraints) and soft rules (statistical regularities) differently, can be evaluated on any dataset and on any predictive model expressed over a relational vocabulary, and can be computed using SQL queries that are automatically generated for Horn rules. Beyond evaluating models, RVS can also evaluate the logical consistency of training datasets and help identify poorly defined rules. We evaluate RVS on three benchmarks covering knowledge graph link prediction and relational regression, including rule-based, embedding-based, and neuro-symbolic predictive models. Our results demonstrate that two models achieving comparable predictive accuracy can exhibit substantially different levels of logical compliance, revealing differences in model behavior that standard metrics fail to capture.

08.
arXiv (quant-ph) 2026-06-15

Fourier analysis of quantum neural network with non-linear data embedding

arXiv:2606.14206v1 Announce Type: new Abstract: Fourier analysis has become a crucial tool for understanding the expressivity of Variational Quantum Circuit (VQC) models, as well as an important indicator of barren plateaus (BP). While existing literature has only studied angle-embedded VQCs in a noiseless environment, here we develop the Fourier analysis of VQCs with non-linear data embedding, with particular focus on amplitude embedding, which provides a naturally compact encoding scheme. We first investigate a subtle difference in the domain of input features within amplitude embedding that leads to a distinct expressivity of the zero-frequency Fourier coefficient. By assuming that the ensemble of unitaries generated from the parameter space forms at least a 2-design with respect to the unitary group, we derive, via Weingarten calculus, that the mean of the Fourier coefficients is concentrated at zero, and the variance scales at an exponentially decaying order with respect to the multi-dimensional frequency magnitude. When a noise channel with unitary Kraus operators and probabilities $\{p_k\}$ is taken into account, the variance is further suppressed by a factor $\left(\sum_k p_k^2\right)^{Q}

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

Visual Generation in the New Era: An Evolution from Atomic Mapping to Agentic World Modeling

Recent visual generation models have made major progress in photorealism, typography, instruction following, and interactive editing, yet they still struggle with spatial reasoning, persistent state, long-horizon consistency, and causal understanding. We argue that the field should move beyond appearance synthesis toward intelligent visual generation: plausible visuals grounded in structure, dynamics, domain knowledge, and causal relations. To frame this shift, we introduce a five-level taxonomy: Atomic Generation, Conditional Generation, In-Context Generation, Agentic Generation, and World-Modeling Generation, progressing from passive renderers to interactive, agentic, world-aware generators. We analyze key technical drivers, including flow matching, unified understanding-and-generation models, improved visual representations, post-training, reward modeling, data curation, synthetic data distillation, and sampling acceleration. We further show that current evaluations often overestimate progress by emphasizing perceptual quality while missing structural, temporal, and causal failures. By combining benchmark review, in-the-wild stress tests, and expert-constrained case studies, this roadmap offers a capability-centered lens for understanding, evaluating, and advancing the next generation of intelligent visual generation systems.

10.
arXiv (CS.LG) 2026-06-19

Full-Self Diagnostics (FSD): Physics-Grounded Visual Biomarker Inference from Smartphone Video via Inverse Problems and Operator Learning

arXiv:2606.19372v1 Announce Type: cross Abstract: We present Full-Self Diagnostics (FSD), a unified mathematical framework for recovering latent physiological states from unconstrained 9-second facial videos captured by consumer smartphones. The approach integrates five mutually reinforcing components: (1) a physics-based forward model derived from the radiative transfer equation and chromophore absorption that maps camera observables to biomarker concentrations; (2) an information-theoretic observability theory proving that multi-channel visual signals (spectral, pulse, respiratory, micro-expression, and oculomotor) contain strictly increasing mutual information with physiological state; (3) a stable, Tikhonov-regularized inverse problem with domain-uniform identifiability guarantees; (4) an operator-learning formulation that enables generalization across devices, resolutions, and populations; and (5) a supervised learning procedure, interpretable as stochastic variational inference, that continuously refines the model from paired biosensor ground truth with performance improving proportionally to one over the square root of the number of paired observations. Empirical validation on 38812 real-world paired scans across 59 subjects demonstrates practical performance. Self-collected data from the lead author (glucose range 35-550 mg/dL) yields MARD of 29.86 percent with 97.57 percent of predictions in Clarke Error Grid Zones A+B and only 0.27 percent in the dangerous Zone E. A well-managed diabetic participant achieves MARD of 17 percent in the narrower 70-180 mg/dL band. These results confirm that consumer-grade facial video encodes sufficient structured information for clinically relevant, non-invasive biomarker inference under fully unconstrained conditions, with performance scaling predictably as more paired data becomes available.

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

Diffusion Language Models: An Experimental Analysis

Large Language Models (LLMs) have revolutionized language modeling through autoregressive generation, enabling strong performance across a wide range of tasks. Recently, Diffusion Language Models (DLMs) have emerged as an alternative paradigm that generates text through iterative denoising rather than next-token prediction, allowing parallel refinement of entire sequences. While numerous diffusion-based architectures have been proposed, differences in evaluation protocols, datasets, inference budgets, and generation hyperparameters make it difficult to compare their capabilities and understand the trade-offs they offer. In this work, we present a systematic experimental analysis of modern DLMs. Specifically, we evaluate eight state-of-the-art DLMs across eight benchmarks spanning reasoning, coding, translation, knowledge, and structured problem solving, while explicitly considering both generation quality and computational efficiency. Beyond downstream evaluation, we analyze the impact of key inference-time factors, including denoising steps, context length, block size, and parallel unmasking strategies, and complement large-scale experiments with controlled comparisons of smaller models trained under identical conditions. Our analysis highlights the strengths and limitations of diffusion-based language modeling across different tasks, architectures, and inference budgets. We show that the behavior of DLMs is strongly influenced by generation-time design choices, leading to distinct trade-offs between performance and computational efficiency. Overall, our study provides practical insights into the capabilities and deployment characteristics of contemporary DLMs.

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

Spectral Adaptive Conformal Prediction for Structured Non-Exchangeable Data

arXiv:2606.15950v1 Announce Type: cross Abstract: Conformal prediction gives prediction intervals with finite-sample coverage when the data are exchangeable. Many time-indexed datasets are not exchangeable. They have seasons, recurring regimes, changing frequencies, or other forms of structured dependence. This paper studies a simple way to use that structure. We propose spectral adaptive conformal prediction, a method that forms weighted conformal quantiles using local spectral similarity and then updates the target miscoverage level online. The spectral weights choose calibration residuals that look relevant to the current test point. The adaptive update corrects the long-run miss rate when uncertainty changes over time. We give an approximate coverage result for the fixed spectral weighted quantile and a deterministic long-run calibration result for the adaptive update. Simulations with recurring regimes and slowly changing frequencies, together with three U.S. real-data examples, show that the hybrid method can improve on fixed spectral weighting, while also showing that spectral weighting must be monitored through effective sample size diagnostics.

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

DynamicPTQ: Mitigating Activation Quantization Collapse via Residual-Stream Dynamics

arXiv:2606.12487v1 Announce Type: new Abstract: Post-training quantization (PTQ) is essential for efficient large language model inference, but reliably quantizing activations remains challenging when weights, activations, and KV caches are all quantized to 4-bit precision. A key difficulty lies in massive activations, whose extreme values dominate the activation range and amplify quantization errors. State-of-the-art methods mainly mitigate massive activations through transformation-based smoothing, such as orthogonal rotations and affine scaling, but overlook the cross-layer dynamics of the residual stream. In this paper, we show that massive activations emerge and disappear in a phase-wise pattern across network depth, triggering large residual changes. These changes cause newly injected layer-wise updates to dominate the 4-bit quantization scale and weaken historical residual information. To characterize this behavior, we introduce Jump Ratio and Historical Feature SNR. This suggests that static transformation-based smoothing cannot fully resolve dynamic quantization instability caused by cross-layer residual changes. Based on this analysis, we propose DynamicPTQ, a Dynamic Post-Training Quantization policy for phase-aware mixed-precision activation quantization. DynamicPTQ identifies quantization-sensitive layers from residual-stream dynamics and assigns 8-bit activation precision only to these layers, while keeping weights, KV caches, and other activations in 4-bit precision. It can be directly integrated with strong PTQ baselines such as QuaRot, SpinQuant, and FlatQuant. Experiments on LLaMA-2 and LLaMA-3 show that DynamicPTQ consistently improves perplexity and zero-shot QA performance under W4A4KV4 quantization, while achieving 1.05 to 1.07 times throughput improvement with modest memory overhead. These results demonstrate a practical path toward robust low-bit LLM inference.

14.
arXiv (CS.AI) 2026-06-16

Early Diagnosis of Wasted Computation in Multi-Agent LLM Systems via Failure-Aware Observability

arXiv:2606.01365v2 Announce Type: replace Abstract: Failure-aware observability diagnoses wasted computation in multi-agent LLM systems before final-answer evaluation can explain what went wrong. We propose a trace-based framework for a three-agent architecture – orchestrator, search agent, and execution agent – that converts structured events into online signals for loops, budget pressure, low information gain, and tool instability, then adds offline semantic grounding metrics and selective LLM-as-judge evaluation. On 165 GAIA validation traces under identical caps, 98 runs produce usable final answers and 67 fail or stop without one. Among warned failed runs, 58.1% of tokens are spent after the first warning on average, indicating substantial opportunity for intervention. A 10-task Level-2 pilot uses warnings to diversify search or require evidence, reducing post-warning token fraction from 0.638 in the baseline to 0.304. The results support a layered design: cheap online signals help the orchestrator redirect or halt redundant behavior, while deeper semantic checks identify whether completed answers are grounded enough to trust.

15.
bioRxiv (Bioinfo) 2026-06-16

PhenoBIC: operator-free single-cell spatial phenotyping in multiplex imaging data using deep learning of cell staining patterns

Multiplex imaging is a valuable tool for spatially examining tissue microenvironments at the single-cell level to uncover biological and clinical insights. However, most multiplex image analysis workflows currently require manual intervention for cell phenotyping, which slows progress, demands human effort, and yields operator-dependent outputs. Here, we developed PhenoBIC, a pre-trained deep learning model for image classification of the multiplexed biomarker signals in a cell (Biomarker Imprint of a Cell) to classify cell phenotypes. We show that PhenoBIC (F1-score ~0.88) outperforms manual gating (widely used) and other machine learning-based computational approaches for cell marker expression classification. We validated this across multiple biomarkers, tissue sampling strategies (whole biopsies and tissue microarrays), multiplex panels, imaging platforms, and tissue types. We have released our in-house training and validation datasets of ~1.4 million manually curated cell expression ground truth labels. We have also open-sourced PhenoBIC and enabled its community-wide deployment via the QuPath interface.

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

FLaRA: Predicting Future Latent Representations for Accident Anticipation

Anticipating traffic accidents from dashcam videos is a critical challenge in intelligent transportation systems. Existing methods typically map visual context directly to a collision probability without explicitly modeling the future evolution of the driving scene. In this paper we propose FLaRA (Predicting Future Latent Representations for Accident Anticipation), a novel predictive architecture that shifts this paradigm by forecasting future latent representations for accident anticipation. Building upon the Video Joint-Embedding Predictive Architecture (V-JEPA2), our model conditions a predictor network on observed context frames to predict the forthcoming latent features of the scene. A classifier then operates on these predicted future representations rather than only on past observations. To ensure these forecasts remain grounded in realistic future dynamics, we introduce a joint training objective that simultaneously optimizes an auxiliary feature-level reconstruction loss and a cross-entropy classification loss. Extensive evaluations on the Nexar dataset, alongside cross-domain validations on the DAD, DADA-2000, and DoTA benchmarks, demonstrate that our approach achieves state-of-the-art performance while maintaining realistic early warning capabilities.

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

Integrable Massless and Massive Fermions

作者:

arXiv:2603.11172v2 Announce Type: replace-cross Abstract: One-dimensional integrable fermions can be classified into massless and massive regimes, and the $R$-operator for the latter can be constructed from that of the former. Here, I define integrable massless fermions by the simultaneous satisfaction of the Yang-Baxter equation (YBE) and Shastry's decorated YBE (DYBE) by the $R$-matrix. This notion is strictly more general than Maassarani's `free-fermion algebra', yet more restrictive than the notion of free fermions in exactly solvable quantum models or in integrable two-dimensional classical vertex models dual to quantum spin chains. Within this framework, there emerge two archetypal mechanisms for opening a spectral gap and generating massive fermions: (i) breaking time-reversal symmetry by coupling to external field, and (ii) introducing time-reversal symmetric interactions. These paradigms are realized, respectively, in the XY chain in a longitudinal field and in the Hubbard model, both of which possess non-relativistic, bivariate $R$-matrices. Integrability conditions on local Hamiltonians for both massless and massive fermions are identified, and schematic procedures for uniquely determining their $R$-matrices are proposed.

18.
medRxiv (Medicine) 2026-06-22

Biopsychosocial determinants of HPV vaccine perception in university students of both sexes in Cucuta, Colombia, 2024: a cross-sectional study

Colombia has been internationally recognised as a paradigmatic case of vaccine confidence crisis since the 2014 Carmen de Bolivar event, and national HPV vaccination coverage remains far below the World Health Organization 2030 target. Most published evidence focuses on female adolescents and on cervical cancer; the perception of the HPV vaccine in university-age populations of both sexes–and across the broader spectrum of HPV-attributable disease–remains comparatively understudied. We aimed to describe the influence of biopsychosocial determinants on HPV vaccine perception among university students of both sexes in Cucuta, Norte de Santander, Colombia. We conducted a cross-sectional study with a mixed quantitative-qualitative approach in 2024 among four universities (Universidad de Santander, Universidad Francisco de Paula Santander, Universidad de Pamplona and Universidad Libre; combined enrolment 21,033 students). Using convenience sampling stratified by institution, 750 actively enrolled undergraduate students of both sexes (18-60 years) completed a structured online questionnaire adapted from previously validated instruments. The instrument captured sociodemographic information, HPV knowledge and HPV vaccine perception. Data were analysed using Students t-test, one-way analysis of variance, Tukey post-hoc tests, effect sizes and 95% confidence intervals, with a 0.05 significance threshold. Of 750 respondents, 54.2% were women, 61.3% were under 20 years of age, and 75.1% attended public universities. HPV knowledge was high in 39.2%, intermediate in 42.4% and low in 18.4%; women and students aged 26 years or older displayed higher knowledge. Although 91.2% had heard of HPV and 82.5% knew that both sexes could acquire it, recognition of clinical manifestations and complications was uneven: cervical cancer 51.7%, penile cancer 30.5%, vaginal warts 45.9% and warts in the penis, larynx, anus or rectum 34.0%. Vaccine-specific knowledge was low in 77.1%, with men disproportionately represented (85.9% versus 69.5% in women). Overall positive perception of HPV vaccination was 66.6%, slightly higher in women (68.8%) than men (63.9%), in students aged 26 years or older (70.1%) and in students from private universities (68.1% versus 65.9%). Inferential analysis identified sex (Cohens d = -0.357), type of university (d = 0.189) and HPV knowledge (partial eta-squared = 0.096) as the only significant determinants. Age, socioeconomic stratum, age at sexual debut and vaccine-specific knowledge did not reach meaningful significance. HPV vaccine perception was predominantly positive but conditioned by three biopsychosocial determinants, with HPV knowledge as the primary driver. The persistent gender gap reflects historical anchoring of HPV messaging in cervical disease and female-targeted campaigns. Public-health strategies should adopt comprehensive, gender-inclusive educational interventions that explicitly visibilise non-cervical HPV-related cancers and address both sexes from a common evidence base.

19.
medRxiv (Medicine) 2026-06-18

AlphaGenome identifies a deep intronic variant in a family with PLA2G6-associated neurodegeneration: Closing the diagnostic gap in rare genetic diseases

A molecular diagnosis remains out of reach for a substantial subset of patients with clinically recognizable Mendelian disorders, even after comprehensive next-generation sequencing. Causal variants in non-coding regions are difficult to detect and interpret using standard pipelines. Deep intronic variants that disrupt splicing are a known but underexplored source of pathogenic alleles, and systematic tools to evaluate them at scale have only recently emerged. We aimed to resolve an incomplete genetic diagnosis in two siblings with early-onset parkinsonism, prominent neuropsychiatric features, and autonomic dysfunction consistent with PLA2G6-associated neurodegeneration (PLAN), an autosomal recessive condition. Prior clinical exome sequencing, genome sequencing, Multiplex Ligation-dependent Probe Amplification (MLPA), and long-read sequencing had identified only a single heterozygous PLA2G6 missense variant, c.2132C>G (p.Pro711Arg). We used AlphaGenome to score 91 non-coding variants shared among the affected siblings and their father within 1 megabase of the PLA2G6 locus. The deep-learning model identified an intronic variant (c.2034+355G>A) that was predicted to create a cryptic splice acceptor site that could result in inclusion of a 160-bp cryptic exon. Tissue-specific predictions indicated the aberrant splicing would be detectable in blood, confirmed by junction-spanning RNA-seq reads from an unrelated carrier. This analysis completed a compound heterozygous PLAN diagnosis nearly two decades after symptom onset and demonstrates the utility of sequence-to-function models. Systematic integration of tools like AlphaGenome into rare disease workflows offers a practical, low-barrier route to closing the diagnostic gap for patients with compelling Mendelian phenotypes and incomplete genetic diagnoses.

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

Beyond Problem Solving: UOJ-Bench for Evaluating Code Generation, Hacking, and Repair in Competitive Programming

arXiv:2606.12864v1 Announce Type: cross Abstract: Despite strong performance in competitive programming, the role of Large Language Models (LLMs) in supporting human learning in the same setting remains largely unexplored. In this work, we introduce UOJ-Bench, a benchmark designed to evaluate not only the problem-solving ability of LLMs, but also their ability to identify errors in human-written code – a crucial educational activity traditionally supported by running test cases over online judge systems. UOJ-Bench consists of three distinct tasks: code generation, code hacking, and code repair, all constructed from real-world code submissions on the Universal Online Judge (UOJ) and evaluated through UOJ's native judging infrastructure. Our results show that under one-shot evaluation, even the strongest models fail to identify errors in more than 50% of a set of submissions that have been found to be incorrect by UOJ users. While test-time scaling improves success rates to above 90%, the substantial computational costs incurred from model inference limit its practicality for large-scale deployment. Despite these limitations, we find that the best-performing models under test-time scaling can uncover errors in over 5% of full-score submissions across roughly 30 problems, suggesting that frontier LLMs can already provide complementary signals beyond standard judging systems.

21.
arXiv (quant-ph) 2026-06-12

A Quantum Algorithm for Random Number Generation

arXiv:2606.13034v1 Announce Type: new Abstract: We present a quantum algorithm for random number generation that achieves a provable quadratic speedup over classical Markov chain mixing, building on the Diaconis-Shahshahani Fourier analysis of the top-to-random card shuffle. The algorithm integrates three quantum primitives into a unified mixing circuit: the Quantum Fourier Transform (QFT), which diagonalizes the Markov transition operator; controlled phase rotations, which encode the shuffle eigenvalue spectrum; and the Grover diffusion operator, which acts as a quantum analogue of the Aldous-Diaconis strong uniform stopping time by reflecting amplitudes about their mean at each iteration. For an n-qubit register, the mixing time is O(\sqrt{n \log n}) iterations. Extending to m qudits of local dimension d reduces this to O(\sqrt{\log_d N}) iterations, where N = d^m, compared to the classical O(n \log n) bound. The qudit formulation further reduces QFT circuit depth from O(\log^2 N) to O(\log_d^2 N) gates per layer by encoding the same N-state space using m = \log_d N subsystems instead of \log_2 N qubits. We validate both variants on IBM superconducting hardware.

22.
PLOS Computational Biology 2026-06-12

Ten simple rules for executing an inherited research plan in computational biology

by Sahar Javaheri Tehrani, Toni Ingolf Gossmann Trainees in computational biology frequently inherit research plans whose aims, datasets, analytical strategies, and technical constraints were defined before their arrival. These plans often emerge from grants, collaborations, legacy codebases, shared high-performance computing environments, or partially completed analyses. While such plans provide a useful scaffold, they rarely specify all implementation details, prior assumptions, evaluation criteria, or dependencies needed for reliable execution. The transition from inheriting a partially articulated plan to producing reproducible results therefore creates an execution gap: a phase in which trainees must reconstruct what the project is, which elements are fixed, which remain negotiable, and which technical or organizational assumptions need to be tested before full-scale analysis begins. In this Ten Simple Rules article, we provide a practice-oriented framework for stabilizing inherited computational biology projects before workflows, benchmarks, and decision paths become entrenched. We do not claim that the individual practices described here are novel in isolation. Rather, our contribution is to organize familiar practices into a sequenced framework for a recurrent but under-articulated phase of computational research: inherited-plan execution. Computational biology makes this phase especially important because projects often combine heterogeneous datasets, fragile software environments, undocumented preprocessing choices, benchmarking assumptions, distributed collaborators, and asymmetrical access to contextual knowledge. By making this transition visible and operational, the rules aim to help trainees, supervisors, and collaborators reduce ambiguity, test feasibility, document decisions, and support reproducible and equitable project execution under real-world constraints.

23.
arXiv (CS.LG) 2026-06-11

Apertus LLM Family Expansion via Distillation and Quantization

arXiv:2605.29128v2 Announce Type: replace Abstract: The wide adoption of LLMs has led to their use in great variety of applications and scenarios, such as chatbot assistants and data annotation, creating the need for the models to satisfy certain budget and hardware constraints. This has led to the trend of LLMs being released in batches consisting of similar models of various sizes for the family of models to adhere to as wide of a range of constraints as possible. In this paper, we validate distillation and quantization as a cost-effective way to expand model families to new sizes and hardware formats. Based on the open-recipe Apertus 8B LLM, we produce Apertus-v1.1 - a distilled family of models with up to 4B parameters trained on 1.7T permissive license tokens. We demonstrate cost-efficiency and strong accuracy performance of our approach for covering large ranges of hardware and systems requirements.

24.
arXiv (CS.LG) 2026-06-16

Scalable and Interpretable Representation Alignment with Ordinal Similarity

arXiv:2606.16379v1 Announce Type: new Abstract: Evaluating representation similarity is fundamental to representation learning. However, existing metrics suffer from significant limitations: they lack interpretability due to shifting baselines, lack robustness to outliers, and are computationally intractable for large datasets, forcing reliance on heuristic approximations. To address this, we develop an ordinal-similarity framework, instantiated by the Triplet (TSI) and Quadruplet (QSI) Similarity Indices, which measure alignment by quantifying the consistency of ordinal relationships. We theoretically demonstrate this formulation is inherently interpretable, robust to outliers, and computationally efficient. Finally, we establish a formal equivalence between TSI and local neighborhood alignment, measured by Mutual Nearest Neighbors. Empirically, we validate these properties and show that ordinal similarity offers a scalable approach to measuring alignment, enabling practitioners to better understand and design representations.

25.
arXiv (CS.CV) 2026-06-15

GarmentSketch: Large-scale Sketch-to-Fashion Benchmark

Fashion sketching is a cornerstone of design workflows, allowing rapid visualization of creative concepts prior to physical prototyping. Yet, progress in sketch-based fashion image synthesis has been hindered by the absence of large-scale, high-quality paired resources. To bridge this gap, we present GarmentSketch, a novel dataset comprising 26,249 fashion sketches across 21 garment categories, each paired with detailed textual descriptions. Captions were produced through a multi-stage pipeline that integrates multiple multimodal large language models (MLLMs) with human-in-the-loop refinement, ensuring both semantic accuracy and descriptive richness. We benchmark GarmentSketch on state-of-the-art generative models, providing baseline performance for sketch-guided text-to-image generation. Our experiments reveal both the promise and the current limitations of existing methods. By offering a comprehensive and richly annotated resource, GarmentSketch establishes a foundation for advancing sketch understanding, fine-grained fashion image generation, and creative human-AI collaboration in design. The dataset will be available at: https://khangbdd.github.io/garmentsketch.